Improving the Diagnosis and Monitoring of Critically ill Patients and the Role of Blood Gas Testing

SPECIAL REPORT

Improving the Diagnosis and Monitoring of Critically Ill Patients and the Role of Blood Gas Testing The Role of Blood Gas Analysis in the Management of Patients with Severe COVID-19 Blood Gas Analysis: Applications for Decentralized Testing Considerations in Selecting a Blood Gas Analyzer Clinical Guidelines and Recommendations for Blood Gas Analysis

CTHC-UK-144 June 2020

Published by Global Business Media

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IMPROVING THE DIAGNOSIS AND MONITORING OF CRITICALLY ILL PATIENTS AND THE ROLE OF BLOOD GAS TESTING

SPECIAL REPORT

Improving the Diagnosis and Monitoring of Critically Ill Patients and the Role of Blood Gas Testing The Role of Blood Gas Analysis in the Management of Patients with Severe COVID-19

Contents

Blood Gas Analysis: Applications for Decentralized Testing Considerations in Selecting a Blood Gas Analyzer Clinical Guidelines and Recommendations for Blood Gas Analysis

Foreword

2

Dr. Sophie Laurenson BSc. BSc. (Hons.), PhD. (Cantab), Editor

The Role of Blood Gas Analysis in the Management of Patients with Severe COVID-19

3

Professor Daniel Martin OBE, Intensive Care Consultant, Royal Free Hospital, London, UK CTHC-UK-144 June 2020

Published by Global Business Media

Published by Global Business Media Global Business Media Limited 62 The Street Ashtead Surrey KT21 1AT United Kingdom Switchboard: +44 (0)1737 850 939 Fax: +44 (0)1737 851 952 Email: info@globalbusinessmedia.org Website: www.globalbusinessmedia.org Publisher Kevin Bell Business Development Director Marie-Anne Brooks Editor Dr. Sophie Laurenson BSc. BSc. (Hons.), PhD. (Cantab) Senior Project Manager Steve Banks Advertising Executives Michael McCarthy Abigail Coombes Production Manager Paul Davies For further information visit: www.globalbusinessmedia.org The opinions and views expressed in the editorial content in this publication are those of the authors alone and do not necessarily represent the views of any organisation with which they may be associated.

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Introduction COVID-19 and Oxygenation Assessment and Monitoring of the Hypoxaemic Critically Ill Patient Respiratory Support for Patients with COVID-19 Blood Gas Systems: More Than Just Blood Gases Point of Care Testing During a Pandemic Conclusions

Blood Gas Analysis: Applications for 8 Decentralized Testing Sophie Laurenson, BSc. BSc. (Hons.), PhD. (Cantab), EMBA, MRSNZ

Introduction The Physiology and Pathology of Gas Exchange Fundamentals of Blood Gas Analysis Blood Gas Analyzers: Integrated Analysis of Critical Analytes Demand for Blood Gas Testing Blood Gas Analysis at the Point-Of-Care (PoC): Improving Clinical Workflows and Efficiency Conclusion

Considerations in Selecting a Blood Gas Analyzer

11

Sophie Laurenson, BSc. BSc. (Hons.), PhD. (Cantab), EMBA, MRSNZ

Introduction Assay Menu and Performance Criteria User-Friendly, Convenience: Considerations for Selecting Blood Gas Analyzers Quality Control (QC) and Quality Assurance (QA) Networking and Cybersecurity in Decentralized Testing Environments Conclusion and Future Outlook

Clinical Guidelines and Recommendations for Blood Gas Analysis

14

Sophie Laurenson, BSc. BSc. (Hons.), PhD. (Cantab), EMBA, MRSNZ

Introduction Reference Measurements and Interpretation American Association for Respiratory Care (AARC) Guidelines: 2013 Acute Respiratory Distress Syndrome (ARDS) Conclusion

References 16 WWW.HOSPITALREPORTS.EU | 1

IMPROVING THE DIAGNOSIS AND MONITORING OF CRITICALLY ILL PATIENTS AND THE ROLE OF BLOOD GAS TESTING

Foreword T

he levels of gases, electrolytes, and

of clinical settings, allowing improved clinical decision-

metabolites in circulation influence the

making. Over the last four decades, technological

equilibrium between oxygen delivery and tissue

advances have translated into improvements in the

demand, as well as the acid�base balance of the

performance and design of blood gas analyzers.

human body. Deviations in this equilibrium manifest

Multiple manufacturers offer analyzers with expanded

in numerous diseases affecting the respiratory,

testing menus for use in clinical laboratories or at the

cardiovascular, and metabolic systems. Blood

point-of-care (PoC). Healthcare providers have a

gas analysis evaluates abnormalities in the degree

range of options available to meet their demands

of pulmonary gas exchange and metabolism,

for accuracy, safety, and convenience. The third

including the adequacy of ventilation, oxygenation,

article in this report discusses some of the key

and acid-base status. The values of carbon dioxide

metrics to use in selecting a blood gas analyzer

and oxygen are expressed as the partial pressure

for point-of-care or laboratory settings. Improved

of carbon dioxide (PaCO2) and the partial pressure

clinical informatics capabilities enable healthcare

of oxygen (PaO2).

professionals to collect, store, and analyze test data

The first article in this report is authored by Professor

in a secure environment, providing timely access

Daniel Martin OBE. Professor Martin is an Intensive

to data for actionable clinical insights. This article

Care Consultant at the Royal Free Hospital in London,

also highlights the importance of cybersecurity in

U.K. He describes the critical role of blood gas testing

safeguarding patient data and the broader informatics

in the management and monitoring of COVID-19

systems of healthcare organizations. The final article

patients in intensive care settings. The second article

focuses on clinical guidelines and recommendations

further discusses the utility of blood gas analysis in

for blood gas analysis, including clinical indications

the diagnosis and management of critically ill patients

and guidance for sampling, handling, and analysis

and describes measures to meet the global demand

of blood gas specimens.

for blood gas testing.

