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CONTENTS / SUMÁRIO Rev Col Bras Cir 2018; 45(4) ORIGINAL ARTICLES Elaboration of a tracheostomy conduct protocol in the Amazonas cancer reference hospital Elaboração de protocolo de condutas em traqueostomias no hospital referência de tratamento do câncer do Amazonas Maria Carolina Coutinho Xavier Soares; Fernando Luiz Westphal; Luiz Carlos Lima; Jefferson Moreira Medeiros ......................................... e1744 Healing modulation in glaucoma surgery after application of subconjunctival triamcinolone acetate alone or combined with mitomycin C: an experimetal study Modulação da cicatrização na cirurgia do glaucoma após aplicação de acetato de triancinolona subconjuntival isolado ou em associação à mitomicina C: estudo experimental Hayana Marques do Aragão Rangel; Hévila Tamar Rolim; Paula Vidigal; Ivana Duval de Araújo; Sebastião Cronemberger ........................... e1861 Retrospective study of patients with cutaneous melanoma treated at the Federal University of São Paulo Estudo retrospectivo dos pacientes portadores de melanoma cutâneo atendidos na Universidade Federal de São Paulo Tácito Ferreira; Ivan Dunshee de Abranches Oliveira Santos; Andrea Fernandes Oliveira; Lydia Masako Ferreira .......................................... e1715 Experimental study of femoral vein reconstruction with sugarcane biopolymer tubular graft Estudo experimental de reconstrução da veia femoral com enxerto tubular do bipolímero de cana-de-açúcar Daniella Maria Souza Silva; Esdras Marques Lins; Sílvio Romero Barros Marques; Amanda Vasconcelos Albuquerque; José Lamartine Andrade Aguiar ....................................................................................................................................................................................................... e1837 Surgical treatment of extravasation injuries: experience of the Hospital das Clínicas of the Faculty of Medicine, University of São Paulo Opções de tratamento cirúrgico em lesões cutâneas por extravasamento acidental de drogas: experiência do Hospital das Clínicas da Faculdade de Medicina da USP Dimas André Milcheski; Wellington Menezes Motta; Rodolfo Costa Lobato; Araldo Ayres Monteiro Júnior; Rolf Gemperli ......................... e1912

REVIEW ARTICLES Anesthetic therapy for acute pain relief after laparoscopic cholecystectomy: systematic review Terapêutica anestésica para o alívio da dor aguda pós-colecistectomia videolaparoscópica: revisão sistemática Renato Ribeiro de Jesus; Adebaldo Maia Leite; Simone Soares Leite; Márcio Carneiro Vieira; Nivaldo Ribeiro Villela ..................................... e1885

Rev Col Bras Cir

Rio de Janeiro

Vol 45

Nº 4

jul/aug

2018


Órgão Oficial do Colégio Brasileiro de Cirurgiões EDITOR Guilherme Pinto Bravo Neto TCBC-RJ Associate Professor, Department of Surgery, Faculdade de Medicina, Universidade Federal do Rio de Janeiro-UFRJ-Rio de Janeiro-RJ-Brasil.

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NATIONAL CONSULTANTS ALCINO LÁZARO DA SILVA, ECBC-MG - Universidade Federal de Minas Gerais - MG ALUIZIO SOARES DE SOUZA RODRIGUES, ECBC-RJ - Universidade Federal do Rio de Janeiro - UFRJ - RJ ANTONIO PELOSI DE MOURA LEITE, ECBC-SP - Instituto de Moléstias Cardiovasculares de São José do Rio Preto - SP DARIO BIROLINI, ECBC-SP - Faculdade de Medicina da Universidade de São Paulo - SP EUGÊNIO AMÉRICO BUENO FERREIRA, ECBC-SP - Faculdade de Medicina de Jundiaí - SP FERNANDO LUIZ BARROSO, ECBC-RJ - Hospital Municipal de Ipanema - RJ. FERNANDO MANOEL PAES LEME, ECBC-RJ - Faculdade de Medicina de Campos - RJ GASPAR DE JESUS LOPES FILHO, TCBC-SP - Universidade Federal de São Paulo - SP GUILHERME EURICO BASTOS DA CUNHA, ECBC-RJ - Universidade Federal Fluminense - RJ HELÁDIO FEITOSA DE CASTRO FILHO, TCBC-CE Universidade Federal do Ceará - CE ISAC JORGE FILHO, TCBC-SP - Universidade de Ribeirão Preto - SP. JOSÉ REINAN RAMOS, TCBC-RJ - Hospital Vitória-RJ LUIZ GUILHERME BARROSO ROMANO, ECBC-RJ MARCOS F. MORAES, ECBC-RJ - Universidade Gama Filho-RJ

