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Documentação

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Data:

OXYMAG VENTILADOR DE TRANSPORTE

20/10/2010

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Verificado por:

Aprovado por:

Marcelo Onodera

Toru 21/10/2010

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1600185 Folha:

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85 – Dados clínicos, Papers

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1. Objective The objective of this document is to demonstrate the equivalence of essential characteristics of the transport ventilator Oxymag with the devices or functions, which is the subject of published reports listed in the annex. 2. References  

Directive MDD 93/42/EEC – Annex X MEDDEV 2.7.1 - Evaluation of clinical Data

3. Method This document will provide a brief comparative between the Oxymag transport ventilator ventilation modes and the articles listed in the annex. 4. Comparatives 4.1. Volume Controlled Ventilation (VCV) mode Doc 1 -Volume-Controlled Ventilation: Article cited by Anesthesia UK: Draeger Medical. Shows the principles of the VCV ventilation mode which is similar to the Oxymag Ventilator as described in the instruction manual. This article describes a possible risk of lung injury due to high pressures that can be reduced by using pressure-limited ventilation. Anaesthesia UK is an educational site with training resources for anaesthetic professionals. It provides interactive practice questions, journal abstracts and reference articles for the Primary FRCA, Final FRCA, Irish FCARCSI, European Diploma of Anaesthesiology, American Board examinations, and currently receives over 30,000 page views daily. The site currently has over 22,000 registered clinicians. Doc 2 - VCV Mode Application : Article cited by Department of Anesthesiology and Pain Medicine and Pain Research Institute, Yonsei University College of Medicine, Korea. Shows the clinical application of the VCV Mode and its benefits.

4.2. Pressure Controlled Ventilation (PCV) mode Doc 3 - Pressure-Controlled Ventilation: Article cited by Anesthesia UK: Draeger Medical. Shows the principles of the PCV ventilation mode which is similar to the Oxymag Ventilator as described in the instruction manual. Volume-controlled and pressure-controlled ventilation are compared. Anaesthesia UK is an educational site with training resources for anaesthetic professionals. It provides interactive practice questions, journal abstracts and reference articles for the Primary MAGNAMED TECNOLOGIA MÉDICA LTDA


Documentação

F006-02

Projeto:

Data:

OXYMAG VENTILADOR DE TRANSPORTE

20/10/2010

Elaborado por:

Verificado por:

Aprovado por:

Marcelo Onodera

Toru 21/10/2010

Tatsuo 21/10/2010

Objeto / Título do Documento:

Código:

1600185 Folha:

2/6 Revisão:

85 – Dados clínicos, Papers

02

FRCA, Final FRCA, Irish FCARCSI, European Diploma of Anaesthesiology, American Board examinations, and currently receives over 30,000 page views daily. The site currently has over 22,000 registered clinicians. Doc 4 - Pressure-Control Ventilation: Shows the clinical application of the PCV Mode. Doc 5 - Comparativo e Aplicação Clínica do VCV e PCV: Show a comparative study and its clinical application of the VCV and PCV Ventilation Mode using the TAKAOKA´s Anesthesia Machine, model Nikkey. TAKAOKA is the largest manufacturer of anesthesia machine in Brazil. The principles of the VCV and the PCV modes described of this article is the same as described on the instruction manual of the Oxymag Ventilator. In this study, involving healthy children submitted to the general anesthesia using two modes of mechanical ventilation, any interference was observed in the cardio respiratory stability along the surgical period.

4.3. (Volume and Pressure) Synchronized Intermittent Mandatory Ventilation (V-SIMV and PSIMV) mode Doc 6 - Effect_of_Synchronized_Intermittent_Mandatory Ventilation: Article that shows the clinical study of the SIMV Ventilation mode which is described on the instruction manual of Oxymag Ventilator. According to this article, SIMV, pressure support ventilation, assist control ventilation, have been widely used. These types of ventilation are reported to provide good patient–ventilator interaction and to give good results when weaning from mechanical ventilation. This article was published in Anesthesiology - American Society of Anesthesiologists. The American Society of Anesthesiologists is an educational, research and scientific association of physicians organized to raise and maintain the standards of the medical practice of anesthesiology and improve the care of the patient.

4.4. Pressure Support Ventilation (PSV) mode Doc 7 - Pressure Support: Article that shows the impact of the Pressure Support Ventilation on Anesthesia Practice. PSV Mode is implemented in the Oxymag Ventilator as described in the instruction manual. This article shows that the PSV mode is an invaluable addition to the practice of anesthesia. The use of PSV allows patients to breathe spontaneously while reducing the patient’s work of breathing. This can be a clinical benefit in both outpatient and same day surgical anesthesia.PSV provides a new and clinically useful ventilation strategy that was only common in the intensive care units and for the extremely ill pulmonary patient. With PSV in anesthesia, a larger patient population can be served. This article was written by Datex-Ohmeda that is the world’s leading supplier of anesthesia systems, equipment, and services and an emerging leader in critical care. MAGNAMED TECNOLOGIA MÉDICA LTDA


Documentação

F006-02

Projeto:

Data:

OXYMAG VENTILADOR DE TRANSPORTE

20/10/2010

Elaborado por:

Verificado por:

Aprovado por:

Marcelo Onodera

Toru 21/10/2010

Tatsuo 21/10/2010

Objeto / Título do Documento:

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1600185 Folha:

3/6 Revisão:

85 – Dados clínicos, Papers

02

Doc 8 - Performance_Characteristics of Five_New_Anesthesia Ventilators: Shows a comparative study of five anesthesia machines in PSV Ventilation Mode. The characteristics described on table 1 of the study are similar to the PSV Mode described in the instruction manual of the Oxymag Ventilator.

4.5. Continuous Positive Airway Pressure (CPAP) mode

Doc 9 – CPAP Principles: The Oxymag ventilator provides a ventilation mode called CPAP (Continuous Positive Airway Pressure). One of the applications of CPAP ventilation mode is to treat patients with OSAHS (Obstructive Apnoea-Hypopnoea Syndrome). In the first article written by Dr. R. Farré from Barcelona University references that at least 5% and 2% of the adult male and female population respectively are suffering from OSAHS. OSAHS is characterized by recurrent obstructions during sleep caused by an abnormal increase in the collapsibility of the upper airway, which is triggered by several factors, including anatomical alterations and obesity. The short-term symptoms described by OSAHS patients are related to alterations in normal ventilation (choking, gasping or dry mouth) and disruption of sleep architecture caused by recurrent arousals (excessive sleepiness, lack of attention and irritability). Patients with OSAHS have an increased risk of traffic accidents, probably as a result of somnolence. Moreover, the nocturnal events chronically experienced by OSAHS patients contribute to the development of long-term comorbidities, such as cardiovascular and cerebrovascular diseases and inflammatory, metabolic, cognitive and mood alterations. The article follows describing the principle of functioning of CPAP device based on a blower and an exhalation port (intended leak orifice) and practical issues regarding this system. Furthermore, the article presents the principle and practical issues of auto-adjusting CPAP devices. Doc 10 – CPAP Benefits: shows a survey from 204 patients that used a CPAP therapy. A questionnaire was sent to the patients, and they had to answer about use of CPAP, sleepiness and road traffic incidents before and after CPAP, changes in nocturnal and daytime function, problems with CPAP therapy, and weight change. This study documents experience and perceptions of CPAP in a large sample of unselected CPAP users with a wide range of illness severity. Although necessarily limited by its use of mainly selfreported and retrospective information, the study provides evidence of patient-perceived, CPAPinduced improvement across a wide range of function, including sleepiness, driving competence, cognitive function, work efficiency, well-being, and nocturnal symptoms.

4.6. Noninvasive Ventilation (NIV)

Doc 11 - Noninvasive Ventilation for Critical Care: Oxymag ventilator provides a functionality called NIV (Noninvasive Ventilation) where the mechanical ventilation is done by mask instead of intubation. Being an article from CHEST, one of the most worthy references in critical care medicine, this article represents the best practice or reflects the “state of the art” related to this subject. The MAGNAMED TECNOLOGIA MÉDICA LTDA


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OXYMAG VENTILADOR DE TRANSPORTE

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article presents the recommendation of using NIV for different types of patient. This ventilatory assistance without an artificial airway, has emerged as an important ventilatory modality in critical care. This has been fueled by evidence demonstrating improved outcomes in patients with respiratory failure due to COPD exacerbations, acute cardiogenic pulmonary edema, or immunocompromised states, and when NIV is used to facilitate extubation in COPD patients with failed spontaneous breathing trials. NIV for acute respiratory failure: the strongest level of evidence, including multiple randomized controlled trials, supports the use of NIV to treat exacerbations of COPD as a first choice to treat acute respiratory failure. Similarly strong evidence supports the use of noninvasive positive pressure techniques to treat acute cardiogenic pulmonary edema. Another NIV application supported by multiple randomized trials is to facilitate extubation in COPD patients. Immunocompromised Patients: the use of NIV is also well supported for immunocompromised patients who are at high risk for infectious complications from endotracheal intubation, such as those with hematologic malignancies, AIDS, or following solid-organ or bone marrow transplants. In a randomized trial of patients with hypoxemic respiratory failure following solid-organ transplantation, NIV use decreased intubation rate and ICU mortality compared with conventional therapy with oxygen. Asthma: several uncontrolled series and one randomized trial support the use of NIV for acute asthma. Postoperative Respiratory Failure: either NIV or CPAP may be helpful in averting postoperative respiratory failure by preventing atelectasis and/or improving gas exchange as suggested by three randomized controlled trials in patients undergoing different surgical procedures. When used appropriately, NIV improves patient outcomes and the efficiency of care. Although it is still used in only a select minority of patients with acute respiratory failure, it has assumed an important role in the therapeutic armamentarium. With technical advances and new evidence on its proper application, this role is likely to expand.

4.7. Airway Pressure Release Ventilation (APRV) mode Doc 12 - APRV Theory and Practice: The Oxymag ventilator provides a ventilation mode called APRV when the adjustment of I:E ratio in inverted (i.e. inspiratory phase greater than expiratory phase). Airway Pressure Release Ventilation has been described as continuous positive airway pressure (CPAP) with regular, brief, intermittent releases in airway pressure. The release phase results in alveolar ventilation and removal of carbon dioxide (CO2). Airway pressure release ventilation, unlike CPAP, facilitates both oxygenation and CO2 clearance. APRV is consistent with lung protection strategies that strive to limit lung injury associated with mechanical ventilation. The article shows the principle of functioning of this ventilation mode presenting the curve Airway Pressure x Time of the conventional volume targeted ventilation and the curve of APRV. Besides the article presents a table establishing the comparison among other conventional ventilation modes.

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OXYMAG VENTILADOR DE TRANSPORTE

20/10/2010

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Tatsuo 21/10/2010

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1600185 Folha:

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02

The author presents the history of mechanical ventilation in a brief chapter specially showing studies how the mechanical ventilation has been contribute with acute respiratory distress syndrome (ARDS). In this chapter the author describes the goals of the ventilation and how the APRV mode can reach these goals. After this chapter the author present the terminology of the ventilation mode, in other words, how we can adjust this mode in the ventilator. Then the article describes the indication, advantages and disadvantages of this ventilation mode, as described below in a brief table: Advantages: 1. Lower Paw for a given tidal volume compared with volume-targeted modes, e.g., AC, SIMV 2. Lower minute ventilation, i.e., less dead space ventilation 3. Limited adverse effects on cardio-circulatory function 4. Spontaneous breathing possible throughout entire ventilatory cycle 5. Decreased sedation use 6. Near elimination of neuromuscular blockade use Potential Disadvantages: 1. Volumes change with alteration in lung compliance and resistance 2. Process of integrating new technology 3. Limited access to technology capable of delivering APRV 4. Limited research and clinical experience The article describes an application of APRV in a case of acute lung injury and finishes it describing how the ventilation mode can be adjusted in weaning and the conclusions. According to his conclusion, the presence of APRV in the Oxymag will contribute to the increase of clinical practice of this mode and the comparison with other modes. The author shows that there is a lack of weaning consensus, in other words, the use of Oxymag in the weaning can shoot researches.

4.8. Pressure Limited Ventilation (PLV) mode

Doc 13 – PLV: The pressure limited ventilation (PLV) is a ventilation mode that will be provided by Oxymag for neonates. This article shows the cardiopulmonary effects of Pressure Limited Ventilation (PLV) during Acute Lung Injury (ALI), evaluating the gas exchange and hemodynamic effects. This evaluation consisted on measurements of several parameters (right atrial, pulmonary artery, left atrial, arterial, lateral pleural and pericardial pressures, Paw, ventricular stroke volume, mean expired CO2, and arterial and mixed venous oxygen contents, airway resistance and static lung compliance) in seven male mongrel dogs in laboratory. The protocol consisted of observing the effects of various types of positive-pressure ventilation during control and ALI conditions. Hemodynamic variables were averaged over the entire ventilatory cycle and a minimum of three breaths was used to derive mean pressures and stroke volume. Muscle paralysis was induced at the beginning of each condition to abolish spontaneous movement.

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OXYMAG VENTILADOR DE TRANSPORTE

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Results: After ALI, static lung compliance, PaO2, and pH decreased, whereas airway resistance and PaO2 increased. For a constant lung volume, pericardial and pleural pressures were not different between control and ALI. Both absolute dead space and intrapulmonary shunt fraction increased after ALI. Ventilation did not alter hemodynamics during ALI. Conclusions: Changes in lung volume determine pericardial and pleural pressure. PLV strategies do not alter hemodynamics but result in less of an increase in Vd/Vt (dead space / tidal volume) than would be predicted from the obligatory decrease in tidal volume. 5. Conclusion

The technical literature used in this report shows that the ventilation modes of the Oxymag Transport Ventilator are already validated and widely used worldwide. All ventilation modes of the equipment were evaluated using the literature and demonstrated their equivalences. There were no side effects identified and based on the Technical File of the Oxymag Ventilator, specially the Risk Management File and the Safety and Performance Tests register, we can consider that all risks are acceptable when weighed against the intended benefits of the device.

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OXYMAG VENTILADOR DE TRANSPORTE

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Doc 1 – Volume-Controlled Ventilation

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Anaesthesia UK : Volume-controlled ventilation

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Volume-controlled mechanical ventilation is delivered with a constant inspiratory flow, resulting in increasing airway pressure through inspiration. To maintain this fixed rate of gas flow the pressure must rise through inspiration. The actual preset tidal volume remains constant as lung compliance and resistance change. The inspiratory flow rate alters the velocity with which gas flow is delivered (Figure 1). Ventilation with a high inspiratory flow delivers the pre-selected tidal volume more quickly. If the ventilator is time cycled between inspiration and expiration and the tidal volume has been delivered before all the time allowed for inspiration has elapsed, an inspiratory pause occurs and the pressure drops below the peak inspiratory pressure. There is no fresh gas flow during this inspiratory pause. High inspiratory flow during volume-controlled ventilation has detrimental effects on lung ventilation. Therefore, low inspiratory flow rates should be used to keep the peak ventilatory pressure as low as possible. This ensures more homogeneous ventilation.

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The risk of lung injury can be reduced by using pressure-limited ventilation (Figure 2). In older ventilators, pressure limitation stops the inspiratory flow, resulting in a reduction in target tidal volume. In more modern ventilators, once the pressure limit is reached, the flow decelerates to maintain the peak pressure at the pressure limit for the rest of the breath. This ensures the tidal volume delivered is as close to the target tidal volume as possible for the set pressure limit. A pressure limit of 30–35 cm H2O is appropriate in adults. Insert Figure 2

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Doc 2 – VCV Mode Application

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Doc 3 – Pressure-Controlled Ventilation

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Pressure-controlled mechanical ventilation rapidly achieves a fixed pressure throughout the breath by delivering a decelerating inspiratory flow pattern (Figure 3). The result is a tidal volume that varies with lung compliance and resistance. For example, if there is an increase in airway resistance, or reduction in lung compliance, the delivered tidal volume decreases and hypoventilation results. Pressure-controlled ventilation is usually closely monitored with alarms set for a minimal acceptable tidal and/or minute volume. Volume-controlled and pressure-controlled ventilation are compared in Figure 4. Figure 3

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The common modes are as follows. Controlled mandatory ventilation (CMV) with no allowance for spontaneous breathing is the most common mode used in the operating theatre during routine anaesthesia. In synchronized intermittent mandatory ventilation (SIMV) controlled breaths (volume- or pressure-controlled) are delivered to a preset respiratory rate separate from the spontaneous breaths.

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In assist-controlled ventilation, triggered spontaneous breaths are assisted identically to the controlled breaths. In pressure-support ventilation, spontaneous patient breaths trigger a set amount of pressure to assist the breath. Biphasic positive airway pressure (BIPAP) is a mixture of spontaneous breathing and time-driven, pressure-controlled ventilation (Figure 5). This system alternates between two adjustable pressure levels of continuous positive airway pressure (CPAP). Spontaneous breaths are possible at both pressure levels at all times. Cycling between the two levels produces gas flow and a resulting mechanical breath. Figure 5

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Doc 4 – Pressure-Control Ventilation

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Steven Sittig, rrt

Ventilation

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Pressure-Control Ventilation: “Primum non nocere” — Options in Limiting Pulmonary Barotrauma

T

he application of mechanical ventilation is a practice in which the respiratory clinician may face widely varying conditions in a patient’s pulmonary compliance. Decreased compliance in the pulmonary system can lead to significant problems in providing mechanical ventilatory support. The clinician must try to obtain a balance in obtaining acceptable ventilation and oxygenation parameters and the consequences of the needed support on the patient’s lung parenchyma. To use a famous quote credited to Hippocrates: “As to diseases, make a habit of two things — to help, or at least do no harm.” Pressure-control ventilation is most often prescribed for patients with severe adult respiratory distress syndrome (ARDS). ARDS is initially characterized by the formation of noncardiac pulmonary edema and, in later stages, by the formation of hyaline membrane and pulmonary fibrosis. These conditions lead to reduced pulmonary compliance,

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progressive atelectasis, and impaired gas exchange, especially oxygenation.1 Since severe physiologic shunting is the cause of this hypoxemia, it does not respond well to oxygen therapy. This leads to a classic clinical hallmark of ARDS called refractory hypoxemia.2

RTs must always

compliance. By utilizing conventional volume ventilation, the majority of the delivered tidal volume is routed to these normal compliance lung fields. This can lead to overdistension of these areas and further insult to the lung parenchyma.

be aware of the

potential harm that may be caused while providing mechanical ventilation in any situation. This type of patient requires high peak airway inspiratory pressures to deliver preset tidal volumes in the traditional volume-control modes of ventilation. A significant problem with ARDS is that the lung is not uniformly affected. While a majority of the lung fields may have low compliance due to atelectasis, hyaline membrane formation, surfactant deficiency, and pulmonary fibrosis, other lung fields may have normal

Pressure-control ventilation is an alternative mode of controlled ventilation. When a patient is placed on pressurecontrol ventilation, the clinician sets the rate, inspiratory time, positive end-expiratory pressure (PEEP), and, most importantly, the peak airway pressure limit. The ventilator acts as a constant pressure generator, limited to a preset value set by the clinician. Once this pressure is reached, it is held at that level till a limiting


Ve n t i l a t i o n f o r L i f e

factor (such as the end of the inspiratory cycle) occurs. A major advantage in utilizing pressurecontrol mode is that the patient can receive as much inspiratory flow as needed. These inspiratory flows can be as high as 120 to 200 L/min. dependent on the flowlimit capabilities of the ventilator. By limiting the delivered peak airway pressure, the clinician helps limit the pulmonary barotrauma delivered to the lung. The peak alveolar pressure, which is a major factor in ventilatorinduced injury, can climb no higher than the preset pressure. Some researchers have suggested that, due to the relationship of lung injury to hyperinflation, the term barotrauma should be replaced by the term volutrauma. These

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researchers feel this volutrauma is not caused by the peak airway pressure or the PEEP level but the difference found across the alveolus known as the transalveolar pressure. In a normal subject, a transalveolar of 30–35 cm H2O achieves the alveolar size associated with total lung capacity. Therefore, it is not surprising to associate trauma to alveolar membranes with repeated exposure to tidal transalveolar pressures greater than 35 cm H2O. This mechanical ventilation-induced trauma produces alveolar membranes that are susceptible to becoming permeable to water and protein. Initial settings

When the decision is made to institute pressure-control ventilation, many important clinical decisions must be made to ensure the new ventilator settings are not doing more harm than good. When pressure-control ventilation is instituted, the clinician must set the maximal delivered peak pressure, PEEP level, inspiratory time, and rate. Remember that in pressurecontrol ventilation, delivered tidal volume, minute volume, and alveolar ventilation is a product of the set peak pressure, inspiratory time, and compliance of the respiratory system. Determining the correct initial set peak pressure when converting to pressurecontrol ventilation from volume-control ventilation can be a challenge; the clinician must try to use a set peak pressure that will deliver approximately the same tidal volume that was being delivered

during volume ventilation. This peak pressure level can be calculated by determining the difference in pressure between the end inspiratory plateau pressure and the set PEEP level during a volume-controlled breath. As stated earlier, set peak pressures greater than 35 cm H2O should be avoided if possible to help decrease insult to the alveolar membranes. Due to the heterogenous nature of the lung injury seen in ARDS, a minimal level of PEEP needs to be applied to prevent tidal end expiratory collapse of the edematous airway tissue. When this tissue collapses, there is a decrease in respiratory system compliance; and distinct points of inflection are noted on the static pressure volume curve. Application of PEEP levels above this lower point of inflection on the pressure volume curve known as the “Pflex” is thought to be beneficial, but determining an accurate value for the deflection point has been reported as imprecise when estimating it off static pressure volume curves.3 Providing this minimal level of PEEP support, it is felt, prevents the recurring process of alveolar tidal recruitment and subsequent collapse. It is also felt that this minimal PEEP level may help limit progressive microatelectasis and inactivation of surfactant.4 A minimum level of 7–12 cm H2O has been suggested as a good starting point. If higher levels of PEEP are implemented, it is recommended that a pulmonary artery catheter be placed so that cardiac function may be accurately assessed.


Ve n t i l a t i o n f o r L i f e

The next parameter that is vital in determining delivered tidal volume is the set inspiratory time. A lot of the literature on pressure-control ventilation concerns the use of prolonged inspiratory times and inverse inspiratory-to-expiratory-time ratios (I:E). This facet of pressure-control ventilation helps increase delivered mean airway pressure (Paw) and helps improve oxygenation.5 The downside to this is that it is very uncomfortable for the patient. Most have to be sedated and paralyzed in order to maximize the benefits. The possible need for prolonged pharmacological paralysis can have severe longterm consequences, almost as severe as ARDS itself. I had the privilege of hearing a lecture by Marshall L. Post, RRT, about pressure-control ventilation at the AARC International Respiratory Congress in New Orleans in 1997. In his lecture he described how he and his staff used graphics to optimize the set inspiratory time. By using this real-time diagnostic tool, they were able to maximize the set inspiratory time and delivered tidal volume without developing auto-PEEP. The set respiratory rate and inspiratory time were manipulated to allow both inspiratory and expiratory flow to reach baseline. It allowed them to pressure ventilate the patient without subjecting the patient to the possible long-term harm that could have been caused by prolonged paralysis and sedation. Newer-generation ventilators now offer a combination of pressure-control and volume-

control modes of ventilation. In this combined pressure-control volume-regulated mode, the delivered peak pressure is limited; but a set tidal volume and minute volume can be delivered. Then, even if compliance changes, set minute ventilation is guaranteed and peak pressure is limited. For those of you who have read this article and have wondered what the phrase “primum non nocere” means, it is a tenet credited to Hippocrates and used in the Hippocratic oath. It means, “First Do No Harm.” We as respiratory clinicians must always be aware of the potential harm that may be caused while providing mechanical ventilation in any situation. •

Trauma-Injury Infection and Critical Care, 45(2), 268-272. ADDITIONAL READING Tobin, M.J. (Ed.). (1994). Principles and practice of mechanical ventilation. New York: McGraw-Hill.

Steven Sittig is a pediatric respiratory therapist at Mayo Clinic in Rochester, MN. REFERENCES 1. Luce, J.M. (1998). Acute lung injury and the acute respiratory distress syndrome. Critical Care Medicine, 26(2), 369-376. 2. Fulkerson, W.J., MacIntyre, N., Stamler, J., & Crapo, J.D. (1996). Pathogenesis and treatment of the adult respiratory distress syndrome. Archives of Internal Medicine, 156(1), 29-38. 3. O’Keefe, G.E., Gentilello, L.M., Erford, S., & Maier, R.V. (1998). Imprecision in lower “inflection point” estimation from static pressurevolume curves in patients at risk for acute respiratory distress syndrome. Journal of Trauma-Injury Infection & Critical Care, 44(6), 1064-1068. 4. Verbrugge, S.J., Sorm, V., & Lachmann, B. (1997). Mechanisms of acute respiratory distress syndrome: Role of surfactant changes and mechanical ventilation. Journal of Physiology and Pharmacology, 48(4), 537-557. 5. Gore, D.C. (1998). Hemodynamic and ventilatory effects associated with increasing inverse inspiratoryexpiratory ventilation. Journal of

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85 – Dados clínicos, Papers

01

Doc 5 – Comparativo e Aplicação Clínica do VCV e PCV

MAGNAMED TECNOLOGIA MÉDICA LTDA


  

     

                  

                             

   

    

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Documentação

F006-02

Projeto:

Data:

OXYMAG VENTILADOR DE TRANSPORTE

20/10/2010

Elaborado por:

Verificado por:

Aprovado por:

Marcelo Onodera

Toru

Tatsuo

Objeto / Título do Documento:

Código:

1600185 Folha:

1/1 Revisão:

85 – Dados clínicos, Papers

01

Doc 6 – Effect of Synchronized Intermittent Mandatory Ventilation

MAGNAMED TECNOLOGIA MÉDICA LTDA


Anesthesiology 2001; 95:881– 8

© 2001 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.

Effect of Synchronized Intermittent Mandatory Ventilation on Respiratory Workload in Infants after Cardiac Surgery Hideaki Imanaka, M.D.,* Masaji Nishimura, M.D.,† Hiroshi Miyano, M.D.,* Hideki Uemura, M.D.,‡ Toshikatsu Yagihara, M.D.§

of breathing (WOB).1,2 SIMV assists the spontaneous breathing of the patient with a preset number of ventilator-delivered breaths each minute. Because it can flexibly provide ventilatory support over a range of levels, SIMV has two main indications: as a primary means of ventilatory support and as a weaning tool.1 Weaning involves a gradual decrease in the number of mandatory breaths and an increase in the proportion of the ventilatory requirement assumed by the patient. Recently, SIMV using continuous flow, time- and patient-cycled, pressure-limited ventilation has been applied to infants and children.3–5 SIMV is superior to conventional intermittent mandatory ventilation because it improves patient breathing patterns and oxygenation.4 –7 However, reports about the effects of SIMV on the respiratory workloads of infants are few.8 It remains to be clarified whether infants respond by increasing tidal volume as well as the frequency of spontaneous breaths when we progressively increase the load to breathing, in this case by decreasing SIMV rates. Given the difference in respiratory control mechanisms between adults and infants,9 this answer is not obvious. In adults, WOB decreases as the SIMV rate increases.1,10 –12 When SIMV is used to wean adult patients from mechanical ventilation, the rate of SIMV is usually decreased gradually, depending on the patient’s tolerance. Extubation is performed when the SIMV rate is successfully reduced to less than 5 breaths/min.2 However, no study has shown that this protocol is similarly valid when weaning infants from the ventilator. We tested the hypothesis that pressure control SIMV reduces the respiratory workloads of infants in proportion to the SIMV rate and examined which SIMV rate in infants provides respiratory workloads most similar to those after extubation.

Background: Synchronized intermittent mandatory ventilation (SIMV) is commonly used in infants and adults. However, few investigations have examined how SIMV reduces respiratory workload in infants. The authors evaluated how infants’ changing respiratory patterns when reducing SIMV rate increased respiratory load. The authors also investigated whether SIMV reduces infant respiratory workload in proportion to the rate of mandatory breaths and which rate of SIMV provides respiratory workloads similar to those after tracheal extubation. Methods: When 11 post– cardiac surgery infants aged 2–11 months were to be weaned with SIMV, the authors randomly applied five levels of mandatory breathing: 0, 5, 10, 15, and 20 breaths/min. All patients underwent ventilation with SIMV mode: pressure control ventilation, 16 cm H2O; inspiratory time, 0.8 s; triggering sensitivity, 0.6 l/min; and positive endexpiratory pressure, 3 cm H2O. After establishing steady-state conditions at each SIMV rate, arterial blood gases were analyzed, and esophageal pressure, airway pressure, and airflow were measured. Inspiratory work of breathing, pressure–time products, and the negative deflection of esophageal pressure were calculated separately for assisted breaths, for spontaneous breaths, and for total breaths per minute. Measurements were repeated after extubation. Results: As the SIMV rate decreased, although minute ventilation and arterial carbon dioxide tension were maintained at constant values, spontaneous breathing rate and tidal volume increased. Work of breathing, pressure–time products, and negative deflection of esophageal pressure increased as the SIMV rate decreased. Work of breathing and pressure–time products after extubation were intermediate between those at a SIMV rate of 5 breaths/min and those at 0 breaths/min. Conclusion: When the load to breathing was increased progressively by decreasing the SIMV rate in post– cardiac surgery infants, tidal volume and spontaneous respiratory rate both increased. In addition, work of breathing and pressure–time products were increased depending on the SIMV rate.

PATIENT-TRIGGERED ventilation (PTV), which includes synchronized intermittent mandatory ventilation (SIMV), assist control ventilation, and pressure support ventilation, is commonly used in adults because patient–ventilator synchrony is thought to enhance patient acceptance of mechanical ventilation and decrease the work

Subjects and Methods The study was approved by the ethics committee of the National Cardiovascular Center (Osaka, Japan), and written informed consent was obtained from the parents of each patient.

* Staff Physician, Surgical Intensive Care Unit, ‡ Staff Surgeon, Department of Cardiovascular Surgery, National Cardiovascular Center. † Associate Professor, § Director, Intensive Care Unit, Osaka University Hospital, Osaka, Japan. Received from the Surgical Intensive Care Unit, National Cardiovascular Center, Osaka, Japan. Submitted for publication January 19, 2001. Accepted for publication May 22, 2001. Support was provided solely from institutional and/or departmental sources. Presented in part at the International Conference of American Thoracic Society and American Lung Association, Toronto, Canada, May 8, 2000.

Patients Eleven infants who had undergone cardiac surgery to repair congenital heart disease were included in this study (table 1). Enrollment criteria were: (1) corrective surgery for cardiac anomalies; (2) stable hemodynamics;

Address reprint requests to Dr. Imanaka: Surgical Intensive Care Unit, National Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita, Osaka, Japan 565-8565. Address electronic mail to: imanakah@hsp.ncvc.go.jp. Individual article reprints may be purchased through the Journal Web site, www.anesthesiology.org.

Anesthesiology, V 95, No 4, Oct 2001

881


IMANAKA ET AL.

882

Table 1. Patient Profile Age BW Height No. (months) (kg) (cm) Gender Diagnosis 1 2 3 4 5

10 11 2 7 3

8.10 10.6 4.46 4.78 3.37

67 81 57 64 59

F M M F M

6 7 8

7 11 5

4.32 8.45 4.46

61 74 59

F F F

3.42 9.00 6.14 6.10

57 71 68 65

F F F

9 6 10 11 11 7 Mean 7.3

Operation

CPB ETT Size (min) (mm ID)

VSD VSD closure 91 VSD VSD closure 80 VSD VSD closure 80 ASD ASD closure 37 VSD, VSD and ASD closure 82 ASD VSD, MR VSD closure, MVP 91 VSD VSD closure 75 VSD, VSD and ASD closure 56 ASD VSD VSD closure 137 VSD VSD closure 73 VSD VSD closure 80 80.2

CRS (ml 䡠 cm H2O⫺1 䡠 kg⫺1)

CCW Length of MV (ml 䡠 cm H2O⫺1 䡠 kg⫺1) FIO2 (h)

4.0 4.5 4.0 3.5 3.5

1.00 1.26 0.64 1.26 1.13

5.67 3.65 2.94 7.39 7.52

0.4 0.35 0.4 0.4 0.4

3 4 5 6 7

4.0 4.5 4.0

0.67 0.98 1.36

2.53 3.45 4.00

0.4 0.5 0.4

4 7 5

3.5 4.5 3.5

0.99 0.83 0.78 0.99

4.90 4.75 2.68 4.50

0.4 0.4 0.5 0.41

5 5 5 5.1

BW ⫽ body weight; CPB ⫽ duration of cardiopulmonary bypass; ETT ⫽ endotracheal tube; CRS ⫽ compliance of the respiratory system; CCW ⫽ compliance of the chest wall; FIO2 ⫽ inspired oxygen fraction; MV ⫽ mechanical ventilation; VSD ⫽ ventricular septal defect; ASD ⫽ atrial septal defect; MR ⫽ mitral regurgitation; MVP ⫽ mitral valve plasty.

and (3) leakage around the uncuffed endotracheal tube (3.5– 4.5 mm ID) of less than 5% of the inspired tidal volume (VT). We excluded candidates if they had chronic lung disease, central nervous system disorders, postoperative phrenic nerve damage, or any metabolic disorder. We diagnosed phrenic nerve damage if (1) the attempt to wean infants from mechanical ventilation was unsuccessful, (2) abnormal elevation of the unilateral diaphragm was noted on the chest radiograph during continuous positive airway pressure or after extubation, and (3) paradoxical movement of the affected hemidiaphragm was confirmed by fluoroscopic imaging. All patients were kept in the supine position during the measurements. Arterial blood pressure, heart rate, central venous pressure, and pulse oximeter signal (PM-1000; Nellcor Inc., Hayward, CA) were monitored continuously in all patients. No sedatives or opioids were administered during the measurement, although fentanyl (23– 47 ␮g/kg total) and midazolam (0.36–1.61 mg/kg) had been administered during the surgery (145–375 min). We did not use neuromuscular blocking agents or any reverse. Measurements Flow, volume, and airway pressure (Pao) were measured at the airway opening. A heated pneumotachometer (range, 0 –35 l/min; model 3500; Hans-Rudolph Inc., Kansas City, MO) was placed at the proximal end of the endotracheal tube. The pressure difference across the pneumotachometer was measured with a differential pressure transducer (TP-602T, ⫾5 cm H2O; Nihon Kohden, Tokyo, Japan), amplified (AR-601G; Nihon Kohden), and converted to flow values. Volume was calculated from digital integration of flow using data acquisition software (Windaq; Dataq Instruments Inc., Akron, OH). Intrapleural pressure was estimated from esophageal pressure (Pes). An esophageal balloon (6 French; Bicore, Irvine, CA) was introduced transnaAnesthesiology, V 95, No 4, Oct 2001

sally and positioned in the lower third of the esophagus. The balloon was inflated with 0.2 ml air at the start of each measurement. The position of the esophageal balloon was adjusted using an occlusion technique when the patients regained spontaneous breathing.13,14 We compared the maximal deflection in Pes with the maximal deflection in Pao while the infants made respiratory effort against occlusion of the airway opening. When the ratio of Pes to airway pressure was maximal (⬎ 0.95), we secured the position of the balloon. Pes and Pao at the proximal end of the endotracheal tube were measured using differential pressure transducers (TP-603T, ⫾50 cm H2O; Nihon Kohden) and amplified (AR-601G). Respiratory inductive plethysmography (RIP; SY07 Respitrace Plus; NIMS, Miami Beach, FL) was used to estimate inspiratory time (TI), VT, and asynchrony between the rib cage and the abdomen. A rib cage band was positioned at the nipple line, and an abdomen band was positioned 0.5 cm below the umbilicus. Baseline calibrations for RIP were made using the qualitative diagnostic calibration procedure.15 Maximum compartment amplitude (MCA) was calculated as the sum of the absolute value from trough to peak of the rib cage and abdominal compartments, regardless of their timing in relation to the sum signal.15 When the motions of the rib cage and the abdomen are in phase, the ratio of MCA/VT is equivalent to 1.0, where VT is calculated from the summed signal of the rib cage and the abdomen. When the motions are out of phase, the ratio of MCA/VT exceeds 1.0. The airway and esophageal pressure transducers were simultaneously calibrated at 20 cm H2O using a water manometer. Flow was calibrated at 10 l/min with a calibrated flowmeter (P/N 9220; Bird Corp., Palm Springs, CA) using a gas mixture with exactly the same oxygen concentration for each patient. Volume was calibrated with a 50-ml calibration syringe.