Blood gas analysis enables healthcare professionals to evaluate patients across a range

Dr Sophie Laurenson Editor

Dr. Sophie Laurenson is a scientist and social entrepreneur. She obtained a Ph.D. in Oncology (Biophysics / Biochemistry) from the University of Cambridge in 2007 and has worked in industry and academia for 17 years. Currently, she is the Founder and Managing Director of Limeburners Bay International AG, developing medical technology for resource-limited settings.

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IMPROVING THE DIAGNOSIS AND MONITORING OF CRITICALLY ILL PATIENTS AND THE ROLE OF BLOOD GAS TESTING

The Role of Blood Gas Analysis in the Management of Patients with Severe COVID-19 Professor Daniel Martin OBE, Intensive Care Consultant, Royal Free Hospital, London, UK Advanced blood gas analysers can support the monitoring and management of COVID-19 patients.

Introduction Airborne infectious diseases are a constant threat to society. Transmissible via the air in droplet or aerosol form, and through contact with contaminated surfaces, they primarily affect the respiratory tract leading to a range of illnesses with varying severity. In 2019, a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged, spreading rapidly to cause coronavirus disease 2019 (COVID-19) and eventually resulted in a pandemic that changed the world. To date, 14.8 million people have tested positive for the virus, and over 600,000 are known to have died from COVID-1938. These figures are likely to be underestimates of the total disease burden and will have increased by the time this report is published. Approximately 80% of people who are affected by COVID-19 develop mild symptoms (most commonly a fever, persistent cough, and shortness of breath), which requires no specific treatment. Around 15% of those infected with the virus will develop severe acute respiratory failure with breathlessness and hypoxaemia, requiring hospital admission for the administration of oxygen1. If giving oxygen by simple measures such as a nasal cannula or face mask fails to correct the hypoxaemia then admission to an intensive care unit (ICU) may be required. This occurs in around 5% of those infected, and most will go on to require mechanical ventilation via an endotracheal tube2-4. Unfortunately, the mortality of those admitted to the ICU is approximately 50%5,6. Older people, males, and those with diabetes, obesity, and hypertension appear to be prone to a more severe form of the infection. In the absence of a definitive treatment for COVID-19, supporting respiratory function is the cornerstone of the current strategy to promote survival in

patients with COVID-19. Optimum application of all of the various modalities available to improve oxygenation in hospitalised patients relies on rapid, accurate, and reliable measurement of arterial oxygenation by point-of-care test (POCT) arterial blood gas (ABG) analysis to titrate to the required physiological target.

COVID-19 and Oxygenation At the cellular level, oxygen is essential for the preservation of energy production via oxidative phosphorylation. When oxygen is in short supply, normal cellular function deteriorates and ultimately fails altogether. A continuous supply of oxygen must be maintained along a pathway known as the oxygen cascade (Figure 1). The cascade describes the journey taken by oxygen from the air, along the respiratory tract, into the blood, and then via the circulatory system to the tissues that use it. Oxygen transport can be impaired by pathology at any point along this pathway.

COVID-19 primarily affects gas exchange at the interface between the respiratory and cardiovascular systems, where gaseous oxygen and carbon dioxide are exchanged at the alveolar membrane. Of the five commonly described physiological causes of hypoxaemia (Table 1), ventilation-perfusion (VA/Q) mismatching is likely to be the dominant factor in COVID-19.

Commonly, patients present to the hospital with rapid, shallow breathing, but often without the other classic signs of respiratory distress, such as increased work of breathing. The typical picture is a type-1 respiratory failure with severe hypoxaemia but a normal (or low) arterial partial pressure of carbon dioxide (PaCO2). Chest X-ray and computed tomography (CT) scanning of the lungs tends to show patchy areas of consolidation throughout both lungs and widespread ground-

Approximately 80% of people who are affected

by COVID-19 develop mild symptoms (most commonly a fever, persistent cough, and shortness of breath), which requires no specific treatment

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IMPROVING THE DIAGNOSIS AND MONITORING OF CRITICALLY ILL PATIENTS AND THE ROLE OF BLOOD GAS TESTING

Table 1. The relationship between alveolar–arterial oxygen partial pressure difference and physiological causes of hypoxaemia

(Patho-)physiology

A-aPO2

Hypoventilation

←→

Low inspired oxygen tension

←→

Right-to-left shunt (pulmonary or cardiac)

↑

Ventilation–perfusion mismatch

↑

Impaired diffusion

↑

A-aPO2: Alveolar-arterial partial pressure difference

At the cellular level, oxygen is essential for the preservation of energy production via oxidative phosphorylation

glass opacities7. Perfused alveolar units that are consolidated or contain pulmonary oedema reduce the VA/Q ratio, resulting in a right to left intra-pulmonary shunt. In addition to this, a high incidence of pulmonary embolism has been noted in patients with COVID-19. This further exacerbates hypoxaemia by creating areas in which ventilated alveolar units are not perfused, increasing the physiological dead space, resulting in a high VA/Q ratio. Thus, in COVID-19, different pathophysiological processes are interacting to create severe and sustained hypoxaemia and progressive hypercapnia that can be challenging to treat (Figure 1).