ORLANDO MARQUES VIEIRA, ECBC-RJ - Universidade Federal do Rio de Janeiro-RJ ROBERTO SAAD JR., TCBC-SP - Faculdade de Ciências Médicas da Santa Casa de São Paulo-SP SAMIR RASSLAN, ECBC-SP - Faculdade de Medicina da Universidade de São Paulo-SP SAUL GOLDENBERG, ECBC-SP - Universidade Federal de São Paulo- Escola Paulista de Medicina - SP

INTERNATIONAL CONSULTANTS ARNULF THIEDE - Department of Surgery, University of Würzburg Hospital, Oberdürrbacher Str. 6, D-97080 Würzburg, Germany CLAUDE DESCHAMPS - M.D - The Mayo Clinic, MN,USA EDUARDO PARRA-DAVILA - Florida Hospital Celebration Health - 400 Celebration Pl, Kissimmee, FL 34747, USA. EMILIO DE VICENTE LÓPEZ – Sanchinarro Hospital, Madrid, Spain KARL H. FUCHS - Markus-Krankenhaus Frankfurter Diakonie-Kliniken, Wilhelm- Epstein-Straße 4, 60435 Frankfurt am Main MURRAY BRENNAN - HeCBC Department of Surgery, Memorial SloanKettering Cancer Center, New York NY, USA ULRICH ANDREAS DIETZ - Department of Surgery I, University of Würzburg, Medical School, Würzburg, Germany W. WEDER - Klinikdirektor-UniversitätsSpital Zürich, Switzerland

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Original Article

DOI: 10.1590/0100-6991e-20181744

Elaboration of a tracheostomy conduct protocol in the Amazonas cancer reference hospital Elaboração de protocolo de condutas em traqueostomias no hospital referência de tratamento do câncer do Amazonas Maria Carolina Coutinho Xavier Soares, ACBC-AM1,2; Fernando Luiz Westphal, TCBC-AM2; Luiz Carlos Moreira Medeiros2

de

Lima2; Jefferson

A B S T R A C T Objective: to create a multidisciplinary conducts manual for tracheostomies in adult and pediatric patients in the Amazonas State Oncology Control Center Foundation. Methods: we developed a protocol using the modified Delphi method, which consisted in the application of two series of questionnaires to 20 professionals of the unit. Results: thirteen professionals completed the two steps. In the first stage, there was consensus in 53 out of 92 questions (57.6%). The questions that obtained consensus formed the text of the second stage, divided into eight chapters and evaluated by marking the answers offered on a Linkert scale. All the chapters presented in the second stage obtained consensus, meaning that the sum of the answers "agree" and "fully agree" were above 70%. Conclusion: using the data obtained in the consensus, we elaborated a tracheostomy conduct protocol and a care guidelines manual for the patients and their caregivers. Keywords: Clinical Protocols. Tracheostomy. Medical Oncology. Hospitals. University.

INTRODUCTION

T

airways and preventing orotracheal intubation

racheostomy (TCT) is the surgical procedure that consists of opening the anterior wall of

the trachea, communicating it with the external environment through the insertion of a cannula, making the airway patent1. It is a common procedure in oncology, especially in head and neck oncology2. Studies of head and neck surgeons in various departments reported that 26 to 39% of the specialists performed the procedure frequently in cases of flaps and large resections, in a preventive way1-3. This procedure in the management of airways in cancer patients has also been indicated for patients with tumor masses and submitted to previous radiotherapy, causing obstruction of the

(OTI)4,5. Studies have shown that the mean number of routine tracheostomies in squamous cell carcinoma resections is between 23 and 30%, and in selected cases, up to 74%3,6. This procedure generates innumerable changes in the patient's daily life: in respiratory dynamics, in the behavior and interpersonal relationship, and in personal care. For these changes to occur with better results, a lot of care is needed. For all these care, the importance of a multidisciplinary team for the management of tracheostomies (physicians, dentists, speech therapists, physiotherapists, nurses, nutritionists) was observed both in the hospital settings and in the outpatient follow-up.