EFFECTS OF SIMV ON WOB IN INFANTS

883

Study Protocol We used V.I.P. Bird ventilators (Bird Corp.) with continuous flow, time- and patient-cycled, pressure-limited ventilation. Initial ventilatory settings were as follows: assist control mode; positive end-expiratory pressure, 3 cm H2O; pressure control ventilation, 16 cm H2O; TI, 0.8 s; continuous flow, 20 l/min; and triggering sensitivity, 0.6 l/min. The inspired oxygen fraction (FIO2) was adjusted by attending physicians to maintain an arterial oxygen pressure (PaO2) greater than 100 mmHg. We started taking measurements when the patients had recovered spontaneous breathing in the surgical intensive care unit and had satisfied our weaning criteria: ratio of PaO2 to FIO2 greater than 200; pH greater than 7.30; VT greater than 5 ml/kg; and respiratory rate less than 50 breaths/min at a backup ventilatory rate of 6 breaths/min and a pressure control of 7 cm H2O.14 Next, we measured compliance of the respiratory system (CRS) and chest wall (CCW). After hyperventilating the patients for 2 or 3 min to lessen their inspiratory efforts, we switched ventilatory settings to TI of 1.5–2 s, respiratory rate of 10 breaths/min, and pressure control of 16 cm H2O. At the end-inspiratory phase, conditions of zero gas flow to permit the measurement of quasi-static compliance were confirmed on the computer display that we used to monitor data acquisition (fig. 1). Compliance was calculated using the following formulas16: CRS ⫽ VT/共end-inspiratory Pao ⫺ end-expiratory Pao兲 CCW ⫽ VT/共end-inspiratory Pes ⫺ end-expiratory Pes兲 We repeated the measurements five times and averaged them. Then, we switched the ventilatory mode to SIMV. Five levels of mandatory breathing (0, 5, 10, 15, and 20 breaths/min) were applied in random order, with pressure control ventilation of 16 cm H2O, TI of 0.8 s, positive end-expiratory pressure of 3 cm H2O, continuous flow of 20 l/min, triggering sensitivity of 0.6 l/min, and termination sensitivity of 5% of the peak inspiratory flow. Randomization was performed using computergenerated numbers. A setting of zero-rate SIMV is equivalent to a continuous positive airway pressure of 3 cm H2O. After establishing steady-state conditions (approximately 15 min), airflow, Pao, Pes, rib cage signals, and abdominal signals of RIP were recorded. All these signals were digitally recorded at a sampling rate of 100 Hz for each parameter (Windaq) during the last 5 min at each setting. Arterial blood samples were analyzed with a calibrated blood gas analyzer (ABL 505; Radiometer, Copenhagen, Denmark). All subjects underwent successful extubation 90 min after completion of all measurements. After extubation, we waited at least 60 min and repeated the measurement of Pes, rib cage signals, and abdominal signals of RIP and arterial blood gas analysis during quiet breathing. We did Anesthesiology, V 95, No 4, Oct 2001

Fig. 1. Quasi-static measurement of compliance. Flow, airway pressure (Pao), and volume (Vol) tracings in patient 5 after hyperventilation. At the end-inspiratory phase, conditions of zero gas flow were observed. See text for details. Ventilatory settings: inspiratory time of 2 s, respiratory rate of 10 breaths/ min, and pressure control of 16 cm H2O.

not measure the flow directly after extubation because it was likely that the stimuli of face masks would alter the patients’ inspiratory patterns. Instead, we computed the volume using RIP signals.14,15 Data Analysis The respiratory workload was assessed at mandatory rates of 0, 5, 10, 15, and 20 breaths/min and during unassisted breathing after extubation. The onset of inspiration was defined as the point at which Pes started to decrease. The end of inspiration was determined in two ways: (1) as the zero crossing of inspiratory flow during mechanical ventilation (fig. 2) or (2) as the peak of the RIP value after extubation. We confirmed that the values of each definition of TI were equivalent during mechanical ventilation (precision and bias, 0.01 ⫾ 0.04 s). TI, the ratio of inspiratory time to total respiratory cycle time (TI/TT), and respiratory rate were calculated using the flow or RIP signal. VT and minute ventilation were obtained from the expiratory flow. Inspiratory WOB done by the patient was computed as previously described.7,11,17 First, we established a Campbell diagram, which consisted of the inspiratory Pes/VT


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Pes to estimate the inspiratory muscle load. The PTP for each respiratory cycle was calculated as the area subtended by the Pes tracing and the chest wall static recoil pressure for inspiratory time (fig. 2). The chest wall static recoil pressure curve was obtained from values for CCW and volume. The PTP per breath (PTPb; cm H2O · s) was calculated both for assisted and for spontaneous breaths. The PTP per minute (PTP/min; cm H2O · s · min⫺1) was obtained in the same manner as was WOB/min. Negative deflection of esophageal pressure (⌬Pes) was also measured as the maximal negative excursion from the baseline over breath. After extubation, values for VT, minute ventilation, WOB, PTP, and MCA/VT were calculated from the volume obtained by the RIP. All recorded breaths for 5 min were analyzed at each SIMV rate. The values of respiratory rate, VT, ⌬Pes, WOB, and PTP were averaged separately for assisted breaths, for spontaneous breaths, and for the total of all breaths. Statistical Analysis Data are presented as mean ⫾ SD. Using repeatedmeasures analysis of variance, mean values were compared across different levels of ventilatory support (SIMV rate of 0, 5, 10, 15, and 20 breaths/min, and after extubation). When significance was observed, multiple comparison testing of means was performed using the paired Student t test with Bonferroni correction. Comparisons between data for the spontaneous and assisted cycles at each SIMV rate were made by the two-tailed Student t test. Statistical significance was set at P ⬍ 0.05.

Results Fig. 2. Airway pressure (Pao), flow (inspiration upward), and esophageal pressure (Pes) tracings in patient 10. Pressure–time product was calculated using the integral of the difference between Pes and the chest wall recoil pressure. Work of breathing was calculated using the Campbell diagram. See text for details. The first and second vertical broken lines show the start and end of inspiration. The hatched area represents integration of the Pes versus either time or volume. The dotted area shows contribution of the chest wall recoil pressure to pressure–time product or work of breathing.

curve and chest wall compliance curve (fig. 2, bottom). Then we evaluated WOB per breath during each respiratory cycle by computing the area bound by the two curves. WOB per liter of ventilation (WOB/l; J/l) was computed as WOB per breath divided by the breath’s tidal volume. WOB/l was expressed separately for assisted breaths and for spontaneous breaths. WOB per minute (WOB/min; J · min⫺1 · kg⫺1) was calculated as the total inspiratory work done by the patient during both assisted and spontaneous cycles in 1 min and was normalized by body weight. The pressure–time product (PTP) is regarded as an index of oxygen cost of breathing of the respiratory muscles as well as WOB17–19: here, we used the PTP of Anesthesiology, V 95, No 4, Oct 2001

The infants ranged in age from 2 to 11 months (median, 7 months), and body weight ranged from 3.37 to 10.6 kg (table 1). Mean duration of cardiopulmonary bypass was 80 min (table 1). In six patients with a body weight less than 5 kg, blood priming and modified ultrafiltration (150 –1,170 ml) were applied during cardiopulmonary bypass. All patients underwent successful extubation within 7 h after the study, and no side effects were noted through this study. Table 2 shows respiratory parameters under each ventilatory setting. As the SIMV rate was reduced, the frequency of spontaneous breaths and total breaths increased without significant change in T I/T T. The minute ventilation was kept stable within the range of 221–254 ml · min⫺1 · kg⫺1 at all SIMV rates. At each SIMV rate, VT was greater in assisted breaths than in spontaneous breaths (P ⬍ 0.01). As the SIMV rate decreased, VT increased significantly both during spontaneous breaths and during assisted breaths (P ⬍ 0.01). pH, arterial carbon dioxide pressure (PaCO2), PaO2, heart rate, arterial blood pressure, and central venous pressure were not affected significantly by the SIMV setting.


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Table 2. Parameters at Each Ventilatory Setting SIMV Rate (breaths/min)

Respiratory rate (breaths/min) SB rate (breaths/min) SIMV rate (breaths/min) Inspiratory time (s) TI/TT Minute ventilation (ml 䡠 min⫺1 䡠 kg⫺1) Tidal volume SB (ml/kg) SIMV (ml/kg) pH PaCO2 (mmHg) PaO2 (mmHg) Heart rate (beats/min) Systolic BP (mmHg) Mean BP (mmHg) CVP (mmHg)

20

15

10

5

0

After Extubation

22.8 ⫾ 4.2 2.8 ⫾ 4.3 20.0 ⫾ 0.2 0.89 ⫾ 0.07 0.34 ⫾ 0.07 254 ⫾ 37

24.4 ⫾ 5.6 9.2 ⫾ 5.6*† 15.1 ⫾ 0.3 0.88 ⫾ 0.07 0.35 ⫾ 0.08 239 ⫾ 36

26.2 ⫾ 5.3 16.2 ⫾ 5.4*† 10.1 ⫾ 0.2 0.84 ⫾ 0.09 0.36 ⫾ 0.05 233 ⫾ 38

28.3 ⫾ 4.9* 23.3 ⫾ 4.8*†‡ 5.0 ⫾ 0.1 0.80 ⫾ 0.10 0.37 ⫾ 0.04 225 ⫾ 40

28.4 ⫾ 6.0* 28.4 ⫾ 6.0*†‡§ ND 0.80 ⫾ 0.14 0.37 ⫾ 0.04 221 ⫾ 43

31.1 ⫾ 6.7*†‡ 31.1 ⫾ 6.7*†‡§ ND 0.66 ⫾ 0.11*†‡§ 0.33 ⫾ 0.05 229 ⫾ 54

4.4 ⫾ 0.9 12.1 ⫾ 2.0 7.43 ⫾ 0.04 40.1 ⫾ 4.3 172 ⫾ 24 146 ⫾ 13 101 ⫾ 13 74 ⫾ 10 7.8 ⫾ 2.6

5.2 ⫾ 0.8 12.6 ⫾ 1.9 7.42 ⫾ 0.04 42.2 ⫾ 3.9 162 ⫾ 29 147 ⫾ 15 99 ⫾ 12 74 ⫾ 9 7.8 ⫾ 2.4

6.0 ⫾ 1.1 13.4 ⫾ 2.2 7.41 ⫾ 0.03 42.7 ⫾ 4.8 167 ⫾ 27 147 ⫾ 15 101 ⫾ 12 74 ⫾ 8 8.0 ⫾ 2.1

6.7 ⫾ 1.2*† 13.9 ⫾ 2.2*† 7.41 ⫾ 0.03 43.2 ⫾ 5.0 160 ⫾ 24 146 ⫾ 17 101 ⫾ 13 75 ⫾ 7 7.7 ⫾ 2.1

7.8 ⫾ 0.9*†‡§ ND 7.41 ⫾ 0.04 43.2 ⫾ 4.8 159 ⫾ 29 146 ⫾ 17 102 ⫾ 15 75 ⫾ 9 8.2 ⫾ 2.4

7.4 ⫾ 1.0*† ND 7.41 ⫾ 0.04 41.7 ⫾ 4.4 189 ⫾ 85 143 ⫾ 13 100 ⫾ 8 75 ⫾ 6 7.5 ⫾ 1.9

After extubation, volume was measured by respiratory inductive plethysmography. * P ⬍ 0.05 versus SIMV 20.

† P ⬍ 0.05 versus SIMV 15.

‡ P ⬍ 0.05 versus SIMV 10.

§ P ⬍ 0.05 versus SIMV 5.

SIMV ⫽ synchronized intermittent mandatory ventilation; SB ⫽ spontaneous breath; ND ⫽ not detected; TI/TT ⫽ a ratio of inspiratory time to total respiratory cycle time; PaCO2 ⫽ arterial carbon dioxide tension; PaO2 ⫽ arterial oxygen tension; BP ⫽ blood pressure; CVP ⫽ central venous pressure.

Figure 3 is a representative tracing of the Pes for mandatory breaths and for spontaneous breaths at five levels of SIMV and breathing after extubation. Reducing the SIMV rates resulted in greater negative deflection in Pes both for mandatory breaths and for spontaneous breaths. After extubation, the negative deflection in Pes was smaller than at the SIMV rate of 0 breaths/min (table 3). Work of Breathing and Pressure–Time Products As the SIMV rate was decreased, WOB increased in proportion on both a per-liter basis (fig. 4) and a perminute basis (table 3). After extubation, WOB was larger than at SIMV rates of 15 and 20 breaths/min (P ⬍ 0.05); WOB after extubation was equivalent to a value intermediate between that at 0 breaths/min SIMV and that at 5 breaths/min SIMV. Similarly, the values of PTP/min increased in accordance with withdrawal of SIMV rates (fig. 5 and table 3). After extubation, values of PTP/min were equivalent to values intermediate between those at 0 and 5 breaths/min SIMV and were significantly larger than at SIMV rates of 15 and 20 breaths/min (P ⬍ 0.05). The values of MCA/VT observed in RIP were approximately equal to 1.0 at high rates of SIMV, whereas they tended to increase when the SIMV rate was decreased (table 3).

Discussion The main findings of this study are: (1) when the rate of assisted breaths during SIMV was decreased, VT during spontaneous breaths increased, the respiratory rate increased, and minute ventilation and PaCO2 remained constant; (2) in proportion to the rate of assisted breaths, Anesthesiology, V 95, No 4, Oct 2001

SIMV reduced WOB, PTP, and ⌬Pes; and (3) WOB and PTP values after extubation were intermediate to those found between 5 and 0 breaths/min SIMV. Clinical Implications In adults, increasing the SIMV rate decreases respiratory work.1,10 –12 This finding has been empirically extrapolated to infants, and applying SIMV and then gradually decreasing the SIMV rate has been used as a means of weaning infants from mechanical ventilation.3 We undertook this study because in the absence of an extensive body of experimental evidence, it was difficult to be confident about how effective the SIMV weaning strategy is for infants. Our findings show that the respiratory workload of infants decreases directly in proportion to the SIMV rate. WOB and PTP values increased in a linear manner as the rate of SIMV was decreased from 20 to 0 breaths/min. When the SIMV rate was reduced, VT increased, respiratory rate increased, and the same minute ventilation was maintained. These results suggest that SIMV may be effective as a weaning strategy for infants. Patient-triggered Ventilation and SIMV In adults, SIMV, pressure support ventilation, assist control ventilation, and other types of PTV have been widely used. These types of PTV are reported to provide good patient–ventilator interaction and to give good results when weaning from mechanical ventilation.2 Although technological innovation, in particular of the sensors and microprocessors that control ventilators, has made it possible to extend PTV to pediatric patients, there are few reports of experimental investigations into


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Fig. 3. Representative tracings of esophageal pressure. (Left) Mandatory breath. (Right) Spontaneous breath. (Top to bottom) Synchronized intermittent mandatory ventilation (IMV) rates of 20, 15, 10, 5, and 0 breaths/min, and after extubation.

the application of PTV to small children. Greenough et al.20 evaluated the triggering function of PTV machines in neonates, while Bernstein and Cleary4 – 6 evaluated patient–ventilator synchrony during PTV. Jarreau et al.7 demonstrated that PTV with peak inspiratory pressures of 10 and 15 cm H2O reduces WOB in infants more than

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conventional intermittent mandatory ventilation does. Dimitriou et al.8 suggested that assist control ventilation provides faster weaning compared with SIMV, although they did not evaluate WOB. SIMV has proved superior to conventional intermittent mandatory ventilation because of its delivery of a larger and more consistent tidal volume,4 improved oxygenation in neonates with respiratory distress syndrome,5 and reduction of mean airway pressure at similar oxygenation index values.6 In these studies, the focus has been on neonate–ventilator synchrony and on gas exchange. For infants, we could find only limited information regarding (1) how infants change respiratory pattern when increasing respiratory load during SIMV, (2) whether infants’ WOB is reduced in proportion to the SIMV rate, and (3) the SIMV rates at which infants should undergo extubation. To our knowledge, the current study is the first to evaluate respiratory workloads in infants from near-full SIMV support to postextubation spontaneous breathing. We found that respiratory workload was reduced in proportion to the level of SIMV, which is not the case in adults.10,11 In these post– cardiac surgery infants, we detected small amounts of respiratory work at a high level of SIMV, whereas in ventilator-dependent adults, WOB was found to be high at all levels of SIMV.10,11 Leung et al.12 recently found that increasing levels of SIMV and pressure support ventilation cause progressive and proportional decreases in the PTP/min values of adults. Our protocol involved infants who had undergone cardiac surgery. When the lungs of such patients are inflated with relatively high peak inspiratory pressure (19 cm H2O) during SIMV, the Hering-Breuer reflex may suppress their inspiratory efforts more efficiently than it does in adults. In fact, we found that inspiratory effort was less at high SIMV rates and that this resulted in greater triggering delay and longer inspiratory time (table 2). Second, the infants in our study showed near-normal lung mechanics21 (respiratory system compliance of healthy infants at

Fig. 4. Work of breathing per liter (WOB/l) at synchronized intermittent mandatory ventilation (SIMV) rates of 20, 15, 10, 5, and 0 breaths/min, and after extubation. (Left) Mean WOB/l for all breaths. (Right) WOB/l presented separately for spontaneous (SB) and assisted breaths (SIMV). *P < 0.05 versus SIMV rates of 20 breaths/min; †P < 0.05 versus 15 breaths/min; ‡P < 0.05 versus 10 breaths/min; §P < 0.05 versus 5 breaths/min.

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Fig. 5. Pressure–time products per minute (PTP/min) for each patient. The values are presented after combining spontaneous and assisted breaths. SIMV ⴝ synchronized intermittent mandatory ventilation.

1–12 months, 1.3–2.1 ml · cm H2O⫺1 · kg⫺1) and gas exchange status (table 1), whereas in previous reports on adults,10,11 the patients were dependent on mechanical ventilation because of acute lung disease in the medical intensive care unit10 or acute exacerbation of chronic obstructive pulmonary disease.11 The normal lung mechanics and lower respiratory drives of the infants in our study may have reduced the SIMV requirement. Infants and children with primary lung diseases would respond differently to decreases in SIMV rates.

Third, our protocol was conducted with continuous flow and flow-triggered SIMV, whereas previous reports used pressure triggering without continuous flow. During pressure-triggered SIMV, insufficient flow delivery during early inspiration may increase WOB during spontaneous breathing cycles because the demand valve circuitry is not responsive enough for efficient synchronization.1 In contrast, continuous flow and flow triggering may require less absolute work during spontaneous cycles and may provide more efficient support at low SIMV rates than demand valve systems.22–24 Fourth, we applied a mode of pressure control ventilation, whereas previous reports on adults used volume-controlled ventilation with a fixed flow supply profile. Pressure control ventilation reduces breathing effort more effectively than volume-controlled ventilation does when used in conjunction with flow triggering.23,24 The flow profile during pressure target ventilation may provide better synchrony from a low level to a high level of SIMV support. Extubation In the infants we studied, who had relatively normal lung mechanics and gas exchange status, WOB, PTP, and ⌬Pes values after extubation were intermediate between those at SIMV of 5 and 0 breaths/min. During continuous positive airway pressure, although values for WOB and PTP tended to be higher than at SIMV of 5 breaths/min and after extubation, the differences did not reach significance. Provided that clinical and gas exchange levels are satisfactory, low levels of SIMV may indicate the feasibility of extubation.

Table 3. Respiratory Workloads at Each Ventilatory Setting SIMV Rate (breaths/min)

WOB/l (J/l) SB (J/l) SIMV (J/l) WOB/min (J 䡠 min⫺1 䡠 kg⫺1) SB (J 䡠 min⫺1 䡠 kg⫺1) SIMV (J 䡠 min⫺1 䡠 kg⫺1) PTP/min (cm H2O 䡠 s 䡠 min⫺1) PTPb (cm H2O 䡠 s) SB (cm H2O 䡠 s 䡠 breaths⫺1) SIMV (cm H2O 䡠 s 䡠 breaths⫺1) ⌬Pes (cm H2O) SB (cm H2O) SIMV (cm H2O) MCA/VT

20

15

10

5

0

After Extubation

0.09 ⫾ 0.08 0.25 ⫾ 0.08 0.08 ⫾ 0.07 0.023 ⫾ 0.022 0.007 ⫾ 0.009 0.020 ⫾ 0.016 14.1 ⫾ 19.2

0.17 ⫾ 0.09* 0.30 ⫾ 0.10 0.14 ⫾ 0.07 0.042 ⫾ 0.023 0.017 ⫾ 0.012 0.027 ⫾ 0.013 32.2 ⫾ 20.1*

0.30 ⫾ 0.11*† 0.37 ⫾ 0.13† 0.23 ⫾ 0.08*† 0.070 ⫾ 0.028* 0.038 ⫾ 0.021 0.031 ⫾ 0.011 55.8 ⫾ 21.1*†

0.38 ⫾ 0.14*†‡ 0.42 ⫾ 0.15† 0.28 ⫾ 0.12*† 0.088 ⫾ 0.036*† 0.068 ⫾ 0.030*† 0.020 ⫾ 0.008 74.3 ⫾ 25.5*†‡

0.50 ⫾ 0.18*†‡§ 0.50 ⫾ 0.18*†‡§ ND 0.112 ⫾ 0.041*† 0.112 ⫾ 0.041*†‡§ ND 93.8 ⫾ 27.4*†‡§

0.46 ⫾ 0.14*†‡ 0.46 ⫾ 0.14† ND 0.103 ⫾ 0.031*† 0.103 ⫾ 0.030*†‡ ND 81.8 ⫾ 25.2*†‡㛳

1.6 ⫾ 0.5 0.4 ⫾ 0.5

2.0 ⫾ 0.7 0.9 ⫾ 0.5

2.6 ⫾ 0.9 1.5 ⫾ 0.6*†

2.8 ⫾ 1.0† 1.9 ⫾ 0.9*†

3.4 ⫾ 1.2*†‡ ND

2.7 ⫾ 1.1㛳 ND

0.9 ⫾ 1.1 3.1 ⫾ 1.3 0.6 ⫾ 0.8 1.05 ⫾ 0.05

2.0 ⫾ 1.2* 3.8 ⫾ 1.5 1.1 ⫾ 0.8 1.08 ⫾ 0.06

3.5 ⫾ 1.5*† 4.7 ⫾ 1.8 1.8 ⫾ 1.1*† 1.08 ⫾ 0.05

4.6 ⫾ 1.9*†‡ 5.1 ⫾ 1.9† 2.5 ⫾ 1.8*† 1.11 ⫾ 0.09

6.0 ⫾ 2.4*†‡§ 6.0 ⫾ 2.4†‡ ND 1.13 ⫾ 0.12

5.1 ⫾ 2.1*†㛳 5.1 ⫾ 2.1㛳 ND 1.13 ⫾ 0.15

After extubation, volume was measured by respiratory inductive plethysmography. * P ⬍ 0.05 versus SIMV 20.

† P ⬍ 0.05 versus SIMV 15.

‡ P ⬍ 0.05 versus SIMV 10.

§ P ⬍ 0.05 versus SIMV 5.

㛳 P ⬍ 0.05 versus SIMV 0.

SIMV ⫽ synchronized intermittent mandatory ventilation; WOB ⫽ work of breathing; SB ⫽ spontaneous breath; ND ⫽ not detected; PTP ⫽ pressure–time product; PTPb ⫽ pressure–time product per breath; ⌬Pes ⫽ negative deflection of esophageal pressure; MCA/VT ⫽ maximum compartment amplitude/tidal volume.

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Limitations The current study has several limitations. First, after tracheal extubation, we used RIP to calculate tidal volume, PTP, and WOB. The accuracy of RIP calibration may have been less precise because the chests of post– cardiac surgery patients are typically covered with chest tubes and bandages. Second, the patients in our study had relatively normal lung mechanics after corrective surgery for congenital heart diseases. Several patients had retarded gain of body weight, probably due to proceeding heart failure, although lung mechanics seemed normal for the body weight. The response of more seriously compromised patients to machine support may be quite different. Further studies are needed to corroborate the relevance of our findings for acutely ill and ventilator-dependent infants. Third, the number of patients was small, and the values of WOB and PTP included wide variations (table 3). However, in each patient, these parameters showed consistent changes in response to reducing the SIMV rate (fig. 5). Finally, because we did not measure the electrical activity of respiratory muscles, this report says nothing about the role of inspiratory neuromuscular output relating to the external inspiratory force.11 In conclusion, after cardiac surgery, for infants with healthy lungs, SIMV reduces WOB and PTP in proportion to the level of assisted breathing. The analysis of WOB and PTP shows that low levels of SIMV may indicate the feasibility of tracheal extubation.

References 1. Sassoon CSH: Intermittent mandatory ventilation, Principles and Practice of Mechanical Ventilation. Edited by Tobin MJ. New York, McGraw-Hill, 1994, pp 221–37 2. Esteban A, Frutos F, Tobin MJ, Alía I, Solsona JF, Valverdú I, Fernández R, De La Cal MA, Benito S, Tomás R, Garriedo D, Macías S, Blanco J: A comparison of four methods of weaning patients from mechanical ventilation. N Engl J Med 1995; 332:345–50 3. Donn SM, Nicks JJ: Special ventilatory techniques and modalities, I: Patienttriggered ventilation, Assisted Ventilation of the Neonate, 3rd edition. Edited by Goldsmith JP, Karotkin EH. Philadelphia, WB Saunders, 1996, pp 215–28 4. Bernstein G, Heldt GP, Mannino FL: Increased and more consistent tidal volumes during synchronized intermittent mandatory ventilation in newborn infants. Am J Respir Crit Care Med 1994; 150:1444 – 8 5. Cleary JP, Bernstein G, Mannino FL, Heldt GP: Improved oxygenation

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during synchronized intermittent mandatory ventilation in neonates with respiratory distress syndrome: A randomized, crossover study. J Pediatr 1995; 126: 407–11 6. Bernstein G, Mannino FL, Heldt GP, Callahan JD, Bull DH, Sola A, Ariagno RL, Hoffman GL, Frantz ID III, Troche BI, Roberts JL, Dela Cruz TV, Costa E: Randomized multicenter trial comparing synchronized and conventional intermittent mandatory ventilation in neonates. J Pediatr 1996; 128:453– 63 7. Jarreau PH, Moriette G, Mussat P, Mariette C, Mohanna A, Harf A, Lorino H: Patient-triggered ventilation decreases the work of breathing in neonates. Am J Respir Crit Care Med 1996; 153:1176 – 81 8. Dimitriou G, Greenough A, Giffin F, Chan V: Synchronous intermittent mandatory ventilation modes compared with patient triggered ventilation during weaning. Arch Dis Child 1995; 72:188 –90 9. Greenough A, Milner AD: Control of the respiratory system, Neonatal Respiratory Disorders. Edited by Greenough A, Roberton NRC, Milner AD. London, Arnold, 1996, pp 27– 47 10. Marini JJ, Smith TC, Lamb VJ: External work output and force generation during synchronized intermittent mechanical ventilation. Am Rev Respir Dis 1988; 138:1169 –79 11. Imsand C, Feihl F, Perret C, Fitting JW: Regulation of inspiratory neuromuscular output during synchronized intermittent mechanical ventilation. ANESTHESIOLOGY 1994; 80:13–22 12. Leung P, Jubran A, Tobin MJ: Comparison of assisted ventilator modes on triggering, patient effort, and dyspnea. Am J Respir Crit Care Med 1997; 155: 1940 – 48 13. Coates A, Stocks J, Gerhardt T: Esophageal manometry, Infant Respiratory Function Testing. Edited by Stocks J, Sly PD, Tepper RS, Morgan WJ. New York, Wiley-Liss, 1996, pp 241–58 14. Takeuchi M, Imanaka H, Miyano H, Kumon K, Nishimura M: Effect of patient-triggered ventilation on respiratory workload in infants after cardiac surgery. ANESTHESIOLOGY 2000; 93:1238 – 44 15. Adams JA: Respiratory inductive plethysmography, Infant Respiratory Function Testing. Edited by Stocks J, Sly PD, Tepper RS, Morgan WJ. New York, Wiley-Liss, 1996, pp 139 – 64 16. Nunn JF: Elastic forces and lung volumes, Nunn’s Applied Respiratory Physiology, 4th edition. Edited by Nunn JF. Oxford, Butterworth-Heinemann, 1993, pp 36 – 60 17. Sassoon CSH, Mahutte CK: Work of breathing during mechanical ventilation, Physiological Basis of Ventilatory Support. Edited by Marini JJ, Slutsky AS. New York, Marcel Dekker, 1998, pp 261–310 18. Sassoon CSH, Light RW, Lodia R, Sieck GC, Mahutte CK: Pressure-time product during continuous positive airway pressure, pressure support ventilation, and T-piece during weaning from mechanical ventilation. Am Rev Respir Dis 1991; 143:469 –75 19. McGregor M, Becklake MR: The relationship of oxygen cost of breathing to respiratory mechanical work and respiratory force. J Clin Invest 1967; 40: 971– 80 20. Greenough A, Pool J: Neonatal patient triggered ventilation. Arch Dis Child 1988; 63:394 –7 21. Fletcher ME, Baraldi E, Steinbrugger B: Passive respiratory mechanics, Infant Respiratory Function Testing. Edited by Stocks J, Sly PD, Tepper RS, Morgan WJ. New York, Wiley-Liss, 1996, pp 283–327 22. Nishimura M, Imanaka H, Yoshiya I, Kacmarek RM: Comparison of inspiratory work of breathing between flow-triggered and pressure-triggered demand flow systems in rabbits. Crit Care Med 1994; 22:1002–9 23. Aslanian F, El Atrous S, Isabey D, Valente E, Corsi D, Harf A, Lemaire F, Brochard L: Effects of flow triggering on breathing effort during partial ventilatory support. Am J Respir Crit Care Med 1998; 157:135– 43 24. Giuliani R, Mascia L, Recchia F, Caracciolo A, Fiore T, Ranieri M: Patientventilator interaction during synchronized intermittent mandatory ventilation: Effect of flow triggering. Am J Respir Crit Care Med 1995; 151:1–9


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OXYMAG VENTILADOR DE TRANSPORTE

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Doc 7 – Pressure Support

MAGNAMED TECNOLOGIA MÉDICA LTDA


The PSV mode is an invaluable addition to the practice of anesthesia. The use of PSV allows patients to breathe spontaneously while reducing the patient’s work of breathing. This can be a clinical benefit in both outpatient and same day surgical anesthesia. The increased use of LMAs means more spontaneous breathing is permitted during anesthesia. PSV offers significant benefits in patients breathing with LMAs because lower airway pressures are required, there by decreasing leaks around the LMA seal.

Clinical Focus

Additional reading: 1. Brimacombe J, Keller C, Hörmann C. Pressure Support Ventilation versus Continuous Positive Airway Pressure with the Laryngeal Mask Airway. Anesthesiology 2000;92:1621-1623 2. Rathegeber J. Grundlagen der maschinellen Beatmung: Handbuch für Ärzte und Pflegepersonal. Aktiv Druck & Verlag. Göttingen 1999 3. Peter N, Göran H. Ventilatory Support by Continuous Positive Airway Pressure Breathing Improves Gas Exchange as Compared with Partial Ventilatory Support with Airway Pressure Release Ventilation. Anesth Analg 2001; 92:950-958 4. Hiroaki T, Toshiaki T, Tomoko I, Tomihiro F, Toshio I, Yuko N, Yoshinori K. The Effect of Breath Termination Criterion on Breathing Patterns and the Work of Breathing During Pressure Support Ventilation. Anesth Analg 2001; 92:161-165

PSV provides a new and clinically useful ventilation strategy that was only common in the intensive care units and for the extremely ill pulmonary patient. With PSV in anesthesia, a larger patient population can be served.

ED4137-B/12 02 1 © 2002 Datex-Ohmeda, Inc. All rights reserved. Subject to change without notice. Printed in USA. Datex®, Ohmeda® and other trademarks are property of Instrumentarium Corp. or its subsidiaries. All other product and company names are property of their respective owners.

Conclusion

by Datex-Ohmeda

Pressure Support Ventilation: Impact on Anesthesia Practice Assisting the spontaneously breathing patient Guest Editors George Arndt, MD Professor of Anesthesiology Department of Anesthesiology University of Wisconsin at Madison, Madison, WI

Dr. Eric Peters Resident in Anesthesiology Department of Anesthesiology University of Wisconsin at Madison, Madison, WI

Datex-Ohmeda, Inc. P.O. Box 7550, Madison, WI 53707-7550, USA Tel. 800 345 2700 • Fax 608 221 4384 clinical.affairs@us.datex-ohmeda.com Please visit our websites for additional educational material www.datex-ohmeda.com • www.us.datex-ohmeda.com

From the Ventilation Series


Pressure Support Ventilation: Impact on Anesthesia Practice Though Pressure Support Ventilation (PSV) has been available in the intensive care setting since 1981, it has only recently become available for use during general anesthesia. Aside from technical issues relating to the basic differences between ICU and OR ventilation, there have been few opportunities to employ spontaneous breathing during anesthesia until the early 1990s and the introduction of the Laryngeal Mask Airway (LMA). The LMA, coupled with newer inhalation anesthetics, has encouraged clinicians to allow patients to breathe spontaneously through much, or all, of the anesthetic. PSV can be used to assist those patients in whom spontaneous breathing is elected. The following Clinical Focus, produced by the Department of Clinical Affairs, will discuss PSV for anesthesia. What is PSV? While many other names have been used, the basic idea behind PSV is to support spontaneous breathing by applying pressure to the airway in response to patient initiated breaths. PSV is patient triggered and either flow or time cycled. For PSV to be of value during clinical anesthesia the patient must be breathing spontaneously. Other ventilation modes such as Synchronous Intermittent Mandatory Ventilation (SIMV), either alone or in combination with PSV are available for patients who require a mandatory minute volume provided by a mechanical ventilator. During PSV, once a breath is initiated the ventilator pressurizes the airway to a given inspiratory support

pressure (Psupport). This pressure is usually from 5 to 10 cm H2O pressure and provides the additional ventilatory support required to offset the effects of general anesthesia. Each PSV assisted breath is terminated according to a preset decrease in flow or after a specific duration, as a backup. By applying pressure to the airway immediately upon sensing a patient breathe, PSV enhances inspiratory flow and provides improved gas distribution within the lungs. This enhanced gas distribution results in a lower peak airway pressures which is quite advantageous when LMAs are used; lower pressure results in less gas leakage around an LMA seal. If LMA seal leaks are present, PSV is able to better compensate for these leaks since the airway pressure is maintained irrespective of the volume, accounting for the delivered tidal volume and leak volume. The advantage of PSV is its ability to assume some of the patient’s increased work of breathing imposed by the patient breathing system used during anesthesia. PSV can also counter the reduction in functional residual capacity as well as the decrease in muscle contraction produced when modern inhalation anesthetics are used. In supporting a patient’s spontaneous breathing, PSV provides for sustained or enhanced tidal volumes, maintains normal end-tidal CO2 concentrations, and provides for ventilator assistance even when using airway devices that may introduce leaks such as the LMA.

Inhalation Agents and PSV While PSV can be used anytime in a patient that has the ability to initiate a spontaneous breath, it is best suited to anesthetics where a normal, or near normal, respiratory rate is expected. Such cases may include agents like sevoflurane or desflurane. These two agents are well suited to permitting spontaneous breathing and, as a consequence, for the application of PSV. Sevoflurane is becoming the standard for use in children. Desflurane is increasingly common for rapid recovery in adults. How to implement PSV While some parameters used during PSV are patient controlled, a pressure support level (Psupport) must be adjusted on the ventilator. Since the volume, rate, and timing of each breath are patient controlled there is no adjustment for these during PSV. If clinical conditions require, positive end-expiratory pressure may be added. The initial level of Psupport will vary from patient to patient depending on the patient’s pulmonary physiology, compliance and other clinical issues. Since the patient’s tidal volume is determined by individual lung characteristics and breathing efforts, the effect of the added support will be ventilator augmented tidal volumes. Clinically, it is easiest to start with lower levels of pressure support, in the 5 - 10 cm H2O range, gradually increasing the support pressure to a level where an adequate tidal volume is maintained.


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OXYMAG VENTILADOR DE TRANSPORTE

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Doc 8 – Performance Characteristics of Five New Anesthesia Ventilators

MAGNAMED TECNOLOGIA MÉDICA LTDA


䡵 LABORATORY INVESTIGATIONS Anesthesiology 2006; 105:944 –52

Copyright © 2006, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.

Performance Characteristics of Five New Anesthesia Ventilators and Four Intensive Care Ventilators in Pressure-support Mode A Comparative Bench Study Samir Jaber, M.D., Ph.D.,* Didier Tassaux, M.D.,† Mustapha Sebbane, M.D.,‡ Yvan Pouzeratte, M.D.,‡ Anne Battisti,§ Xavier Capdevila, M.D., Ph.D.,㛳 Jean-Jacques Eledjam, M.D., Ph.D.,# Philippe Jolliet, M.D.**

istics comparable to those of the intensive care unit machines. Increasing fresh gas flow (1 to 10 l/min) in the internal circuit did not influence the pressure-support ventilation performance of the anesthesia ventilators. Conclusion: Regarding trigger sensitivity and the system’s ability to meet inspiratory flow during pressure-supported breaths, the most recent anesthesia ventilators have comparable performances of recent-generation intensive care unit ventilators.