Assessment and Monitoring of the Hypoxaemic Critically Ill Patient While pulse oximetry is the mainstay of monitoring systemic oxygenation in mild to moderate disease, as hypoxaemia worsens, ABG analysis becomes a critical component of patient management and decision-making. It is also useful to remember that oximetry saturation (SpO2) is error-prone and may differ from the arterial oxygen saturation

(SaO2) measured by the co-oximeter of an ABG system8. ABG analysis is essential in patients with respiratory failure to assess the severity of their condition, determine its cause, and monitor the effectiveness of treatments. One of the first things to determine in a hypoxaemic patient is whether they have type-1 (hypoxaemic) or type-2 (hypercapnic) respiratory failure, which requires measurement of PaCO2 levels. In the majority of patients with early COVID-19 related respiratory failure, PaCO2 is either normal or low (type-1), the latter likely due to the hypoxic ventilatory response triggering hyperventilation.

Knowledge of the PaO2 value allows clinicians to make a more comprehensive assessment of the severity of hypoxaemia than can be made from SpO2 alone. The term hypoxaemia has no strict definition other than a level of arterial oxygen that is lower than ‘normal’. The normal PaO2 in a healthy individual is generally accepted to be between 10.7-13.3 kPa. Quantification of the severity of respiratory failure needs to take into account the concentration of oxygen a patient is breathing, and this is usually expressed as the P/F (PaO2:FiO2) ratio. P/F ratio is used as part of the diagnostic criteria for acute respiratory distress syndrome (ARDS), with 300 mmHg (40 kPa) being the current threshold for diagnosis (Table 2)9. The alveolar-arterial (A–a) oxygen partial pressure difference can also be calculated using ABG data. This may help in elucidating the cause of hypoxaemia (Table 1); however, the alveolar gas equation must be used to estimate the alveolar partial pressure of oxygen (PaO2) as it cannot be easily measured (Equation 1).

Table 2. Severity of acute respiratory distress syndrome as determined by P/F ratio9

ARDS Severity

PaO2/FiO2

Mild

200-300 mmHg

Moderate

100-200 mmHg

Severe

< 100 mmHg

Values are relevant for patients with a PEEP of ≥ 5 cmH2O

Figure 1. The oxygen cascade and potential effects COVID-19 has on it

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PaO2/FiO2: ratio of arterial partial pressure of oxygen to fractional inspired oxygen concentration; PEEP: positive end-expiratory pressure

IMPROVING THE DIAGNOSIS AND MONITORING OF CRITICALLY ILL PATIENTS AND THE ROLE OF BLOOD GAS TESTING

Equation 1. Calculation of the alveolar partial pressure of oxygen using the alveolar gas equation

PaO2 = PiO2 - PaCO2 x (FiO2/RQ) PiO2 = FiO2 (PB - PH2O) PaO2 : alveolar partial pressure of oxygen PiO2 :

Inspired partial pressure of oxygen

PaCO2 : arterial partial pressure of carbon dioxide FiO2 :

Fractional inspired oxygen concentration

RQ :

respiratory quotient (0.8 in healthy individuals)

PB :

barometric pressure

Respiratory Support for Patients with COVID-19 Correct interpretation of ABG data facilitates the appropriate selection of treatment modality for an individual patient with COVID-19.

Mild hypoxaemia may be managed with the administration of oxygen via simple nasal cannula, while a higher requirement for oxygen will require either a variable or fixed performance oxygen mask. If these modalities prove inadequate, non-invasive ventilation can be considered in one of two formats. The first is continuous positive airway pressure (CPAP) ventilation; this may be of benefit in early type-1 respiratory failure as the maintenance of positive pressure at the end of expiration acts to prevent alveolar collapse. This, in turn, reduces VA/Q mismatching, improves lung compliance, and reduces the work of breathing. The second is bilevel positive airway pressure (BiPAP); it is appropriate for patients with type-2 respiratory failure, where the delivery of additional pressure during inspiration should increase minute ventilation and reduce PaCO2.

These non-invasive modes of ventilation may allow the correction of hypoxaemia without the need for escalation to intubation and mechanical ventilation. CPAP, in particular, has been used extensively in patients with COVID-19, and strategies for its use have been outlined10.

Alongside clinical signs, ABG analysis can help to signal when non-invasive ventilation is failing, and intubation and mechanical ventilation are required. The PaCO2 will begin to rise, and PaO2 will fall further as patient fatigue and respiratory failure worsens.

The decision to intubate is a complex and multi-factorial one based on ABG results, clinical signs, disease trajectory, and the likelihood of a long-term successful outcome. Once intubated, frequent ABG analysis is essential for the titration of positive end-airway pressure (PEEP), respiratory rate, and FiO2. Traditionally in ARDS, PEEP was set according to FiO2, as outlined in the ARDSnet guidelines11. However, it has been noted that such high levels of PEEP may be disadvantageous in patients with COVID-19, as lung compliance appears to be better than was expected12. This means that a more individualised

approach to setting PEEP is required, taking into account lung compliance measurements and the gas exchange response to a range of levels of PEEP. ABG analysis also helps to determine the mode of ventilation best suited for an individual patient. Airway pressure release ventilation (APRV), an inverse ratio pressurecontrolled mode of ventilation that permits unrestricted spontaneous breathing, is thought to promote alveolar recruitment and therefore improve oxygenation13. It does, however, require careful titration of its settings against ABGs to avoid excessive hypercapnia and assess the effectiveness of the recruitment process.

After the acute phase of illness has subsided, active weaning from mechanical ventilation will be required. This can be a lengthy process if pulmonary inflammation develops into fibrosis, if patients develop critical illness polyneuropathy (a form of severe weakness that follows critical illness) or if there is severe cardiac dysfunction.

In those patients for whom extubation has not been possible after approximately two weeks, the formation of a tracheostomy will be necessary to aid ventilatory weaning. Complete separation from mechanical ventilation may take many weeks for some patients, and the risk of recurrent bacterial ventilator acquired pneumonia is high.

Throughout this time, weaning plans will need to be adjusted according to the patient’s process, and ABG analysis is a key component in the judgement of daily success.