1 - Amazonas Oncology Control Center Foundation (FCECON), Head and Neck Surgery Service, Manaus, AM, Brazil. 2 - Federal University of Amazonas (UFAM), Master's Degree in Surgery – PPGRACI, Manaus, AM, Brazil.

Rev Col Bras Cir 45(4):e1744


Soares Elaboration of a tracheostomy conduct protocol in the Amazonas cancer reference hospital

2

At the Amazonas State Oncology Control

Exclusion criteria were non-completion of the two

Center Foundation (FCECON), there are professionals

stages of the questionnaire for any reason, and loss

from

of the working relationship with FCECON during the

numerous

specialties

attending

patients

with TCT, but there were no routine to adapt the

study.

conducts guidelines in tracheostomies to the reality

The Delphi method does not use statistical

of our patients. There is no uniform treatment

computation to define the ideal number of experts

model for the tracheostomy patients during their

for the consensus to be adequate. It suggests

hospitalization, standardization of materials and

the choice of the participants according to their

procedures, nor a guideline model for home-

knowledge and experience in the subject treated,

based procedures. The elaboration of a routines

always preferring to choose the best qualified

manual, taking into account the experience of those

of the service8,9. Some authors suggest some

involved in TCT care at the FCECON, would bring

basic characteristics to guide the selection of the

clinical subsidy for reproducibility of actions. The

components of the study: specialists who will use

presentation of information synthesized from the

the results obtained in the protocol in their daily

literature, elaborated in topics to elucidate the day-

practice; specialists who lead teams related to the

to-day questions, is efficient in improving teamwork,

subject studied; specialists considered as reference

reflecting better results in reduction of complications

on the subject8. For the present study, we invited

and improvement in patients' quality of life7.

20 experts.

The objective of this study was to create a

The team of researchers prepared the

multidisciplinary protocol for tracheostomy conducts

initial questionnaire. The questions from the first

in adult and pediatric FCECON patients in need

questionnaire are a literature review product, using

of the procedure and to use the protocol data to

the MEDLINE and LILACS databases. We used the

elaborate a basic home care manual and emergency

terms

management guidelines for caregivers and patients.

We also searched textbooks and TCT protocols

"tracheostomy"

and

"traqueostomia".

from other services. We selected 37 texts for the

METHODS

elaboration of the protocol sentences.

The project was approved by the Ethics in Research Committee of the FCECON, CAAE number 61650316.1.0000.0004. For the elaboration of the FCECON tracheostomy conducts protocol, we used the modified Delphi method, which consists of the application of a series of questionnaires to specialists. Inclusion criteria were being a graduate-level FCECON professional working with tracheostomized patients in their daily practice, and at least five years of experience in the field.

We defined the primary variables as conduct blocks:

indications,

specialized

routine

procedures, care,

complications,

cannula

exchange,

decannulation, patient and family orientations. We defined the questions elaborated in each of these main blocks as secondary variables. The specialist had the opportunity to add answers he/she thought were important to the protocol. At the end of each question, there was room for opinions, additions, and corrections.

Rev Col Bras Cir 45(4):e1744


Soares Elaboration of a tracheostomy conduct protocol in the Amazonas cancer reference hospital

We

invited

the

selected

experts

to

RESULTS

participate in the study, and those who accepted, signed an informed consent form. We delivered the first questionnaire to the specialists. The research team did not follow the responses completion. After filling, the researcher collected the questionnaire, which was placed in unidentified envelopes. The preparation of a second questionnaire resulted from the analysis of the answers presented in the first questionnaire. We placed all the answers that obtained above 65% consensus in the second questionnaire. We repeated in the second stage relevant questions that did not display consensus on the first questionnaire. The second questionnaire converted the answers that obtained consensus into text. The text was divided into eight chapters for better analysis. After reading each chapter, the specialist reported his/her impression by ticking an item from the Linkert scale quoted below: 1. strongly disagree; 2. I disagree; 3. neutral; 4. agree; 5. strongly agree. We delivered the second questionnaire to the specialists following the same protocol of the first