Background: During the past few years, many manufacturers have introduced new modes of ventilation in anesthesia ventilators, especially partial-pressure modalities. The current bench test study was designed to compare triggering and pressurization of five new anesthesia ventilators with four intensive care unit ventilators. Methods: Ventilators were connected to a two-compartment lung model. One compartment was driven by an intensive care unit ventilator to mimic “patient” inspiratory effort, whereas the other was connected to the tested ventilator. The settings of ventilators were positive end-expiratory pressures of 0 and 5 cm H2O, and pressure-support ventilation levels of 10, 15, and 20 cm H2O with normal and high “patient” inspiratory effort. For the anesthesia ventilators, all the measurements were obtained for a low (1 l/min) and a high (10 l/min) fresh gas flow. Triggering delay, triggering workload, and pressurization at 300 and 500 ms were analyzed. Results: For the five tested anesthesia ventilators, the pressure-support ventilation modality functioned correctly. For inspiratory triggering, the three most recent anesthesia machines (Fabius, Dra¨gerwerk AG, Lu ¨ beck, Germany; Primus, Dra¨gerwerk AG; and Avance, GE-Datex-Ohemda, Munchen, Germany) had a triggering delay of less than 100 ms, which is considered clinically satisfactory and is comparable to intensive care unit machines. The use of positive end-expiratory pressure modified the quality of delivered pressure support for two anesthesia ventilators (Kion, Siemens AG, Munich, Germany; and Felix, Taema, Antony, France). Three of the five anesthesia ventilators exhibited pressure-support ventilation performance character-

THE new-generation anesthesia ventilators tend to be more innovative and sophisticated than their predecessors to allow a better adaptation of the machines to patients’ ventilatory needs. During the past few years, many manufacturers have introduced new modes of ventilation in anesthesia ventilators, especially partial-pressure modalities.1–5 Pressure-support ventilation (PSV) is a ventilatory mode in which the patient’s spontaneous inspiratory effort triggers the ventilator to provide a variable flow of gas that increases until airway pressure reaches a selected level. Thus, during each spontaneous inspiration, the patient receives pressure-limited assisted ventilation. PSV is used in the intensive care setting to improve patient–ventilator synchrony and facilitate weaning.6 –9 A few studies have suggested that the use of PSV during general anesthesia could provide some advantages (reduction of atelectasis, improved gas exchange, decreased level of sedation).6,10 –13 More often, the use of PSV in the operating room was performed in anesthetized patients with a laryngeal mask airway. Therefore, PSV use progressively increased in the operating room, because spontaneous breathing alone or with ventilatory assistance is recommended with laryngeal mask airway because of leaks.14 Moreover, studies reported that PSV improves gas exchange and reduces work of breathing in anesthetized adults and children with an endotracheal tube6,12 or laryngeal mask airway.11,13 Several lung model studies, however, demonstrated that technical differences among intensive care unit (ICU),4,15–17 transport,18,19 and home ventilators17,20 may markedly affect their performance, especially regarding the trigger function and the pressurization process. Overall, these studies showed that considerable progress has been made in the performance and functionality of these devices. However, although today

This article is accompanied by an Editorial View. Please see: Tantawy H, Ehrenwerth J: Pressure-support ventilation in the operating room: Do we need it? ANESTHESIOLOGY 2006; 105:872–3.

* Assistant Professor in Anesthesiology and Critical Care, ‡ Assistant in Anesthesiology and Critical Care, # Professor of Anesthesiology and Critical Care, Department of Anesthesia and Critical Care B (DAR B), Ho ˆ pital Saint-Eloi, Centre Hospitalier Universitaire Montpellier, Universite´ Montpellier 1. † Assistant in Anesthesiology and Critical Care, § Chest Physiotherapist, ** Assistant in Critical Care, Division of Medical Intensive Care, Cantonal University Hospital, Geneva, Switzerland. 㛳 Professor of Anesthesiology and Critical Care, Department of Anesthesia and Critical Care A (DAR A), Ho ˆ pital Lapeyronie, Centre Hospitalier Universitaire Montpellier, Universite´ Montpellier 1. Received from the Department of Anesthesia and Critical Care B (DAR B), Ho ˆ pital Saint-Eloi, CHU Montpellier, Universite´ Montpellier 1, Montpellier, France. Submitted for publication September 14, 2005. Accepted for publication June 7, 2006. Support was provided solely from institutional and/or departmental sources. Equipment used in the study was provided by the manufacturers, each of which is listed within this article. Address correspondence to Dr. Jaber: Department of Anesthesia and Critical Care B (DAR B), Ho ˆ pital Saint Eloi, 80 avenue Augustin Fliche, 34295 Montpellier Cedex 5, France. s-jaber@chu-montpellier.fr. Individual article reprints may be purchased through the Journal Web site, www.anesthesiology.org.

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Table 1. Main Characteristics of Anesthesia and ICU Ventilators Tested

Inspiratory Trigger

Units

Pressurization Phase in Pressure Support

Main Inspiratory:Expiratory Cycling Criteria

Anesthesia ventilators

Felix (Taema, Antony, France) Kion (Siemens AG, Munich, Germany) Fabius (Dra¨ger AG, Lu¨beck, Germany) Primus (Dra¨ger)

Avance (GE-DatexOhmeda, Munchen, Germany) ICU ventilators Servo 900 (Siemens) Servo 300 (Siemens)

Flow trigger

Flow: 1 to 10 l/min

Fixed

Flow or pressure trigger

1 to 9 arbitrary units

Fixed

Flow trigger and pressure trigger

Flow: 2 to 15 l/min

Adjustable with the maximum flow

Flow trigger and pressure trigger

Flow: 0.3 to 15 l/min

Slope adjustable from 0 to 2 s

Flow trigger

Flow: 1 to 10 l/min

Fixed

Pressure trigger

Pressure: 0 to ⫺20 cm H2O Flow: 2 l/min; pressure: 0 to ⫺17 cm H2O

Fixed

Adjustable flow or pressure trigger

Horus (Taema)

Adjustable flow and pressure trigger

Evita 4 (Dra¨ger)

Adjustable flow and pressure trigger

Flow: 0.1 to 5 l/min; pressure: ⫺0.5 to ⫺5 cm H2O Flow: 0.3 to 15 l/min

Adjustable pressure ramp slope (0 to 10% of maximum inspiratory time) Adjustable pressure ramp slope (50 to 150 cm H2O/s) Duration adjustable from 0 to 2 s

Fixed, 25% of peak inspiratory flow Fixed, 5% of peak inspiratory flow Fixed, 25% of peak inspiratory flow for adults and 5% for children Fixed, 25% of peak inspiratory flow for adults and 5% for children Fixed, 25% of peak inspiratory flow

Fixed, 25% of peak inspiratory flow Fixed, 5% of peak inspiratory flow

Adjustable 0 to 30 l/min Fixed, 25% of peak inspiratory flow

ICU ⫽ intensive care unit.

there are numerous anesthesia ventilators available providing PSV with a standard anesthesia circle system, no studies have evaluated their technical performance. The aim of the current study was to evaluate in a bench study the performance of the new generation of anesthesia ventilators for delivering PSV and to assess how they compare with ICU ventilators.

Materials and Methods Ventilators Tested The five anesthesia ventilators evaluated were the Felix (Taema, Antony France), Kion (Siemens AG, Munich, Germany), Fabius GS (Dra¨gerwerk AG, Lu ¨ beck, Germany), Primus (Dra¨gerwerk AG), and Avance workstation (GE-Datex-Ohmeda, Munchen, Germany) equipped with the model 7900 ventilator. This last ventilator can also be found in the GE-Datex-Ohmeda Aestiva, Aisys, and Aespire anesthesia workstations. The four ICU ventilators tested were the Servo 900C (Siemens), Servo 300 (Siemens), Horus (Taema), and Evita 4 (Dra¨gerwerk AG). The main characteristics of anesthesia and ICU ventilators tested are presented in table 1. The machines were provided by the manufacturers Anesthesiology, V 105, No 5, Nov 2006

after a full revision had been made just before our investigation. All machines were stock, no modification was performed, and all were tested in operating conditions conforming to the manufacturer’s specifications. Test Lung Model All ventilators were connected to a classic, validated twocompartment lung model (Pneu View AI 2601I TTL; Michigan Instruments, Grand Rapids, MI) which has been described in detail in previous studies.17,20 Briefly, the model consists of two separate chambers linked by a rigid metal strip. One chamber is connected to an ICU ventilator (Evita 4; Dra¨gerwerk AG), which is set in volume control mode to mimic patient inspiratory effort (fig. 1). The magnitude and duration of the latter can thus be adjusted by changing the settings on this “driving” ventilator. The two chambers being linked, inflation of the first necessarily inflates the second, which is connected to the ventilator being tested. The onset of passive inflation is therefore detected as an “inspiratory” effort by the tested device, which triggers a pressure-support response. The elastance (E) and airway resistance (R) of each compartment can be adjusted separately. Thus, the model allows simulation of various magnitudes of inspiratory effort, types of respiratory mechan-


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Fig. 1. Schematic representation of the experimental setup.

ics, and tested ventilator settings. The ventilator circuits connected to each chamber were equipped with a pneumotachograph and pressure transducer (Biopac Systems, Goleta, CA). Data were acquired online via an analog– digital converter (MP100; Biopac Systems), sampled at 500 Hz, and stored in a laptop computer for subsequent analysis (Acqknowledge software; Biopac Systems). All measurements were performed in ambient temperature and pressure-saturated conditions. Automatic body temperature and pressure-saturated compensation was disabled on the Evita 4, and all other devices were calibrated in ambient temperature and pressure-saturated conditions. Gas compressibility was not accounted for, given its negligible quantitative contribution in the conditions of the current tests.21 Measured Variables Inspiratory trigger and pressurization ramp were evaluated as previously reported.16,17,20 Figure 2 shows the method used to calculate the trigger characteristics and the pressurization phase during PSV based on the airway pressure–time curve. Inspiratory Trigger. At each sensitivity condition tested, triggering performance was assessed according to three criteria: the time delay, the pressure fall, and the airway pressure–time product per cycle. ●

Triggering delay (DT): time between the onset of inspiratory effort and that of detectable pressurization. Pressure fall (DP): the maximal decrease in airway pressure measured from its baseline value. DP reflects in such way the inspiratory work required to trigger the ventilator; therefore, the lower its value, the smaller the work required of inspiratory muscles.22 Airway pressure–time product per cycle (PTP, cm H2O ⫻ ms) during the trigger phase, defined as the area under the Paw signal during the DT interval (computed as DP ⫻ DT).

Pressurization. The pressure–time products at 300 and 500 ms for each respiratory cycle (PTP300 and Anesthesiology, V 105, No 5, Nov 2006

Fig. 2. Schematic drawing of the assessment of the performance of the ventilator triggering systems. DP (cm H2O) and DT (ms) are the changes in pressure and time delay, respectively, required to open the inspiratory valve. PTP is the pressure–time product, expressed as DP ⴛ DT (cm H2O ⴛ ms). The triggering systems were adjusted to their maximal sensitivity. PEEP ⴝ positive end-expiratory pressure.

PTP500) are computed as the area under the time–pressure curve 300 and 500 ms after the onset of inspiratory effort. These two parameters reflect the speed of pressurization and the device’s capacity to maintain the set pressure during inspiratory effort. They depend both on the ventilator’s performance and the magnitude of inspiratory effort, the former being determined by the pressurization ramp and the flow generated by the device’s bellows or piston. PTP300 and PTP500 are expressed in cm H2O 䡠 s. Experimental Protocol DT, DP, PTP, PTP300, and PTP500 were measured as described above and in figure 2 at three successive levels of PSV: 10, 15, and 20 cm H2O. To mimic normal and strong inspiratory efforts by patients, the tidal volumes of the driving ventilator were set at 220 and 440 ml, respectively. These efforts were actually associated with pressures 100 ms after occlusion (P0.1) of 2 cm H2O (normal effort) and 4 cm H2O (strong effort), respectively, as measured on the bench.16,19 The duration of inspiratory effort on the driving ventilator was set at 1 s for all tests. Inspiratory trigger was set at the maximum sensitivity without the presence of autotriggering. The pressurization slope was set to its steepest value. When the inspiratory:expiratory cycling criteria was adjustable, it was maintained at its default value. During the tests, E and R of the “driving” chamber were set to normal (E ⫽ 20 cm H2O 䡠 l⫺1, R ⫽ 5.6 cm H2O 䡠 l⫺1 䡠 s).


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Fig. 3. Performance of the triggering systems, assessed by pressure drop (DP), trigger delay (DT), and pressure–time product (PTP) of the five anesthesia ventilators and the four intensive care unit ventilators assessed with a normal level of inspiratory effort (P0.1 ⴝ 2 cm H2O) with positive end-expiratory pressure ⴝ 0 (ZEEP; Z) and positive end-expiratory pressure ⴝ 5 cm H2O (PEEP; P) for the three pressure-support ventilation (PSV) levels: 10, 15, and 20 cm H2O. * P < 0.05 comparisons between machines. # P < 0.05 comparisons between ZEEP and PEEP.

For all ICU and anesthesia ventilators, the measurements were performed at positive end-expiratory pressure (PEEP) of 0 and 5 cm H2O for each of the two different efforts (normal and strong) and for the three PSV levels (10, 15, and 20 cm H2O). For the five anesthesia ventilators, two levels of fresh gas flow were tested: 1 and 10 l/min. Thus, 12 conditions were evaluated for each ICU ventilator and 24 conditions were tested for each anesthesia ventilator. Anesthesiology, V 105, No 5, Nov 2006

Statistical Analysis All parameter values represent the average of three to five breaths obtained during steady state. All results are expressed as mean ⫾ SD or median with 95% confidence interval, depending on the normal or nonnormal distribution of the variables. Comparative statistics relied on the Kruskal-Wallis one-way analysis of variance on ranks. Post hoc analysis was performed with the Scheffe´ test if analysis of variance reached significance. Significance was set at P ⬍ 0.05.


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Fig. 4. Performance of the triggering systems, assessed by pressure drop (DP), trigger delay (DT), and pressure–time product (PTP) of the five anesthesia ventilators and the four intensive care unit ventilators assessed with a high level of inspiratory effort (P0.1 ⴝ 4 cm H2O) with positive end-expiratory pressure ⴝ 0 (ZEEP; Z) and positive end-expiratory pressure ⴝ 5 cm H2O (PEEP; P) for the three pressure-support ventilation (PSV) levels: 10, 15, and 20 cm H2O. * P < 0.05 comparisons between machines. # P < 0.05 comparisons between ZEEP and PEEP.

Results One hundred sixty-eight conditions were evaluated, 120 for the anesthesia ventilators and 48 for the ICU ventilators. None of the ventilators mistriggered, nor did any ventilator prematurely cycle to expiration. Specific Triggering System Evaluation DT, DP, and PTP values measured in zero end-expiratory pressure (ZEEP) and with PEEP for all studied ventilators at a level of P0.1 ⫽ 2 and P0.1 ⫽ 4 cm H2O are presented in figures 3 and 4, respectively. On ZEEP, the inspiratory trigger time delay was signifAnesthesiology, V 105, No 5, Nov 2006

icantly shorter with the ICU ventilators compared with all of the anesthesia ventilators except for the Primus and the Avance. PEEP had no impact on the inspiratory time delay in all ICU ventilators, whereas for anesthesia ventilators, it influenced the performance of the trigger system for two of the ventilators (Felix and Kion) whatever the level of PSV studied (10, 15, or 20 cm H2O). For the Kion, changes in pressure and trigger time delay required to open the inspiratory valve significantly increased with PEEP compared with ZEEP. The opposite was observed with the Felix, in which DT was significantly shorter in PEEP than in ZEEP (figs. 3 and 4).


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Fig. 5. Pressure–time products at 300 and 500 ms for each respiratory cycle (PTP300 and PTP500), computed as the area under the time–pressure curve 300 ms (top) and 500 ms (bottom) after the onset of inspiratory effort, with normal inspiratory effort (P0.1 ⴝ 2 cm H2O) with positive end-expiratory pressure ⴝ 0 (ZEEP; Z) and positive end-expiratory pressure ⴝ 5 cm H2O (PEEP; P) for the three pressuresupport ventilation (PSV) levels: 10, 15, and 20 cm H2O. * P < 0.05 comparisons between machines. # P < 0.05 comparisons between ZEEP and PEEP.

For all machines, DT was not affected by the magnitude of inspiratory effort, except for the Kion, whose TD significantly increased with PEEP (figs. 3 and 4) as inspiratory effort increased. For all anesthesia ventilators tested, increased fresh gas flow from 1 to 10 l/min did not significantly modify triggering performance on ZEEP or PEEP. Dynamic Evaluation of PSV PTP300 and PTP500 values measured on both ZEEP and PEEP for all studied ventilators according to a level of P0.1 ⫽ 2 cm H2O (normal effort) are presented in figure 5 and to a level of P0.1 ⫽ 4 cm H2O (strong effort) are presented in figure 6. At all levels of PSV studied (10, 15, and 20 cm H2O), the pressurization capacity of all ICU ventilators was comparable, whereas it varied among the anesthesia ventilators, the difference being more marked with PEEP. At 300 ms in PEEP, the values obtained with the Felix and the Kion were half those obtained with the Fabius, Primus, and Avance. For all ICU ventilators except the Servo 900, PTP300 was not affected by the magnitude of inspiratory effort. However, with the anesthesia ventilators, PTP300 tended to decrease as inspiratory effort increased (figs. 5 and 6). Anesthesiology, V 105, No 5, Nov 2006

Discussion The current study is the first to provide a strictly protocoled bench test evaluation of the performance in delivering pressure support of five new-generation anesthesia ventilators. The major findings of this trial can be summarized as follows: (1) For the five tested anesthesia ventilators, the PSV modality functions correctly; (2) performance was more homogeneous among the modern ICU ventilators than among the anesthesia ventilators; (3) the use of PEEP modified the quality of delivered pressure support in two anesthesia ventilators (Kion and Felix) but not in the three others (Fabius, Primus, and Avance); and (4) increasing fresh gas flow (1 to 10 l/min) in the internal circuit did not influence the PSV performance of the anesthesia ventilators. This bench test study also showed that triggering delay is less than 100 ms for all ICU ventilators except in the older Servo 900C as reported by previous studies 15–17,19 and is less than 100 ms only for only two anesthesia ventilators (Primus and Avance) (figs. 3 and 4). The inspiratory workload required to trigger the ventilators (i.e., PTP) is very low for the modern ICU ventilators, in line with previous studies of these machines.17,20 The most recently developed anesthesia


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Fig. 6. Pressure–time products at 300 and 500 ms for each respiratory cycle (PTP300 and PTP500), computed as the area under the time–pressure curve 300 ms (top) and 500 ms (bottom) after the onset of inspiratory effort, with a high level of inspiratory effort (P0.1 ⴝ 4 cm H2O) with positive end-expiratory pressure ⴝ 0 (ZEEP; Z) and positive end-expiratory pressure ⴝ 5 cm H2O (PEEP; P) for the three pressure-support ventilation (PSV) levels: 10, 15, and 20 cm H2O. * P < 0.05 comparisons between machines. # P < 0.05 comparisons between ZEEP and PEEP.

ventilators exhibited comparable performance, the highest PTP being measured in the Kion, which is the first anesthesia ventilator with PSV mode and the oldest of the anesthesia ventilators tested. The best characteristics of the pressurization phase for the anesthesia ventilators were obtained with the Fabius, Primus, and Avance under all tested conditions and were comparable with those of obtained with the ICU ventilators. The Fabius, Primus, and Avance are “piston ventilators,” which use an electric motor to compress gas in the breathing circuit, creating the driving force for mechanical insufflation to proceed. Therefore, they use no driving gas and may be used without depleting the oxygen cylinder in case of oxygen pipeline failure. These features may explain in part that these more recent anesthesia ventilators have comparable performance to modern ICU ventilators. It is important for the users to know that the Fabius GS and the Fabius Tiro have the same ventilator (electrical piston) and use the same software management that regulates the ventilator. Similarly, the Primus (worldwide outside of the United States) and the Apollo (United States) anesthesia stations have the same ventilator (electrical piston). But the implemented software that regulates the ventilator is different between the Anesthesiology, V 105, No 5, Nov 2006

Fabius GS/Tiro and Primus/Apollo. This difference may explain in part the differences in performances obtained with the two ventilators (Fabius vs. Primus). The newer technologies used by manufacturers, i.e., microprocessors, servo valves, and fast and potent turbines, have substantially improved both modern anesthesia and ICU ventilators regarding global trigger response. It seems that the industry has so far chosen not to invest heavily in the development of PSV on anesthesia ventilators. This might seem surprising, because PSV has been available on ICU ventilators for more than 20 yr. Two main factors probably account for this. The first is of a technical nature. Indeed, an anesthesia ventilator is composed of two circuits, one for driving gas, the other for the patient circuit with the anesthetic gases, with independent bellows, and the resultant large internal volume makes it more difficult to implement fast-responding and efficient triggering mechanisms. The second factor is mainly clinical, i.e., that whereas ICU ventilators need to provide a mode of partial ventilatory support tailored to the patient’s breathing pattern during weaning, the need for such a mode in anesthesia has only become apparent in recent years. The need is probably linked to the use of laryngeal masks, which is a spontaneous-assisted mode with leaks resembling nonin-


PRESSURE-SUPPORT VENTILATION AND ANESTHESIA VENTILATORS

vasive ventilation in some aspects, and the increasing use of local–regional anesthesia combined with light sedation during which spontaneous breathing is maintained. Pressure-support ventilatory modes have recently been introduced as readily available options on newer anesthesia ventilators. Unlike ICU ventilators, which vent exhaled gases to the atmosphere and directly release gas from the wall outlet into the circuit, anesthesia ventilators recirculate exhaled gases into the inspiratory limb. It has been suggested but never evaluated that in pressuresupport mode, this feature mandates a large internal volume, which may in turn alter the performance of triggering and pressurization systems.5,23 In the current study, we did not find a significant difference for the performance of triggering and pressurization systems between a low (1 l/min) and a high (10 l/min) fresh gas flow for all anesthesia ventilators and all tested dynamic conditions. We tested the influence of PEEP on the quality of the trigger and pressure delivering because recent studies suggested that use of PEEP may have some benefits on pulmonary function.24 –28 Limitations The most important limitation of this study is the fact that it was performed on a lung model instead of in patients. It is possible that performance in patients may differ greatly from the performance demonstrated here. The advantage of the model is that mechanical characteristics can be standardized and reproduced. In addition, the test lung was modified to simulate spontaneous breathing. Hence, the different machines were tested under similar conditions during dynamic experiments. However, it is clear that these laboratory conditions are not real life and, therefore, that the results of these bench studies should be extrapolated to patients with caution. Therefore, a clinical study evaluating these characteristics and other aspects of the performance of anesthesia ventilators, e.g., on gas exchange and comfort in the operating room, should be performed. In addition, and perhaps more importantly, little is known about the validated indications of PSV in anesthetized patients. Further exploration of this topic is clearly warranted.

Conclusion For the five tested anesthesia ventilators, PSV functioned correctly. The efficiency of delivering PSV for the anesthesia ventilators is acceptable, comparable to oldergeneration ICU ventilators (i.e., Servo 900C); however, it did not reach the level of performance of the newgeneration ICU ventilators for three of the five tested anesthesia ventilators. The use of PEEP modified the quality of delivered Anesthesiology, V 105, No 5, Nov 2006

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pressure support for two anesthesia ventilators (Kion and Felix). Increasing fresh gas flow (1 to 10 l/min) in the internal circuit did not influence PSV performance of the tested anesthesia ventilators. Regarding trigger sensitivity and the system’s ability to meet inspiratory flow during pressure-supported breaths, the most recent anesthesia ventilators have performances comparable to those of the modern ICU ventilators. Further clinical studies should now be conducted to better define the indications of PSV during anesthesia. The authors thank Je´ro ˆ me Pigeot (Biomedical Engineer, Fisher-Paykell, Courtaboeuf, France) for his technical assistance during the bench study.

References 1. Jaber S, Langlais N, Fumagalli B, Cornec S, Beydon L, Harf A, Brochard L: Performance studies of 6 new anesthesia ventilators: Bench tests. Ann Fr Anesth Reanim 2000; 19:16–22 2. Stayer SA, Bent ST, Campos CJ, Skjonsby BS, Andropoulos DB: Comparison of NAD 6000 and servo 900C ventilators in an infant lung model. Anesth Analg 2000; 90:315–21 3. Stayer SA, Andropoulos DB, Bent ST, McKenzie ED, Fraser CD: Volume ventilation of infants with congenital heart disease: A comparison of Dragger, NAD 6000 and Siemens, Servo 900C ventilators. Anesth Analg 2001; 92:76–9 4. Takeuchi M, Williams P, Hess D, Kacmarek R: Continuous positive airway pressure in new-generation mechanical ventilators: A lung model study. ANESTHESIOLOGY 2002; 96:162–72 5. Tung A, Drum M, Morgan S: Effect of inspiratory time on tidal volume delivery in anesthesia and intensive care unit ventilators operating in pressure control mode. J Clin Anesth 2005; 17:8–15 6. Christie JM, Smith RA: Pressure support ventilation decreases inspiratory work of breathing during general anesthesia and spontaneous ventilation. Anesth Analg 1992; 75:167–71 7. Kuhlen R, Putensen C: Maintaining spontaneous breathing efforts during mechanical ventilatory support. Intensive Care Med 1999; 25:1203–5 8. Pearl RG, Rosenthal MH: Pressure support ventilation: Technology transfer from the intensive care unit to the operating room. Anesth Analg 1992; 75:161–3 9. Putensen C, Zech S, Wrigge H, Zinserling J, Stuber F, Von-Spiegel T, Mutz N: Long-term effects of spontaneous breathing during ventilatory support in patients with acute lung injury. Am J Respir Crit Care Med 2001; 164:43–9 10. Hedenstierna G, Tokics L, Lundquist H, Andersson T, Strandberg A, Brismar B: Phrenic nerve stimulation during halothane anesthesia: Effects of atelectasis. ANESTHESIOLOGY 1994; 80:751–60 11. Brimacombe J, Keller C, Hormann C: Pressure support ventilation versus continuous positive airway pressure with the laryngeal mask airway: A randomized crossover study of anesthetized adult patients. ANESTHESIOLOGY 2000; 92: 1621–3 12. Bosek V, Roy L, Smith RA: Pressure support improves efficiency of spontaneous breathing during inhalation anesthesia. J Clin Anesth 1996; 8:9–12 13. von Goedecke A, Brimacombe J, Hormann C, Jeske H, Kleinsasser A, Keller C: Pressure support ventilation versus continuous positive airway pressure ventilation with the ProSeal laryngeal mask airway: A randomized crossover study of anesthetized pediatric patients. Anesth Analg 2005; 100:357–60 14. Devitt J, Wenstone R, Noel A, O’Donnell M: The laryngeal mask airway and positive-pressure ventilation. ANESTHESIOLOGY 1994; 80:550–5 15. Bunburaphong T, Imanaka H, Nishimura M, Hess D, Kacmarek R: Performance characteristics of bilevel pressure ventilators: A lung model study. Chest 1997; 111:1050–60 16. Richard JC, Carlucci A, Breton L, Langlais N, Jaber S, Maggiore S, Fougere S, Harf A, Brochard L: Bench testing of pressure support ventilation with three different generations of ventilators. Intensive Care Med 2002; 28:1049–57 17. Tassaux D, Strasser S, Fonseca S, Dalmas E, Jolliet P: Comparative bench study of triggering, pressurization, and cycling between the home ventilator VPAP II and three ICU ventilators. Intensive Care Med 2002; 28:1254–61 18. Miyoshi E, Fujino Y, Mashimo T, Nishimura M: Performance of transport ventilator with patient-triggered ventilation. Chest 2000; 118:1109–15 19. Zanetta G, Robert D, Guerin C: Evaluation of ventilators used during transport of ICU patients: A bench study. Intensive Care Med 2002; 28:443–51 20. Battisti A, Tassaux D, Janssens J, Michotte J, Jaber S, Jolliet P: Performance characteristics of ten mechanical ventilators in pressure support: A comparative bench study. Chest 2005; 127:1784–92. 21. Lofaso F, Brochard L, Hang T, Lorino H, Harf A, Isabey D: Home versus intensive care pressure support devices: Experimental and clinical comparison. Am J Respir Crit Care Med 1996; 153:1591–9


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22. Aslanian P, El Atrous S, Isabey D, Valente E, Corsi D, Harf A, Lemaire F, Brochard L: Effects of flow triggering on breathing effort during partial ventilatory support. Am J Respir Crit Care Med 1998; 157:135–43 23. Marks J, Schapera A, Kraemer R, Katz J: Pressure and flow limitations of anesthesia ventilators. ANESTHESIOLOGY 1989; 71:403–8 24. Pelosi P, Ravagnan I, Giuretta G, Panigada M, Bottino N, Tredici S, Eccher G, Gattinoni L: Positive end-expiratory pressure improves respiratory function in obese but not in normal subjects during anesthesia and paralysis. ANESTHESIOLOGY 1999; 91:1221–31 25. Pontoppidan H: From continuous positive-pressure breathing to ventilatorinduced lung injury. ANESTHESIOLOGY 2004; 101:1015–7

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26. Bre´geon F, Delpierre S, Chetaille B, Kajikawa O, Martin T, Autillo-Touati A, Jammes Y, Pugin J: Mechanical ventilation affects lung function and cytokine production in an experimental model of endotoxemia. ANESTHESIOLOGY 2005; 102:331–9 27. Maeda Y, Fujino Y, Uchiyama A, Matsuura N, Mashimo T, Nishimura M: Effects of peak inspiratory flow on development of ventilator-induced lung injury in rabbits. ANESTHESIOLOGY 2004; 101:722–8 28. Boker A, Haberman C, Girling L, Guzman R, Louridas G, Tanner J, Cheang M, Maycher B, Bell D, Doak G: Variable ventilation improves perioperative lung function in patients undergoing abdominal aortic aneurysmectomy. ANESTHESIOLOGY 2004; 100:608–16


Documentação

F006-02

Projeto:

Data:

OXYMAG VENTILADOR DE TRANSPORTE

20/10/2010

Elaborado por:

Verificado por:

Aprovado por:

Marcelo Onodera

Toru

Tatsuo

Objeto / Título do Documento:

Código:

1600185 Folha:

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85 – Dados clínicos, Papers

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Doc 9 – CPAP Principles

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Main image: Royce Degrie istockphoto

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Correspondence R. Farré Unitat de Biofísica i Bioenginyeria Facultat Medicina Universitat de Barcelona-IDIBAPS and CIBER de Enfermedades Respiratorias Casanova 143 08036 Barcelona Spain

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Potential conflicts of interest None declared.

E-mail: rfarre@ub.edu

PRINCIPLES OF CPAP AND AUTO-ADJUSTING CPAP DEVICES R. Farré1,2, J.M. Montserrat2,3 1

Biophysics and Bioengineering Unit, Faculty of Medicine, Dept, Hospital Clinic, Faculty of Medicine, Universitat de Barcelona (IDIBAPS), Barcelona, and 2 CIBER Enfermedades Respiratorias, Bunyola, Spain. 3 Pneumology

This article was originally printed in Breathe, the journal of the ERS School. Breathe 2008; 5: 42–50.

SUMMARY Obstructive apnoea–hypopnoea syndrome (OSAHS) is very prevalent. It causes a considerable reduction in patients’ quality of life and induces important short- and long-term consequences, such as traffic accidents and cardiovascular diseases. The application of continuous positive airway pressure (CPAP) by means of a nasal mask is currently the most widespread and effective treatment for OSAHS. The present review article will address the following questions. What is the physiological rationale of CPAP? What are the principles of CPAP equipment? How can we optimise its use? What are auto-adjusting CPAP devices and how do they operate? To what extent are they useful in the treatment of OSAHS?

INTRODUCTION OSAHS is the most prevalent of all sleep breathing disorders. This

syndrome is currently a public health problem because, according to several studies, up to 5% and 2% of the adult male and female population, respectively, are suffering from OSAHS [1, 2]. Given that this sleep disorder is directly associated being overweight [3, 4], it is expected that the prevalence of OSAHS will increase in parallel with the growing epidemics of obesity in Western and developing countries [5]. OSAHS is characterised by recurrent obstructions during sleep caused by an abnormal increase in the collapsibility of the upper airway, which is triggered by several factors, including anatomical alterations and obesity [6, 7]. Figure 1a illustrates the case of a normal subject during sleep in supine position. During inspiration there is a negative (lower than atmospheric) pressure in the lumen of the upper airway and, consequently, its soft wall would tend to collapse. However, in a normal upper airway, the surrounding muscles are able to exert sufficient force to maintain the airway open, regardless of negative intraluminal pressure

during inspiration, allowing normal ventilation during sleep (figure 1a). In contrast, in an OSAHS patient, the upper airway muscles are unable to withstand the collapsing force due to negative intraluminal pressure, so the upper airway tends to collapse. Depending on the degree of abnormal increase in upper airway collapsibility, the OSAHS patient can experience partial upper airway obstruction (figure 1b) or total collapse (figure 1c). In the former case, a hypopnoea appears because the reduction in airway lumen results in an increased resistance high enough to reduce ventilation, even though the inspiratory effort is increased. When the upper airway is completely collapsed (figure 1c), the patient is no longer able to inspire and experiences an obstructive apnoea. In the most severe cases of OSAHS the collapsibility of the upper airway during sleep increases considerably and collapse is induced even in cases where the intraluminal pressure is zero (atmospheric level) or slightly positive. In these severe patients, therefore, the upper airway is collapsed not only

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during inspiration but also during expiration. Figure 2 shows some of the signals recorded during a polysomnographic study and illustrates the sleep events experienced by a patient with severe OSAHS. The breathing flow signal shows three apnoeas (identified by zero flow) lasting ~20 s each. These apnoeas were obstructive because the patient was exerting breathing efforts, as indicated by the thoracoabdominal movement signals. Each obstructive event finished with a short arousal, as evidenced by the electroencephalogram (EEG) signals. Since the patient was temporarily awake during the arousal (although not conscious of the short awakening), the upper airway muscles were activated (indicated by the genioglossus electromyogram (EMG) in figure 2) and the airway was open; the patient was, therefore, able to ventilate. However, as the patient fell asleep again immediately after the arousal, airway obstruction resumed: after a few breathing cycles with snoring, a new apnoea ensued (figure 2). The arterial oxygen saturation measured by pulse oximetry (SpO2) shows that, as a consequence of the recurrent apnoeas, this patient experienced intermittent hypoxaemia with a repetition period of ~40 s (figure 2). The short-term symptoms described by OSAHS patients are related to alterations in normal ventilation (choking, gasping or dry mouth) and disruption of sleep architecture caused by recurrent arousals (excessive sleepiness, lack of attention and irritability). Patients with OSAHS have an increased risk of traffic accidents, probably as a result of somnolence [8]. Moreover, the nocturnal events chronically experienced by OSAHS patients contribute to the development of long-term comorbidities, such as cardiovascular and cerebrovascular diseases and inflammatory, metabolic, cognitive and mood alterations [9-14].

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a)

b)

c)

d) CPAP

Figure 1. Diagram showing the upper airway patency during inspiration: a) in a normal subject; b) in a patient experiencing an obstructive hypopnoea with snoring (represented by the sound produced); c) in a patient experiencing an obstructive apnoea; and d) in a patient subjected to nasal CPAP. The red arrows in b) and c) indicate net collapsing force on the upper airway wall. The red arrows in d) indicate that application of nasal CPAP results in a net force opening the upper airway.

EEG1 EEG2 EMG Snoring Flow Tho Abd Tho+Abd SP,O2 Apnoea

Arousal

Apnoea

Arousal

Apnoea Arousal

Figure 2. Physiological signals recorded during a nocturnal polysomnography in a patient with OSAHS. EEG1 and EEG2 correspond to the C4/A1 and C3/A2 EEG channels. EMG refers to EMG of the genioglossus. Snoring was monitored by a sound recording. Flow refers to the breathing flow. Red rectangles in EEG1 indicate arousals. Vertical white lines indicate 10-s periods. Tho: Thoracic breathing effort; Abd: Abdominal breathing effort; SpO2: arterial oxygen saturation measured by pulse oximetry (ranging from 93â&#x20AC;&#x201C;76% in this example).