The term hypoxaemia has no strict definition other than a level of arterial oxygen that is lower than ‘normal’

Blood Gas Systems: More Than Just Blood Gases Modern blood gas analysers provide much more than just pH and gas exchange measurements.

Also, they have an ever-increasing array of additional biochemical information (Figure 2). Two of the most frequent and arguably most important of these during the COVID-19 pandemic were glucose and lactate. With almost 20% of hospitalised COVID-19 patients having a diagnosis of diabetes14, frequent monitoring of blood glucose became a key component of their ICU management. Presentation with diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic syndrome (HHS) was also WWW.HOSPITALREPORTS.EU | 5

IMPROVING THE DIAGNOSIS AND MONITORING OF CRITICALLY ILL PATIENTS AND THE ROLE OF BLOOD GAS TESTING

Figure 2. POC RAPIDPoint 500e System Touchscreen

The decision to intubate is a complex and multi-factorial one based on ABG results, clinical signs, disease trajectory, and the likelihood of a long-term successful outcome

frequently observed, both of which require frequent blood gas analysis to avoid harm.

The calculation of base deficit and anion gap help differentiate the causes of acidaemia. The measurement of blood lactate has become an integral component of the assessment of patients with sepsis, particularly in the critically ill15. In patients with COVID-19, a rising lactate is likely to signify organ hypoperfusion due to low cardiac output, meaning the need for intravenous fluid resuscitation and potentially the need for vasopressor or inotropic support.

Other measurements key to the successful management of critically ill patients include haemoglobin concentration, sodium, potassium, magnesium, and creatinine. POCT analysis of all of these additional measurements will speed up diagnoses and facilitate a more rapid implementation of life-saving interventions.

Point of Care Testing During a Pandemic The delivery of precision care for critically ill patients with COVID-19 would be extremely challenging without access to POCT blood gas analysis. Every hospital must decide the POCT strategy that works for their specific setting and consider the strengths and weaknesses of different devices available on the market.

Key criteria for devices that can deliver POCT blood gas analysis are summarised in Table 3.

All of these factors need to be considered when selecting instruments for different areas of a hospital, along with the training required for staff who will use them. A blood gas instrument should no longer be thought of as a stand-alone device. If integrated into a hospitalâ&#x20AC;&#x2122;s information technology network, it can transform patient care. Minimising variation of the systems across a hospital will

Table 3. Properties of an ideal point of care blood gas analysis system

Property Features Accuracy Sample integrity must be core to the design of the system to ensure test results must reflect those produced in a standard laboratory setting.

The system needs to be able to perform meticulous quality checks in the background, at every stage of analysis.

Accessibility The system must have operational simplicity. Devices must be close to the bedside and in sufficient numbers to reflect the workload of the area.

Reliability The system must be able to cope with high numbers of samples without affecting performance.

Robustness Systems need to be able to withstand the rigorous environments found in some clinical settings.

Security and connectivity There is a need for heightened cyber security and data connectivity in modern data enabled healthcare services. Barcode reading sensors save time and reduce errors*. Integration with hospital information technology systems is essential.

Support Servicing, repairs, assistance and supplies are crucial components to a well-functioning system. *see Figure 3

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IMPROVING THE DIAGNOSIS AND MONITORING OF CRITICALLY ILL PATIENTS AND THE ROLE OF BLOOD GAS TESTING

Figure 3. POC RAPIDPoint 500e Barcode Scanning of Syringe

Table 4. Potential advantages to using hand-held POCT blood gas analysers in a pandemic

Immediate bedside access to testing saves vital time in life-threatening situations Devices are easily and quickly decontaminated due to their size Simplicity of use as a result of cartridge-based technology Cartridges ensure no blood comes into contact with the internal workings of the device Multiple cartridge options provide a broad array of POCTs

help maintain a high level of competence and confidence amongst staff, particularly in times when teams may be working in unfamiliar environments. Many blood gas instruments now feature cartridge-based technology, reducing the need for high-level technical support.

An increased capacity for POCT blood gas analysis may be required in certain areas of a hospital during a pandemic, so there needs to be a plan of which devices are moved into key areas when patient numbers begin to rise.

One strategy adopted by some hospitals is to use hand-held POCT systems (Figure 4); the potential advantages are summarised in Table 4. Portable analysers offer flexibility that cannot be matched by larger benchtop systems, so they should be considered as part of any expansion plan during a pandemic. Also, by bringing the analysis device directly to the bedside, hand-held systems provide a solution to the infection-control issues surrounding the transportation of samples around a unit or hospital.

Conclusions Over the last few decades, POCT analysis has revolutionised intensive care medicine and allowed clinicians to optimise patient care in real-time. COVID-19 has taught us many lessons

A blood gas instrument should no longer be thought of as a stand-alone device.

If integrated into a hospitalâ&#x20AC;&#x2122;s information technology network, it can transform patient care

Figure 4. An example of a cartridge-based hand held blood gas analyser

about pathophysiology and strategic planning, which will undoubtedly shape healthcare in the future. POCT blood gas analysis has proven to be an essential part of the treatment of hospitalised patients with COVID-19 and must be central to future pandemic planning.

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IMPROVING THE DIAGNOSIS AND MONITORING OF CRITICALLY ILL PATIENTS AND THE ROLE OF BLOOD GAS TESTING

Blood Gas Analysis: Applications for Decentralized Testing Sophie Laurenson, BSc. BSc. (Hons.), PhD. (Cantab), EMBA, MRSNZ Blood gas analysis measures the levels of pH, oxygen, carbon dioxide, and bicarbonate in circulation. These assays are used to evaluate abnormalities in the degree of pulmonary gas exchange and metabolism and are used in the evaluation of numerous clinical indications.