3

The 20 invited health professionals who accepted to participate in the FCECON study were of several specialties: intensive care physician, oncology emergency physician, physiotherapist, intensive care nurse, cancer surgeon, head and neck surgeon, thoracic surgeon, operating room nurse, stomatotherapist nurse, endoscopy nurse. Thirteen (65%) professionals participated in the two series of questionnaires and we analyzed only their responses in the protocol. Table 1 shows the profile of participants who completed all project steps. Table 1. Profile of the professionals who fully participated in the questionnaires of the tracheostomy protocol.

Professional specialty Pediatric surgeon Head and neck surgeon Oncological surgeon Stomatology nurse Operating room nurse Endoscopy nurse

Number of professionals 1 5 3 1 2 1

stage. After analysis of the responses from the

The time of return of the questionnaires

second questionnaire, the chapters that obtained

completed in the first stage ranged from two to 90

the answers agree and strongly agree above 70%

days. We presented 92 questions in the first stage,

consensus integrated the final protocol text. We

ten discursive and 82 multiple-choice. We allowed

also prepared a manual for the patient with the data

the expert to assign as many options as he/she

from the protocol.

deemed correct in the multiple-choice questions. In

We calculated descriptive statistics for each

all of these, there was as option for the specialist to

question item. We display the answers considered

mark if the question theme was not part of his/her

valid in percentage . The calculation of p-values

daily practice. When this alternative was marked,

does not apply to this type of project9. We used

the question was discarded when performing the

the Excel software to record data. We delivered the

quantification of valid answers. There was room to

consensus and the patients' manual to the hospital's

add comments on relevant issues. After analyzing

clinical director.

the completed questionnaires, 53 questions had

8

Rev Col Bras Cir 45(4):e1744


Soares Elaboration of a tracheostomy conduct protocol in the Amazonas cancer reference hospital

4

a 65% consensus (Table 2). Twelve comments

53.8%, "strongly agree" (Table 3). When analyzing

of subjects that were not in the initial text were

the six re-submitted questions, only one reached

added.

70% acceptance for consensus.

Table 2. Results of the first stage of the Delphi method.

Profile of the questions Questions presented Questions selected by consensus

Number of questions 92 53

To integrate the protocol, we selected the texts that presented consensus above 70% by the experts, by means of the sum of the answers "agree" and "strongly agree". During the final writing of the protocol, we chose to describe in the final text the questions that did not obtain consensus among the

Using the consensus data from the first

experts using the data that already are consensus

stage, we elaborated the text of the second stage

in the literature, since they are of great importance

to be presented to professionals. Six questions from

and could not be discarded from the final protocol.

the first stage were fully re-submitted, since they

With the data resulting from the consensus,

were considered relevant for the protocol, though

we elaborated a tracheostomy protocol for the

without consensus (below 65%). We divided the

hospital staff and a manual for the patient and his/

text of the second stage into eight chapters to be

her caregivers with general guidelines (Table 4).

evaluated more clearly: general concepts, indications, procedure,

technique,

complications,

care,

DISCUSSION

decannulation and caregivers. The time of delivery of the answered questionnaire in the second stage ranged from one to 21 days. In the general chapter, 30.8% of the respondents marked "agree", and 69.2%, "strongly agree". In the indications chapter, 38.5% of the respondents marked "agree", and 53.8%, "strongly" agree; 7.7% marked "neutral". In the procedure part, 38.5% of the experts answered "agree", and 61.5%, "strongly agree". In the technique block, 53.8% of the experts marked "agree", and 23.1%, "strongly agree"; 15.4% answered "neutral", and 7.7%, "disagree". In the complications chapter, 61.5% of the respondents marked "agree", and 38.5%, "strongly agree". In the care part, 46.2% of the respondents answered "agreed", and 53.8%, "strongly agree". In the decannulation chapter, 38.5% of the respondents marked "agree", and 53.8%, "strongly agree"; 7.7% answered "neutral". In the caregivers part, 46.2% of the respondents marked "agree", and