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CPAP Several approaches can be used to treat OSAHS. The first option is to recommend that the patient loses weight, avoids sleeping in a supine position and avoids the consumption of alcohol and sedative drugs. However, in most patients, these behavioural measures are not effective for normalising sleep, and more active treatments are required. It has been shown that in some patients the nocturnal use of mandibular advancement devices aimed at protruding the mandible could be effective for increasing the dimensions of the upper airway and maintaining its patency during sleep [15]. Other patients could benefit from surgical treatment to reduce anatomical upper airway obstruction in the nose, oropharynx

and hypopharynx [16]. However, for the vast majority of OSAHS patients the most effective treatment is the nocturnal application of nasal CPAP [17]. Nasal CPAP does not eliminate the primary causes that increase upper airway collapsibility in OSAHS. In fact, CPAP is a palliative treatment for mechanically preventing upper airway obstruction. Nocturnal CPAP, applied by means of a nasal mask (figure 1d), imposes a positive intraluminal pressure on the upper airway that plays a role similar to that of normal upper airway muscles. As illustrated in figure 1d, CPAP opens the upper airway and prevents its partial or total obstruction. The effectiveness of CPAP in preventing upper airway collapse in OSAHS is illustrated by the computed tomography (CT)

a)

b)

c)

d)

Figure 3. Axial CT scans of the upper airway obtained during sleep from a patient with OSAHS. a) and b) Two head sections of the untreated patient. c) and d) The same two sections during application of CPAP. The yellow arrows indicate the upper airway lumen.

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scan of a patient’s pharyngeal area during sleep (figure 3). The upper images (figure 3a and b) show two sections of the upper airway obtained when the patient was sleeping under normal conditions (no CPAP). The right scan section (figure 3b) shows that the lumen of the upper airway was extremely reduced, indicating a virtually closed airway. When the patient was subjected to CPAP, the upper airway lumen increased considerably at this point of obstruction. The other upper airway sections also increased their lumen when CPAP was applied, indicating that nasal pressure prevented obstruction along the whole collapsible airway (figure 3c and d). The value of nasal pressure that normalises breathing during sleep does not depend on the severity of a particular patient’s OSAHS, as measured by the number of nocturnal respiratory events (apnoeas and hypopnoeas per h) but, instead, depends on the degree of collapsibility of the patient’s upper airway. Accordingly, each patient should be subjected to an individual CPAP titration procedure during sleep, in order to determine the optimal nasal pressure for treatment. Figure 4 shows the data corresponding to a 1-night CPAP titration in a patient with OSAHS. At the beginning of the night, when awake, the patient was subjected to a minimal CPAP of 4 cmH2O (0.4 kPa). When the patient started to sleep, respiratory events (mainly obstructive apnoeas) and marked oxygen desaturations appeared. The sleep technician then gradually intensified the application of nasal pressure. As CPAP increased, the number of apnoeas decreased and the number of hypopneas increased, indicating that the upper airway obstruction was being progressively reduced and breathing was being normalised (figure 4). Similarly, the magnitude of oxygen desaturations was also progressively decreasing. When CPAP was equal to 9 cmH2O (0.9 kPa), there were no longer any obstructions or desaturations.


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0 100

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75 33 8 15 102

01

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Figure 4. Data from a 1-night CPAP titration in a patient with OSAHS. Staging: sleep status (W: wake; R: REM; 1-4: non-REM sleep stages 1-4). Body pos: body posture. CPAP: nasal pressure applied. Desat: arterial oxygen desaturation, as indicated by SpO2. The plot at the bottom indicates the number of different respiratory events detected: obstructive apnoeas, mixed apnoeas, central apnoeas and hypopnoeas. The numbers in the boxes shows the total number of events with a fall in SpO2 >4%. The time scale indicates time from titration start.

The normalisation of sleep was reflected by the fact that the patient achieved rapid eye movement (REM) sleep. Subsequently, the technician maintained CPAP at 9-10 cmH2O (0.9-1.0 kPa) for 3-4 h, observing no clear improvement between 9 and 10 cmH2O. The quality of sleep was good, as the patient experienced two more REM sleep periods. To test whether CPAP could be reduced while maintaining normal sleep, the technician reduced nasal pressure to 8 cmH2O (0.8 kPa), with the result that hypopnoeas and oxygen desaturations appeared again, indicating that 9-10 cmH2O (0.9-1.0 kPa) was the optimal nasal pressure for treating this OSAHS patient.

PRACTICAL ISSUES REGARDING CPAP EQUIPMENT Although in a patient treated with CPAP the primary causes of OSAHS remain present, from the functional viewpoint, his/her sleep resembles that of a healthy subject. However, CPAP is effective only as long as the patient is subjected to the treatment. In this regard, it has been shown

that there is a linear dose-response relationship between the number of hours of CPAP use per night and the attainment of normal levels of objective and subjective daytime sleepiness [18]. Accordingly, any effort made to improve the patient’s acceptance of CPAP treatment will enhance the effectiveness of the therapy [19]. To this end, it is important to select high-quality CPAP equipment, use it in accordance with the manufacturer’s specifications and train patients on CPAP therapy. The CPAP systems used for OSAHS treatment are usually based on a blower and an exhalation port (intended leak orifice), as shown in figure 5. The blower takes room air and generates a constant airflow through a flexible tubing (~1.5 m length, ~2 cm internal diameter). When the patient is not breathing and the nasal mask is adequately fitted on the patient’s face to avoid leaks between the mask and the skin, all the airflow generated by the blower reaches the atmosphere again through the exhalation port. Accordingly, the pressure (CPAP) at the nasal mask is the product of the airflow and the resistance of the

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exhalation port. For a given exhalation port, the value of CPAP can be increased or decreased by modulating the magnitude of the flow generated by the blower. In addition to being the nasal pressure source, the airflow generated by the blower plays also the important role of avoiding rebreathing. To this end, a minimum airflow through the exhalation port is required to adequately renew the air inhaled by the patient. In commercially available CPAP devices, the pressure ensuring sufficient air renewal, and, therefore, the minimum selectable CPAP value, is generally ~4 cmH2O (0.4 kPa). In most devices, the exhalation port is an orifice characterised by nonlinear resistance. This type of resistor has the advantage of a range of blower airflow (and therefore machine noise) covering the full range of therapeutic CPAP values (4-16 cmH2O; 0.4-1.6 kPa) that is lower than that of an exhalation port with linear resistance. The exhalation port can be either an orifice in the mask wall (as in figure 5) or a special device connecting the tubing outlet and the nasal mask. In the latter case, the air volume in the nasal mask is an additional small dead space for breathing. As indicated in figure 5, for a given airflow generated by the blower the value of nasal pressure is constant, as long as the patient is not breathing. When the patient inspires, however, an air fraction from the blower flow enters the lungs and hence the airflow through the exhalation port is reduced. Therefore, nasal pressure, which depends on this flow magnitude, is decreased and the equipment represents a load to the patient’s breathing. This conventional design of CPAP equipment (figure 5) poses two main technical problems with regard to optimising the system for patient comfort. First, given that the effective resistance of the exhalation port is considerable, the patient’s breathing flow mainly circulates through the tubing and

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Blower

Air filter

Blower airflow Leak airflow Inspiratory airflow

Leak orifice

CPAP tube CPAP device

Humidifer

Mask

Figure 5. Diagram of a conventional CPAP system.

blower [20]. Consequently, the blower should be designed to generate high pressure while presenting a low load (resistance) to breathing. Secondly, in order to keep the nasal pressure (i.e. CPAP) constant, the blower should be able to automatically modify the generated airflow with the aim of keeping the airflow constant through the exhalation port, regardless of the patient’s breathing. One common method for this type of regulation is the measurement of the flow and pressure generated at the CPAP device and the calculation of the pressure at the nasal mask from the known airflow resistance of the tubing and exhalation port. This procedure requires the tubing and the exhalation port connected to the CPAP machine to be matched, otherwise the calculation of nasal pressure would be incorrect. In order to circumvent this potential problem, some CPAP devices measure mask pressure directly by means of a thin catheter placed along the CPAP tubing. As it is important to maintain a fairly constant nasal pressure, the main CPAP device quality index is given by the magnitude of the “swings” in nasal pressure during breathing: the smaller the swings, the better the CPAP equipment. An adequate selection of CPAP equipment (i.e. compatible CPAP machine, tubing and exhalation mask) does not ensure correct treatment application, as two types

of unintended leaks could reduce the performance of the CPAP setting. An air leak between the nasal mask and the skin as the result of an unsuitable mask fitting could affect the therapy: the flow generated by the blower would increase (and, hence, the noise) and the nasal pressure could be lower than expected. Such a leak could also cause patient discomfort, particularly if the leak airflow is directed toward the eyes. The need to reduce mask leaks as much as possible highlights the importance of adequately choosing the nasal mask type that best fits the patient. Good mask fitting should be achieved without any excessive compression, as this would damage the patient’s skin and, therefore, compromise tolerance of CPAP. Another type of leak that could

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negatively affect CPAP treatment occurs when the patient’s mouth is partially open. In this case, there is a constant airflow through the upper airway, from the nostrils at positive pressure to the mouth at zero (atmospheric) pressure, with the result that the effective pressure at the upper airway lumen is lower than expected. The use of a chinstrap could help to prevent mouth leaks in some patients. An important additional problem related to mouth opening during CPAP is the presence of a continuous flow of dry and cold room air, which could result in nasal and throat mucosa dryness and irritation, thereby causing discomfort, and even rhinitic symptoms, to the patient. A possible way of reducing the risk of this nasal drying is to use a heated humidifier (figure 5) [21]. The potential advantage of a humidifier is counterbalanced by some potential drawbacks: the need to clean the water chamber to avoid contamination; more expensive equipment; and increased breathing route resistance. Although humidifiers are useful for some patients, there is no clear evidence to recommend their systematic use for CPAP therapy in OSAHS patients. Prescribing updated and highquality CPAP equipment is obviously important for patient

Figure 6. Training session on the use of CPAP.

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Flow L/s

Upper airway collapsibility in OSAHS patients depends on several factors; therefore, it may vary in the short and long term. Different body postures during sleep (supine posture promotes airway collapse, compared with lateral decubitus) could cause changes within a single night. This well-known fact is taken into account during routine CPAP titration, when at least supine sleep posture is studied. Moreover, changes in upper airway collapsibility within consecutive nights could be the result of alcohol ingestion or drug treatment, particularly with drug affecting muscle tone. Furthermore, within a longer time period (over a period of weeks or months), upper airway collapsibility could change as the patient’s body weight varies. Given that the CPAP required to avoid obstructive events is directly determined by upper airway collapsibility, the optimal CPAP would be not the same over time. Consequently, a conventional CPAP device would apply a fixed nasal pressure that could be higher or lower than required, depending on the patient’s current situation. Autoadjusting CPAP devices are designed

In addition to conventional CPAP equipment elements (figure 5), auto-adjusting CPAP devices incorporate a complex algorithm (figure 7). The sensors in the device estimate the patient’s breathing by assessing snoring, flow pattern and, in some devices, airway obstruction. The first step in the algorithm of an auto-adjusting CPAP device is to correctly detect and classify the different breathing events (normal breathing, apnoea, hypopnoea, snoring and flow limitation) from the available signals. The device must be able to distinguish true obstructive events from typical artefacts, such as those caused by awakening of the patient, cough, sighs or mouth breathing. The second step in the autoadjusting CPAP device algorithm is to modify the nasal pressure applied in response to the breathing

1.0 0.5 0 -0.5 -1 15 10 5 0

Auto-adjusting CPAP device Sensors (flow, snoring...) Event and artifact detection Decision on CPAP change CPAP Patent upper airway

Figure 7. Diagram showing the rationale of automatic CPAP devices.

events that are detected. Figure 8 is an example of the functioning of an auto-adjusting CPAP device. The device was subjected to a bench test by connecting it to a simulated OSAHS patient who, depending on the applied pressure, exhibited apnoeas, hypopnoeas, flow limitation events or normal breathing. Initially, the simulated

Press cmH2O

AUTO-ADJUSTING CPAP DEVICES

to solve this problem. These “intelligent” devices are intended to detect a patient’s respiratory events and modify the applied CPAP to normalise patient’s breathing.

Flow L/s

compliance. However, it should be mentioned that patient adherence to CPAP is considerably improved by implementing some routine protocols to the start and follow-up of the treatment [19, 22]. On the one hand, initial educational and training sessions before CPAP titration allow the patient to better understand the treatment and improve adaptation to the equipment (figure 6). On the other hand, periodic follow-up sessions are useful for answering any questions posed by the patient about the treatment, and also for the early detection and solution of problems, such as discomfort with the mask, air leaks or rhinitic sideeffects, that could reduce adherence to the treatment [19, 22].

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patient was breathing normally and the applied CPAP was 4 cmH2O (0.4 kPa). Subsequently, as the simulated patient fell asleep, apnoeas ensued. The device detected the apnoeas and increased the CPAP. As the CPAP became progressively higher, the simulated patient then exhibited hypopneas and flow limitation; finally, the breathing pattern was normalised when CPAP reached 12 cmH2O (1.2 kPa). From then on, the auto-setting device slightly decreased or increased CPAP to detect the appearance and disappearance of abnormal breathing. This process maintained the optimal CPAP (minimum value avoiding breathing events) for the simulated patient. Given that auto-adjusting CPAP is a relatively new technology, some issues affecting its potential clinical use are still open to debate. In

contrast to the detection and classification of events [23], there are no generally accepted criteria for defining the optimum method of modifying nasal pressure in response to breathing events. For instance, after how many apnoeas/hypopnoeas/snoring events should pressure be increased? What should the step for increasing pressure be? What should the rate for modifying pressure be? If no events are detected, how long should the device wait before reducing pressure? Given the number of open points, each manufacturer of an auto-adjusting CPAP device uses a proprietary algorithm that is usually undisclosed. Consequently, devices provide different results when subjected to the same breathing pattern [24, 25]. As an example, figure 9 shows the response of three currently available auto-adjusting CPAP

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devices when subjected to a normal breathing pattern, followed by a persistent period of flow limitation during a well-controlled bench test. Two devices responded by increasing nasal pressure, but the pressure increase rate was clearly different. The third device did not modify pressure when subjected to an abnormal breathing pattern (figure 9). This lack of response could be caused by the deviceâ&#x20AC;&#x2122;s inability to detect the event when it occurred, or it could mean that the device algorithm did not consider this well-detected and classified event as a reason for modifying pressure. Such differences between devices, which have also been documented in patient studies, make it difficult to assess the costeffectiveness of auto-adjusting CPAP and to compare different clinical studies, as the results are always dependent on the device used in each test [25].

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a high level of CPAP. However, the cost-effectiveness of autoadjusting CPAP for OSAHS treatment needs to be better substantiated in future studies [17].

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6

8

10

12 Time min

14

16

18

Figure 9. Nasal pressure applied by three commercially available auto-adjusting CPAP devices when subjected, on the bench, to an initial pattern of normal breathing (up to minute 5) followed by a pattern of persistent flow limitation. The flow signal is shown on the top; a detail of the flow patterns in minute 5 shows the transition from the normal to the flowlimited breathing pattern (positive flow corresponds to inspiration). The green lines indicate 10 cmH2O (1.0 kPa) of nasal pressure (Press).

To date, several clinical studies have been carried out to test the therapeutic application of autoadjusting CPAP for treating OSAHS. Although these devices have been shown to apply a mean nasal pressure lower than conventional fixed CPAP devices, their effectiveness in reducing the number of sleep breathing events is similar with both nasal pressure modalities [26-28]. Accordingly, the currently available data do not

make it possible to recommend systematic application of autoadjusting CPAP to the general spectrum of OSAHS patients, particularly taking into account its great cost when compared with conventional CPAP. This CPAP modality could be better suited for selected subpopulations of OSAHS patients, for instance those exhibiting a clear number of respiratory events when changing body posture or those treated with

Interestingly, auto-adjusting CPAP devices can be also used for an application different from the original intention (continuous tailoring of a patient’s treatment). In fact, these devices are able to carry out simplified CPAP titration either in the sleep laboratory or in a patient’s home. Instead of manually modifying nasal pμressure to determine the optimal CPAP, auto-adjusting devices can automatically determine the optimal pressure, thereby reducing the workload in sleep laboratories (figure 8). CPAP titration at home has the advantage that the patient is sleeping in his/her actual environment and that the titration process can be extended to several nights at an affordable cost (when compared with titration in the sleep laboratory). Simplified titration with auto-adjusting CPAP devices has proven useful when applied to selected subpopulations of patients [29, 30]. However, the generalised use of this titration modality should be cautious [17, 31], as a number of patients require full polysomnographic CPAP titration in the sleep laboratory. ■

REFERENCES 1. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993; 328: 1230–1235. 2. Duran J, Esnaola S, Rubio R, Iztueta A: Obstructive sleep apneahypopnea and related clinical features in a population-based sample of subjects aged 30 to 70 yr. Am J Respir Crit Care Med 2001; 163: 685-689. 3. Schwartz AR, Patil SP, Laffan AM, Polotsky V, Schneider H, Smith PL. Obesity and obstructive sleep apnea: pathogenic mechanisms and

52

THE BUYERS’ GUIDE TO RESPIRATORY CARE PRODUCTS

therapeutic approaches. Proc Am Thorac Soc 2008; 5: 185-192. 4 Young T, Peppard PE, Taheri S. Excess weight and sleep-disordered breathing. J Appl Physiol 2005; 99: 1592-1599. 5. Prentice AM. The emerging epidemic of obesity in developing countries. Int J Epidemio. 2006; 35: 93-99. 6. Patil SP, Schneider H, Schwartz AR, Smith PL. Adult obstructive sleep apnea: pathophysiology and diagnosis. Chest 2007;132: 325-337. 7. Eckert DJ, Malhorta A. Pathophysiology of adult obstructive sleep apnea. Proc Am Thorac Soc


BG-05 CPAP:BG-05 CPAP

27/7/09

21:34

Page 53

PRINCIPLES OF CPAP AND AUTO-ADJUSTING CPAP DEVICES

05

REFERENCES continued 2008; 5: 144–153. 8. Mulgrew AT, Nasvadi G, Butt A, et al. Risk and severity of motor vehicle crashes in patients with obstructive sleep apnoea/hypopnoea. Thorax 2008; 63: 536-541. 9. Sateia MJ. Neuropsychological impairment and quality of life in obstructive sleep apnea. Clin Chest Med 2003; 24: 249–259. 10. Arzt M, Young T, Finn L, et al. Association of sleep-disordered breathing and the occurrence of stroke. Am J Respir Crit Care Med 2005; 172: 1447–1451. 11. Wolk R, Somers VK. Sleep and the metabolic syndrome. Exp Physiol 2007; 92: 67-78. 12. Caples SM, Garcia-Touchard A, Somers VK. Sleep-disordered breathing and cardiovascular risk. Sleep 2007;30: 291-303. 13. Golbin JM, Somers VK, Caples SM. Obstructive sleep apnea, cardiovascular disease, and pulmonary hypertension. Proc Am Thorac Soc 2008; 5: 200-206. 14. Tasali E, Ip MSM. Obstructive sleep apnea and metabolic syndrome: alterations in glucose metabolism and inflammation. Proc Am Thorac Soc 2008; 5: 207-217. 15. Chan ASL, Lee RWW, Cistulli PA. Non-positive airway pressure modalities: mandibular advancement devices/positional therapy. Proc Am Thorac Soc 2008; 5: 179-184. 16. Won CHJ, Li KK, Guilleminault C. Surgical treatment of obstructive sleep apnea: upper airway and maxillomandibulr surgery. Proc Am Thorac Soc 2008; 5: 193-199. 17. Sanders MH, Montserrat JM, Farré R, Givelber RJ. Positive pressure therapy: a perspective on evidencebased outcomes and methods of application. Proc Am Thorac Soc 2008; 5: 161-172. 18. Weaver TE, Maislin G, Dinges DF, et al. Relationship between hours of CPAP use and achieving normal levels of sleepiness and daily functioning. Sleep 2007; 30: 711719. 19. Weaver TE, Grunstein RR. Adherence to continuous positive airway pressure therapy: the challenge to effective treatment. Proc Am Thorac Soc 2008; 5: 173178. 20. Farré R, Montserrat JM, Ballester E, Navajas D. Potential rebreathing after continuous positive airway

pressure failure during sleep. Chest 2002; 121: 196-200. 21. Mador MJ, Krauza M, Pervez A, Pierce D, Braun M. Effect of heated humidification on compliance and quality of life in patients with sleep apnea using nasal continuous positive airway pressure. Chest 2005;128: 2151-2158. 22. Santamaria J, Iranzo A, Montserrat JM, de Pablo J. Persistent sleepiness in CPAP treated obstructive sleep apnea patients: evaluation and treatment. Sleep Med Rev 2007; 11: 195-207. 23. Redline S, Budhiraja R, Kapur V, et al. The scoring of respiratory events in sleep: reliability and validity. J Clin Sleep Med 2007; 3: 169-200. 24. Rigau J, Montserrat JM, Wohrle H, et al. Bench model to simulate upper airway obstruction for analyzing automatic continuous positive airway pressure devices. Chest 2006; 130: 350-361. 25. Brown LK. Autotitrating CPAP: how shall we judge safety and efficacy of a “black box“? Chest 2006; 130: 312-314. 26. Ayas NT, Patel SR, Malhotra A, et al. Auto-titrating versus standard continuous positive airway pressure for the treatment of obstructive sleep apnea: results of a metaanalysis. Sleep 2004; 27: 249-253. 27. Nolan GM, Ryan S, O’Connor TM, McNicholas WT. 2006. Comparison of three auto-adjusting positive pressure devices in patients with sleep apnoea. Eur Respir J 2006; 28: 159-164. 28. Meurice JC, Cornette A, Philip-Joet F, et al. Evaluation of autoCPAP devices in home treatment of sleep apnea/hypopnea syndrome. Sleep Med 2007; 8: 695-703. 29. Masa JF, Jimenez A, Duran J, et al. Alternative methods of titrating continuous positive airway pressure: a large multicenter study. Am J Respir Crit Care Med 2004; 170: 1218-1224. 30. Mulgrew AT, Fox N, Ayas NT, Ryan CF. Diagnosis and initial management of obstructive sleep apnea without polysomnography. Ann Int Med 2007; 146: 157-166. 31. Rodenstein D. Determination of therapeutic continuous positive airway pressure for obstructive sleep apnea using automatic titration: promises not fulfilled. Chest 2008; 133: 595-597.

THE BUYERS’ GUIDE TO RESPIRATORY CARE PRODUCTS

53


Documentação

F006-02

Projeto:

Data:

OXYMAG VENTILADOR DE TRANSPORTE

20/10/2010

Elaborado por:

Verificado por:

Aprovado por:

Marcelo Onodera

Toru

Tatsuo

Objeto / Título do Documento:

Código:

1600185 Folha:

1/1 Revisão:

85 – Dados clínicos, Papers

01

Doc 10 – CPAP Benefits

MAGNAMED TECNOLOGIA MÉDICA LTDA


Self-Reported Use of CPAP and Benefits of CPAP Therapy : A Patient Survey Heather M. Engleman, Nima Asgari-Jirhandeh, Andrew L. McLeod, Crichton F. Ramsay, Ian J. Deary and Neil J. Douglas Chest 1996;109;1470-1476 DOI 10.1378/chest.109.6.1470 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/109/6/1470

CHEST is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright 1996 by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692

Downloaded from chestjournal.chestpubs.org by guest on July 5, 2010 1996 BY THE AMERICAN COLLEGE OF CHEST PHYSICIANS


Use of CPAP and Benefits Self-Reported of CPAP Therapy* A Patient

Survey1

Heather M. Engleman, BSc; Nima Asgari-Jirhandeh, BSc; Andrew L. McLeod, MBChB; Crichton F. Ramsay, MRCP; Ian /. Deary, PhD; and Neil J. Douglas, MD The benefits of continuous positive airway pressure (CPAP) therapy in patients with the sleep ap¬ nea/hypopnea syndrome (SAHS) are poorly documented and patients use CPAP less than physicians recommend. To establish patients' perceptions of benefit from CPAP and to identify determinants of CPAP use, 204 CPAP users completed a questionnaire relating to use of CPAP therapy, sleepi¬ ness, and road traffic incident rate before and after CPAP, perceived change in daytime function and nocturnal symptoms with treatment, and problems with CPAP. Variables from these domains of interest were examined, reduced through principal components analysis and correlated to assess associations between these and polysomnographic measures of illness severity. Self-reported CPAP use averaged 5.8±SD 2 h a night. Subjective sleepiness rated by the Epworth sleepiness scale and road traffic incident rate were significantly reduced by CPAP (p<0.0001). A broad range of function and symptom items were highly significantly improved with CPAP (p<0.0001), corroborating the cost to community and industry from SAHS and the preventive value of CPAP. Road traffic incident rate before treatment was correlated with pre-CPAP sleepiness and SAHS severity. Subjective CPAP use correlated with sleepiness before treatment but not with SAHS severity. CPAP mask problems and side effects were not associated with reduced CPAP use, but "nuisance" complaints of awakenings, noise, and sore eyes from CPAP correlated negatively with reported use. Greater reported CPAP use was associated with better resolution of sleepiness and greater improvement in daytime func¬ tion and nocturnal symptoms. (CHEST 1996; 109:1470-76)

Key words: automobile accidents; compliance; CPAP; sleep apnea/hypopnea syndrome Abbreviations: AHI=apnea+hypopnea index; CPAP=continuous positive airway pressure; MSLT=multiple sleep latency SNSL=Scottish National test;

SAHS=sleep apnea/hypopnea syndrome;

positive airway pressure (CPAP) T^Tasal-contmuous ^ is the treatment of choice for the

therapy sleep (SAHS) and related disor¬ syndrome apnea/hypopnea ders. CPAP is effective in reducing nocturnal events of -*-

For editorial comment see page 1416 SAHS and may improve objective daytime sleepi¬ ness,1"4 cognitive function,1"3 and well-being.1,2 Yet CPAP is frequently rejected by patients,5,6 at least because of the unwieldy and inconvenient partly nature of the treatment. Patients' use of CPAP is likely to be determined by perceived benefits and drawbacks *From the Department of Respiratory Medicine (Ms. Engleman and Mrsr. Asgari-Jirhandeh, McLeod, Ramsey, and Douglas) and of Psychology (Dr. Deary), University of Edinburgh, DepartmentUK. Edinburgh, oi the survey are available from the authors by 'Copies contacting Heather Engleman, Scottish National Sleep Laboratory, Scottish

Infirmary ofEdinburgh, Lauriston Place, Edinburgh EH3 9YW, UK; phone (+44)131 536-2355; fax (+44)131 536-3255. Supported by a grant from the British Lung Foundation (H.M. Engleman).received 5, 1995; revision Manuscript July accepted November 29.

Sleep Laboratory

of treatment, but the composition of these factors is not well understood. Studies of CPAP use, its determinants, and effects are highly variable in terms of patient selection and outcome measures employed, and thus in results Studies based primarily on objective reported.1"20 measures of function may neglect patient assessment of benefit.1'4,7 Those studies using self-reported measures5,6,18"20 usually examine limited areas of function, often sleepiness alone, while open-ended question¬ naire formats12 restrict comparability between studies. With two exceptions,15,20 studies of the effects of CPAP have been performed in small patient samples of less than 100 patients. Average CPAP use rate varies from 3.2 to 6.7 h a night, depending on whether new CPAP users,1'8,916 cross-sectional CPAP clinic populations,15'18,20 or se¬ lected long-term acceptors of CPAP14,17,19 are studied. The literature on the determinants of CPAP compli¬ ance and acceptance is contradictory, with CPAP use

predicted by polysomnographic severity in some6'18,19

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and not in other studies,5,8,9,12,1416 by prior sleepiness in some5,6 but not in others,8,9,12,18 and compliance adversely affected by side effects in some8,12,18 but not in other studies.5,9,11,14,20 A particular area of interest is the effect of CPAP on driving competence. The road traffic accident rate in SAHS is increased by a factor of two to seven times that of the normal population,21,22 and a report has related driving accident rate to SAHS severity.23 A proportion of accidents in SAHS patients will be sleep related, causing more fatalities than other accidents.24 Labo¬ ratory-based studies, whether using monotonous driv¬ ing-based vigilance tasks1,13 or more realistic simula¬ tors,25 suggest improved driving performance after CPAP1,13 and Previous small studies, conducted with 222^ and 1427 SAHS patients, respectively, have indicated fewer reported road traffic incidents following CPAP. This questionnaire-based study therefore assessed reported use of CPAP and a wide range of perceived benefits and drawbacks of CPAP therapy in our clinic so that these factors could be described population, and relationships between them could be examined.

uvulopalatopharyngoplasty.25

Materials and Methods

Study Design A questionnaire was sent in June 1994 to all patients issued CPAP units by the Scottish National Sleep Laboratory (SNSL) for 2 weeks

or longer. Questionnaire data were supplemented with information, obtained from SNSL records, on age, sex, polysomnographic SAHS severity, objective CPAP use from run-time clock readings, and objective daytime sleepiness on the multiple sleep latency test (MSLT).28 Posttreatment MSLTs were conducted after at least 4 weeks of receiving CPAP. Information from the questionnaire and SNSL sources was grouped into domains of illness severity, CPAP compliance, road traffic incidents and sleepiness before and after CPAP, perceived change in function and symptoms, problems with CPAP use, and weight change. CPAP users underwent polysomnography before commencing treatment. The criteria for prescribing CPAP were reported symp¬ toms of SAHS in association with an apnea + hypopnea index (AHI) of greater than 5/h sleep, or in association with snoring and recur¬ rent microarousals. Patients received practical demonstration and experience during the daytime in the mechanisms and use of CPAP and underwent a mask fitting before a night of CPAP titration. Telephone advice and appointments with nursing staff were avail¬ able during office hours for patients experiencing problems. Patients were reviewed in an outpatient clinic 4 weeks after com¬ mencement of therapy, when problems with CPAP were sought. Subsequent follow-up interval varied between 2 and 6 months de¬

pending on whether problems were present.

Questionnaire All 253 patients issued a CPAP unit by the SNSL, and their partners, were sent a four-page questionnaire inquiring about use of CPAP, sleepiness and road traffic incidents before and after CPAP, changes in nocturnal and daytime function, problems with

CPAP therapy, and weight change. Self-Reported CPAP Use: Patients were asked how many nights per week and for how long each night CPAP was used.

Epworth Sleepiness Score: Patients' subjective sleepiness after

and, retrospectively, before CPAP was rated by patients and their partners using the Epworth sleepiness scale.29,30

Road Traffic Incidents: Drivers were asked their yearly mileage and the frequency of road traffic incidents in the 5 years before starting CPAP and in the time since CPAP was commenced. Selfreported incidents were divided into near-misses, casualty-free collisions ("minor" collisions), and accidents causing injury ("major" collisions) and further subdivided for those believed to be sleep related or not. The rates of road traffic incidents per 10,000 miles were calculated for each class of event. Function and Symptoms: Patients were asked to rate changes in function and symptoms on a bipolar five-point scale with options of much worse, worse, no change, better, and much better, coded -2,-l,0,+l, and +2, respectively. Items rated by patients were snoring, breathing pauses, daytime sleepiness, sleep quality, tired¬ ness, concentration ability, ability to drive long distances safely, work efficiency, time taken off work, sex drive, and general health. Partners were asked to rate change in patients' snoring, breathing pauses, daytime sleepiness, and temper. Problems With CPAP Use: Patients were presented with a 12-item list of side effects and problems with CPAP use, and asked to indicate on a four point-scale whether each problem was absent, a minor problem, a significant problem but not interfering with CPAP use, or a significant problem interfering with CPAP use. The items comprised nasal stuffiness, dry throat, red/sore eyes, leaking mask, cold airstream, nosebleeds, mask rubbing, difficulty exhaling, more frequent awakenings, excessive noise from CPAP unit, stom¬ ach bloating/'flatulence, and chest wheeze. Change in Weight: Patients were asked to report any weight gain or loss since the commencement of CPAP treatment. Items not completed by or inapplicable to individuals were ex¬ cluded from relevant item analyses. Statistics

The significance ofinterindividual differences was assessed using Wilcoxon tests. Principal components analysis31 was conducted to reduce the number of variables for a rank correlation analysis, which examined associations between domains. All analyses were per¬ formed using specific software (SPSS-PC+).32

Results

Questionnaire Response Of 253 patients (26 female) issued CPAP units, 215 (85%) returned questionnaires. Nonresponders were significantly younger (mean [±SD] age, 46±9 years)

than responders (53±10 years; p<0.0001), but were otherwise no different from the responders, who had a mean AHI33 of 47±38 per hour slept, 47±40 microarousals34 per hour slept, average minimum oxygen saturation of 74±18%, and mean duration of CPAP treatment of 632 days (range, 16 to 2,921

days). Eleven patients (5% of responders) stated that they no longer used CPAP. Three patients cited mask dis¬ comfort as a factor, three cited lack of benefit, and one each cited frequent awakenings, excessive CPAP pres¬ sure, and throat dryness. One patient's nasal stuffiness, following nasal surgery, precluded CPAP use. Three patients gave no reason for discontinuing treatment. Of CPAP 21 had an AHI users,

patients (10%)

less than

15. The responses of the 204 patients (17 female) who

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1471


Table

1.Sleepiness Before and After CPAP Pre-CPAP, Mean±SD

Post-CPAP, Mean±SD

15±6 14±6 4.6±3.4

7±5 8±5 6.6±3.2

Epworth sleepiness score (patient) Epworth sleepiness score (partner) MSLT, min

p Value <0.0001 <0.0001 <0.001

Table 2.Mileage-Adjusted Road Traffic Incident Rates Before and After CPAP Pre-CPAP, Mean±SD Incident rate

Post-CPAP, Mean±SD

p Value

0.32±1.53 0.09±0.52 0.001±0.015 0.41±1.63

<0.0001 >0.3 >0.2 0.0001

0.11 ±0.63 0.03±0.20

<0.0001 >0.2 >0.1 <0.0001

(per 10,000 miles)

0.92 ±2.96 Minor 0.09±0.44 Major 0.005±0.027 1.02±3.17

Near-miss

Total incidents

Sleep-related incident rate (per 10,000 miles) Near-miss

Total incidents

0.86±2.94 Minor 0.07±0.43 Major 0.003 ±0.021 0.93±3.15

0 0.14±0.68

indicated that they were continuing with CPAP ther¬ apy were analyzed.

Self-Reported and Objective CPAP Use Self-reported compliance in 204 CPAP users aver¬ aged 5.8±2.0 h per night, ranging from 0.1 to 9.5 h per CPAP run-time clock readings, night. Synchronous available in 62 patients, yielded an average objective CPAP use of 5.1 ±2.5 h per night, significantly lower than that reported by the same patients (6.0± 1.9 h per night; p=0.0003). Subjective and objective compliance data were significantly correlated (r=0.68; p<0.0001).

¦ Sleep-related incidents 0 All incidents

Change in Subjective and Objective Sleepiness With

CPAP Patients'

patient CPAP,

sleepiness,waswhether subjectively rated by partner, significantly improved with objective daytime sleepiness assessed by Pre-CPAP

or as was

MSLT (Table 1).

MSLT data were available

in 52 patients and post-MSLT data were available in 41

patients. Pre-CPAP scores on Epworth scale and MSLT correlated significantly (r=-0.38; p=0.01), but post-CPAP scores for the two measures of sleepiness

did not (r=0.06; p>0.3). Changes in Road Traffic Incidents With CPAP Information on road traffic incidents was obtained from 147 driving patients. Sleep-related near-miss in¬ cidents, unadjusted for time receiving CPAP therapy, were reported by 39% and 5% of patients, respectively, before and after therapy (Fig 1). No sleep-related major collisions were reported after the commence¬ ment of CPAP treatment. Mileage- and time-adjusted road traffic incident rates showed a significant reduc¬ tion in the rate of near-miss incidents after CPAP

therapy (Table 2). Change in Function and Symptoms With CPAP All items relating to function and symptoms, rated by patients and partners (Table 3), showed highly sig¬ nificant improvements with CPAP, except sex drive.

Before After NEAR-MISSES

Before After MINOR COLLISIONS

Before

After

MAJOR

COLLISIONS

Figure 1. Prevalence of road traffic incidents before and after CPAP.

Problems With CPAP Patients' reports of problems with CPAP use are shown in Table 4. No life-threatening complications, such as meningitis, pneumoencephaly, or pneumo¬

thorax, were seen.