Introduction

The levels of gases, electrolytes, and metabolites in circulation influence the equilibrium between oxygen delivery and tissue demand, as well as the acidbase balance of the human body

The interplay between the cardiovascular and respiratory systems is critical in maintaining homeostasis. The levels of gases, electrolytes, and metabolites in circulation influence the equilibrium between oxygen delivery and tissue demand, as well as the acid-base balance of the human body. Deviations in this equilibrium manifest in numerous diseases affecting the respiratory, cardiovascular, and metabolic systems. Blood gas analysis enables healthcare professionals to evaluate patients across a range of clinical settings, allowing improved clinical decision-making.

The Physiology and Pathology of Gas Exchange The lungs play a critical role in gas exchange by mediating the exchange of gases between air and blood through passive diffusion16. However, the lungs constitute only one component of a broader system, including the cardiovascular system (the heart, vasculature, and blood) and metabolic organs. The processes of ventilation and perfusion rely on harmony between each of the components of the cardiorespiratory system.

Many cardiopulmonary diseases are caused by disturbances in either ventilation or perfusion of the lung alveoli and are evaluated using blood gas analysis17.

Fundamentals of Blood Gas Analysis Blood gas analysis evaluates abnormalities in the degree of pulmonary gas exchange and metabolism, including the adequacy of ventilation, oxygenation, and acid-base status18. The values of carbon dioxide and oxygen are expressed as the partial pressure of carbon dioxide (PaCO2) and the partial pressure of oxygen (PaO2).

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They are essential factors in the diagnosis and treatment of patients with pulmonary and other critical conditions. The pH and bicarbonate concentration assist in the diagnosis of renal and metabolic diseases. Many modern blood gas analyzers also test for electrolytes (Na+, K+, Cl-, Ca++) and metabolites such as glucose and lactate. Co-oximetry tests measure concentrations of hemoglobin species including oxygenated hemoglobin (oxyHb), deoxygenated hemoglobin (deoxyHb), carboxyhemoglobin (COHb), and methemoglobin (MetHb) to determine blood oxygen saturation.

Blood gas analysis is used routinely in patient care throughout different levels of the health system. It is pivotal in initial evaluations of patients presenting with dyspnea or respiratory distress.

Within lower levels of care, oxygenation status is often assessed using non-invasive techniques such as pulse oximetry or subcutaneous measurement of carbon dioxide19. Patients that progress to severe pulmonary diseases such as acute respiratory distress syndrome (ARDS), and respiratory failure require routine blood gas testing and monitoring20. Blood gas analysis is also used to diagnose other critical conditions such as sepsis and septic shock21, heart failure and cardiac arrest, and hypovolemic shock. Metabolic disorders such as diabetic ketoacidosis, renal tubular acidosis, and inborn errors of metabolism also cause abnormalities in blood gas values17.

Interpreting blood gas analysis results can be challenging, as the factors affecting blood gas values are often multifactorial and complex22.

There are five leading causes of hypoxemia, including ventilation/perfusion (VQ) mismatch, hypoventilation, reduced F iO 2, shunting, impaired diffusion of oxygen across the alveolar membrane23. Each of these mechanisms may contribute to deviations in oxygen and carbon

IMPROVING THE DIAGNOSIS AND MONITORING OF CRITICALLY ILL PATIENTS AND THE ROLE OF BLOOD GAS TESTING

POC epoc Blood Analysis System offers patient-side testing of critical analytes

dioxide tensions. Blood gas values may be further affected by compensatory mechanisms intended to balance gas exchange instabilities through increasing ventilation, improving oxygen extraction, or increasing cardiac output.

In addition to diagnosis, blood gases, electrolytes, and metabolites are commonly used to evaluate disease severity, intervention efficacy, and prognosis. Systematic interpretation of blood gas values assists in understanding whether the primary disorder is respiratory or metabolic in origin, acute or chronic in nature, and the severity of abnormalities24. There are various modalities available to assess and treat patients presenting with cardiorespiratory diseases. Selecting the optimum management strategy relies on the accurate, rapid measurement of analytes to titrate treatments to the required physiological target.

Blood Gas Analyzers: Integrated Analysis of Critical Analytes The first commercially-available blood gas analyzers were introduced into clinical laboratories in the 1960s25. They have become the mainstay of intensive care patient management in hospital settings. Subsequent technological advances in electronics, sensors, and informatics have enabled the miniaturization of blood gas instruments and consumables, facilitating their use in decentralized care settings.

The first combined blood gas and electrolyte analyzer was launched in the 1980s, enabling measurements of pCO2, pO2, as well as the electrolytes sodium (Na+), potassium (K+), and calcium (iCa), and hematocrit26. The introduction of blood gas analyzers capable of measuring these analytes in whole blood further expanded their utility in critical care analyzers. Modern analyzers are capable of executing a broad menu including pH, pCO2, pO2, Na+, K+, Cl-, iCa, iMg,

Many cardiopulmonary diseases are caused by disturbances in either ventilation or perfusion of the lung alveoli and are evaluated using blood RAPIDPoint 500e Blood Gas System provides results

gas analysis

in 60 seconds

hematocrit, glucose, lactate, creatinine, urea, hemoglobin, O2 saturation, and co-oximetry.

Expanded test menus enable critical care blood gas analyzers to provide actionable findings across many clinical indications.

Demand for Blood Gas Testing Blood gas analysis is used to evaluate numerous diseases of cardiopulmonary and metabolic origin. Consequently, it is one of the most frequently ordered tests in healthcare organizations. Severe pulmonary disease has a substantial impact on global public health.