In 2013, Mitchell developed a TCT consensus using the Delphi method, with 110 initial questions. At the end of the second stage, 77 sentences were approved and 36 discarded. For the elaboration of this study's consensus, nine specialists participated, whose specialties were adult and pediatric surgeons, nurses, physiotherapists and emergency physicians10. Another published consensus on TCT brought together professional experts (19 professionals) who carried out a joint review of the literature of 40 articles, and from these data, they elaborated the consensus. These professionals also sought to adapt the literature to their local reality. It was also performed only by doctors and nurses11. In the present study, there was no consensus among the professionals regarding the ideal time of orotracheal intubation to indicate tracheostomy. Recent studies advocate the early

Rev Col Bras Cir 45(4):e1744


Soares Elaboration of a tracheostomy conduct protocol in the Amazonas cancer reference hospital

5

Table 3. Results of the second stage of the Delphi method.

Chapter of the text/Positive responses from professionals General Indications Procedure Technique Complications Care Decannulation Caregivers

Strongly agree

Agree

69.2% 53.8% 61.5% 23.1% 38.5% 53.8% 53.8% 53.8%

30.8% 38.5% 38.5% 53.8% 61.5% 46.2% 38.5% 46.2%

Neutral

Disagree

7.7% 15.4%

7.7%

7.7%

Table 4. Summary of the protocol obtained by using the answers from the experts.

Main tracheotomy indications in the FCECON

Procedure

• Obstruction of high airways due to cancers or swelling caused by radiotherapy. • Laryngo-tracheal stenosis. • Prophylaxis of airway obstruction in the postoperative period of extensive head and neck surgery. • Prolonged orotracheal intubation, need of mechanical ventilation. Adults: between seven and 15 days of orotracheal intubation, without possibility of ventilation weaning during this period. Children: one can wait for up to four weeks, scheduling an early procedure if there is no foreseen resolution of the cause. • Difficult airways. • Explain to the patient and family in advance about the procedure, submit the consent form for signature. A copy is in the possession of the family and the other copy of the form must be in the medical record. • Define the location of the procedure: the tracheotomy is a routine procedure performed in the operating room. In special situations, it can be performed in ICU, or at the bedside in the event of emergencies without transport possibility. Tracheostomy in the operating room without setting the patient on the operating table, doing the procedure on the bed of the patient, is possible in special cases (patients with morbid obesity, in cases in which the mobilization offers risks, such as fractures). • Team for the procedure: surgeon, auxiliary, scrub nurse, anesthesiologist, nurse. • Tracheostomy under general anesthesia: patient in IOT and children. Tracheostomy under local anesthesia: patient with airway obstruction, without possibility of IOT. • Materials needed for a tracheotomy: equipment for monitoring of vital signs (blood pressure, ECG, SpO2, capnograph), lights, goggles, surgical scrubs, surgical gowns, sterile fields, sterile gloves, antiseptics, Kelly clamp, curved scissors, Farabeuf retractors, electric scalpel, anatomic tweezers, toothed tweezers, scalpel handle n# 3 and 15 blade, 3.0 needle nylon suture, suction catheter, vacuum, tracheostomy cannula: when performing a tracheotomy in adults, evaluate the availability of the chosen cannula (plastic with cuff, plastic cuff-free, metallic). Always provide one cannula of the estimated number for the patient, one bigger and one smaller. • Cannula sizes, considerations: the diameter of the tracheostomy cannula must occupy approximately 2/3 to 3/4 of tracheal lumen, the final size to be set when viewing the trachea. One must evaluate the cannula length in obese patients

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Continuation Table 4.