1472

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Change in Weight Reported weight rose significantly but trivially from treatment commencement (mean gain, 1±8 kg; p=0.005). Most patients (55%) reported no change in weight. Principal Components Analysis Principal components analysis was conducted to examine the structure of intercorrelations between responses within the function/symptom items and CPAP-related problem items, respectively. By speci¬ fying items patterns of similarities in responses on the mul¬ within these two domains, this technique tiple allows cognate variables, all associating significantly with an underlying component, to be identified. Items loading significantly on a component can then be consolidated into a summary score, thus allowing the number of variables for subsequent correlation to be rationally reduced. Items with excessively skewed distributions (nose¬ bleeds, wheezing, sore eyes, difficulty exhaling) or with reduced sample sizes (sex drive, bloating, work effi¬ ciency, days taken off work, ability to drive long distances safely) were excluded from the principal components analyses. Components with eigenvalues greater than 1 were extracted and rotated, to increase interpretability, using the varimax method. Signifi¬ cance for variable factor loadings was set at 0.30. The items relating to change in function and symp¬ toms with CPAP reduced to two rotated components, the first having significant loadings on tired/sleep quality/general health/concentration ability/excessive daytime sleepiness (called "daytime function") and the second on snoring/breathing pauses (called "nocturnal items in this analysis also had symptoms"). Allon seven the first unrotated principal compo¬ high loadings nent. This indicated that, in addition to the two clearly separable components, daytime function and noctur¬ nal symptoms, the total score from the seven items could be used as a "general function" measure. Principal components analysis revealed that prob¬ lems with CPAP use formed three rotated compo¬ nents, with significant loadings on frequent awaken¬ ings/noise/sore eyes (called "nuisance"), leaking mask/ mask rubbing (called "mask problems"), and dry throat/nasal stuffiness "side

effects"). daytime func¬ tion, nocturnal symptoms, general function, nuisance, (called

Scores for created variables named

mask problems, and side effects were constructed by

summing item scores loading on each of these com¬ ponents. General function, nocturnal symptoms, and

daytime function were all highly significantly improved with CPAP (p<0.0001), with 95%, 95%, and 91% of patients, respectively, reporting improvement on each of these summary scores. Nuisance, mask problems,

Table 3.Change in Function and Symptoms With CPAP

Percentage Reporting Improvement

Measure Patient

Change in Score, Mean±SD

rating

Breathing pauses Snoring Daytime sleepiness Sleep quality Tiredness Ability to drive long distances safely Concentration Work efficiency

94 92 84 81

79 77 68 66

General health

61 32 22

Time taken off work Sex drive Partner rating

95 90 79 49

Snoring

Breathing pauses Daytime sleepiness

Temper *p<0.0001.

1.6±0.6*

1.6±0.7* 1.3±0.8* 1.2±0.9* 1.0±0.8* 1.3±0.9* 0.9±0.9* 0.9±0.9* 0.8±0.9* 0.5±0.8* 0.1±0.9

1.6±0.7* 1.4±0.8* 1.1±0.9* 0.6±1.0*

and side effects were rated as present in some degree by 66%, 72%, and 73% of patients, respectively.

Rank Correlation

predictive associations among domains of road traffic incident rates, severity, sleepiness, in and and change symptoms function, problems with CPAP use were assessed with rank correlation (Table 5). Subjective CPAP use was not significantly corre¬ lated with any objective index of severity of SAHS, but was positively correlated with pre-treatment Epworth sleepiness score and negatively correlated with the of nuisance of CPAP therapy reported. CPAP degree nuisance was negatively correlated with SAHS sever¬ ity. Improvements in daytime function and nocturnal symptoms correlated with baseline Epworth sleepiness Putative

illness

Table 4.Percentage of Patients Reporting Problems With CPAP Use

Percentage Reporting Percentage Reporting Problem

Nasal stuffiness 64 Mask leak 63 Dry throat 62

Cold airstream 45 Noise from CPAP unit Mask rubbing 41

Bloating/flatulence More frequent 32 awakenings

37

Red/sore eyes 31 Chest wheeze 21

Difficulty exhaling 18 Nosebleeds 10

41

Severe Problem 4 <1 1 2 2 1 <1 2 1 <1 1 0

CHEST / 109 / 6 / JUNE, 1996 Downloaded from chestjournal.chestpubs.org by guest on July 5, 2010 1996 BY THE AMERICAN COLLEGE OF CHEST PHYSICIANS

1473


Table 5.Rank Correlation Among Polysomnography, CPAP Use, Sleepiness, Changes in Function and Symptoms, Road Traffic Incidents, and CPAP Programs* AHI AHI AROUSALS

MINO2

SUBJUSE

PBE-ESS POST-ESS NUISANCE MASK PROB SIDE EFF

dDAYFUNC dNOCTSYMP dGENFUNC

X

0.61f -047f 0.04 0.11 -0.11

-0.13* -0.03 0.07 0.03 0.13 0.09

AROUSALS X X

-0.27f 0.00 0.13 -0.03 -0.12 -0.06

0.20§ -0.02 0.11 0.04

MIN02

SUBJUSE

x x X -0.08

x X x X

-0.29* 0.20$

0.22$ -0.18$ -0.15* 0.17$

-0.04 0.00 0.01

-0.21* -0.05

-0.19*

-0.07

0.441 0.35f 0.46*

PREESS

POST¬ ESS

NUISANCE

MASK PROB

SIDE EFF

X X X X X

X X X X X X 0.11

X X X X X X X

-0.07 0.11

0.28* 0.19$

X X X X X X X X

X X X X X X X X X -0.10

0.11 -0.03 0.09 0.06

0.20$ -0.43* -0.17* 0.13* -0.20$ -0.22$ 0.1 -0.44* -0.20$

0.05 0.10 0.12 0.09

BNMSLP

BNMNON

BMINSLP

BMINNON

0.15

0.20* -0.25$

0.07 0.04 0.12

0.06 0.08 -0.10

-0.01 -0.02 0.10

0.54*

-0.12

0.29*

-0.27f

-0.07 -0.09

*Cell sample size varies from 117 to 203 patients; p values are adjusted accordingly; X=redundant cell; short horizontal line (.)=nonpredictive cell. AROUSALS=microarousal index; MIN02=minimum oxygen saturation; SUBJUSE=subjective CPAP use; PRE-ESS=pre-CPAP Epworth sleepiness score; POST-ESS=post-CPAP Epworth sleepiness score; NUISANCE=nuisance-type problems with CPAP use; MASK PROBS=mask-related problems with CPAP use; SIDE EFF=CPAP side effects; dDAYFUNC ^change in daytime function; dNOCTSYMP=change in nocturnal symptoms; dGENFUNC=change in general function/symptoms; BNMSLP=sleep-related near-miss incidents before CPAP; BNMNON=nonsleep-related near-miss incidents before CPAP; BMINSLP=sleep-related minor collisions before CPAP; BMINNON=sleep-related minor collisions before CPAP.

fp=0.001. *p=0.05. *p=0.01.

CPAP use, and negatively with reported score on CPAP. The frequency of Epworth sleepiness before incidents treatment was correlated with driving the score, Epworth sleepiness frequency of microarou¬ sals, and the extent of nocturnal hypoxemia. score

and

Discussion

This study documents experience and perceptions of CPAP in a large sample of unselected CPAP users with a wide range of illness severity. Although neces¬ sarily limited by its use of mainly self-reported and retrospective information, the study provides evidence of patient-perceived, CPAP-induced improvement across a wide range of function, including sleepiness, driving competence, cognitive function, work effi¬ ciency, well-being, and nocturnal symptoms. Further¬ more, coherent correlations linked pre-CPAP driving competence, use of CPAP, and benefit from CPAP to variables. predictive The study is based on retrospective, self-reports from CPAP users, which may be compromised by poor memory of past events occurring prior to treatment or

by a tendency to overreport improvements, having psychologically "invested" in CPAP therapy. Despite these drawbacks, retrospective ratings of pretreatment status may provide counterbalancing benefits. A lack of awareness of impairment before treatment, noted by others,16,35 may result from the absence of a normal frame of reference in constantly sleepy, untreated pa¬ tients. In these, retrospective measures may be more reliable. The reversal of sleepiness and driving impair¬

ment with treatment may also encourage greater frankness on the part of patients regarding their pre¬ vious deficits, who need no longer fear being banned from driving. The results of this study, showing wideranging improvements in daytime function and noc¬ turnal symptoms, are unlikely to be due only to retro¬ spective inaccuracies and placebo-like effects, having been shown also in a prospective, randomized, place¬ bo-controlled study of the effects of CPAP.1

CPAP Use

Self-reported CPAP use was significantly associated with outcome measures assessing posttreatment sleep¬ iness and improvement in function and symptoms, confirming and extending findings of others showing correlations between compliance and subjective change in sleepiness with treatment.18'19 The observed triangular association among pre-CPAP sleepiness, subsequentis compliance, and posttreatment sleepiness (Table 5) suggestive of a positively reinforcing loop. Poorer compliance was associated with greater rates of collisions after treatment, providing ad¬ sleep-related ditional corroboration of the benefits of CPAP. Mean objective CPAP compliance demonstrated in this study (5.1 h a night) was closely in agreement with that of others in cross-sectional CPAP clinic se¬ ries,15'18,20 which included both new and long-term users. Patients overestimated CPAP use by around 1 h per night, a finding that is consistent across this and other studies.918,20 Degree of CPAP compliance was linked only to prior sleepiness and not to illness sever-

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Clinical

Investigations


ity, confirming the hypothesis that sleepiness is the primary determinant of CPAP acceptance.5'6 Apart from the nuisance problem factor (see below), prob¬

lems with CPAP use were not associated with reduced

compliance. Sleepiness Subjective sleepiness, assessed by the Epworth scale, was significantly improved with CPAP, sleepiness with average scores after treatment falling within the normal range.30 The Epworth sleepiness scale, al¬ though subjective and completed retrospectively, may be a relatively robust measure of sleepiness, dealing with memorable behavior of napping rather than transient mood states of sleepiness. Sleep onset latency on the MSLT was improved but was not normalized by CPAP. This observation has been reported previously by ourselves and others,1"3'7'810 with only one study showing normalization of sleep onset latency with CPAP.4 The small magnitude of change in objective daytime sleepiness, with posttreatment scores lying in the range associated with moderate sleepiness,28 may indicate only partial resolution of sleepiness with CPAP. Alternatively, it may reflect insensitivity of the MSLT to treatment-induced changes in sleepiness, as has been suggested by others.10 Road Traffic Incidents The survey documents a high prevalence of sleeprelated road traffic incidents in untreated patients, with 39% ofall driving patients being aware of sleep-related near-miss incidents before treatment (Fig 1). These results are compatible with the findings of others of increased accident rates in SAHS patients.2122 Selfreported mileage-adjusted rates of near-miss incidents were significantly improved after CPAP. Thus, the study shows significant improvement in actual driving competence with CPAP, consistent with studies sug¬ gesting that treatment may improve driving skills on simulators.1,13'25 These findings confirm previous smaller-scale reports of lowered driving incidents fol¬ lowing CPAP.26'27 Although no significant difference in sleep-related collision rate after CPAP was ob¬ served, the low frequency of such events before CPAP in a small population (Fig 1) may contribute to this finding. Road traffic incidents before treatment were significantly correlated with sleepiness and polysom¬ nographic measures of sleep fragmentation and hy¬ poxemia. These findings of putative predictors for driving competence in both sleepiness and illness se¬ verity in SAHS extend those of Findley et al.23 Function and

Symptoms

CPAP-treated patients reported highly significant improvements in all symptom and function items, ex¬

cept sex drive. The high frequency of reported im¬ provements in daytime function items, especially those relating to concentration, work efficiency, absence from work, and ability to drive distances safely, sug¬ gests that these areas of function are compromised in a significant proportion of patients with SAHS (Table 4). Together with the data on road traffic incidents, the above findings suggest a high cost to community and industry from SAHS and a substantial preventive value for CPAP. The magnitude of reported improvement in daytime function and nocturnal symptoms was related to severity of initial illness. Greater reported improve¬ ments in daytime function and in nocturnal symptoms were associated with greater reported CPAP use, greater sleepiness before treatment, and lesser sleep¬ iness after treatment.

Problems With CPAP Use Reported problems with CPAP use, which most patients classified as "minor" in nature, were remark¬ ably frequent, despite intervention during patient fol¬ low-up. Problems with CPAP use have been associated previously with reduced compliance by ourselves and others,818 but significant relationships between prob¬ lems and reported CPAP use were limited to the nui¬

problem complex. In contrast to nuisance prob¬ lems, mask problem and side effect scores were not associated with lower SAHS severity, reported CPAP or satisfaction with treatment. sance

use,

Nuisance Problems

The nuisance complex, describing complaints relat¬ ing to noise, frequent awakenings, and sore eyes with CPAP treatment, exhibited an interesting pattern of association with putative determinants and effects (Table 5). This problem complex was weakly correlated with milder polysomnographic illness, lower subse¬ quent CPAP use, and lesser perceived benefit. One of the nuisance complex items, noise from CPAP units, has been associated with lower SAHS severity,20 but not previously with lesser CPAP compliance. Although high scorers for nuisance problems had milder initial illness and poorer subsequent CPAP compliance, recent research suggests that even pa¬ tients with milder indexes of illness severity receive objective benefits for cognitive function from CPAP.1 Thus patients' unawareness of the benefits of CPAP is insufficient justification for withholding treatment. The lack of correlation between polysomnographic indexes of illness severity and CPAP use confirms the value of CPAP therapy in "heavy snorers disease"36 or "upper airway resistance syndrome"37 as well as SAHS. It may be that patient education can aid insight into illness-induced impairment and thus promote im¬ proved compliance with and benefit from CPAP. CHEST/109/6/JUNE,

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1996

1475


ACKNOWLEDGMENT: We thank the nursing, technical, and administrative staff of the SNSL for their contributions to this

project. References 1 Engleman HM, Martin SE, Deary IJ, et al. Effect of continuous

set up during a split-night polysomnography. therapy (nCPAP) Sleep 1994; 17:512-15 18 Rauscher H, Formanek D, Popp W, et al. Self-reported vs mea¬ sured compliance with nasal CPAP for obstructive sleep apnea. Chest 103:1675-80

1993;

19 Meurice

Lancet 1994; 343:572-75 hypopnoea syndrome.Kline LR, et al. Effects of one night with¬ NB, Pack AI, out nasal CPAP treatment on sleep and sleepiness in patients with obstructive sleep apnea. Am Rev Respir Dis 1993; 147:1162-68 3 Bedard M-A, Montplaisir J, Malo J, et al. Persistent neuropsy¬ deficits and vigilance impairment in sleep apnea syn¬ chological drome after treatment with continuous positive airways pressure (CPAP). J Clin Exp Neuropsychol 1993; 15:330-41 4 Lamphere J, Roehrs T, Wittig R, et al. Recovery of alertness af¬ 96:1364-67

pressure treatment in

2 Kribbs

"

ter CPAP in apnea. Chest 1989; 5 Waldhorn RE, Herrick TW, Nguyen MC, et al.

Long-term

compliance with nasal continuous positive airway pressure ther¬ apy of obstructive sleep apnea. Chest 1990; 97:33-8 6 Rauscher H, Popp W, Wanke T, et al. Acceptance of CPAP therapy for sleep apnea. Chest 1991; 100:1019-23 7 Engleman HM, Cheshire KE, Deary IJ, et al. Daytime sleepiness, cognitive performance and mood after CPAP therapy for the sleep apnoea hypopnoea syndrome. Thorax 1993; 48:911-14 8 Engleman HM, Martin SE, Douglas NJ. Compliance with CPAP therapy in patients with the sleep apnoea/hypopnoea syndrome. Thorax 1994; 49:263-66 9 Kribbs NB, Pack AI, Kline LR, et al. Objective measurement of patterns of nasal CPAP use by patients with obstructive sleep apnea. Am Rev Respir Dis 1993; 147:887-95 10 Sangal RB, Thomas L, Mitler MM. Disorders of excessive sleepiness: treatment improves ability to stay awake but does not reduce sleepiness. Chest 1992; 102:699-703 11 Nino-Murcia G, McCann CC, Bliwise DL, et al. Compliance and side effects in sleep apnea patients treated with nasal continuous positive airway pressure. West J Med 1989; 150:165-69 S, Mateika, et al. Treatment of obstructive continuous positive airway pressure: with nasal sleep apnea patient compliance, perception of benefits, and side effects. Am Rev Respir Dis 1992; 145:841-45 13 Findley LJ, Fabrizio MJ, Knight H, et al. Driving simulator per¬ formance in patients with sleep apnea. Am Rev Respir Dis 1989; 140:529-30 14 Fletcher EC, Luckett RA. The effect of positive reinforcement on hourly compliance in nasal continuous positive airwayDispressure users with obstructive sleep apnea. Am Rev Respir 1991; 143:936-41 15 Krieger J. Long-term compliance with nasal continuous positive airway pressure (CPAP) in obstructive sleep apnea patients and nonapneic snorers. Sleep 1992; 15:S42-46 16 Reeves-Hoche MK, Meek R, Zwillich CW. Nasal CPAP: an ob¬ jective evaluation of patient compliance. Am J Respir Crit Care 12 Hoffstein V, Viner

Med 1994; 149:149-54

17

Fleury B, Rakatonanahary D, Tehindrazanarivelo AD, et al. Long-term compliance to continuous positive airway pressure

J-C, Dore P, Paquereau J, et al. Predictive factors of with nasal continuous positive airway

long-term compliance

positive airway treatment on daytime function in sleep apnoea/

105:429-33

sleep

apnea

syndrome.

Chest 1994;

Pepin JL, Leger P, Veale D, et al. Side effects of nasal continu¬ positive airway pressure in sleep apnea syndrome: study of 193 patients in two French sleep centers. Chest 1995; 107:375-81 21 George CF, Nickerson PW, Hanly PJ, et al. Sleep apnoea patients have more automobile accidents [letter]. Lancet 1987; 2:447 22 Findley LJ, Unverzagt ME, Surratt PM. Automobile accidents involving patients with obstructive sleep apnea. Am Rev Respir Dis 1988; 138:337-40 23 Findley LJ, Fabrizio M, Thommi G, et al. Severity of sleep ap¬ nea and automobile accidents. N Engl J Med 1989; 320:868-69 24 Home JA, Reyner LA. Sleep related accidents. BMJ 1995; 20

ous

310:565-67 25 Haraldsson P-O, Carenfelt C, Persson HE, et al. Simulated long-

driving performance before and after uvulopalatopharyn¬ 53:106-10 goplasty. ORL 1991; 26 Suratt P, Findley L. Effect of nasal CPAP treatment on automo¬ bile driving simulator performance and on self-reported auto¬ mobile accidents in subjects with sleep apnea. Am Rev Respir Dis term

1992; 145:A169 27 Minemura H, Akashiba T, Yamamoto H, et al. Traffic accidents in obstructive sleep apnea patients and effects of nasal CPAP treatment. Jpn J Thorac Med 1993; 31:1103-08 28 Thorpy MJ. The clinical use of the multiple sleep latency test. Sleep 1992; 15:268-76 29 Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991; 14:540-45 30 Johns M W. Reliability and factor analysis of the Epworth sleep¬ iness scale. Sleep 1992; 15:376-81 31 Childs D. Essentials of factor analysis, 2nd ed. London: Cassell, 1990 32 Norusis MJ/SPSS Inc. SPSS/PC+ advanced statistics V2.0 guide. Chicago: SPSS Inc, 1988 33 Gould GA, Whyte KF, Rhind GB, et al. The sleep hypopnea syndrome. Am Rev Respir Dis 1988; 137:895-98 34 Cheshire K, Engleman H, Deary I, et al. Factors impairing day¬ time performance in patients with sleep apnea hypopnea syn¬ drome. Arch Intern Med 1992; 152:538-41 35 Dement WC, Carskadon MA, Richardson G. Excessive daytime in the sleep apnea syndrome. In: Guilleminault C, sleepiness Dement WC, eds. Sleep apnea syndromes. New York: Alan R. Liss, 1978; 23-46 36 Lugaresi E, Coccagna G, Cirignotta F. Snoring and its clinical implications. In: Guilleminault C, Dement WC, eds. Sleep apnea syndromes. New York: Alan R. Liss, 1978; 13-21 37 Guilleminault C, Stoohs R, Clerk A, et al. A cause of excessive daytime sleepiness: the upper airway resistance syndrome. Chest 1993; 104:781-87

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Clinical Investigations


Self-Reported Use of CPAP and Benefits of CPAP Therapy : A Patient Survey Heather M. Engleman, Nima Asgari-Jirhandeh, Andrew L. McLeod, Crichton F. Ramsay, Ian J. Deary and Neil J. Douglas Chest 1996;109; 1470-1476 DOI 10.1378/chest.109.6.1470 This information is current as of July 5, 2010 Updated Information & Services Updated Information and services can be found at: http://chestjournal.chestpubs.org/content/109/6/1470 Citations

Cited Bys This article has been cited by 42 HighWire-hosted articles: http://chestjournal.chestpubs.org/content/109/6/1 470#related-urls

Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.chestpubs.org/site/misc/reprints.xhtml Reprints Information about ordering reprints can be found online: http://www.chestpubs.org/site/misc/reprints.xhtml Citation Alerts Receive free e-mail alerts when new articles cite this article. To sign up, select the "Services" link to the right of the online article. Images in PowerPoint format Figures that appear in CHEST articles can be downloaded for teaching purposes in PowerPoint slide format. See any online figure for directions.

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Documentação

F006-02

Projeto:

Data:

OXYMAG VENTILADOR DE TRANSPORTE

20/10/2010

Elaborado por:

Verificado por:

Aprovado por:

Marcelo Onodera

Toru

Tatsuo

Objeto / Título do Documento:

Código:

1600185 Folha:

1/1 Revisão:

85 – Dados clínicos, Papers

01

Doc 11 – Noninvasive Ventilation for Critical Care

MAGNAMED TECNOLOGIA MÉDICA LTDA


Noninvasive Ventilation for Critical Care* Erik Garpestad, John Brennan and Nicholas S. Hill Chest 2007;132;711-720 DOI 10.1378/chest.06-2643

The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/132/2/711.full.html

CHEST is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright 2007 by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. (http://chestjournal.chestpubs.org/site/misc/reprints.xhtml) ISSN:0012-3692

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CHEST

Postgraduate Education Corner CONTEMPORARY REVIEWS IN CRITICAL CARE MEDICINE

Noninvasive Ventilation for Critical Care* Erik Garpestad, MD, FCCP; John Brennan, MD; and Nicholas S. Hill, MD, FCCP

Noninvasive ventilation (NIV), the provision of ventilatory assistance without an artificial airway, has emerged as an important ventilatory modality in critical care. This has been fueled by evidence demonstrating improved outcomes in patients with respiratory failure due to COPD exacerbations, acute cardiogenic pulmonary edema, or immunocompromised states, and when NIV is used to facilitate extubation in COPD patients with failed spontaneous breathing trials. Numerous other applications are supported by weaker evidence. A trial of NIV is justified in patients with acute respiratory failure due to asthma exacerbations and postoperative states, extubation failure, hypoxemic respiratory failure, or a do-not-intubate status. Patients must be carefully selected according to available guidelines and clinical judgment, taking into account risk factors for NIV failure. Patients begun on NIV should be monitored closely in an ICU or other suitable setting until adequately stabilized, paying attention not only to vital signs and gas exchange, but also to comfort and tolerance. Patients not having a favorable initial response to NIV should be considered for intubation without delay. NIV is currently used in only a select minority of patients with acute respiratory failure, but with technical advances and new evidence on its proper application, this role is likely to further expand. (CHEST 2007; 132:711–720) Key words: acute respiratory failure; COPD; mechanical ventilation; noninvasive ventilation Abbreviations: ALI ⫽ acute lung injury; APACHE ⫽ acute physiology and chronic health evaluation; CHF ⫽ congestive heart failure; CI ⫽ confidence interval; CPAP ⫽ continuous positive airway pressure; CPE ⫽ cardiogenic pulmonary edema; DNI ⫽ do not intubate; Fio2 ⫽ fraction of inspired oxygen; NIV ⫽ noninvasive ventilation; PEEP ⫽ positive end-expiratory pressure

most important developments in the O nefieldofofthemechanical ventilation over the past 15 years has been the emergence of noninvasive ventilation (NIV) as an increasing part of the critical care armamentarium. Although similar techniques such *From the Division of Pulmonary, Critical Care, and Sleep Medicine, Tufts-New England Medical Center, Boston, MA. Dr. Hill has received honoraria and research grants from and served on the medical advisory boards of ResMed, Inc., and Respironics, Inc. He has received a research grant from Versamed, Inc. Drs. Garpestad and Brennan have no conflicts of interest to disclose. Manuscript received October 28, 2006; revision accepted March 12, 2007. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal. org/misc/reprints.shtml). Correspondence to: Nicholas S. Hill, MD, FCCP, Division of Pulmonary, Critical Care and Sleep Medicine, Tufts-New England Medical Center, 750 Washington St, Boston, MA 02111; e-mail: nhill@tufts-nemc.org DOI: 10.1378/chest.06-2643 www.chestjournal.org

as intermittent positive pressure breathing were used widely during previous decades, unlike NIV they were used mainly to provide intermittent aerosol therapy. The term NIV includes other forms of ventilatory assistance that avoid airway invasion, such as negative pressure ventilation, but the vast majority of NIV applications now use positive pressure. Noninvasive application of continuous positive airway pressure (CPAP) will be considered a form of “NIV” here when used to treat certain types of respiratory failure, but it is not a “true” form of ventilatory assistance because the positive pressure does not increase intermittently to assist inspiration. The emergence of NIV has been fueled by its relative ease of application compared to alternative forms of noninvasive ventilation, as well as its demonstrated ability to improve patient outcomes in certain forms of acute respiratory failure compared to previously standard therapy, including endotraCHEST / 132 / 2 / AUGUST, 2007

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711


cheal intubation.1 This update will focus on recent developments regarding acute applications of NIV, including the expanding evidence base, technical advances, and assessment of current utilization. We emphasize techniques for proper patient selection and implementation that are critical if success rates reported in the literature are to be duplicated.

NIV for Acute Respiratory Failure Recommended Indications Many applications of NIV have been tried in the critical care setting, but as of yet, only four are supported by multiple randomized controlled trials and metaanalyses. COPD Exacerbations The strongest level of evidence, including multiple randomized controlled trials,2–7 supports the use of NIV to treat exacerbations of COPD. Also, metaanalyses by Ram et al8 and Keenan et al9 demonstrate more rapid improvements in vital signs and gas exchange as well as reductions in the need for intubation (relative risk, 0.41; 95% confidence interval [CI], 0.33 to 0.53; risk reduction, 28%), decreased mortality (relative risk, 0.52; 95% CI, 0.35 to 0.76; risk reduction, 10%), and decreased hospital length of stay (⫺ 3.24 days; 95% CI, ⫺ 4.42 to ⫺ 2.06 days and ⫺ 4.57 days, respectively). The Cochrane analysis8 also noted more rapid improvements in vital signs, pH, and gas exchange, and reduced complication rates and hospital lengths of stay. Based on these observations, NIV should now be considered the ventilatory modality of first choice to treat acute respiratory failure caused by exacerbations of COPD. Acute Cardiogenic Pulmonary Edema Similarly strong evidence supports the use of noninvasive positive pressure techniques to treat acute cardiogenic pulmonary edema (CPE).10 –17 Recent metaanalyses18 –20 on the use of NIV to treat acute pulmonary edema have shown that both CPAP and NIV lower intubation and mortality rates compared to conventional therapy with oxygen, although the reduction in mortality rate was statistically significant only in one of the metaanalyses.20. A randomized trial17 comparing CPAP directly to NIV showed no difference in outcomes between the two to treat CPE, a finding confirmed in a recent metaanalysis by Ho and Wong.21 Accordingly, by virtue of its greater simplicity and lesser expense, CPAP has been suggested as the initial noninvasive 712

choice for acute CPE. However, some studies22 have observed more rapid improvements in gas exchange and vital signs with NIV than with CPAP alone, so NIV may be preferable for patients with persisting dyspnea or hypercapnia after initiation of CPAP. Facilitating Extubation in COPD Patients Another NIV application supported by multiple randomized trials is to facilitate extubation in COPD patients. Candidates for early extubation are those who were intubated for COPD exacerbations because they were poor candidates for or failed NIV initially and are unable to pass a T-piece trial even though they have improved sufficiently to tolerate NIV. Ferrer et al23 confirmed earlier findings of Nava et al24 in such patients, randomizing 43 patients with “persistent” weaning failure (failure of three consecutive T-piece trials) to be extubated to NIV or weaned using conventional methods. They observed that NIV-treated patients had shorter durations of intubation (9.5 days vs 20.1 days) and ICU (14 days vs 25 days) and hospital stays (14.6 days vs 40.8 days), decreased incidence of nosocomial pneumonia (24% vs 59%), and improved ICU and 90-day survivals (80% vs 50%) [all p ⬍ 0.05]. These studies strongly support the use of NIV to facilitate extubation in patients with hypercapnic respiratory failure and to avoid the complications of prolonged intubation. But it must be applied cautiously: only in patients who are otherwise good candidates for NIV and were not difficult intubations. Immunocompromised Patients The use of NIV is also well supported for immunocompromised patients who are at high risk for infectious complications from endotracheal intubation, such as those with hematologic malignancies, AIDS, or following solid-organ or bone marrow transplants. In a randomized trial25 of patients with hypoxemic respiratory failure following solid-organ transplantation, NIV use decreased intubation rate (20% vs 70%, p ⫽ 0.002) and ICU mortality (20% vs 50%, p ⫽ 0.05) compared with conventional therapy with oxygen. Hilbert et al26 observed fewer intubations (46% vs 77%) and a lower mortality rate (50% vs 81%) [both p ⬍ 0.05] among immunocompromised patients (mainly hematologic malignancies, but some after solid-organ transplantation or with AIDS) with acute respiratory failure randomized to NIV as opposed to conventional therapy. The sizable reductions in mortality in these studies strongly support the early use of NIV as the initial ventilatory modality in immunocompromised patients with acute respiratory failure, although morbidity and mortality rates are still likely to be high. Postgraduate Education Corner

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Conditions for Which NIV Should Be Considered

Do-Not-Intubate Patients

These applications are supported by a single randomized controlled trial, historically controlled trials, or multiple trials yielding conflicting evidence. NIV can be tried if patients are selected and monitored carefully.

Use of NIV for patients with acute respiratory failure who have a do-not-intubate (DNI) status has aroused debate. Concerns have been raised that the modality might merely prolong the dying process while mask discomfort outweighs any palliative effect.36 However, a prospective observational study by Levy et al37 showed that patients with reversible diagnoses such as COPD and CHF had a betterthan-even chance of surviving the hospitalization if treated with NIV (52% and 75%, respectively), whereas those with pneumonia or cancer had much lower likelihoods of hospital survival. Schettino et al38 reported similar findings in their observational cohort and noted low success rates for NIV in postextubation respiratory failure, hypoxemic respiratory failure, and end-stage cancer. Some have proposed resolving the conflict about the use of NIV in DNI patients by specifying the goals of therapy.39 Patients with reversible processes such as COPD exacerbations or CHF may wish to survive the acute illness and thus use NIV as a form of life support. They are willing to endure some discomfort to achieve this aim. Others desire palliation, aiming to alleviate dyspnea or briefly prolong survival to settle affairs. In these latter circumstances, excessive mask discomfort would justify stopping therapy because the goal of palliation is not being met. Differentiating between and agreeing on these aims requires close and effective communication between caregivers, patient and family.

Asthma Several uncontrolled series27–29 and one randomized trial30 support the use of NIV for acute asthma. In the randomized trial,30 a pilot, 33 patients with acute dyspnea but not in respiratory failure were randomized to standard therapy with nasal bilevel ventilation for 3 h or standard therapy with sham NIV. NIV improved expiratory flow rates more rapidly (80% of patients had a ⬎ 50% increase in FEV1 in the first hour, compared to only 20% in the sham group) and reduced the need for hospitalization.30 The authors speculated that the positive pressure had a salutary effect on airway dilatation, although these results have yet to be replicated. A case report31 raised concerns about the use of NIV for asthma, and a recent metaanalysis by Ram et al32 concluded that routine use of NIV in severe acute asthma could not be recommended. We believe that a cautious trial should still be considered in asthmatics not responding to the first hour of conventional therapy, but more study is warranted. Postoperative Respiratory Failure Either NIV or CPAP may be helpful in averting postoperative respiratory failure by preventing atelectasis and/or improving gas exchange as suggested by three randomized controlled trials in patients undergoing different surgical procedures. Following thoracoabdominal aneurysm repair, prophylactic use of CPAP reduces overall pulmonary complications.33 Squadrone et al34 compared CPAP vs conventional oxygen therapy in patients with hypoxemic respiratory failure after major elective abdominal surgery. The CPAP group had lower rates of intubation, pneumonia, and sepsis. In the only randomized, controlled trial of NIV in postoperative patients, Auriant et al35 found that NIV reduced intubation and mortality rates in patients with hypoxemic respiratory failure following lung resection. These trials indicate that either CPAP or NIV should be strongly considered to prevent or treat postoperative respiratory failure, mainly after lung resection in patients with underlying COPD or congestive heart failure (CHF). Although multiple studies support this application, further studies need to focus on the use of NIV following specific surgical procedures before firmer recommendations can be made. www.chestjournal.org

Hypoxemic Respiratory Failure Randomized controlled trials suggest that patients with hypoxemic respiratory failure (ie, severe respiratory distress, Pao2/fraction of inspired oxygen (Fio2) ⬍ 200 and a non-COPD cause for respiratory failure) benefit from use of NIV.40,41 In 105 such patients, Ferrer et al41 found that compared to conventional therapy, NIV reduced the intubation rate (52 to 25%), the incidence of septic shock (31 to 12%) and ICU mortality (39 to 18%), and improved 90-day mortality (all p ⬍ 0.05). Notably, almost one third of the patients had CPE, which would be expected to respond favorably to NIV, but patients with pneumonia were the ones that benefited the most in this study. This latter finding contrasts with earlier trials that showed an association between pneumonia and NIV failure42– 44 and the need for intubation in approximately two thirds of patients with pneumonia treated initially with NIV.45 One randomized controlled trial46 studying patients with severe communityacquired pneumonia showed that NIV improved outcomes including survival at 2 months but only in CHEST / 132 / 2 / AUGUST, 2007

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patients with underlying COPD. In one prospective cohort study,47 risk factors for NIV failure in patients with acute hypoxemic respiratory failure included the diagnoses of ARDS or severe community-acquired pneumonia, more severe hypoxemia (Pao2/ Fio2 ⬍ 146 after the first hour of treatment), and age ⬎ 40 years. In another study48 of NIV to treat hypoxemic respiratory failure, shock, severe hypoxemia, and severe metabolic acidosis were associated with poor outcomes. In a prospective analysis49 of selected patients with acute lung injury (ALI)/ARDS treated with NIV as the initial ventilator modality, a simplified acute physiology score II ⬎ 34 and a Pao2/Fio2 ⱕ 175 after 1 h of therapy predicted failure. The outcome of NIV is also very poor when used to treat hypoxemic respiratory failure in patients with idiopathic pulmonary fibrosis,48 and this application should be discouraged. A concern that must be stressed is that the diagnostic category of hypoxemic respiratory failure is very broad and benefits accruing to certain subsets of patients within the larger diagnostic category could obscure adverse consequences in smaller subgroups. Thus, with the exception of use for CPE, which is supported by strong evidence, NIV should be used only with caution in carefully selected patients with hypoxemic respiratory failure, and those at high risk for failure should be considered for early intubation, especially if oxygenation fails to improve substantially within the first hour or two (Fig 1). Extubation Failure The use of NIV to prevent or treat extubation failure has also raised concerns. Respiratory failure following extubation imparts a poor prognosis; the duration of mechanical ventilation is lengthened, the likelihood of discharge to a chronic care facility is increased, and mortality may reach 40%.50 Esteban et al51 evaluated the ability of NIV to avoid extubation failure by randomizing patients to NIV or conventional therapy if risk factors developed, including hypercapnea, hypoxemia, acidemia, or tachypnea, after a routine extubation. Surprisingly, NIV not only failed to lower the reintubation rate compared to conventional therapy (approximately 50% in both groups) but it also increased ICU mortality. This was thought to be related to delayed reintubations in the NIV group, an average of 10 h later than in the conventional therapy group. The authors51 concluded that NIV is “not effective in averting the need for reintubation in unselected patients in whom respiratory failure develops after extubation” and that it “may in fact be harmful.” However, only 10% of the enrolled patients had COPD. Also, approxi714

mately 25% of the conventional therapy group was crossed over to NIV when they met criteria for respiratory failure, and only 25% of these patients required reintubation. Thus, results of the study51 do not apply to COPD patients and suggest that rather than initiating NIV early in patients deemed at risk for postextubation failure, one should wait until there are clear indications for NIV so that appropriate patients can be selected. Two subsequent trials support these latter inferences. Ferrer et al52 identified patients at risk for postextubation failure by virtue of age ⱖ 65 years, a history of CHF, or an APACHE (acute physiology and chronic health evaluation) II score ⱖ 12. Although postextubation respiratory failure and need for intubation were significantly reduced by NIV overall, most of the benefit was attributable to the hypercapnic subgroup, amounting to about one third of the patients, who also had a significantly lower mortality rate than control subjects (4% vs 41%, p ⬍ 0.05). Nava et al53 used NIV in patients at “high risk” for extubation failure, using criteria similar to those of Esteban et al,51 but risk was higher because patients had to have failed at least one T-piece trial. Once again, the need for reintubation (8% vs 18%, p ⫽ 0.027) was reduced compared to the conventional therapy group. Also, ICU mortality was 10% less in the NIV group (p ⬍ 0.01) mediated by the reduced need for reintubation. Thus, a trial of NIV appears to be warranted in patients at high risk for extubation failure, particularly if they have hypercapnic respiratory failure.