The estimated incidence is 34 and 5-7 cases per 100,000 patients per year in the U.S.A. and European countries, respectively27, 28. In lowincome countries, under-reporting is common, although it has been observed that 4% of all hospital admissions present with clinical signs and symptoms similar to those of ARDS29. In the U.S.A., ARDS patients represent 7% of ICU patients and 16% of those requiring mechanical ventilation18. Historical estimates of severe pulmonary diseases such as ALI and ARDS WWW.HOSPITALREPORTS.EU | 9

IMPROVING THE DIAGNOSIS AND MONITORING OF CRITICALLY ILL PATIENTS AND THE ROLE OF BLOOD GAS TESTING

POC epoc Blood Analysis System offers a broad menu on a single test card

Blood gas analysis is used to evaluate numerous diseases of cardiopulmonary and metabolic origin.

Consequently, it is one of the most frequently ordered tests in healthcare organizations

indicated that cases in Europe were significantly lower than those reported in the USA. However, the recent COVID-19 pandemic is likely to alter historical estimates of incidence and prevalence, as many health systems have experienced increased utilization of ICU facilities.

Intensive care medicine requires significant resources, and costs are projected to rise with the introduction of new therapeutic and diagnostic modalities. Up to 25% of ICU expenditure is consumed by laboratory testing, a trend which is also increasing30-32. Arterial blood gas analysis (ABG) is the most frequently ordered laboratory test in ICU facilities33. A study of testing utilization at the Brigham and Womenâ&#x20AC;&#x2122;s Hospital in Boston, MA, showed almost 100,000 ABG tests ordered per year34. Improving the efficiency of clinical workflows helps to contain costs while enhancing patient care experiences and outcomes.

Blood Gas Analysis at the Point-Of-Care (PoC): Improving Clinical Workflows and Efficiency PoC testing is frequently used in critical care settings to deliver decentralized care to patients in emergency departments (EDs), Intensive Care Units (ICUs), and ambulances35. Rapid assessment of blood gas and electrolytes may improve clinical outcomes in critically ill patients

through efficient clinical decision making and reduced therapeutic turnaround time (TTAT). This is enabled by making data rapidly available at the point-of-use. PoC tests are commonly simplified systems with self-contained components and user-friendly interfaces. These features allow them to be used by healthcare professionals outside of the clinical laboratory environment. Rapid sample processing and simplified instruments also reduces sampling and preanalytic testing errors, affecting blood gas analysis. Finally, PoC instruments require small sample volumes, facilitating serial testing for patient monitoring while minimizing patient discomfort or adverse side-effects. In combination, the convenient, user-friendly nature of PoC blood gas analyzers has expanded testing capacity for many healthcare organizations.

Conclusion Blood gas analysis is one of the most important services in the care of critically ill patients. The levels of pH, oxygen, carbon dioxide, and bicarbonate in circulation are used to evaluate abnormalities in the degree of pulmonary gas exchange and metabolism in numerous clinical indications. To meet the increasing global demand for blood gas testing services, point-of-care analyzers enable decentralized testing in emergency departments, intensive care units and remote settings.

Blood gas analysis is essential for the diagnosis and treatment of patients with a range of critical conditions

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IMPROVING THE DIAGNOSIS AND MONITORING OF CRITICALLY ILL PATIENTS AND THE ROLE OF BLOOD GAS TESTING

Considerations in Selecting a Blood Gas Analyzer Sophie Laurenson, BSc. BSc. (Hons.), PhD. (Cantab), EMBA, MRSNZ Blood gas analysis is one of the most frequently ordered tests for many healthcare organizations. Healthcare providers have a range of options available to meet their demands for accuracy, safety, and convenience.

Modern blood gas analyzers offer broad menus, with integrated capabilities for measuring blood gases, electrolytes, metabolites, and co-oximetry RAPIDPoint 500e Blood Gas System capillary sampling

Introduction Over the last four decades, technological advances have translated into improvements in the performance and design of blood gas analyzers. Multiple manufacturers offer analyzers with expanded testing menus for use in clinical laboratories or at the point-of-care (PoC) [36].

Healthcare providers have a range of options available to meet their demands for accuracy, safety, and convenience. Improved clinical informatics capabilities enable healthcare professionals to collect, store, and analyze test data in a secure environment, providing timely access to data for actionable clinical insights.

Assay Menu and Performance Criteria Modern blood gas analyzers offer broad menus, with integrated capabilities for measuring blood gases, electrolytes, metabolites, and co-oximetry. Menu and systems integration provides convenience for healthcare professionals

who wish to investigate multiple parameters that are relevant to patient oxygenation and metabolic status. In decentralized testing environments, this is especially important as additional clinical laboratory facilities may not be available on-demand37.

One of the most critical aspects in evaluating any diagnostic assays is to assess the analytical performance. Accuracy, precision, sensitivity, and specificity are all critical metrics on which tests should be measured. PoC tests often show greater analytical imprecision compared to automated laboratory analyzers37. Comparisons between laboratory analyzers and PoC instruments require rigorous investigation to ensure that results are consistent across healthcare organizations.

PoC tests generally require smaller sample volumes, which is beneficial for reducing patient discomfort when serial testing is needed38.

However, lower analytical volumes may be more challenging to analyze, contributing to reduced assay sensitivity.

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IMPROVING THE DIAGNOSIS AND MONITORING OF CRITICALLY ILL PATIENTS AND THE ROLE OF BLOOD GAS TESTING

In any laboratory

Single test card offers a comprehensive test menu on the epoc Blood Analysis System

or clinical setting, implementing rigorous QC/QA programs is necessary to ensure accurate, reproducible performance

One of the significant advantages of PoC testing is the ability to conduct blood gas analysis in decentralized settings, close to the patient. Decentralized testing enables more efficient clinical decision making, leading to improved outcomes in time-sensitive settings. For PoC testing to be practical, the time-to-result (TTR) for each test should be minimal39. The extent to which multiple analytes can be tested simultaneously is also an important metric as this affects the overall throughput of each PoC analyzer instrument.