Technique

• The preferred position of the patient: supine, in cervical hyperextension, cushion between the shoulder blades and round pad under the head. Always assess if there is any contraindication for this position. • In case of impossibility of cervical hyperextension, the neck can be set in neutral position. The team must be prepared for a higher technical difficulty in this position. • Antisepsis should be made from the anterior edge of the jaw to the upper third of the thorax. Laterally, until the lateral edges of the sternocleidomastoid muscles. • The incision of the skin in adults can be transverse or longitudinal. The choice of incision should be the surgeon’s, according to each patient. In children, the preferred incision is the transverse. • After the retraction of sterno-hyoid and thyroid muscles, one identifies the thyroid isthmus. Cranial retraction of the isthmus is indicated when possible, but isthmotomy may be carried out if necessary. • Avoid lateral dissection to the trachea (avoid injury of recurrent laryngeal nerve, internal jugular vein, vagus nerve, carotid artery). • Avoid inferior dissection (avoid injury of brachycephalic artery and innominate vein). • The opening of the trachea should ideally be made between the second and fourth tracheal rings. • Prudent identification of tracheal rings to avoid injury to cricoid cartilage and to first tracheal ring. • The surgeon defines the technique used in the tracheotomy according to the needs of the patient: transverse opening between the tracheal rings, resection of the anterior portion of the tracheal ring, resection of the upper and lateral flap, maintaining a fixed lower border (Bjork flap). In children, the transverse opening between the tracheal rings is indicated. • In cases of difficult tracheostomy, the suggestion of a technical approach is the placement of repair sutures in the trachea, externalizing to the skin, aiming to identify the path in cases of decannulation. • When in children, the use repair sutures in the trachea is routine, even in tracheostomies without technical difficulties, since the repositioning in accidental decannulation are always more difficult in this age group. • When positioning the tracheostomy cannula, care must be taken not to injure the posterior wall of the trachea. • Evaluation of the correct positioning of the cannula after its passage is made by capnography or pulmonary auscultation. • The fixation of the cannula after placement in the trachea is through ribbons around the neck. • Initial dressing should be done using gauze around the cannula.

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Continuation Table 4.

Complications

• Materials considered indispensable for the treatment of complications of tracheostomies should be available in places where there are patients with tracheostomy, as well as hospital admission, emergency and ICU sectors: tracheostomy tubes of all sizes (in the adult ward: 5-0, 5-5, 6-0, 6 -5, 7-0, 7-5, 8-0, 8-5; in the pediatric ward: 3-0, 3-5, 4-0, 4-5, 5-0, 5-5), aspiration hose, (in an adult ward: 8, 10, 12, 14; in the pediatric ward: 4, 6, 8), aspirator, small surgery kit, monitoring, Oxygen source, AMBU bag. • Accidental decannulation: call for help of a professional with experience; if there is no contraindication, place a cushion between the shoulder blades and try to reposition the cannula; if it is not possible to use a cushion, try to reposition in a neutral position; if there are repair sutures, exert a light traction on it and reposition the cannula; in case of repositioning failure, check if there is a professional with experience in the unit and call for help again; monitoring and oxygen supply; make sure all the emergency materials mentioned above are close. • Post-tracheostomy bleeding: initial evaluation by the currently available physician if the surgeon is not immediately reachable; early evaluation of the surgeon; assess whether bleeding originates around the cannula or in its interior; provide monitoring and oxygenation to the patient; aspirate cannula in case of bleeding originating inside the cannula; evaluate the patient's medical chart if the patient is using anticoagulant drugs. • Respiratory insufficiency by secretion plug in the cannula: suspect if the patient with tracheostomy has respiratory difficulties; if the patient has a plastic cannula, aspirate it; if there is no improvement or there is resistance in the passage of the tube when trying to aspirate the cannula, nebulize the patient with saline 0.9% and try again the aspiration; if the patient has a metal cannula, remove the inner cannula immediately and clean the cannula; if there is no improvement in the breathing pattern after aspiration and cleaning, it is necessary to change the cannula. If one does not have training in cannula exchange, call for help; provide monitoring and oxygen source immediately, while calling for help. Make available all urgency list materials. • Pneumothorax and pneumomediastinum after procedure: perform chest X-ray after the procedure, in cases of dyspnea; in children chest radiography is performed routinely in all tracheostomies; if there is pneumothorax, perform closed drainage of the thorax in water seal. • Tracheo-cutaneous fistula: epithelialization of the path from the orifice of the trachea to the skin, which remains patent after removal of the cannula; clinically diagnosed by the patient's complaint of persistence of airflow and secretion through the tracheostomy orifice after removal of the cannula; evaluation with the surgeon to correct the fistula. • Tracheoesophageal fistula: one may suspect when food exits through the tracheostomy cannula, or when there are recurrent pneumonias; bronchoscopy and upper endoscopy are indicated when there is a suspected diagnosis. • Post-tracheostomy dysphagia: if the patient has a cannula with a cuff, assess whether the cuff is not hyperinflated; check for associated laryngo-tracheal aspiration; assessment of speech therapy.