Selection of Patients for NIV Selection of appropriate patients is crucial for the optimization of NIV success rates and resource utilization. Often, NIV must be started before laboratory data are available because patients may deteriorate during the delay and increase the risk of NIV failure. As depicted in Figure 1, patients with respiratory distress and an appropriate diagnosis should be considered for NIV. At the bedside, the clinician must make two fundamental judgments: (1) whether the patient needs ventilatory assistance based on symptoms and signs of increased work of breathing or arterial blood gas derangements, and (2) whether such patients are candidates for NIV or should be promptly intubated. These determinations are key to the appropriate application and outcome of NIV and are based on the diagnosis, bedside observations, the clinician’s experience, and consideration of available guidelines (Table 1). The timing of NIV initiation is important too. NIV should be started early, as soon Postgraduate Education Corner

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Figure 1. Algorithm illustrating the principles of patient selection and practical application of NIV. Patients are started on NIV if respiratory distress develops in the setting of de novo or acute-on-chronic respiratory failure, or following surgery or extubation. They should have an appropriate diagnosis and meet guidelines demonstrating the need for ventilatory assistance and absence of contraindications. After starting NIV, they should be closely monitored and checked at 1 to 2 h to establish that they are responding favorably. If they have ALI/ARDS and are not good candidates, have contraindications or fail the 1- to 2-h checkpoint, they should be intubated unless they have a DNI status, in which case some patients might still benefit from palliation of respiratory distress. NIV to facilitate weaning should be considered for intubated patients. Patients who respond favorably to NIV should be monitored closely and reassessed periodically to determine whether they are ready to attempt weaning, which is usually accomplished by temporary discontinuation. If they have persisting respiratory failure after temporary discontinuation, long-term nocturnal NIV should be considered. www.chestjournal.org

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Table 1—Selection Guidelines for NIV in the Acute Setting Appropriate diagnosis with potential reversibility Establish need for ventilatory assistance Moderate-to-severe respiratory distress and Tachypnea (respiratory rate ⬎ 24/min for COPD, ⬎ 30/min for CHF); accessory muscle use or abdominal paradox Blood gas derangement (pH ⬍ 7.35, Paco2 ⬎ 45 mm Hg, or Pao2/Fio2 ⬍ 200) Exclude patients with contraindications to NIV Respiratory or cardiac arrest Medical instability (hypotensive shock, myocardial infarction requiring intervention, uncontrolled ischemia or arrhythmias) Unable to protect airway Unable to fit mask Untreated pneumothorax Recent upper airway or esophageal surgery Excessive secretions* Uncooperative or agitated* *Relative contraindications.

as indications appear, because delay may permit further deterioration and increase the likelihood of failure.54 Coma has been considered a contraindication to NIV in the past, but in a prospective cohort study, Gonzalez Diaz et al55 observed a high success rate of NIV in patients with hypercapnic coma. Also, Scala et al56 showed in a case study that NIV may be successfully used in COPD patients with acute respiratory failure and altered consciousness, although more severely impaired consciousness was associated with higher failure rates. Predictors of NIV success or failure may also be helpful in selecting patients (Table 2). The best predictor of success is a favorable response to NIV within the first 2 h. In a prospective cohort study of nearly 800 COPD patients treated with NIV, Confalonieri et al57 identified four factors—APACHE II score, pH, respiratory rate, and Glasgow coma score—that, when combined in a chart, showed good predictive value at baseline. These factors had even better predictive value after 2 h of NIV use; if all four factors were favorable, the chance of success was 97%; whereas if all were unfavorable, failure was a virtual certainty (99%). Antonelli et al47 made similar observations in patients with hypoxemic respiratory failure: if Pao2/ Fio2 failed to increase ⬎ 146 after the first hour of NIV therapy, or if the patient had pneumonia and ARDS, the risk of NIV failure was increased. These observations, combined with those of Esteban et al,51 demonstrating worse outcomes in NIV-treated patients having delayed reintubations, emphasize the importance of carefully reassessing patients soon after NIV initiation (1- to 2-h checkpoint as depicted in Fig 1). If they fail to improve sufficiently, they 716

Table 2—Factors Associated With NIV Success in the Acute Setting Synchronous breathing with ventilator Dentate Less air leaking Fewer secretions Good tolerance Respiratory rate ⬍ 30/min* Lower APACHE II score (⬍ 29)* pH ⬎ 7.30* Glasgow coma score 15* Pao2/Fio2 ⬎ 146 after first hour if hypoxemic respiratory failure COPD, CPE No pneumonia, ARDS Best predictor of success is a good response to NPPV within 1 to 2 h: Reduction in respiratory rate Improvement in pH Improvement in oxygenation Reduction in Paco2 *If all four are present in COPD patients at baseline, the likelihood of success is 94%; if present after 2 h of therapy, the likelihood of success is 97%.46

should be promptly intubated because a delay in needed intubation permits the development of a respiratory crisis, requiring emergent intubation and increasing the likelihood of morbidity or mortality. Advances in Technology Interfaces A well-fitting and comfortable interface (or mask) is crucial to the success of noninvasive ventilation. Although nasal masks have certain advantages over oronasal (or full face) masks including greater comfort, less likelihood of causing claustrophobia, and easier speech and expectoration, they also permit more air leakage through the mouth and have been associated with a higher rate of initial intolerance during acute applications of NIV.58 Thus, oronasal masks are preferred initially for most critical care applications, although a nasal mask should still be considered for patients with claustrophobia or frequent expectoration or for long-term applications. Other mask types that are receiving attention include the Total Face Mask (Respironics; Murrysville, PA), which seals around the perimeter of the face and may enhance mask tolerance in some patients, and the helmet, which has not yet been approved by the Food and Drug Administration for NIV in the United States but has been investigated in Europe.59,60 The latter device consists of a plastic cylinder that fits over the head and seals around the neck and shoulders. Compared to the full face mask in a case-control study61 of NIV to treat COPD Postgraduate Education Corner

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patients with acute respiratory failure, the helmet achieved similar improvements in vital signs, equivalent intubation and mortality rates and caused fewer complications, but Paco2 tended to be higher at the end of the treatment period despite a higher level of pressure support. Also, noise levels within the helmet may be as high as 100 decibels, compared to 70 decibels with a full-face mask.62 Thus, although the helmet has some advantages over the full face mask with regard to comfort and complications, it has other disadvantages including less efficient CO2 removal and noisiness that limit its current utility. Dead Space and Rebreathing By virtue of its single-ventilator-circuit design, bilevel ventilation has raised concerns about rebreathing.63 A lung model study64 demonstrated that masks with smaller volumes were associated with less rebreathing and an in-mask exhalation port minimized rebreathing compared to an in-line port. Another lung model study65 used a mannequin face to demonstrate that an in-mask exhalation port over the bridge of the nose minimized dynamic dead space, sometimes to levels below physiologic, presumably by flushing CO2 from the nose and mouth. The correlation between dynamic dead space and actual mask volume was poor, probably because of air streaming, and dead space was also minimized if positive expiratory pressure flushed CO2 from the ventilator tubing. Whether these differences in dead space and rebreathing are clinically important remains unclear, but these studies support the use of in-mask exhalation ports and positive expiratory pressure during bilevel ventilation. Ventilators NIV is usually delivered either by blower-based portable positive pressure “bilevel” ventilators derived from home-based CPAP systems or “critical care” ventilators designed to deliver invasive mechanical ventilation. No study has shown better NIV success rates for one type of ventilator than the other, but the ventilator mode used and specific settings are important for patient comfort and decreased work of breathing. Pressure support ventilation is rated as more tolerable by patients than assist-control modes,66 and some studies67– 69 have demonstrated greater comfort with proportional assist ventilation than with pressure support, presumably because it is targeted to inspiratory flow as a surrogate of patient effort and can respond nearly instantaneously to changes in demand. Proportionalassist ventilation has only recently been approved by the Food and Drug Administration, but it has been available elsewhere in the world for almost a decade. www.chestjournal.org

The perceived need for multiple adjustments to compensate for patient elastance and resistance as well as added cost have probably limited greater use of this mode despite the finding in one of the controlled trials that proportional assist required fewer adjustments than pressure support.68 Other desirable attributes of ventilators for NIV include the ability to compensate for air leaks, which helps to assure delivery of adequate tidal volumes.70 Because NIV lowers humidity of delivered gas, humidification is useful to bring relative humidity back toward the ambient range, possibly enhancing comfort.71 Heated passover humidifiers have minimal effects on delivered pressures, whereas heat and moisture exchangers are to be avoided because they can interfere with the ability of NIV to reduce work of breathing.72 Ventilator Settings L’Her et al73 showed that patients with acute lung injury treated with NIV require pressure support levels of at least 10 to 15 cm H2O to reduce work of breathing. Not surprisingly, higher levels of positive end-expiratory pressure (PEEP) [10 cm H2O vs 5 cm H2O] were more effective at improving oxygenation. Combining higher levels of pressure support with high-level PEEP can detract from patient comfort, however, so compromises may be necessary to optimize settings; maximal oxygenation may have to be sacrificed if patient comfort and reduction in work of breathing are prioritized. Many noninvasive ventilators now offer adjustable “rise times” or pressurization rates—the time taken to achieve the target inspiratory pressure— to optimize patient comfort. Prinianakis et al74 found that a rapid pressurization rate was most effective at reducing work of breathing in COPD patients, but a slightly slower rate was associated with better comfort ratings. Guidelines, Utilization, and Outcomes Sinuff et al75 found that a NIV guideline influenced caregiver behavior, leading to greater ICU utilization and more ordering of pulmonary consultations and arterial blood gases. However, overall mortality rate was unchanged and, of concern, the mortality rate actually increased in patients without COPD or CHF as the cause of their acute respiratory failure, who were excluded from NIV use by the guideline. The results highlight the need for ongoing guideline evaluation and modification because they could increase resource utilization and the cost of care if they mandate ICU use and frequent laboratory testing among all NIV patients, some of whom could conceivably be managed in less costly environments. CHEST / 132 / 2 / AUGUST, 2007

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Studies of NIV utilization in the acute care setting have found that enormous disparity exists between different institutions. In a 1997 survey of NIV use in European ICUs, Carlucci et al76 found that 20% of ICUs surveyed used no NIV at all and, overall, NIV was used in 16% of all ventilator starts. A subsequent UK survey77 found that 52% of hospitals were not using NIV. A more recent survey78 in the United States found that although only 1 of 71 responding hospitals used no NIV, some used it in ⬍ 5% of ventilator starts and others in ⬎ 50%. Overall average use among ventilator starts was 20%, but only a third of patients with COPD or CHF received NIV as their initial ventilator therapy. Major reasons for not using NIV more were lack of physician knowledge and inadequately trained staff, suggesting that education may help to enhance utilization. However, progress is being made, as indicated by Demoule et al,79 who found that the overall percentage for NIV among ventilator starts in European ICUs had risen to 23% by 2002; and Girou et al,80 who showed that increasing use of NIV in CHF and COPD patients (from approximately 20 to 90% of ventilator starts) over a 7-year period in a French ICU was associated with a decrease in the rate of nosocomial pneumonias from 20 to 8% and in ICU mortality rate from 21 to 7% (all p ⬍ 0.05). The latter study80 also illustrates the value of increasing experience using NIV after establishing an NIV program.

Conclusion The role of NIV in the management of acute respiratory failure has been further clarified in recent years. Evidence is strong to support the use of NIV in the initial management of acute respiratory failure in patients with COPD exacerbations, acute CPE, and immunocompromised states, and to facilitate extubation in patients with COPD with failed spontaneous breathing trials. A trial of NIV is justified in patients with asthma exacerbations, postoperative respiratory failure, extubation failure, hypoxemic respiratory failure or a DNI status, but because supporting evidence is not as strong, they should be carefully selected according to available guidelines and clinical judgment, taking into account risk factors for NIV failure. Once begun, patients should be closely monitored in an ICU or step-down unit until adequately stabilized, paying attention not only to vital signs and gas exchange, but also to comfort and tolerance. If patients do not have a favorable initial response to NIV, clinicians should strongly consider intubation without delay. When used appropriately, NIV improves patient outcomes and the efficiency of care. Although it is still used in only a select minority 718

of patients with acute respiratory failure, it has assumed an important role in the therapeutic armamentarium. With technical advances and new evidence on its proper application, this role is likely to expand.

References 1 Liesching T, Kwok H, Hill NS. Acute applications of noninvasive positive pressure ventilation. Chest 2003; 124:699 –713 2 Brochard L, Isabey D, Piquet J, et al. Reversal of acute exacerbations of chronic obstructive lung disease by inspiratory assistance with a face mask. N Engl J Med 1990; 323:1523–1530 3 Bott J, Carroll MP, Conway JH, et al. Randomised controlled trial of nasal ventilation in acute ventilatory failure due to chronic obstructive airways disease. Lancet 1993; 341:1555– 1557 4 Kramer N, Meyer TJ, Meharg J, et al. Randomized, prospective trial of noninvasive positive pressure ventilation in acute respiratory failure. Am J Respir Crit Care Med 1995; 151: 1799 –1806 5 Plant PK, Owen JL, Elliott MW. Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial. Lancet 2000; 355:1931–1935 6 Dikensoy O, Ikidag B, Filiz A, et al. Comparison of noninvasive ventilation and standard medical therapy in acute hypercapnic respiratory failure: a randomised controlled study at a tertiary health centre in SE Turkey. Int J Clin Pract 2002; 56:85– 88 7 Celikel T, Sungur M, Ceyhan B, et al. Comparison of noninvasive positive pressure ventilation with standard medical therapy in hypercapnic acute respiratory failure. Chest 1998; 114:1636 – 642 8 Ram FS, Picot J, Lightowler J, et al. Non-invasive positive pressure ventilation for treatment of respiratory failure due to exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2004; 3:CD004104 9 Keenan SP, Sinuff T, Cook DJ, et al. Which patients with acute exacerbation of chronic obstructive pulmonary disease benefit from noninvasive positive pressure ventilation? A systematic review of the literature. Ann Intern Med 2003; 138:861– 870 10 Bersten AD, Holt AW, Vedig AE, et al. Treatment of severe cardiogenic pulmonary edema with continuous positive airway pressure delivered by face mask. N Engl J Med 1991; 325:1825–1830 11 Lin M, Yang Y, Chiany H, et al. Reappraisal of continuous positive airway pressure therapy in acute cardiogenic pulmonary edema: short-term results and long-term follow-up. Chest 1995; 107:1379 –1386 12 Nava S, Carbone G, DiBattista N, et al. Noninvasive ventilation in cardiogenic pulmonary edema: a multicenter randomized trial. Am J Respir Crit Care Med 2003; 168:1432–1437 13 Crane SD, Elliott MW, Gilligan P, et al. Randomised controlled comparison of continuous positive airways pressure, bilevel non-invasive ventilation, and standard treatment in emergency department patients with acute cardiogenic pulmonary oedema. Emerg Med J 2004; 21:155–161 14 Pang D, Keenan SP, Cook DJ, et al. The effect of positive airway pressure on mortality and the need for intubation in cardiogenic pulmonary edema. Chest 1998; 114:1185–1192 15 Rasanen J, Heikkila J, Downs J, et al. Continuous positive airway pressure by face mask in acute cardiogenic pulmonary Postgraduate Education Corner

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edema. Am J Cardiol 1985; 55:296 –300 16 Lin M, Chiang HT. The efficacy of early continuous positive airway pressure therapy in patients with acute cardiogenic pulmonary edema. J Formos Med Assoc 1991; 90:736 –743 17 Park M, Sangean MC, Volpe Mde S, et al. Randomized, prospective trial of oxygen, continuous positive airway pressure, and bilevel positive airway pressure by face mask in acute cardiogenic pulmonary edema. Crit Care Med 2004; 32:2407–2415 18 Masip J, Roque M, Sanchez B, et al. Noninvasive ventilation in acute cardiogenic pulmonary edema. JAMA 2005; 294: 3124 –3130 19 Winck JC, Azevedo LF, Costa-Pereira A, et al. Efficacy and safety of non-invasive ventilation in the treatment of acute cardiogenic pulmonary edema: a systematic review and metaanalysis. Crit Care 2006; 10:R69 20 Collins SP, Mielniczuk LM, Whittingham HA, et al. The use of noninvasive ventilation in emergency department patients with acute cardiogenic pulmonary edema: a systematic review. Ann Emerg Med 2006; 48:260 –269 21 Ho KM, Wong K. A comparison of continuous and bi-level positive airway pressure non-invasive ventilation in patients with acute cardiogenic pulmonary oedema: a meta-analysis. Crit Care 2006; 10:R4921 22 Mehta S, Jay GD, Woolard RH, et al. Randomized prospective trial of bilevel versus continuous positive airway pressure in acute pulmonary edema. Crit Care Med 1997; 25:620 – 628 23 Ferrer M, Esquinas A, Arancibia F, et al. Noninvasive ventilation during persistent weaning failure: a randomized controlled trial. Am J Respir Crit Care Med 2003; 168:70 –76 24 Nava S, Ambrosino N, Clini E, et al. Non-invasive mechanical ventilation in the weaning of patients with respiratory failure due to chronic obstructive pulmonary disease: a randomized study. Ann Intern Med 1998; 128:721–728 25 Antonelli M, Conti G, Bufi M, et al. Noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: a randomized trial. JAMA 2000; 283:2239 –2240 26 Hilbert G, Gruson D, Vargas F, et al. Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, and acute respiratory failure. N Engl J Med 2001; 344:481– 487 27 Meduri GU, Turner RE, Abou-Shala N, et al. Noninvasive positive pressure ventilation via face mask: first line intervention in patients with acute hypercapnic and hypoxemic respiratory failure. Chest 1996; 109:179 –193 28 Meduri GU, Cook TR, Turner RE, et al. Noninvasive positive pressure ventilation in status asthmaticus. Chest 1996; 110: 767–774 29 Fernandez MM, Villagra A, Blanch L, et al. Non-invasive mechanical ventilation in status asthmaticus. Intensive Care Med 2001; 27:486 – 492 30 Soroksky A, Stav D, Shpirer I. A pilot prospective, randomized, placebo-controlled trial of bi-level positive airway pressure in acute asthmatic attack. Chest 2003; 123:1018 –1025 31 Agarwal R, Malhotra P, Gupta D. Failure of NIV in acute asthma: case report and a word of caution. Emerg Med J 2006; 23:e9 32 Ram FS, Wellington S, Rowe B, et al. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Cochrane Database Syst Rev 2005; 1:CD004360 33 Kindgen-Milles D, Muller E, Buhl R, et al. Nasal continuous positive airway pressure reduces pulmonary morbidity and length of stay following thoracoabdominal aortic surgery. Chest 2005; 128:821– 828 34 Squadrone V, Coha M, Cerutti E, et al. Continuous positive www.chestjournal.org

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airway pressure for treatment of postoperative hypoxemia. JAMA 2005; 293:589 –595 Auriant I, Jallot A, Herve P, et al. Noninvasive ventilation reduces mortality in acute respiratory failure following lung resection. Am J Respir Crit Care Med 2001; 164:1231–1235 Clarke DE, Vaughan L, Raffin TA. Noninvasive positive pressure ventilation for patients with terminal respiratory failure: the ethical and economic cost of delaying the inevitable are too great. Am J Crit Care 1994; 3:4 –5 Levy MM, Tanios MA, Nelson D, et al. Outcomes of patients with do-not- intubate orders treated with noninvasive ventilation. Crit Care Med 2004; 32:2002–2007 Schettino G, Altobelli N, Kacmarek RM. Noninvasive positive-pressure ventilation reverses acute respiratory failure in select “do-not-intubate” patients. Crit Care Med. 2005; 33: 1976 –1982 Curtis RJ, Cook DJ, Sinuff T, et al. Noninvasive positive pressure ventilation in critical and palliative care settings: understanding the goals of therapy. Crit Care Med 2007 (in press) Antonelli M, Conti G, Rocco M, et al. A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure. N Engl J Med 1998; 339:429 – 435 Ferrer M, Esquinas A, Leon M, et al. Noninvasive ventilation in severe hypoxemic respiratory failure: a randomized clinical trial. Am J Respir Crit Care Med 2003; 168:1438 –1444 Ambrosino N, Foglio K, Rubini F, et al. Noninvasive mechanical ventilation in acute respiratory failure due to chronic obstructive pulmonary disease: correlates for success. Thorax 1995; 50:755–757 Honrubia T, Garcia Lopez F, Franco N, et al. Noninvasive vs. conventional mechanical ventilation for acute respiratory failure. Chest 2005; 128:3916 –3924 Antonelli M, Conti G, Moro ML, et al. Predictors of failures of noninvasive positive pressure ventilation in patients with acute hypoxemic respiratory failure: a multi-center study. Intensive Care Med 2001; 27:1718 –1728 Jolliet P, Abajo B, Pasquina P, et al. Non-invasive pressure support ventilation in severe community-acquired pneumonia. Intensive Care Med 2001; 27:812– 821 Confalonieri M, Potena A, Carbone G, et al. Acute respiratory failure in patients with severe community-acquired pneumonia. Am J Respir Crit Care Med 1999; 160:1585–1591 Antonelli M, Conti G, Esquinas A, et al. A multiple-center survey on the use in clinical practice of noninvasive ventilation as a first-line intervention for acute respiratory distress syndrome. Crit Care Med 2007; 35:18 –25 Rana S, Hussam J, Gay P, et al. Failure of non-invasive ventilation in patients with acute lung injury: observational cohort study. Crit Care 2006; 10:R79 Blivet S, Philit F, Sab JM, et al. Outcome of patients with idiopathic pulmonary fibrosis admitted to the ICU for respiratory failure. Chest 2001; 120:8 –10 Nevins ML, Epstein SK. Predictors of outcome for patients with COPD requiring invasive mechanical ventilation. Chest 2001; 119:1840 –1849 Esteban A, Frutos-Vivar F, Ferguson ND, et al. Noninvasive positive-pressure ventilation for respiratory failure after extubation. N Engl J Med 2004; 350:2452–2460 Ferrer M, Valencia M, Nicolas JM, et al. Early noninvasive ventilation averts extubation failure in patients at high risk: a randomized trial. Am J Respir Crit Care Med 2006; 173:164 – 170 Nava S, Gregoretti C, Fanfulla F, et al. Noninvasive ventilation to prevent respiratory failure after extubation in high-risk patients. Crit Care Med 2005; 33:2465– 470 CHEST / 132 / 2 / AUGUST, 2007

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54 Nava S, Navalesi P, Conti G. Time of non-invasive ventilation. Intensive Care Med 2006; 32:361–370 55 Gonzalez Diaz G, Carillo A, Perez P, et al. Noninvasive positive-pressure ventilation to treat hypercapnic coma secondary to respiratory failure. Chest 2005; 127:952–960 56 Scala R, Naldi M, Archinucci I, et al. Noninvasive positivepressure ventilation in patients with acute exacerbations of COPD and varying levels of consciousness. Chest 2005; 128:1657–1666 57 Confalonieri M, Garuti G, Cattaruzza MS, et al. A chart of failure risk for noninvasive ventilation in patients with COPD exacerbation. Eur Respir J 2005; 25:348 –355 58 Kwok H, McCormack J, Cece R, et al. Controlled trial of oronasal versus nasal mask ventilation in the treatment of acute respiratory failure. Crit Care Med 2003; 31:468 – 473 59 Tonnelier JM, Prat G, Nowak E, et al. Noninvasive continuous positive airway pressure ventilation using a new helmet interface: a case prospective pilot study. Intensive Care Med 2003; 29:2077–2080 60 Principi T, Pantanetti S, Catani F, et al. Noninvasive continuous positive airway pressure delivered by helmet in hematological malignancy patients with hypoxemic acute respiratory failure. Intensive Care Med 2004; 30:147–150 61 Antonelli M, Pennisi MA, Pelosi P, et al. Noninvasive positive pressure ventilation using a helmet in patients with acute exacerbation of chronic obstructive pulmonary disease. Anesthesiology 2004; 100:16 –24 62 Cavaliere F, Conti G, Costa R, et al. Noise exposure during noninvasive ventilation with a helmet, a nasal mask, and a facial mask. Intensive Care Med 2004; 30:1755–1760 63 Ferguson GT, Gilmartin M. CO2 rebreathing during BiPAP ventilatory assistance. Am J Respir Crit Care Med 1995; 151:1126 –1135 64 Schettino GPP, Chatmongkolchart S, Hess D, et al. Position of exhalation port and mask design affect CO2 rebreathing during noninvasive positive pressure ventilation. Crit Care Med 2003; 31:2178 –2182 65 Saatci E, Miller DM, Sztell IM, et al. Dynamic dead space in face masks used with noninvasive ventilators: a lung model study. Eur Respir J 2004; 23:129 –135 66 Vitacca M, Rubini F, Foglio K, et al. Noninvasive modalities of positive pressure ventilation improve the outcome of acute exacerbations of COLD patients. Intensive Care Med 1993; 19:450 – 455 67 Fernandez-Vivas M, Caturia-Such J, de la Rosa JG, et al. Noninvasive pressure support versus proportional assist ven-

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tilation in acute respiratory failure. Intensive Care Med 2003; 29:1126 –1133 Gay PC, Hess DR, Hill NS. Noninvasive proportional assist ventilation for acute respiratory insufficiency: comparison with pressure support ventilation. Am J Respir Crit Care Med 2001; 164:1606 –1611 Wysocki M, Richard JC, Meshaka P. Noninvasive proportional assist ventilation compared with noninvasive pressure support ventilation in hypercapnic acute respiratory failure. Crit Care Med 2002; 30:323–329 Mehta S, McCool FD, Hill NS. Leak compensation in positive pressure ventilators: a lung model study. Eur Respir J 2001; 17:259 –267 Holland AE, Denehy L, Buchan CA, et al. Efficacy of a heated passover humidifier during noninvasive ventilation: a bench study. Respir Care 2007; 52:38 – 44 Lellouche F, Maggiore SM, Deye N, et al. Effect of the humidification device on the work of breathing during noninvasive ventilation. Intensive Care Med 2002; 28:1582–1589 L’Her E, Deye N, Lellouche F, et al. Physiologic effects of noninvasive ventilation during acute lung injury. Am J Crit Care Med 2005; 172:1112–1118 Prinianakis G, Delmastro M, Carlucci A, et al. Effect of varying the pressurization rate during noninvasive pressure support ventilation. Eur Respir J 2004; 23:314 –320 Sinuff T, Cook DJ, Randall J, et al. Evaluation of a practice guideline for noninvasive positive pressure ventilation for acute respiratory failure. Chest 2003; 123:2062–2073 Carlucci A, Richard JC, Wysocki M, et al. Noninvasive versus conventional mechanical ventilation. Am J Respir Crit Care Med 2001; 163:874 – 880 Doherty MJ, Greenstone MA. Survey of non-invasive ventilation (NIPPV) in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) in the UK. Thorax 1998; 53:863– 866 Maheshwari V, Paioli D, Rothaar R, et al. Utilization of noninvasive ventilation in acute care hospitals. Chest 2006; 129:1226 –1233 Demoule A, Girou E, Richard JC, et al. Increased use of noninvasive ventilation in French intensive care units. Intensive Care Med 2006; 32:1747–1755 Girou E, Brun-Buisson C, Taille S, et al. Secular trends in nosocomial infections and mortality associated with noninvasive ventilation in patients with exacerbation of COPD and pulmonary edema. JAMA 2003; 290:2985–2991

Postgraduate Education Corner

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Noninvasive Ventilation for Critical Care* Erik Garpestad, John Brennan and Nicholas S. Hill Chest 2007;132; 711-720 DOI 10.1378/chest.06-2643 This information is current as of April 13, 2010 Updated Information & Services

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Data:

OXYMAG VENTILADOR DE TRANSPORTE

20/10/2010

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Verificado por:

Aprovado por:

Marcelo Onodera

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85 – Dados clínicos, Papers

01

Doc 12 – APRV Theory and Practice

MAGNAMED TECNOLOGIA MÉDICA LTDA


AACN Clinical Issues Volume 12, Number 2, pp. 234–246 © 2001, AACN

Airway Pressure Release Ventilation: Theory and Practice P. Milo Frawley, RN, MS,* and Nader M. Habashi, MD†

ventilation begin the ventilatory cycle at a baseline pressure and elevate airway pressure to accomplish tidal ventilation (Figure 1), APRV commences at an elevated baseline pressure (similar to a plateau pressure) and follows with a deflation to accomplish tidal ventilation (Figure 2). In addition, during APRV, spontaneous breathing may occur at either the plateau pressure or deflation pressure levels. This article provides a detailed examination of the terminology, indications, theoretical benefits, advantages, and disadvantages of APRV as well as a discussion of application and weaning procedures.

■ Airway pressure release ventilation (APRV) is a relatively new mode of ventilation, that only became commercially available in the United States in the mid-1990s. Airway pressure release ventilation produces tidal ventilation using a method that differs from any other mode. It uses a release of airway pressure from an elevated baseline to simulate expiration. The elevated baseline facilitates oxygenation, and the timed releases aid in carbon dioxide removal. Advantages of APRV include lower airway pressures, lower minute ventilation, minimal adverse effects on cardio-circulatory function, ability to spontaneously breathe throughout the entire ventilatory cycle, decreased sedation use, and near elimination of neuromuscular blockade. Airway pressure release ventilation is consistent with lung protection strategies that strive to limit lung injury associated with mechanical ventilation. Future research will probably support the use of APRV as the primary mode of choice for patients with acute lung injury. (KEYWORDS: acute lung injury, airway pressure release ventilation, alveolar recruitment, alveolar derecruitment, lung protective strategies)

Airway pressure release ventilation has been described as continuous positive airway pressure (CPAP) with regular, brief, intermittent releases in airway pressure.3,4 The release phase results in alveolar ventilation and removal of carbon dioxide (CO2). Airway pressure release ventilation, unlike CPAP, facilitates both oxygenation and CO2 clearance and originally was described as an improved method of ventilatory support in the presence of acute lung injury (ALI) and inadequate CO2 ventilation.2,5 Airway pressure release ventilation is capable of either augmenting alveolar

Airway pressure release ventilation (APRV) is a mode of ventilation that was first described in 1987.1,2 It uses a philosophy that differs fundamentally from that of conventional ventilation. Whereas conventional modes of

▪▪▪▪▪▪▪▪▪▪ From *Maryland ExpressCare and †Department of Critical Care Medicine, University of Maryland Medical Center, Baltimore, Maryland. Reprint requests to P. Milo Frawley, RN, MS, Maryland ExpressCare, TGR25C, University of Maryland Medical Center, 22 South Greene Street, Baltimore, MD 21201.

 Airway

Pressure Release Ventilation Defined

234


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235

Figure 1. Conventional volume targeted ventilation, e.g., synchronized intermittent mandatory ventilation (SIMV). Any mechanically delivered breath will be defined by its trigger, limit, and cycle off feature. In SIMV, the breath will be triggered by either the patient or by time, the volume delivered will limit the breath, and time will cycle the breath off into exhalation. Cms of H2O = centimeters of water.

ventilation in the spontaneously breathing patient or accomplishing complete ventilation in the apneic patient.6 The CPAP level drives oxygenation, while the timed releases aid in CO2 clearance. Technically, APRV is a time-triggered, pressure-limited, time-cycled mode of mechanical ventilation. In addition, APRV allows unrestricted, spontaneous breathing throughout

the entire ventilatory cycle (Table 1). Advantages of APRV include: significantly lower peak/plateau airway pressures for a given tidal volume; the ability to superimpose spontaneous breathing throughout the ventilatory cycle; decreased sedation; and near elimination of neuromuscular blockade use.7,8 Features that distinguish APRV from other modes of mechanical ventilation include sponta-

Figure 2. Airway pressure release ventilation: this can also be defined by a trigger, limit, and cycle off feature. However, unlike other modes of ventilation, the trigger (time) initiates a drop in airway pressure. The amount of pressure change will be the limit. The cycle off will occur because of time. Airway pressure then returns to the baseline. Cms of H2O = centimeters of water.


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TABLE 1  Classification of Common Modes of Mechanical Ventilation Mode A-C (volume) A-C (pressure) SIMV (volume) PSV PRVC APRV

Trigger

Limit

Cycle Off

Spontaneous Breathing

Flow of Gas

Time or patient

Volume

Time

No

Constant

Time or patient

Pressure

Time

No

Decelerating

Time or patient

Volume

Time

Yes

Constant

Patient Time or patient*

Pressure Volume

Flow of gas Time

No No

Decelerating Decelerating

Time

Pressure

Time

Yes

Decelerating

Note: A mechanically delivered breath is made up of three distinct phases. The Trigger initiates the breath; the Limit will stop the breath from increasing, but does not initiate exhalation; and the Cycle Off, that switches the breath from inspiration to exhalation. Beyond this, modes may or may not allow unsupported, spontaneous breathing. The inspired gas may be delivered using either a constant or decelerating flow of gas. *This mode is designed for patients with no breathing capacity, though they are able to trigger breaths. A-C  assist control; SIMV  synchronized intermittent mandatory ventilation; PSV  pressure support ventilation; PRVC  pressure regulated volume control; APRV  airway pressure release ventilation.

neous breathing throughout the ventilatory cycle and an intermittent pressure release phase that results in a brief decrease in lung volume to assist ventilation.1,2  History of Mechanical Ventilation

The basic principles of ventilator design and management were founded upon patients who developed nonparenchymal respiratory failure (e.g., polio). In the absence of adequate research, those same principles were applied to patients with parenchymal respiratory failure as well (e.g., ALI). Mode selection often was based on availability and simplicity of the ventilator, user experience, and tradition, because little evidence existed to guide management. In 1993, the American College of Chest Physicians (ACCP) consensus conference failed to “agree on an optimum mode of ventilation for any disease state or an optimum method of weaning patients from mechanical ventilation.”9(p1834) The ACCP agreed that well-controlled clinical trials that defined the indications and uses of specific modes of ventilation were lacking. New technology must scientifically show a distinct advantage in safety, expense, ease of operation, or therapeutic outcome.10,11

Despite more than 30 years since its recognition, acute respiratory distress syndrome (ARDS) continues to have a 30% to 50% mortality rate.12,13 Recently, discovery of the potential for mechanical ventilation to produce ventilator-associated lung injury has resulted in the development of new lung protective strategies.14 Lung protective strategies include those described in the “the open lung approach” promoted by Amato et al.15 The open lung approach uses reduced tidal volumes (6 mL/kg) to prevent high-volume lung injury and over-distension of airspaces. In addition, Amato et al.16 used elevated end expiratory pressure (average positive end-expiratory pressure [PEEP] 16 cm water pressure), to prevent low volume lung injury from cyclic airway reopening. The recently completed ARDSNet study compared conventional tidal volume (12 mL/kg) to reduced tidal volume (6 mL/kg).13 The results of the ARDSNet trial13 and a study conducted by Amato et al.16 suggest an association between reduced tidal volume and improved outcome. Although the ARDSNet trial targeted similar PEEP levels in both its groups, study protocols for maintaining saturation resulted in higher levels of set PEEP in the low tidal volume group. In addition, to maintain similar targets for PaCO2, the low tidal volume group had much higher respiratory frequencies, resulting in the de-


Vol. 12, No. 2 May 2001

velopment of intrinsic PEEP. Therefore, the role of elevated levels of end expiratory pressure (PEEP) on survival of the low tidal volume group may have been obscured. Despite improved survival with the low tidal volumes group, survival was less than that of Amato’s16 combined approach (tidal volume reduction and PEEP elevation). As a result, the planned ARDSNet Assessment of Low tidal Volume and Elevated end-expiratory volume to Obviate Lung Injury (ALVEOLI) study will evaluate the role of higher levels of PEEP on survival. ARDSNet ALVEOLI will use data from the pressure-volume curve to develop the PEEP scale (PEEP scale = fraction of inspired oxygen:PEEP). However, recent data suggest that determining optimal PEEP from the pressure-volume curve may be inaccurate.17 In addition, recruitment to prevent cyclic airway closure (low volume lung injury) requires pressure in excess of 30 cm of water pressure. Complete recruitment exceeds the lower inflection point used by Amato et al.16 to determine optimal PEEP levels. Recruitment begins at the lower inflection point and continues to the upper inflection point.18–20 Therefore, elevated baseline airway pressure during APRV may produce near complete recruitment, thus minimizing low volume lung injury from cyclic recruitment. Additionally, APRV is less likely to produce over-inflation or high-volume lung injury, as airway pressures are lowered (released) to accomplish ventilation. Other lung protective strategies include optimization of current modes of ventilation and alteration of ventilator strategies to prevent or reduce ventilator-associated lung injury. Current goals of ventilation include the following: • avoiding extension of lung injury, • minimizing oxygen toxicity by using mean airway pressure (Paw), • recruiting alveoli by raising mean Paw by increasing PEEP and/or prolonging inspiration, • minimizing peak Paw, • preventing atelectasis, and • using sedation and paralysis judiciously.21 Although first described 11 years earlier,1,2 APRV may have benefits for preventing or limiting ventilator-associated lung injury.