User-Friendly, Convenience: Considerations for Selecting Blood Gas Analyzers Blood gas analysis is one of the most frequently ordered tests for many healthcare organizations [34]. Analyzers may be distributed throughout a hospital and in remote locations such as ambulances. Consequently, they should be suitable for different cadres of healthcare professionals to operate, including physicians, nurses, and paramedics, in addition to laboratory professionals40. Systems that are intuitive, user-friendly and low maintenance ensure reproducible, accurate test results.

Many blood gas analyzers designed for use at the point-of-care are small benchtop or handheld instruments. Bench-top analyzers containing individual analyte-specific biosensors have demonstrated high levels of assay performance, validated over decades of clinical use. These systems often have a broad test menu and offer the lowest operating costs.

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Systems that employ self-contained cartridges with biosensors and reagents facilitate simplicity and require minimal maintenance. These are available as benchtop and handheld instruments and are suitable for non-laboratory personnel to use17. Operating costs may be higher, although hands-free automatic sampling reduces pre-analytical sampling errors or between-user variability.

Quality Control (QC) and Quality Assurance (QA) The results of blood gas tests are used to inform clinical decisions in critical conditions.

Inaccurate test results may lead to adverse patient outcomes in these settings. The performance of blood gas analyzers requires continuous quality control (QC). In any laboratory or clinical setting, implementing rigorous QC/ QA programs is necessary to ensure accurate, reproducible performance.

Most QC processes require a comprehensive set of functional checks. Multi-level QC reagents are needed for calibration for all analytes, across their relevant measurement ranges. Sample quality and integrity checks may also be performed throughout a test protocol. Sample quality checks are assisted by sample ports that provide automated quality checks for blood clot management and air bubble detection.

Many modern blood gas analyzers provide onboard QC protocols that can be programmed for automatic operation or on-demand, providing flexibility and additional quality assurance (QA). In

IMPROVING THE DIAGNOSIS AND MONITORING OF CRITICALLY ILL PATIENTS AND THE ROLE OF BLOOD GAS TESTING

the event of a QC failure, extra security features can prevent potentially erroneous results from being reported.

Networking and Cybersecurity in Decentralized Testing Environments For efficient clinical workflows, networking between decentralized medical equipment is critical. Many healthcare organizations implement IT infrastructures that allow remote devices to be connected and communicate with each other. As blood gas analyzers may be distributed throughout hospital settings in the emergency department (ED), intensive care unit (ICU) and laboratories, safe and reliable communication protocols are essential. However, medical devices are often highlighted as a weak point in the IT security of healthcare organizations. Defects in medical device software is the underlying cause of many product recalls41. Security breaches have the potential to affect the effectiveness and safety of medical devices42. They also represent a broader threat to patient and data privacy. Recently, a cybersecurity firm reported that 90% of hospitals had experienced a cybersecurity attack within the previous two years and that networked medical devices had facilitated 17% of the documented attacks43. Robust security measures are required to guard confidential patient data and protect institutional IT infrastructure from cybersecurity

threats. However, traditional IT security solutions are not designed to protect heterogeneous systems with a variety of hardware, software, and operating systems. In these instances, on-device defensive capabilities are critical in preventing unauthorized access to medical device systems and data.

Modern laboratory and point-of-care analyzers offer options for protecting users from cybersecurity threats. Two-step authentication processes can be employed to identify users and their permissions, preventing unauthorized systems access. This feature is also useful for avoiding inappropriate access by staff members without adequate training or restricting the viewing of sensitive data. Embedded anti-malware and firewalls block unknown or unauthorized programs from operating within protected IT systems. Data encryption is a further protective measure that enables the secure transfer of sensitive patient data.

Conclusion and Future Outlook Blood gas analysis in laboratory settings and at point-of-care is essential for the efficient delivery of care to critically ill patients. However, for the successful implementation of PoC testing, multidisciplinary teams of health professionals must be aware of the importance of each step in the analysis process and the need to implement appropriate quality management tools, training, and security protocols.

Recently, a cybersecurity firm reported that 90% of hospitals had experienced a cybersecurity attack within the previous two years and that networked medical devices had facilitated 17% of the documented attacks

Automatic, multi-level QC on the RAPIDPoint 500e Blood Gas System

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Clinical Guidelines and Recommendations for Blood Gas Analysis Sophie Laurenson, BSc. BSc. (Hons.), PhD. (Cantab), EMBA, MRSNZ The American Association for Respiratory Care (AARC) published Clinical Care Guidelines for Blood Gas Analysis and Hemoximetry in 2013, recommending analysis to evaluate the oxygenation and acid-base status of patients presenting in acute settings.

Introduction

Clinical guidelines are statements issued by healthcare organizations, government entities, or non-governmental organizations that include recommendations proposed to optimize patient care

Clinical guidelines are statements issued by healthcare organizations, government entities, or non-governmental organizations that include recommendations proposed to optimize patient care. Guidelines are developed by disease area or discipline specialists, informed by systematic reviews of clinical and scientific evidence44. An assessment of the potential benefits and harms of alternative interventions forms part of clinical guideline formulations. The application of blood gas analysis to the diagnosis, monitoring, and prognosis of various disease areas has been addressed by numerous clinical guidelines for cardiorespiratory and metabolic disease management. In this article, the specific clinical guidelines addressing the use of blood gas analysis in critically ill patients is summarized.

Reference Measurements and Interpretation Interpretation of blood gas results plays an essential role in the diagnosis and treatment of patients with a range of critical conditions.

However, the causes of underlying deviations in blood gas values may be multifactorial and complex to interpret. Although both venous and arterial blood specimens can be used for blood gas analysis, their results should not be used interchangeably. Venous blood has a lower pH level, reduced oxygen, and increased PaCO2 levels compared to arterial blood45. The respiratory system and the metabolic system (primarily the renal system), are responsible for maintaining pH homeostasis at pH = 7.35 to 7.45. Altering the respiratory rate can rapidly compensate for variations in blood pH levels to restore homeostasis. The metabolic system regulates hydrogen ions (H+) and bicarbonate (HCO3-) levels through excretion, a process

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Proper sample handling is critical in blood gas testing

that may take hours or days to restore balance.