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Continuation Table 4.

Routine care and management of the patient with tracheostomy

• Care of the metal cannula: remove the inner cannula; cleaning of the inner cannula can be carried out in running water using a brush, provided that the running water is transparent and without residue; neutral soap may be used in this cleaning, and all residue must be removed; after cleaning the cannula, dry it before repositioning; Daily cleaning frequency: Set cleaning frequency according to the patient's expectoration degree. • Tracheostomy humidification: the presence or absence of crusts and the thickness of the secretion during aspiration of the cannula may help to measure the degree of humidification of the airways; according to thickness and amount of secretion, the patient's nebulization frequency must be defined. • Aspiration of the cannula. Protective equipment for the professional who will perform the procedure: sterile gloves, mask and goggles, lab coat or disposable apron; inform the procedure to the patient; every patient with tracheostomy should have an aspiration mechanism close to their bed (portable or wall vacuum); disposable sterile aspirating catheter, size selected according to the diameter of the cannula; saline solution for cleaning of aspiration catheter; when aspirating, insert the catheter only until the end of the cannula. • Tracheostomy dressing: cleaning with saline solution; Use of gauze on the sides of the cannula continuously; foam and hydrocolloid to be evaluated by the nursing team; suggested minimum frequency for dressing around tracheostomy: once daily; observe daily if there is hyperemia in the skin around the tracheostomy and if there is drainage of secretions, and their appearance. • Tracheostomy cannula replacement: sterile glove, mask, goggles, lab coat or disposable apron for the professional who will perform the exchange; material for aspiration available; one cannula of the same size and other one size smaller; material for dressing; inform the patient about the procedure; remove dressings and clothing that may block the field of vision; cushion in the shoulder blades if there is no contraindication for cervical hyperextension; use of lidocaine gel in the portion of the cannula to be introduced; fitting with a ribbon on the neck; if there is no success in passing a cannula of the same number, try a second time with a smaller cannula and if successful, forward patient for evaluation of the surgeon; check for correct positioning of the cannula after exchange: patient maintaining normal breathing pattern, air outlet through the inner bore of the cannula; if the second attempt with the smaller cannula is unsuccessful, provide an O2 source for patient monitoring; a second person present should call for help in the event of a failure to exchange; frequency of metal cannula replacement: every 30 days; plastic cannula replacement frequency: within 14 days. • Evaluation of the possibility of phonation of the patient after the tracheostomy: speech-language assessment. • Decannulation: should be individualized for each patient in FCECON, according to their underlying disease and staging; evaluate if there are schedules of procedures with anesthesia in the next seven to ten days; resolution of the motive that led the patient to tracheostomy; conscious patient; hemodynamic stability; absence of tracheal or glottic stenosis; no signs of laryngotracheal aspiration; all patients should receive speech-language evaluation prior to the decannulation process; In children, bronchoscopy is necessary for decannulation; after decannulation, there is a need for patient follow-up due to the appearance of early and late complications after withdrawal (bleeding, fistulae, stenosis)

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procedure, relating increased mortality with the

Concerning the frequency of aspiration of

greater difficulty in ventilatory weaning when

the tracheal cannula, there was also no consensus

associated with late tracheostomies (up to 14 days

among the specialists. In the literature, the consensus

after intubation) . When performed in up to seven

is that there is no protocol of aspiration periodicity,

days, the length of ICU stay is reduced .

as it will depend on the amount and fluidity of the

12

13

Regarding the prevention of accidental

secretion eliminated by each patient. Patients with

decannulation in tracheostomies considered difficult,

good cough reflex need fewer aspirations during

there was no consensus on how to approach it.

the day. In the series of questionnaires presented

Studies have already suggested repairing the trachea

to our specialists, we obtained a similar response,

using a suture during the first few days until healing

of individualizing the aspiration frequency for each

of the trajectory . Concerning the opening in the

patient. The cleaning frequency of the internal

trachea, there was no uniform conduct among

cannula follows the same theory of evaluating the

the specialists. Protocols show that all possibilities

patient to define the frequency17.