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237

 Terminology

Unfortunately, a consistent vocabulary for APRV has failed to mature. Four commonly used terms include: pressure high (P High), pressure low (P Low), time high (T High), and time low (T Low).7 P High is the baseline airway pressure level and is the higher of the two airway pressure levels. Other authors have described P High as the CPAP level,22 the inflating pressure,23 or the P1 pressure (P1). P Low is the airway pressure level resulting from the pressure release. Other authors may refer to P Low as the PEEP level,22 the release pressure,23 or the P2 pressure (P2). T High corresponds with the length of time for which P High is maintained; T Low is the length of time for which the P Low is held (i.e. for which the airway pressure is released). The mean airway pressure can be calculated as follows:7 (P High  T High) + (P Low  T Low) T High + T Low

Some ventilators may compute this automatically, making manual calculation redundant. Common terms associated with APRV are summarized in Table 2 and Figure 3. Somewhat confusing to the understanding of APRV have been the subsequent descriptions of modes of ventilation that appear very similar to it. Biphasic positive airway pressure (BIPAP)24,25 differs from APRV only in the timing of the upper and lower pressure levels. In BIPAP, T High usually is shorter than T Low. One description of BIPAP25 subdivides it into four categories, one of which is APRV-BIPAP. Intermittent mandatory pressure release ventilation (IMPRV),26 another mode of ventilation similar to and sometimes confused with APRV, synchronizes the release event with the patient’s spontaneous effort. The release occurs after the patient’s second, third, fourth, fifth, or sixth spontaneous breath. Further, all spontaneous breaths are pressure supported to overcome the resistance associated with breathing through the endotracheal tube and ventilator tubing. Synchronization does not occur with the raising of airway pressure, only the release. Because the concept of dyssynchrony in APRV has not been demonstrated clearly—and has




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AACN Clinical Issues

TABLE 2  Summary of Airway Pressure Release Ventilation Terminology Term Pressure High (P High)7 Pressure Low (P Low)7 Time High (T High)7 Time Low (T Low)7 Mean Paw

Alternative Names

Definition Baseline airway pressure level Higher of the two airway pressures Airway pressure level resulting from pressure release. The lower of the two airway pressures Length of time for which P High is maintained Length of time for which P Low is maintained (P High  T High)  (P Low  T Low) (T High  T Low)7

Units of Measure

CPAP level,22 Inflation pressure,23 P1 PEEP level,22 Release pressure,23 P2

Cm H2O

T1

Seconds

T2

Seconds

â&#x20AC;&#x201D;

Cm H2O

Cm H2O

CPAP  continuous positive airway pressure; Cm H2O  centimeters of water; PEEP  positive end expiratory pressure; Paw  airway pressure.

been stated not to be an issueâ&#x20AC;&#x201D;the necessity of intermittent mandatory pressure release ventilation is questionable.10 Intermittent CPAP27 is based on the principles of APRV but is intended for patients undergoing general anesthesia. Continuous positive airway pressure is applied at a level that will provide an adequate tidal volume, then removed for 1 second to produce tidal ventilation, then reapplied. Unlike APRV, intermittent CPAP is not intended to restore normal functional residual capacity or improve oxygenation, and it can be discontinued abruptly.

BiLevel ventilation28 is defined as augmented pressure ventilation that allows for unrestricted, albeit pressure-supported, spontaneous breathing throughout the ventilatory cycle. Although similar to APRV, it incorporates the option of pressure support in the airway pressure waveform to augment spontaneous breathing.  Indications

for APRV

Airway pressure release ventilation was designed to oxygenate and augment ventilation for patients with ALI or low-compliance

Figure 3. Airway pressure release ventilation terminology. Paw = airway pressure; P High = 30 centimeters of water (cms of H2O); P Low = 0 cms of H2O, T High = 6.0 seconds; T low = 0.8 seconds; calculated mean Paw = 26.5 cms of H2O.


Vol. 12, No. 2 May 2001

lung disease.1,5,6 Airway pressure release ventilation also has been used successfully with patients with airway disease. Similar to CPAP, APRV can unload inspiratory muscles and decrease the work of breathing associated with chronic obstructive pulmonary disease.29 Unlike PEEP (an expiratory flow resistor, which decreases expiratory flow), peak expiratory flow rates are increased during the release phase of APRV, improving expiratory flow limitation. Furthermore, during APRV, exhalation is not limited to the release phase, as it is permitted throughout the respiratory cycle. The main causes of hypoxemia associated with ALI are shunting due to alveolar collapse and reduction in functional residual capacity.1,7,30 Therefore, a primary goal of the treatment of ALI is recruitment of alveoli and prevention of derecruitment. Sustained plateau pressure is used to promote alveolar recruitment, while being maintained at an acceptable level. In addition, the number of respiratory cycles is minimized to prevent both the repetitive opening of alveoli and alveolar stretch, that may result in lung injury. Patients in early-phase ALI often do not have impaired respiratory muscle strength or inadequate respiratory drive. Frequently, CPAP alone is sufficient to restore lung volume and increase lung compliance. However, when assistance with ventilation is required, APRV can be used. Intermittent

Figure 4. Collateral channels of ventilation.

APRV: THEORY AND PRACTICE



239

airway pressure release allows alveolar gas to be expelled via natural lung recoil.1  Importance

of Collateral Channels of Ventilation Maintaining a constant airway pressure may be advantageous for several reasons. Constant airway pressure facilitates alveolar recruitment; enhances diffusion of gases; allows alveolar units with slow time constants to fill, preventing over-distension of alveoli; and augments collateral ventilation.31 Van Allen et al32 noted that complete obstruction of an airway unit did not always result in collapse of the alveoli and, therefore, hypothesized that alternative pathways must exist. The pores of Kohn, located in the septa of the alveoli and open only during inspiration,33 first were believed to be responsible. However, two additional pathways were later credited with playing a role: (1) Lambertâ&#x20AC;&#x2122;s canals connect terminal and respiratory bronchioles with adjacent peribronchial alveoli, and (2) channels of Martin interconnect respiratory bronchioles and serve to bypass the main pathway (Figure 4).34 In normal, healthy lungs, collateral ventilation may barely occur at the functional residual capacity level, i.e. end exhalation. However, alternative pathways may be opened at a higher lung volume.35 The role of alternative pathways in healthy lungs is very limited; but in disease states may be im-


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FRAWLEY AND HABASHI

portant.36 Although collateral ventilation is typically lost in pulmonary edema, collateral pathways may be reopened and oxygenation improved by increasing functional residual capacity.36 Sustained airway pressure, rather than intermittent periods of airway pressure, is more beneficial in the edematous, collapsed lung. Sustained breaths maintain a constant airway pressure and allow collateral channels to assist in producing ventilation. Collateral ventilation efficiency drops as respiratory frequency increases.37 Airway pressure release ventilation uses these concepts, maintaining sufficient airway pressure for an adequate duration to open collapsed alveoli, thus improving recruitment of alveoli and increasing oxygenation.  Advantages

In patients with severe acute respiratory failure, the use of APRV results in significantly lower peak Paw, when compared with continuous positive pressure ventilation (CPPV). Lower airway pressures are thought to be associated with a reduced risk of ventilator-associated lung injury.14 Further, APRV requires lower minute ventilation than CPPV, suggesting less dead-space ventilation.23 Studies of patients with ALI have shown that APRV supports oxygenation and ventilation, while producing lower peak Paw than volume assist-control ventilation5 and intermittent mandatory ventilation.8,11 Similarly, animal studies of injured lungs suggest lower airway pressure, reduced dead space ventilation, and improved oxygenation and ventilation, when compared with intermittent positive pressure ventilation.2 Airway pressure release ventilation recruits lung units by optimizing end-inspiratory lung volume. Ideally, the end-inspiratory pressure, which equates to P High or plateau pressure, should be kept beneath 35 cm of water pressure.9 This protective lung strategy has several positive effects. First, the preset pressure limit prevents, or limits, over-distension of alveoli and high-volume lung injury. Second, APRV affects tidal ventilation by decreasing rather than increasing airway pressure. Decreasing lung volume for ventilation further limits air space over-distension and the potential for high-volume

AACN Clinical Issues

lung injury. Third, maintaining airway pressure optimizes recruitment and prevents or limits low-volume lung injury by avoiding the repetitious opening of alveoli.14 High-volume lung injury occurs as a result of tidal ventilation above the upper inflection point of the pressure-volume curve. Low-volume lung injury results from ventilation beginning beneath the lower inflection point.17 Airway pressure release ventilation begins on the pressure-volume curve between these two points and uses a release, not an increase, of pressure from its baseline. Therefore, oxygenation and ventilation occur predominantly within the upper and lower inflection points (Figure 5). Calzia and Radermacher,38 in their 10-year literature review of APRV, were unable to document any severe adverse effects of APRV and BIPAP on cardio-circulatory function. One case report39 demonstrated an increase in cardiac output and blood pressure when APRV was used. Further, the authors suggested that it should be considered as an alternative therapy to pharmacologic or fluid therapy in the hemodynamically compromised, mechanically ventilated patient. Animal studies indicate that APRV does not compromise circulatory function and tissue oxygenation, whereas CPPV can impair cardiovascular function significantly.40 Spontaneous ventilation has a positive effect on the venous thoracic pump mechanism. Suppressing spontaneous breathing during CPPV can compromise cardiac function by decreasing venous return, thus cardiac output.4 The main advantage of APRV is that it allows for spontaneous breathing to occur at any point in the respiratory cycle. Depending on the patientâ&#x20AC;&#x2122;s need, spontaneous breathing may involve only exhalation, only inspiration, or both. The distribution of ventilation is significantly different when a spontaneous breath is compared with a mechanically controlled or assisted breath. Spontaneous breaths tend to improve ventilation-perfusion matching by preferentially aerating well-perfused, dependent lung regions. Mechanically delivered breaths primarily ventilate areas away from those receiving maximal blood flow. This phenomenon is consistent with earlier research, which demonstrated that spontaneous ventilation opens more alveoli, im-


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241

Figure 5. Pressure-volume curve. Conceptual drawing of airway pressure release ventilation occurring below the upper inflection point and above the lower inflection point, achieving goals of lung protective strategies.

proves regional gas exchange, and reduces atelectasis.41 Putensen et al.42,43 found that by allowing unsupported, spontaneous breathing (using BIPAP or APRV) in both dogs42 and humans43 with ALI, ventilation-perfusion matching improved, as seen by a marked decrease in intrapulmonary shunt. In humans, however, pressure support ventilation preferentially ventilated poorly or nonperfused lung units that already were well ventilated. Furthermore, pressure support ventilation did not convert shunted areas to normal ventilationperfusion units.43 Decreased need for sedation use or neuromuscular blockade use with APRV7,8 and BIPAP25 has been reported. Judicious use of sedation and paralysis in the mechanically ventilated patient was recommended at the American-European Consensus Conference on ARDS.21 Unintentional, prolonged paralysis is now recognized as a complication of the longterm use of paralytics. In addition, a paralyzed diaphragm moves very differently with positive pressure ventilation compared with an active contraction. The paralyzed diaphragm is displaced preferentially along the path of least resistance, that is, into the abdomen of the non dependent region. This displacement leads to favored ventilation of the nondependent lung

regions.41 All of this contributes to both ventilation-perfusion mismatch and possible over-distension of healthy alveoli, leading to further hypoxemia (Table 3).  Disadvantages

Consistent with other pressure-targeted modes of ventilation, APRV is affected by changes in lung compliance and/or resistance. Clinicians need to identify the scenarios that affect lung volume and monitor patients for changes in their tidal volumes. Because APRV is time-cycled, synchrony with the patientâ&#x20AC;&#x2122;s spontaneous respiration does not occur. If a release phase is not synchronous with the patientâ&#x20AC;&#x2122;s effort, discomfort may result. However, because APRV has a dynamic pneumatic system, inspiration and exhalation are facilitated at any time. Dyssynchrony with APRV has not been identified as a problem in the majority of the literature to date.5,6,11 As with any new technology, staff stress and subsequent increased risk to the patient may be noted with the implementation of APRV. Adequate and appropriate on-site training, coupled with off-site support services and backup, will help resolve some of the stress and decrease the risks associated with the in-


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FRAWLEY AND HABASHI

troduction of APRV. Transferring patients to subacute areas as their disease processes improve, may cause these issues to be revisited. Further, these areas may not have access to ventilators capable of delivering APRV, which will require switching the patient to a different mode of ventilation. Similarly, traveling to other departments (e.g., radiology, hyperbaric oxygenation chamber) may require temporary discontinuation of APRV, causing undue anxiety or discomfort in some patients. Finally, only limited research exists regarding the clinical practice of APRV and its comparison with other modes. For example, APRV is suitable for ventilator weaning, though its superiority to mainstream modes, e.g. pressure support ventilation, has not been demonstrated. Weaning, in general, lacks a consensus, and this absence of absolutes exemplifies the great confusion within clinical practice and within the study of mechanical ventilation (Table 3).  Application

of APRV

Little direction on the application of APRV can be found in the literature, other than as suggested by vendors and limited study protocols. However, based on an understanding of pulmonary physiology and pathophysiology, coupled with the theoretical understanding of mechanical ventilation44 and current recommendations from consensus conferences,9,21 the following technique has evolved. When changing a patientâ&#x20AC;&#x2122;s mode of ventilation to APRV, the initial settings are partly deduced from values of conventional ventilation. The clinician converts the plateau pressure of the conventional mode to P High and seeks an expired minute ventilation of 2 to 3 L/minute, less than when on conventional ventilation. This is accomplished by setting P High at the plateau pressure, with a ceiling level for the P High normally at 35 cm of water pressure. P Low is set at 0 cm of water pressure. A P Low of zero produces minimal expiratory resistance, thus accelerating expiratory flow rates, facilitating rapid pressure drops. T High is set at a minimum of 4.0 seconds. A T High of less than 4.0 seconds begins to impact mean Paw negatively. T Low is set between 0.5 and 1.0 seconds (often at 0.8 seconds). With these settings (P High = 35 cm of water pressure, P Low = 0 cm of water

AACN Clinical Issues

TABLE 3  Advantages and Potential Disadvantages of Airway Pressure Release Ventilation Advantages 1. Lower Paw for a given tidal volume compared with volume-targeted modes, e.g., AC, SIMV 2. Lower minute ventilation, i.e., less dead space ventilation 3. Limited adverse effects on cardio-circulatory function 4. Spontaneous breathing possible throughout entire ventilatory cycle 5. Decreased sedation use 6. Near elimination of neuromuscular blockade use Potential Disadvantages 1. Volumes change with alteration in lung compliance and resistance 2. Process of integrating new technology 3. Limited access to technology capable of delivering APRV 4. Limited research and clinical experience Paw  airway pressure; A-C  assist control; SIMV  synchronized intermittent mandatory ventilation; APRV  airway pressure release ventilation.

pressure, T High = 4.0 seconds, T Low = 0.8 seconds), the mean Paw will equal 29.2 cm of water pressure. It is not possible for conventional volume targeted modes to maintain a mean Paw of 29 cm of water pressure and limit the peak or plateau pressures to 35 cm of water pressure, and still produce sufficient tidal ventilation.44 Application of APRV to newly intubated patients usually involves using standard parameters and adjusting the settings accordingly. Commonly, in the patient with moderate to severe ALI we default to P High/P Low of 35/0 cm of water pressure and T High/T Low of 4.0/0.8 seconds and allow spontaneous breathing to take place.44 When attempting to avoid alveolar overdistension, the clinician must be cognizant of the plateau pressure, as this is the best clinically available estimate of average alveolar pressure.9 Although based primarily on animal data, a plateau pressure (or P High) greater than 35 cm of water pressure is associated with lung injury and, therefore, should be kept beneath this level. Rarely, an elevated P High (40â&#x20AC;&#x201C;45 cm of water pressure) may be indicated, especially


Vol. 12, No. 2 May 2001

for patients with low-compliance respiratory systems, (e.g., individuals with morbid obesity, abdominal distension, or chest wall edema), either for the purpose of oxygenation or ventilation.44 Although not optimal, the increased P High would be less than the pressure generated by conventional modes to produce a similar response.22 The P Low of zero is selected because minimal resistance to exhalation is the goal. Higher pressures may impede expiratory gas flow during passive lung recoil. The valid concern of collapsing alveoli with a P Low of zero is negated with the use of a short T Low (0.5–0.8 seconds) to maintain end expiratory lung volume. The minimum T High duration is 4.0 seconds. The goal is to create a nearly continuous airway pressure level, which serves to recruit collapsed alveoli and maintain recruitment, thus optimizing oxygenation and compliance. As a patient’s lung mechanics improve, T High is progressively lengthened to 12 to 15 seconds, usually in 0.5 to 2.0 second increments.44 A further advantage of the long T High is the reduction in the number of opening and closings of the small airways, one of the mechanisms implicated in the development of iatrogenic ALI.14

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243

The T Low probably is the most closely studied of the 4 parameters. Early writings5,22 suggested a T Low of 1.5 seconds as the norm, which allows for complete emptying of the lungs. A longer T Low (3.0–4.0 seconds) in animals with ALI was associated with a decrease in arterial oxygenation and the accumulation of hemorrhagic fluid in the endotracheal tube.5 An excessively long T Low encourages alveolar derecruitment, atelectasis, and airway closure during the release phase. Alternatively, an insufficient T Low potentially may result in inadequate exhalation, leading to dead space ventilation, hypercapnia, and hemodynamic compromise.45 Indeed, an appropriately timed T Low is vital.44 Optimal release time allows for adequate ventilation while minimizing lung volume loss. Essentially, release time should impede complete exhalation in the slower compartments of the lung (i.e., areas of high compliance or high resistance to exhalation) and generate regional intrinsic PEEP. Theoretically, this will enhance alveolar recruitment.4,7 Calculation of T Low depends on expiratory time constants (T), which are a product of the compliance of the respiratory system (CRS) and the resistance of the airways (RAW); that is, T = CRS  RAW.4,45 Low-compli-

Figure 6. Inspiratory and expiratory flow of gas in airway pressure release ventilation.44 In this example, T Low terminates at 40% of the peak expiratory gas flow. Baseline airway pressure is then rapidly re-established. T High = 6.0 seconds; T Low = 0.8 seconds.


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TABLE 4  Example of Airway Pressure Release Ventilation Settings in an Uncomplicated Case of Acute Lung Injury43* T Low (seconds)

Calculated Mean Airway Pressure (cm H2O)

P High (cm H2O)

T High (seconds)

P Low (cm H2O)

35

4.0

0

0.8

29.2

33

4.5

0

0.8

28.0

30

5.0

0

0.8

25.9

28

5.5

0

0.8

24.4

26

6.0

0

0.8

22.9

23

7.0

0

0.8

20.6

20

8.0

0

0.8

18.2

18

10.0

0

0.8

16.7

15

12.0

0

0.8

14.1

*Following the final settings, the patient was transitioned to CPAP of 12 cm of water pressure. CPAP  continuous positive airway pressure; Cm H2O  centimeters of water; P High  pressure high; T High  time high; P low  pressure low; T low  time low.

ance states, such as ARDS, will have lower (or shorter) expiratory time constants and therefore a lower (or shorter) T Low. High resistance diseases, such as asthma, will have longer time constants and require longer release times.45 Determining the correct multiple of time constants to calculate T Low is a challenge of future research. In practice, however, the clinician does not calculate the time constants for each patient, but rather relies on an approximation of the restriction of expiratory flow, as indicated by the expiratory flow of gas waveform (Figure 6). When expiratory flow falls to approximately 25% to 50% of peak expiratory flow, the clinician stops the release time and allows the airway pressure to return to P High.44 The transition to APRV may not result in instant improvement in oxygenation. Consistent with observations of inverse ratio ventilation,4 the positive effects may take several hours to be realized. It appears that the recruitment of alveoli occurs “one by one.” Sydow et al.7 demonstrated that the maximal beneficial effect of APRV upon oxygenation occurred 8 hours after implementation, with no further improvement after 16 hours. In earlier studies, data were collected within the first 60 minutes after transition to APRV and thus the full effect of time on alveolar recruitment was not appreciated.

 Weaning

From APRV

The current technique of weaning from APRV is guided by general principles of weaning used in clinical practice today. Knowledge of the signs of respiratory failure, as well as exclusion or correction of contributing factors preventing successful weaning, such as excessive secretions, bronchospasm, sepsis, anxiety, and diameter of endotracheal tubes and other dead space devices, are paramount. The approach in APRV is to maintain lung volume, improving both oxygenation and ventilation. As such, rarely does a specific point in time occur when weaning is “officially” commenced. Primarily, the method to reduce support is through manipulation of P High and T High. P High will be lowered 2 to 3 cm of water pressure at a time, and T High will be lengthened in 0.5- to 2.0-second increments, depending on patient tolerance. The goal is to arrive at straight CPAP—usually at 12 cm of water pressure—and then the clinician either weans CPAP or simply extubates the patient at 6 to 12 cm of water pressure. Before switching to CPAP, P High often is approximately 14 to 16 cm of water pressure and T High is at 12 to 15 seconds (Table 4).44 Patients with more severe forms of ALI or ARDS are weaned on a slower basis. Changes in mean Paw are monitored closely for their effect on oxygenation. Simi-




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APRV: THEORY AND PRACTICE

larly, exhaled minute ventilation is tracked in conjunction with CO2 removal.

of Mechanical Ventilation. New York: McGraw-Hill, Inc.; 1994:341–348. Burchardi H. New strategies in mechanical ventilation for acute lung injury. Eur Respir J. 1996;9:1063–1072. Stock MC, Downs JB. Airway pressure release ventilation: a new approach to ventilatory support during acute lung injury. Respir Care Clin N Am. 1987;32:517–524. Garner W, Downs JB, Stock MC, Rasanen J. Airway pressure release ventilation (APRV): a human trial. Chest. 1988;94:779–781. Sydow M, Burchardi H, Ephraim E, Zielmann S, Crozier TA. Long-term effects of two different ventilatory modes on oxygenation in acute lung injury: comparison of airway pressure release ventilation and volumecontrolled inverse ratio ventilation. Am J Respir Crit Care Med. 1994;149:1550–1556. Davis K, Johnson DJ, Branson RD, Campbell RS, Johannigman JA, Porembka D. Airway pressure release ventilation. Arch Surg. 1993; 128:1348–1352. Slutsky AS (chairman). ACCP consensus conference: mechanical ventilation. Chest. 1993; 104:1833–1859. Rasanen J. IMPRV: Synchronized APRV, or more [editorial]? Intensive Care Med. 1992;18: 65–66. Rasanen J, Cane RD, Downs JB, et al. Airway pressure release ventilation during acute lung injury: a prospective multicenter trial. Crit Care Med. 1991;19:1234–1241. Milberg JA, Davis DR, Stienberg KP, Hudson LD. Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983–1993. JAMA. 1995;273:306–309. Brower RG, Matthay MA, Morris A, et al. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301–1308. Dreyfuss D, Saumon G. Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med. 1998;157: 294–323. Amato MBP, Barbas CSV, Medeiros DM, et al. Beneficial effects of the “open lung approach” with low distending pressures in acute respiratory distress syndrome: a prospective randomized study on mechanical ventilation. Am J Respir Crit Care Med. 1995; 152:1835–1846. Amato MBP, Barbas CSV, Medeiros DM, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998;338:347–354. Hickling KG. The pressure-volume curve is greatly modified by recruitment: a mathemat-

4.

 Conclusion

Airway pressure release ventilation can maintain oxygenation and ventilation at a level comparable to CPPV. Airway pressure release ventilation is associated with significantly lower peak airway pressures and dead space ventilation. Airway pressure release ventilation uses almost constant airway pressure that not only facilitates alveolar recruitment but also sustains that recruitment once it has occurred. Spontaneous, unsupported breathing during APRV may occur at any point in the ventilatory cycle. Spontaneous breathing is advantageous because it decreases intrapulmonary shunting and improves venous return. The ability to avoid neuromuscular blockade and decreased use of sedation have resulted in fewer complications and decreased drug costs. Finally, ventilator-associated lung injury, which can result from both high- and low-volume lung ventilation, may be balanced and averted. Few clinicians believe that any single, isolated treatment can be responsible for a major improvement in the outcome for patients with ARDS. Combination therapy is expected to be the standard, including such concepts as prone positioning and permissive hypercapnia. Part of that therapy may include the ventilator strategy of APRV, which incorporates the advantages listed above. The authors believe that future research will support the use of APRV as the mode of choice for patients with ALI and ARDS.

5.

6. 7.

8.

9. 10. 11.

12.

13.

14. Acknowledgments

The authors thank Jill Kuramoto for her suggestions and constructive criticism, and Kris Dorman for reviewing the manuscript.

15.

References 1. Downs JB, Stock MC. Airway pressure release ventilation: a new concept in ventilatory support. Crit Care Med. 1987;15:459–461. 2. Stock MC, Downs JB, Frolicher D. Airway pressure release ventilation. Crit Care Med. 1987;15:462–466. 3. Rasanen J. Airway pressure release ventilation. In: Tobin MJ, ed. Principles and Practice

16.

17.

245


246

18.

19.

20.

21.

22.

23. 24.

25.

26.

27.

28. 29.



FRAWLEY AND HABASHI

ical model of ARDS lungs. Am J Respir Crit Care Med. 1998;158:194–202. Jonson B, Richard J-C, Straus C, Mancebo J, Lemaire R, Brochard L. Pressure-volume curves and compliance in acute lung injury: evidence of recruitment above the lower inflection point. Am J Respir Crit Care Med. 1999;159:1172–1178. Gattinoni L, Pelosi P, Crotti S, Valenza F. Effects of positive end-expiratory pressure on regional distribution of tidal volume and recruitment in adult respiratory distress syndrome. Am J Respir Crit Care Med. 1995;151: 1807–1814. Carney DE, Bredenberg CE, Schiller HJ, et al. The mechanism of lung volume change during mechanical ventilation. Am J Respir Crit Care Med. 1999;160:1697–1702. Artigas A, Bernard GR, Carlet J, et al. The American-European consensus conference on ARDS, part 2: ventilatory, pharmacologic, supportive therapy, study design strategies and issues related to recovery and remodeling. Intensive Care Med. 1998;24:378–398. Valentine DD, Hammond MD, Downs JB, Sears NJ, Sims WR. Distribution of ventilation and perfusion with different modes of mechanical ventilation. Am Rev Respir Dis. 1991; 143:1262–1266. Cane RD, Peruzzi WT, Shapiro BA. Airway pressure release ventilation in severe acute respiratory failure. Chest. 1991;100:460–463 Baum M, Benzer H, Putensen C, Koller W, Putz G. Biphasic positive airway pressure (BIPAP): a new form of assisted ventilation. Anaesthesist. 1989;38:432–458. Hormann C, Baum M, Putensen C, Mutz NJ, Benzer H. Biphasic positive airway pressure (BIPAP): a new mode of ventilatory support. Eur J Anaesthesiol. 1994;11:37–42. Rouby JJ, Ben Ameur M, Jawish D, et al. Continuous positive airway pressure (CPAP) vs. intermittent mandatory pressure release ventilation (IMPRV) in patients with acute respiratory failure. Intensive Care Med. 1992;18: 69–75. Bratzke E, Downs JB, Smith RA. Intermittent CPAP: a new mode of ventilation during general anesthesia. Anesthesiology. 1998;89: 334–340. Puritan Bennett Company. Two ventilating strategies in one mode: BiLevel. St. Louis, MO: Puritan Bennett Company; 1999. Petrof BJ, Legare M, Goldberg P, Milic-Emili J, Gottfried SB. Continuous positive airway pressure reduces work of breathing and dyspnea during weaning from mechanical ventilation in severe chronic obstructive pulmonary disease. Am Rev Respir Dis. 1990;141: 281–289.

AACN Clinical Issues

30. Smith RA, Smith DB. Does airway pressure release ventilation alter lung function after acute lung injury? Chest. 1995;107:805–808. 31. Davis K Jr., Branson RD, Campbell RS, Porembka DT. Comparison of volume control and pressure control ventilation: is flow waveform the difference? J Trauma. 1996; 41: 808–814. 32. Van Allen CM, Lindskog GE, Richter, HG. Collateral respiration: Transfer of air collaterally between pulmonary lobules. J Clinical Invest. 1941;10:559. 33. Brashers VL, Davey SS. Alterations of pulmonary functions. In: McCance KL, Huether SE, eds. Pathophysiology: The Biologic Basis for Disease in Adults and Children. 3rd ed. St Louis, MO; Mosby; 1998:1165–1166. 34. Corrin B. Pathology of the Lungs. New York, NY: Churchill Livingstone; 2000:4. 35. Terry PB, Traystman RJ, Newball HH, Batra G, Menkes HA. Collateral ventilation in man. N Engl J Med. 1978;298:10–15. 36. Delaunois L. Anatomy and physiology of collateral respiratory pathways. Eur Respir J. 1989; 2:893–904. 37. Menkes HA, Traystman RJ. Collateral ventilation. Am Rev Respir Dis. 1977;116: 287–309. 38. Calzia E, Radermacher P. Airway pressure release ventilation and biphasic positive airway pressure: a 10-year literature review. Clinical Intensive Care. 1997;8:296–301. 39. Falkenhain SK, Reilley TE, Gregory JS. Improvement in cardiac output during airway pressure release ventilation. Crit Care Med. 1992;20:1358–1360. 40. Rasanen J, Downs JB, Stock MC. Cardiovascular effects of conventional positive pressure ventilation and airway pressure release ventilation. Chest. 1988;3:911–915. 41. Froese AB, Bryan AC. Effects of anesthesia and paralysis on diaphragmatic mechanics in man. Anesthesiology. 1974;41:242–255. 42. Putensen C, Rasanen J, Lopez FA. Ventilationperfusion distributions during mechanical ventilation with superimposed spontaneous breathing in canine lung injury. Am J Respir Crit Care Med. 1994;150:101–108. 43. Putensen C, Norbert JM, Putensen-Himmer G, Zinserling J. Spontaneous breathing during ventilatory support improves ventilation-perfusion distributions in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 1999;159:1241–1248. 44. Habashi NM. APRV: Principles and Practice. Luebeck, Germany: Draegerwerk. In press. 45. Martin LD, Wetzel RC. Optimal release time during airway pressure release ventilation in neonatal sheep. Crit Care Med. 1994;22: 486–493.


Documentação

F006-02

Projeto:

Data:

OXYMAG VENTILADOR DE TRANSPORTE

20/10/2010

Elaborado por:

Verificado por:

Aprovado por:

Marcelo Onodera

Toru

Tatsuo

Objeto / Título do Documento:

Código:

1600185 Folha:

1/1 Revisão:

85 – Dados clínicos, Papers

01

Doc 13 – PLV

MAGNAMED TECNOLOGIA MÉDICA LTDA


Cardiopulmonary Effects of Positive Pressure Ventilation During Acute Lung Injury Jacques-Andre Romand, Weizhong Shi and Michael R. Pinsky Chest 1995;108;1041-1048 DOI 10.1378/chest.108.4.1041 The online version of this article, along with updated information and services can be found online on the World Wide Web at: http://chestjournal.chestpubs.org/content/108/4/1041

CHEST is the official journal of the American College of Chest Physicians. It has been published monthly since 1935. Copyright 1995 by the American College of Chest Physicians, 3300 Dundee Road, Northbrook, IL 60062. All rights reserved. No part of this article or PDF may be reproduced or distributed without the prior written permission of the copyright holder. ( http://chestjournal.chestpubs.org/site/misc/reprints.xhtml ) ISSN:0012-3692

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Effects of Positive Cardiopulmonary Pressure Ventilation During Acute Lung Injury* Romand, MD;f Weizhong Shi, MD; and Jacques-Andre Michael R. Pinsky, MD, FCCP and Study objectives: To ofassess the gas exchange ventilation effects hemodynamic in acutepressure-limited We (PLV) strategies lung injury (ALI). hy¬ in ALI, the reduction of plateau airway pothesized that would be associated with less alveolar pressure (Paw) overdistention and thus have better hemodynamic and gas exchange characteristics than larger tidal volume (Vt) ventilation. Setting: Laboratory. Design: Prospective time-controlled sequential animal study. Measurements: Right atrial, pulmonary artery, left atrial, arterial, lateral pleural (Ppl), and pericardial ventricular stroke volume, mean (Ppc) pressures, Paw, CO2, and arterial and mixed venous oxygen expired contents. Airway resistance and static lung compliance were also measured. Interventions: Intermittent positive pressure ventila¬ tion (IPPV) given before (control) and after induction of ALI by oleic acid infusion (0.1 mL/kg). IPPV at FIo2 of 1, Vt of 12 mL/kg, and frequency adjusted to main¬ tain normocarbia. ALI PLV was given during ALI and defined as that Vt which gave a similar plateau Paw to that of control IPPV. High-frequency jet ventilation (HFJV) and ALI HFJV were also given and defined as of heart rate and mean Paw frequency within 10%control IPPV. similar to that during

HPhe ventilatory support of patients with acute lung ¦*¦ injury (ALI) has evolved over recent years as our of the distribution of lung injury and its understanding interactions with positive-pressure ventilation has in¬ creased. The distribution of lung consolidation in pa¬ tients with ALI is nonhomogeneous1 with aerated lung units displaying normal specific compliance.2 Thus, as airway pressure (Paw) increases, aerated lung units in patients with ALI expand to the same extent as would *From the Cardiopulmonary Research Laboratory, Department of Anesthesiology and Critical Care Medicine, University of Pitts¬

burgh.

f Currently at the Departement d'Anesthesiologie des Soins Inten¬ sify de Chirugie, Hopital Cantonal Universitaire de Geneve, Geneva, Switzerland.

This study was supported in part by a research award from the and Critical Care Medicine and by Department of Anesthesiology the Veterans Affairs Medical Center. Manuscript received January 25,1995; revision accepted March 31.

Results: After ALI, static lung compliance, PaC>2, and pH decreased, whereas airway resistance and PaCC>2 increased. For a constant lung volume, Ppl and Ppc were not different between control and ALI. Both ab¬ solute dead space (Vd) and intrapulmonary shunt fraction increased after ALI, but absolute Vd was lower with ALI PLV and ALI HFJV when compared with ALI IPPV. Ventilation did not alter hemodynamics during ALI.

Conclusions: Changes in lung volume determine Ppc and Ppl. PLV strategies do not alter hemodynamics but result in less of an increase in Vd/Vt than would be predicted from the obligatory decrease in Vt.