The reference levels for carbon dioxide (PaCO2) are 35 to 45 mmHg, and oxygen (PaO2) are 83 to 108 mmHg in adults46. However, reference intervals may vary between institutions based on population differences. Both PaCO2 and PaO2 are lower in infants, and both are affected by altitude (measured as meters above sea level). Abnormalities in PaCO2 indicate a primary respiratory condition, whereas variation in bicarbonate levels indicate a metabolic disease. However, interpreting pH, PaCO2, PaO2, and HCO3- levels in conditions resulting from a combination of respiratory and metabolic issues is often challenging. This challenge is amplified when considering any compensation mechanisms that may be working to restore homeostasis in critically ill patients45.

American Association for Respiratory Care (AARC) Guidelines: 2013 The American Association for Respiratory Care (AARC) published Clinical Care Guidelines for Blood Gas Analysis and Hemoximetry in 201347. These guidelines make the following recommendations based on the Grading of Recommendations Assessment, Development, and Evaluation criteria:

IMPROVING THE DIAGNOSIS AND MONITORING OF CRITICALLY ILL PATIENTS AND THE ROLE OF BLOOD GAS TESTING

“BGA (blood gas analysis) and hemoximetry are recommended for evaluating a patient’s ventilatory, acid-base, and/or oxygenation status. BGA and hemoximetry are suggested for evaluating a patient’s response to therapeutic interventions.

BGA and hemoximetry are recommended for monitoring severity and progression of documented cardiopulmonary disease processes.

Hemoximetry is recommended to determine the impact of dyshemoglobins on oxygenation.

Capillary BGA is not recommended to determine oxygenation status. Central venous BGA and hemoximetry are suggested to determine oxygen consumption in the setting of early goal-directed therapies.”

Blood gas analysis is recommended to evaluate the oxygenation and acid-base status of patients presenting in acute settings.

Following an initial assessment, ongoing serial measurements may be used to monitor patient progress in critical care settings and to gauge the effectiveness of interventions such as supplemental oxygen treatment.

The AARC 2013 guidelines also detail best practices for sampling, handling, and analyzing blood gas test results. Blood gas analysis is prone to errors emanating from the preanalytical steps to control of the analytical instrument and testing process. Sources of error may include sampling errors, abnormal or miscalculated FiO2, barometric pressures, and temperature variation48.

Whole blood is the sample of choice for gas analysis, although arterial and venous blood differ with respect to PO2 measurements.

Healthcare professionals that collect arterial or venous samples should be aware of specific sample collection and handling requirements. Sample preparation and dilution with saline or heparin anticoagulant have been observed as sources of potential error.

The transport and analysis of samples should be prompt. The contamination of anaerobic samples by air can cause discrepancies in PCO2 measurements and has been observed in samples transported using pneumatic tube systems. Drawing blood samples of adequate volume, using appropriate syringes without introducing air bubbles are all recommendations for minimizing errors.

To ensure accurate results, the storage temperatures for blood gas samples before analysis is critical. Variation in temperature can result in inconsistencies in both PaO2 and O2 saturation levels. It is also worth noting

that certain pathologic conditions such as hyperleukocytosis and dyshemoglobinemias can also contribute to discrepancies in PaO2 and O2 saturation.

Acute Respiratory Distress Syndrome (ARDS) Acute respiratory distress syndrome (ARDS) is an inflammatory lung condition resulting from alveolar injury consequent to inflammation from either pulmonary or systemic origins. ARDS is characterized by hypoxemia occurring without heart failure (HF). Bilateral pulmonary infiltrates are observed by chest imaging.

The diagnosis of ARDS is reliant on blood gas analysis results. The Berlin definition9 includes the presence of hypoxemia defined by the ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (F i O 2 ) (PaO 2 /F i O 2 ). This measure of oxygenation is applied to classify ARDS as mild (PaO2/FiO2 of 200–≤300 mmHg), moderate (PaO2/ FiO2 100–≤200 mmHg), or severe (PaO2/FiO2 ≤100 mmHg). Although the PaO2/FiO2 is easy to calculate, it can vary with differing positive end-expiratory pressure (PEEP)49 and tidal volumes50. An alternative to measuring PaO2/ FiO2 is the oxygenation index (OI). OI is defined as the product of mean airway pressure and FiO2, divided by PaO2. The mean airway pressure accounts for variations in PEEP, making this a more reliable indicator of respiratory function51.

Conclusion Blood gas analysis is essential for the diagnosis and treatment of patients with a range of critical conditions. However, the underlying pathologies that contribute to abnormal blood gas values may be multifactorial and complex to interpret.

Reference intervals for pH, PaCO2, PaO2, and HCO3- are all published, although institutions may use different values and interpretation guidelines based on local requirements. The American Association for Respiratory Care (AARC) published Clinical Care Guidelines for Blood Gas Analysis and Hemoximetry in 2013, recommending the use of blood gas analysis in specific clinical settings. They also include best practices for sampling, handling, and analyzing blood gas results. Further, recommendations for using blood gas analysis for the diagnosis and management of specific cardiopulmonary diseases have been published by many organizations. Blood gas results have a vital function in the diagnosis of ARDS.

Blood gas analysis is recommended to evaluate the oxygenation and acid-base status of patients presenting in acute settings.

Following an initial assessment, ongoing serial measurements may be used to monitor patient progress in critical care settings and to gauge the effectiveness of interventions such as supplemental oxygen treatment

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Notes:

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