(CHEST 1995; 108:1041-48)

ALI=acute lung injury; HFJV=high-frequency jet venti¬ lation; IPPV=intermittent positive pressure ventilation;

Paw=airway pressure; PeCC>2=mean expired C02; PEEP=positive end-expiratory pressure; PLV=pressurelimited

ventilation; Ppc=pericardial pressure; Ppl=pleural pressure; Qpa=pulmonary artery flow; Qs/Qt=intrapulmonary shunt fraction; Raw=airway resistance; SV=stroke volume; VD=dead space; Vr=tidal volume

Key words: ARDS; dead space; dog model; heart-lung in¬

teraction; mechanical ventilation; pericardial pressure; pleu¬ ral pressure

normal lungs for the same increase in Paw. Because the total amount of aerated and recruitable lung units available to be ventilated is reduced in patients with ALI, tidal volumes (Vts) that would otherwise be nor¬ mal in non-ALI condition will overdistend smaller to¬ tal aerated lung units in these patients. One manifes¬ tation ofthis regional overdistention will be an increase in end-inspiratoryplateau Paw when otherwise normal

Vts are given. Clinically, increased peak inspiratory Paw is commonly seen in ventilated patients with ALI

and probably reflects regional alveolar overdistention. Assuming that high plateau Paw occurs during me¬ chanical ventilation of patients with ALI, several effects may be seen. First, marked pathophysiologic overdistention of lung units will decrease their regional blood flow because of increasing regional pulmonary vascular resistance, and, thus, dead space (Vd) venti-

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1041


lation will increase. Second, such regional increases in aerated lung pulmonary vascular resistance will divert blood flow to nonoverdistended consolidated or col¬ units, thereby increasing shunt blood flow.3 lapsed lung the extent that increases in local lung units to Third, the cardiac fossa, local intrathoracic pressure compress will rise, which may decrease venous return and thus cardiac output.4"9 Finally, repetitive overexpansion of aerated lung units will injure respiratory epithelial tight junctions, inducing capillary leaks, ALI, and even

death.10'11

Based on all these considerations, increased interest has developed in minimizing lung overdistention in patients with ALI while maintaining adequate arterial Numerous novel ventilatory strate¬ oxygenation.31213 been have developed to address this problem,14"16 gies all of which involve the use of a limited Vt breath while maintaining mean Paw elevations. It is not clear, how¬ ever, what effect pressure-limited ventilation (PLV) has on shunt, Vd, or cardiovascular performance dur¬

ing ALI.

and gas Accordingly, we studied the hemodynamic PLV as of two different of effects types exchange with fixed Vt in ventilation positive-pressure compared strate¬ Different ALL of an animal model ventilatory gies can be used to limit end-inspiratory Paw while Highmaintaining mean Paw at a defined level. this ventilation by accomplishes (HFJV) frequency jet flow and frequency gas combining high inspiratory with small Vt, whereas, low-frequency PLV accom¬ this by decreasing inspiratory flow rate and Vt. plishes It is not clear, however, if these two different strategies have similar hemodynamic and gas exchange effects, because both the degree of change of lung volume and two forms

intrathoracic pressure differ between these of ventilation. Thus, we studied both HFJV and low-

frequency PLV.

Materials

and

Methods

Preparation After

approval of our protocol by the Animal Care and Use

Committee, seven male mongrel dogs weighing 18.3 to 25 kg (mean, 23.3 kg) were anesthetized with IV pentobarbital sodium (30 mL/ with a cuffed endotracheal tube kg). Their tracheas were intubated (9-mm-internal diameter; Hi-Lo National Catheter; Argyle, NY) equipped with a 2.4-mm-internal diameter jet ventilation injection

port (open 5 cm from the distal orifice) and an open port at the distal end for measuring Paw. The dogs were placed in the supine posi¬ tion during the entire experiment. Anesthesia was maintained with a continuous IV infusion of pentobarbital sodium at a rate of 4 mg kg-1 fr1 supplemented by a bolus of 50 to 100 mg IV as .

.

needed. Ventilation during the surgical procedure was provided at a respiratory rate of 20 breaths/min, a Vt of 10 mL/kg, and a forced (Siemens Servo 900 B Ventilator; Siemens; inspired oxygen of 1.0Arterial blood gas values were monitored pe¬ Elema AB, Sweden). (ABL-30; Radiometer; Copenhagen). Corrections in the riodically balance acid-base during the surgical procedure were made by ad¬ ministration of sodium bicarbonate IV to maintain a pH between 7.35 and 7.45, and by increasing the Vt to 15 mL/kg and 1042

subsequently the respiratory rate as necessary to maintain a PaC02 between 35 and 40 mm Hg. A standard lead 2 ECG was used to monitor the heart rate. A calibrated infrared CO2 detector (Capnometer 47210A; Hewlett Packard; Palo Alto, Calif) was connected to the endotracheal tube to monitor the end-expiratory CO2 and was used as an initial guide to adjust the respiratory rate. A saline solution-filled polyethylene catheter with end and mul¬ side holes was placed in the descending aorta and in the right tiple atrium via the peripheral cutdown sites to measure aortic and right atrial pressures, respectively. A 7.5F balloon-tipped flow-directed thermodilution catheter, with an injection port 15 cm from the distal end, was placed in the pulmonary artery to measure the pulmonary arterial pressure (Baxter-Edwards; Irvine, Calif). The blood tem¬ perature was monitored continuously via the thermistor of the artery catheter, and temperature was maintained above pulmonary 35° C using external heating pads. A midline sternotomy was performed, and the heart was in a pericardial cradle. A saline solution-filled polyeth¬ suspended side holes was placed in the ylene catheter with end and multiple left atrium via its appendage to measure the left atrial pressure. A circumferential electromagnetic flow probe (Carolina Medical Electronics; King, NC) was placed snugly around the root of the pulmonary artery. In two dogs, because of anatomic limitations,sotheit flow probe could not be placed around the pulmonary artery was placed around the aortic root. During steady state, mean aor¬ tic and pulmonary blood flow were assumed to be equal. The flow probe signal was linear to ±5% over the range of flow studied. Zero plateau pulmonary artery or aortic flow was taken as the diastolic of the flow signal. Absolute pulmonary artery flow (Qpa) was quantified in vivo during an apneic steady state by the thermodi¬ lution technique (Edwards 9520 cardiac output computer; Amer¬ ican Edwards Laboratory; Santa Ana, Calif) using the average of three 5-mL iced-saline solution injections (each value had to be within 10% of each other to be accepted). Right or left ventricular stroke volume (SV) was derived by inte¬ gration ofthe respective flow signals. Cardiac output was calculated as the product of SV and heart rate. A 10x1.5-cm thin-walled airfilled latex balloon attached to a polyethylene catheter with end and multiple side holes was placed over the left lateral aspect ofthe heart in the long axis direction and secured with stay sutures to measure the pericardial pressure (Ppc). The pericardium was then approx¬ imated with multiple sutures. A second identical air-filled balloon catheter was positioned on the right lateral mid chest wall in the long axis direction at the height of the atria and secured in place with stay sutures to measure the pleural pressure (Ppl). Chest tubes were of all the catheters and balloons bilaterally. The positions placedconfirmed chest closure. The left atrial, were by palpation before and pleural balloon catheters and the flow-probe cable pericardial, were exteriorized. The sternum was approximated, and the fascia and skin were closed in three layers to ensure an airtight seal. The chest tubes were connected to continuous suction at -15 cm H20 and a positive end-expiratory pressure (PEEP) of 5 cm H2O was added to ensure lung reexpansion. As previously described and validated,17 in situ pressure-volume curves were then generated for each balloon, and the volume of air left in the balloon was always lower than the in situ stressed volume ofthe system. The chest tubes were transiently occluded to assess any potential effects of suction applied on the drainage system on Ppc and Ppl. No effects of chest tube clamping were observed. All pressures were referenced to the midthorax. The vascular catheters were connected to low-displace¬ ment transducers (Gould Statham P-50; Gould Inc; Cleveland), and the air-filled Paw, pericardial, and pleural catheters were connected to high-sensitivity transducers (Bell and Howell 4-3271; Gould Inc). Airway, aortic, left and right atrial, Ppl, Ppc, pulmonary artery pressure, and Qpa were continuously recorded on an eight-channel Inc), digitized on line (Advantage A to strip-chart recorder (Gould D; Menlo Park, Calif), and stored on disk for subsequent analysis

Clinical Downloaded from chestjournal.chestpubs.org by guest on July 22, 2010 1995 BY THE AMERICAN COLLEGE OF CHEST PHYSICIANS

Investigations in Critical Care


(IBM AT and customized software). This surgical procedure took approximately 2.5 h. At the end of the experiment, while still anesthetized, each an¬ imal was killed by an IV injection of potassium chloride and a necropsy was performed. Correct placement of all catheters was confirmed. The tips of the vascular catheters were then dissected free of surrounding structures to record the zero hydrostatic pres¬ sure reference. All catheters were patent, and no leaks were found in the balloon catheters. The lungs were then examined grossly to ascertain the distribution and degree of pulmonary parenchymal involvement induced by oleic acid injection. Protocol After stabilization for 30 min, defined as hemodynamic stability in the absence of bleeding, arrhythmias, or ongoing metabolic ac¬ idosis, the protocol was begun (usually 1 h after the completion of surgery). Mechanical ventilation was provided using a constant in¬ spiratory flow pattern by a positive-pressure ventilator (Siemens 900 B) during intermittent positive pressure ventilation (IPPV) runs and by a jet ventilator (Acutronic MK800; Medical Systems; Basel, Switzerland) during the HFJV runs. During HFJV, a one-way valve (exhalation only) was placed at the end of the endotracheal tube to prevent entrainment of room air, which allowed us to deliver an exact amount of gas per HFJV inspiration as previously described by our laboratory.14 HFJV was delivered asynchronously, but at a frequency within 10% of the heart rate to minimize cardiovascular

instability. The protocol consisted of observing the effects of various types of positive-pressure ventilation during control and ALI conditions. Hemodynamic variables were averaged over the entire ventilatory cycle and a minimum of three breaths was used to derive mean pressures and SV. Muscle paralysis (vecuronium bromide, 0.01 mg/kg IV) was induced at the beginning of each condition to abol¬ ish spontaneous movement. The control condition consisted of four sequential ventilatory stages: (1) IPPV (IPPV 1); (2) HFJV; (3) a second episode of IPPV (IPPV 2) to serve as a time control; and (4) apnea used as a baseline minimal heart-lung interaction. The ALI condition consisted of the same ventilatory stages as with the con¬ trol plus an additional PLV stage? consisting of an IPPV-like run in which the Vt was adjusted downward until the plateau Paw was similar to the IPPV plateau Paw during the control. These five ALI are referred to in the text as

ALI IPPV 1, ALI PLV, ALI ALI IPPV 2, and ALI apnea. IPPV was defined as a frequency of 20 breaths/min, the inspiratory/expiratory (I/E) ratio was 1/3, and the Vt was adjusted for a PaCC>2 between 35 and 45 mm Hg, with an average Vt of 12 mL/kg. The plateau Paw was

stages

HFJV,

defined using the flow interrupter technique at end-inspiration. Mean Paw was also recorded during IPPV 1 and was used to de¬ fine HFJV ventilator settings because estimates of plateau Paw during HFJV are difficult to determine. During HFJV, the venti¬ latoryandratethewas fixed within 10%of of the heart rate, the I/E ratio was 1/4, driving pressure the HFJV air flow was adjusted to match the mean Paw as during IPPV 1. Ventilatory settings during IPPV 1 and 2 were identical. By using these three ventilatory modes, we could compare the effects of plateau Paw (IPPV vs PLV), lung

volume (IPPV vs PLV vs HFJV), and mean Paw (IPPV vs PLV and HFJV) on gas exchange and hemodynamics. At the beginning and end of control and ALI conditions, static inflation compliance curves were generated in 100-mL increments up to 500 mL above the resting lung volume using a 1-L supersyringe. Airway resistance (Raw) was estimated at end-inspiratory lung volume using an end-inspiratory hold maneuver, wherein the ratio ofthe immediate decline in airway pressure at end-inspiration to inspiratory gas flow reflected Raw at the end-inspiratory lung volume. This maneuver also allowed for the measurement of pla¬ teau Paw defined as Paw at 6 s of end-inspiratory hold. Thirty-sec¬

ond timed expired gas was collected during each mechanical ven¬ tilation step of the protocol in a 15-L polyester film (Mylar) plastic bag, which was then assayed for mean expired C02 (PeCC^). The volume was also measured during HFJV runs to calculate escaped true Vt. Paired mixed venous and arterial O2 contents were also measured using a co-oximeter adjusted for dog blood (Co-oximeter IL-282; Instrumentation Laboratories; Lexington, Mass). The ratio of Vd to Vt was estimated by the following formula:

(1)

VD/VT=(PaC02-PeC02)/PaC02 Intrapulmonary shunt fraction (Qs/Qt) was estimated by the

formula:

(2)

Qs/Qt=(Cc02-Ca02)/(Cc02-Cv02)

where CcC>2, CaC>2, and CvC>2 were the O2 content of the pulmo¬ nary capillary, systemic arterial, and mixed venous blood, respec¬ tively, and assuming a fully saturated end-capillary blood sample and a plasma oxygen solubility of 0.003 mL O2 per mm Hg of PaC>2. ALI was induced by injection of oleic acid (0.1 mL/kg) in the right atrium over 5 min after the solution was vigorously agitated (Vor¬ tex; Fisher Scientific Industries; Bohemia, NY) for 30 s in 20 mL of 0.9% sodium chloride. The ALI stages of the protocol began approximately 90 min after induction of ALI and after hemody¬

suggested.1819 During ALI IPPV, respiratory rate usually had to be increased in an attempt to maintain normocapnia. Measures for each stage were made only after measures of PeCC>2 were stable for over 5 min and frequency was held constant across the condition. During ALI HFJV, the same settings as during the control stage of HFJV were used. Measurements taken during IPPV 2 and ALI IPPV 2 served as time controls for their respective conditions. Hemodynamic mea¬ surements were performed after stabilization (usually after 3 min) at each ventilatory step for control and ALI conditions. Hemody¬ namic stabilization, as previously

the

namic variables

were averaged over the ventilatory cycle taking approximately ten beats. After induction of ALI, hypoxemia occa¬ sionally was severe enough to require supplemental PEEP to maintain a minimal level of arterial oxygenation (PaO2>50 mm Hg) during the stabilization period and the intervals between the ven¬ tilatory stages. All measurements were taken after the application of supplemental PEEP was discontinued and hemodynamic stabi¬ lization was achieved, usually in 1 or 2 min. Gas exchange measures were not made during apneic steps of the protocol. In five dogs, frothy pulmonary edema occurred during the ALI condition requiring intermittent suctioning of the endotracheal tube and PEEP in between the protocol steps. The entire control and ALI sequences took approximately 20 min and 30 min, respectively, to complete. An infusion of dextran (60 g/L) was given IV during the control condition at 2 to 4 mL kg"1 h"1 and during the ALI con¬ dition at 10 mL kg"1 h"1 to maintain a constant apneic transmu¬ ral left arterial pressure (defined as left arterial pressure minus Ppc). Statistical Analysis Analysis was performed on group data by ventilatory stages and experimental conditions using a two-way analysis of variance for repeated measures. Post hoc analysis was done using the Scheffe test. Paired between .

.

.

.

control and ALI conditions for

comparisons

compliance curves and Raw were done by a two-tailed t-test. Since PaC>2 values among conditions were not distributed normally, we compared these values between conditions by a nonparametric Wilcoxon signed rank test. A p value <0.05 was considered signif¬ icant. All data are shown as mean±SD. Results

Model Characteristics The model was stable

throughout the control and

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1043


1.Ventilatory Effects of Positive-Pressure Ventilation*

Table

Frequency,

Vt,

Stage

Plateau Paw,

Beat/min

mL

mm

Hg

Pa02, Hg

Mean Paw, mm

Hg

mm

Vd/Vt,

PaC02, Hg

mm

PH

3635:

7.38±0.03 7.39±0.06

42±3* 53+8* 44±8*

7.35 ±0.07* 7.22 ±0.06*

Control 7.4±0.9

IPPV

288±20

21±0

HFJV

138±33f

125±19f

285±20

24±4

9.9±1.1**

184+52* 147±60f

36±6* 125+19f

7.8±1.4

ALI ALI IPPV ALI PLV ALI HFJV

2.8+0.3

2.1±0.6f

542±43 559±64

4.4±1.1*§ 3.4±0.7* 3.2±1.0*

60±24* 48+08* 38±llf*

7.29+0.06*

19±7

69±9f 52±9* 55±9* 73±10f

*Data=mean±SD; for abbreviations see text.

ventilatory modes. fp<0.01 ALInon-HFJV IPPV. *p<0.02 ALI IPPV ALI PLV. *p<0.05 vs

vs

vs

the ALI conditions. Besides the arterial pH, which demonstrated a moderate metabolic acidosis during ALI IPPV 2 compared with ALI IPPV 1 (7.23±0.12 and 7.35±0.07, respectively; p<0.03), comparisons of time control between IPPV 1 and IPPV 2 and between ALI IPPV 1 and ALI IPPV 2 demonstrated no differ¬ ence in any measured variable between pair timecontrolled steps of the protocol. Thus, only the initial IPPV sequences were used for subsequent compari¬ sons. Oleic acid-induced ALI was characterized by a decrease in Pa02 and pH, and an increase significant in PaC02 for all stages (Table 1). Furthermore, static total thoracic compliance decreased from 62 ±15 to

H2O (p<0.01) and Raw incrased com¬ the control (7.1±1.4 to 18.6±8.6 cm with pared H20/min; p<0.01). Transpulmonary pressure, which was defined as Paw-Ppl, also increased for a given with ev¬ change in lung volume after ALI (p<0.0001) and inflation However, 1, Ppl Ppc step (Fig top). ery increased by similar amounts during both the control and ALI conditions for similar increases in lung volume (Fig 1, center and bottom, respectively), although the increase in Ppc was proportionally less than the 32±8 mL/cm

increase in

Ppl (p<0.05).

Ventilation Characteristics When Vt was maintained similar to control IPPV IPPV), both plateau and mean Paw during ALI (ALI increased (by 25 and 57% respectively; Table 1); when Paw was maintained constant (ALI PLV), both plateau mean Paw and Vt decreased. ALI HFJV had a lower Vt than either IPPV or ALI IPPV and a lower mean Paw than ALI IPPV. During HFJV, the gas flow Figure 1. Effects of static lung inflation on the following: top: pressure (Paw-Ppl); center: Ppl; and bottom: Ppe transpulmonary for both control (closed circles) and ALI (open diamonds). Data are as mean±SD. Asterisk denotes differences between presented control and ALI (p<0.001).

200 100

Static

lung

300

400

600 500

Static

lung

inflation volume above FRC (ml)

inflation volume above FRC (ml)

200 100

Static

1044

300

500 400

lung inflation volume above FRC (ml)

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Investigations in Critical Care


IPPV

IPPV

AlilPPV

HFJV

ALIPLV

ALIHFJV

Figure 2. Effect of both induction of ALI and different modes of ventilation on (Vt solid bars) and calculated (Vd open bars). See text for description of different modes ofventilation. Data are presented as mean±SD. Asterisk denotes p<0.01 ALI IPPV vs ALI PLV.

had to be decreased to prevent hy(driving pressure) in a significant decrease in which resulted pocapnia, mean Paw compared with IPPV. PaC>2 was constant different modes of ventilation within the during thecontrol and ALI conditions with the exception separate of ALI HFJV during which it was reduced (Table 1). The Pa02 did not change between the two ALI IPPV runs (60±24 to 48±8 mm Hg; p=0.17, paired t test; p=0.1, Wilcoxon signed rank test). After the induction of ALI and despite increasing respiratory frequency from 21 to 36 breaths/min, PaC02 increased by 17% ALI IPPV (p<0.0001, ALI vs control). During during ALI PLV, PaC02 was higher by 30% than during ALI IPPV and ALI HFJV (p<0.05, respectively). These acute increases in PaC02 fully account for the de¬ creases in pH. Despite increasing respiratory fre¬ quency and Raw during ALI conditions, we observed no increase in end-expiratory pleural pressure during any ventilatory mode. Compared with IPPV, both ALI IPPV and ALI PLV had doubled Vd/Vt (Table 1). Calculated physiologic Vd decreased significantly dur-

ALI IPPV

HFJV

ALIPlv

ALI HFJV

Figure 3. Delta Ppl and Ppc before and after the induction of ALI for inspiratory and expiratory pressure swings during positive pres¬ sure ventilation for both Ppl (solid bars) and Ppc (dashed bars). Data are expressed as mean±SD. Asterisk denotes difference between control and ALI (p<0.03), whereas dagger denotes differences be¬ tween HFJV and non-HFJV ventilation values (p<0.04).

ing ALI PLV as compared with ALI IPPV (p<0.05) (Fig 2). The increase in Vd/Vt was 174 and 189% for

ALI IPPV and ALI PLV, respectively, when compared with IPPV. These changes in Vd/Vt were associated with a 17 and 47% increase in PaCC>2, respectively. was greater during control HFJV as Although Vd/Vt with it did not change during ALI, IPPV, compared did increase 27% above control HFJV PaCC>2 although value. Hemodynamic Characteristics ALI was associated with a lower aortic pressure and a higher transmural pulmonary artery pressure (pul¬ monary artery minus Ppc or right ventricular ejection the control (Table 2). No differences pressure) than in were seen SV, heart rate, right atrial pressure, or transmural left atrial pressure (left atrial pressure mi¬ nus Ppc, or left ventricular filling pressure) across dif¬ ferent conditions or modes of ventilation. Interestingly, values during ventilatory modes were hemodynamic not dissimilar to apneic values. The induction of ALI was associated with an increase in Qs/Qt. There were no

differences, however, in Qs/Qt across ventilatory

Table 2.Hemodynamic Effects of Positive-Pressure Ventilation*

Platm,

Ppatm,

Qs/Qt,

SV,

HR,

CO,

mL

Beats/min

L/min

IPPV

14.5±3.2

1.9:! 0.5 1.6d 0.5 1.6d 0.5

144±32 140±29 137±30

6.5±2.8 8.6±5.0

14.8±3.6 13.8±3.7 15.9±3.5

11+3

13.3±2.1 13.2±3.0

128±30 123±28 125±27

7.7±3.7

HFJV Apnea

13.8±3.1 13.7±3.7 17.3±5.1 16.0±4.7

129±22 121±17 129±20 131±17

1.8±0.5 1.7±0.5 2.2±0.8 2.1±0.6

105±33f 102±34f 121±43f 115±27f

5.4±3.4 6.1±4.1 6.3±3.3 6.2±4.0

16.4±2.7f 16.6±2.7f 19.3±5.1f 17.9±3.3f

48±5f 52+4f 55±7f

Stage

Pa, mm

Hg

mm

Hg

mm

Hg

Control

ALI ALI Vt ALI Paw ALI HFJV ALI apnea

*Data=mean±SD; HR=heart rate; CO=cardiac output; Pa=mean arterial pressure; Platm=left atrial pressure relative

Ppatm=pulmonary artery pressure relative to pericardial pressure.

to

9±3

pericardial pressure;

fP<

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1045


modes in either control or ALI conditions. Figure 3 shows the maximal Ppl and Ppc changes (delta) between peak-inspiratory and end-expiratory nadir values. We found no significant changes in delta or delta Ppc between IPPV and ALI IPPV. Delta Ppl and delta Ppc were smaller during ALI PLV than Ppl control IPPV and ALI IPPV. The delta Ppl and Ppc data were quantitatively similar to predicted changes from static compliance data (Fig 1). A delta pressure, defined as the maximum range of pressure changes over time measured at the nadir of the insufflation curve for Ppl and Ppc was also analyzed during the pressure values. Al¬ HFJV runs as peak minus trough values delta different Ppl and Ppcunlike though significantly in ALI were seen in the control and conditions, all other ventilatory models, delta Ppc was greater than delta Ppl during HFJV runs (p<0.05). Inspection of the lungs of all animals at necropsy revealed diffuse patchy areas of hemorrhagic consoli¬ dation, which tended to be greatest in dependent re¬ gions and in the lower lobes. One animal had primary upper-lobe, lingula, and right middle-lobe consolida¬ tion. All animals had clearly defined regions of aerated increases in easily with slight lung units that expanded of A small quantity watery bloodairway pressure. was effusion present in all animals and tinged pleural the tracheas were filled with pink to red frothy fluid. Discussion

This study demonstrates that positive-pressure ven¬ tilation has differential effects on gas exchange and such that selective changes in either hemodynamics, may occur with changes in ventilatory pattern. Over the range of airway pressures analyzed, PLV strategies had similar effects to volume-controlled IPPV on he¬ modynamics and shunt in this canine model of ALL This was true even though the Vt delivered with PLV was almost half that of volume-controlled ventilation. Interestingly, following the induction of ALI, PLV was associated with a lower physiologic Vd, thus minimiz¬ ing the potential alveolar hypoventilation-induced hy¬ that would be predicted to occur. Indeed, for percarbia a 35% decrease in Vt, we measured only a 5% increase in Vd/Vt (Table 1). Furthermore, the primary deter¬ minant of increases in both lateral chest Ppl and Ppc during positive pressure ventilation is the Vt, and nei¬ ther the compliance nor resistance characteristics of the lungs alter this relationship. Finally, ventilation with increased end-ex¬ during ALI was not associated that dynamic hyperinflation piratory Ppl, suggesting was not a component of our model. A decrease in lung compliance has been shown to decrease the transmission of Paw to the pleural potentially minimizing the effect of in¬ space,5,6,20"22 creased airway pressure on right atrial pressure, and subsequently on the pressure gradient for venous re¬ 1046

challenged by O'Quin findings and found that juxtacardiac Ppl the fractional change of Ppl vs airway pressure was only after ALI in a canine model. Fur¬ slightly decreased et al25 Potkin et al24 and

have been turn. These et al23 who measured

thermore,

Viquerat

showed,

in patients with ARDS, that the stepwise reduction in cardiac chamber size with increasing PEEP was asso¬ ciated with a decrease in cardiac output. measured incremen¬ Scharf and tal increases in PEEP before and after induction of ALI in a canine model and found that decreases in

Ingram26

Ppl during

Similarly,

cardiac output occurred independently of lung com¬ on Ppl. Finally, Venus et dependent pliance, but were in swine, demonstrated ALI model an al,27 studying that the transmission of the Paw to the pleural space was reduced by ALI, whereas, with a constant Vt, the were unaltered by changes in lung changes in Ppl These conclusions are in accordance with compliance. our present study. Neither Cabrera et al,8 analyzing the effects of changes in airway pressure on Ppc in an ALI model, nor Pinsky and Guimond,19 examining the dog effect of ALI on the transmission of PEEP to the and pericardial spaces, examined the effects of pleuralvolume Ppc. This study allowed us to lung these itself onstudies to explain the appar¬ unify previousThe anddeterminant of change ent discrepancies. primary in Ppl and Ppc during positive-pressure breathing is the amount of lung inflation. If Vt is not held constant the course of an entire experiment, then throughoutdecreases in transmission of Paw may incor¬ apparent to decreased lung be assumed rectly related totothebeALIduecondition when, in fact, complianceVt alone was for this effect. decreased responsible of the We attribute compliance apparently higher reflected by a significantly lower Ppc as opposed to Ppl, in Ppc compared with Ppl during change amplitude HFJV conditions (Fig 3), to the effect of lung inflation on the heart. According to this model,19 increasing lung volume would compress the heart limiting its size, such that the associated increase in intrathoracic pressure would impede venous return, resulting in a decrease in the right ventricular volume and a smaller increase in Ppc. This is consistent with the hypothesis that when volume changes are rapid enough, as with HFJV, lung mechanical heart-lung interactions are accentuated because insufficient time is allowed for the blood to leave the heart when compared with "conventional" positive pressure breathing. In support of this hypoth¬ esis, we saw that the swings in Ppc during ventilation increased as frequency increased while Ppl swings were unaltered. When we controlled the airway pressure by decreas¬ ing the Vt after induction of ALI (ALI PLV) (Table 2), we did not find any beneficial hemodynamic effects of PLV compared with volume-limited positive-pressure ventilation in the range of airway pressures explored in

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our

canine model. PLV was associated with smaller and excursions ventilation,

pleural

pericardial

during

however, and cardiac output tended to improve at the extremes oflow Vt ventilation (jet ventilation). It is not

clear if these changes would have resulted in hemo¬ differences if the intravascular volume status dynamic had not been well maintained. We vigorously resusci¬ tated these animals during ALI to keep left-side filling pressures constant. This approach was occasionally associated with marked pulmonary edema formation. If resuscitative efforts had been more restrained, we may speculate that decreased mean Ppl induced by PLV might have been associated with a higher venous return.

The observation that the physiologic Vd is moder¬ ately affected by changes in Vt has already been described28 and is attributed to a decrease in the an¬ atomic Vd in normal lungs. When nonhomogeneous however, as in our lung injury conditions prevail, Vt is also likely to allow a better model, decreasing of ventilation and perfusion secondary to matching decreased overinflation. Because overdistention is a potential cause of further lung injury, limiting the air¬ way pressure during mechanical ventilation is a logical ventilatory strategy. The obligatory reduction in Vt usually induces alveolar hypoventilation and has given rise to the term permissive hypercapnia to denote the inevitable increase in arterial Pco2.15'16 The goal of ventilatory therapy in patients with ALI is to maximize gas exchange while minimizing the detrimental effects of positive-pressure breaths on the lungs. Our results suggest that PLV compared with large Vt positivepressure breaths may be better tolerated than previ¬ ously thought. The improved ventilatory efficiency due to the decreases in physiologic Vd ventilation is also associated with lower inspiratory-increase in Ppl. Thus, pressure-limited ventilation strategies may not worsen hemodynamics or gas exchange. Limitations of the Study Our model of ALI follows oleic acid infusion with microembolism of lipids and diffuse endothelial injury. This may alter lung perfusion by mechanisms not as¬ sociated with changes in alveolar pressure. Endothelial injury models, however, reflect the more common sepsis-type lung injury seen clinically in patients with ALL29 Moreover, IV oleic acid induced an ALI in our canine model with a nonhomogeneous distribution of the lesions, decreased lung compliance, pulmonary ventilation-perfusion mismatch, and systemic vasodi¬ lation, mimicking many of the pathophysiologic events occurring in patients with ALL Furthermore, even if mean airway pressure did not increase to the levels usually seen during human ALI, the lesions were se¬ vere enough to produced a 50% decrease in static lung compliance, making the findings of our model relevant.

Another potential limitation of our study was that we varied minute ventilation during our ALI conditions to PaC02 as close to control values as possible. This keep resulted in a greater frequency of ventilation during PLV than during conventional ventilation. Despite this maneuver, we measured a significant increase in PaC02 during ALI conditions. If CO2 flux was not in equilibrium, then calculated Vd/Vt could be inaccu¬ rate. We continuously monitored end-tidal CO2, how¬ ever, and took measurements only after baseline shifts had disappeared. Thus, although we may not have ad¬ equate data to calculate CO2 excretion, the assump¬ tions made in the calculation of Vd/Vt by the Bohr equation are still valid. Our study did not use PEEP, which is used in pa¬ tients to maintain adequate Pa02, because we wanted to analyze the direct effects of changing the ventilatory parameters on hemodynamics and gas exchange. Clearly, increased levels of PEEP would distend fur¬ ther aerated alveoli and, if anything, would have exag¬ gerated the differences in physiologic Vd between and volume-limited ventilation. A fi¬ pressure-limited nal limitation of our study was that extreme hypoxemia and marked decrease in airway compliance were pro¬ duced by the oleic acid injection. This, however, resulted in only minor changes in the mean airway pressure. The absence ofbeneficial effects of pressurecontrolled ventilation on hemodynamics may be re¬ lated to the relatively small decrease in plateau airway pressure achieved. ACKNOWLEDGMENTS: The authors wish to thank Brian Ondulick for his technical assistance, F. Donald, MD, for reviewing this manuscript, and Wendy J. Bouton for her help in preparing the

manuscript.

References 1 Gattinoni L, Mascheroni D, Torresin A, et al. Morphological re¬ sponse

failure:

to

positive end expiratory pressure in acute respiratory

computerized tomography study.

Intensive Care Med

1986; 12:137-42 2 Gattinoni L, Pesenti A, Avalli L, et al. Pressure-volume curve of total respiratory system in acute respiratory failure: computed tomographic scan study. Am Rev Respir Dis 1987; 136:730-36 3 Abraham E, Yoshihara G. Cardiorespiratory effects of pressure

controlled inverse ratio ventilation in severe respiratory failure. Chest 1989; 96:1356-59 4 Morgan BC, Martin WE, Hornbein TF, et al. Hemodynamic ef¬ fects of intermittent positive pressure respiration. Anesthesiology 1966; 27:584-90 5 Chapin JC, Downs JB, Douglas ME, et al. Lung expansion, air¬ way pressure transmission, and positive end-expiratory pressure. Arch Surg 1979; 114:1193-97 6 Cheney FW Jr., Martin WE. Effects of continuous positivepressure ventilation on gas exchange in acute pulmonary edema.

J Appl Physiol 1971; 30:378-81 the effects of intermittent positive pressure breathing on cardiac output in man. Am J Physiol 1948; 152:162-74 8 Cabrera MR, Nakamura GE, Montague DA, et al. Effect of air¬ way pressure on pericardial pressure. Am Rev Respir Dis 1989;

7 Cournand A, Motley HL, Werko L, et al. Physiological studies of

CHEST /108 / 4 / OCTOBER, 1995 Downloaded from chestjournal.chestpubs.org by guest on July 22, 2010 1995 BY THE AMERICAN COLLEGE OF CHEST PHYSICIANS

1047


140:659-67 9 Braunwald E, Binion JT,

Morgan WL, al. Alterations in cen¬ tral blood volume and cardiac output induced by positive pressure breathing and counteracted by metaraminol (Aramine). Circ Res et

1957; 5:670-75

10

Dreyfuss D, Bassett G, Soler P, et al. Intermittent positive-pres¬ sure hyperventilation with high inflation pressures produces pul¬ in rats. Am Rev Dis monary microvascular injury

Respir

1985;

132:880-84 11 Tsuno K, Muira K, Takeya MM, et al. Histopathologic pulmonary

ventilation at high peak airway pres¬ changes from mechanical 143:1115-20 Dis

Am Rev Respir 1991; 12 Chan K, Abraham E. Effects of inverse ratio ventilation on car¬ sures.

diorespiratory parameters

in

severe

respiratory failure. Chest

1992; 102:1556-61 13 Lain DC, DiBenedetto R, Morris SL, et al. Pressure control in¬

as a method to reduce peak inspiratory and pressure provide adequate ventilation and oxygenation. Chest 1989; 95:1081-88 14 Guntapalli KK, Pinsky MR, Marquez J, et al. Determinants of ventilation during high frequency jet ventilation. J Crit Care 1987; verse

ration ventilation

2:93-100

Hickling KG, Henderson SJ, Jackson R. Low mortality associated with low volume pressure limited ventilation with permissive hy¬ percapnia in severe adult respiratory distress syndrome. Intensive Care Med 1990; 16:372-77 16 Hickling KG, Walsh J, Henderson S, et al. Low mortality rate in ARDS using low-volume, pressure-limited ventilation with per¬ missive hypercapnea: a prospective study. Crit Care Med 1994; 22:1568-78 17 McMahon SM, Permutt S, Proctor DF. A model to evaluate pleural surface pressure measuring devices. J Appl Physiol 1969;

15

27:886-89

18

Ashbaugh DG, Uzawa T. Respiratory and hemodynamic changes

1048

after injection of free fatty acids. J Surg Res 1968; 8:417-23 Pinsky MR, Guimond JG. The effects of positive end-expiratory pressure on heart-lung interactions. J Crit Care 1991; 6:1-11 20 Ellman H, Dembin H. Lack of adverse hemodynamic effects of PEEP in patients with acute respiratory failure. Crit Care Med 19

1982; 10:706-11 R, Busija D, Green R, et al. Relationship between mean airway pressure, cardiac output and organ blood flow with normal and decreased respiratory compliance. J Pediatr 1987; 111:101-06 22 Jardin F, Genevray B, Brun-Ney D, et al. Influence of lung and 21 Mirro

chest wall compliances on transmission of airway pressure to the pleural space in critically ill patients. Chest 1985; 88:653-58 23 O'Quin RJ, Marini JJ, Culver BH, et al. Transmission of airway pressure to pleural space during lung edema and chest wall re¬ striction. J Appl Physiol 1985; 59:1171-77 24 Potkin RT, Hudson LD, Weaver LJ, et al. Effect of positive

end-expiratory pressure on right and left ventricular function in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 1987; 135:307-11 25 Viquerat CE, Righetti A, Suter PM. Biventricular volumes and function in patients with adult respiratory distress syndrome ventilated with PEEP. Chest 1983; 83:509-14 26 Scharf SM, Ingram RH Jr. Effects of decreasing lung compliance with oleic acid on the cardiovascular response to PEEP. Am J Physiol 1977; 233:H635-41 27 Venus B, Cohen LE, Smith RA. Hemodynamics and intrathoracic pressure transmission during controlled mechanical ventilation and positive end-expiratory pressure in normal and low compli¬ ance lungs. Crit Care Med 1988; 16:686-90 28 Nunn JF, Hill DW. Respiratory dead space and arterial to endtidal CO2 tension difference in anesthetized man. J Appl Physiol

1960; 15:383-89 29 Schuster DP. ARDS: clinical lessons from the oleic acid model of acute lung injury. Am J Respir Crit Care Med 1994; 149:245-60

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Investigations in Critical Care


Cardiopulmonary Effects of Positive Pressure Ventilation During Acute Lung Injury Jacques-Andre Romand, Weizhong Shi and Michael R. Pinsky Chest 1995;108; 1041-1048 DOI 10.1378/chest.108.4.1041 This information is current as of July 22, 2010 Updated Information & Services Updated Information and services can be found at: http://chestjournal.chestpubs.org/content/108/4/1041 Citations

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1600185-02-85-02 - Dados clínicos, Papers  

1600185-02-85-02 - Dados clínicos, Papers

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