14

of opening the trachea have their indications and complications; in fact, there is no consensus

. In

14,15

The FCECON specialists did not define the minimum time required for the first cannula

children, however, only a longitudinal incision of the

replacement.

trachea with the use of suture repair is suggested .

recommend that the first exchange of the cannula

The conduct in cases of accidental decantation did

be performed, in cases of need, between 48 and

not obtain consensus, although it was re-presented

72 hours at least18,19. The periodic exchanges of

in the second stage. The conduct in the algorithms

metal and plastic cuff cannulae also did not show

of tracheostomy emergencies suggests that, in cases

consensus, and it is recommended that they be

of accidental decantation, one should check if the

changed every 30 days (metallic) and between

patient is breathing, deflate the cuff, and call for

seven and 14 days (plastic)18,19. These data are

help. One can try to reposition the cannula only

fundamental in the infirmary, ICU and outpatient

once . It is of extreme importance that this item

procedures.

16

17

Protocols

Regarding

is reported in a manual of routines, as it is one of

a

already

decannulation

established

protocol,

the main causes of death due to tracheostomy

there was also no consensus. When analyzing the

complications.

comments reported by the specialists, remains

Another issue of great importance that did

the suggestion not to determine a decannulation

not obtain consensus was the approach in cases of

protocol, but to customize decannulation according

cannula obstruction. The literature directs to initially

to the reason of the tracheostomy and associated

verify if the positioning of the cannula is correct,

comorbidities.

to evaluate if the patient is breathing, to stimulate

There was no consensus as to who would

the patient to cough, to aspire to cannula, and to

be the professional of the team that would perform

withdraw the inner cannula and to wash it in cases

the training for the caregivers of patients with

of metal cannula. If none of these maneuvers work,

tracheostomy. The experts' report in the remarks

call for help for cannula replacement or orotracheal

was that each professional did his or her part. The

intubation17.

literature reports similar orientation, describing

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10

the importance of the orientation of all the staff

at FCECON was the option for this adaptation,

as for care of the tracheostomy, and not a single

since they know the patients' routine. There will be

professional

particular cases where it will be necessary for the

.

20,21

Once the protocol id established in

specialist to customize the conduct.

the FCECON, we expect that it will promote a

When reviewing this protocol, annually

standardized multidisciplinary care adapted to the

or every two years, we suggest to try and select a

particularities of the patients. This form of care

larger number of professionals and especially to call

allows that eventual changes in the professional

members of other specialties who did not participate

framework do not modify the treatment model.

in the elaboration of this initial text, so as to

In addition to personalized care, patients and

elaborate a broader manual as to multidisciplinarity,

their caregivers will be advised on care at home.

so important for the patient who is submitted to a

Consulting the specialists in our region who work

tracheostomy.

R E S U M O Objetivo: criar um manual de rotina multidisciplinar de condutas em traqueostomias para pacientes adultos e pediátricos da Fundação Centro de Controle de Oncologia do Estado do Amazonas. Métodos: o protocolo foi desenvolvido por meio do método Delphi modificado, que consistiu na aplicação de duas séries de questionários a 20 profissionais da unidade. Resultados: treze profissionais concluíram as duas etapas. Na primeira etapa, 53 de 92 questões apresentadas obtiveram consenso (57,6%). Estas sentenças que obtiveram consenso formaram o texto da segunda etapa, que foi dividido em oito capítulos que foram avaliados por meio da marcação de respostas oferecidas em uma escala Linkert. Todos os capítulos apresentados na segunda etapa obtiveram consenso, significando que a soma das respostas concordo e concordo plenamente foram todas acima de 70%. Conclusão: utilizando os dados obtidos no consenso, foi elaborado um protocolo de condutas em traqueostomias e um manual de orientações de cuidados para os pacientes e seus cuidadores. Descritores: Protocolos Clínicos. Traqueostomia. Oncologia. Hospitais Universitários.

REFERENCES 1.

2.

3.

Ricz HMA, Mello Filho FV, Freitas LCC, Mamede RCM. Traqueostomia. Medicina (Ribeirão Preto). 2011;44(1):63-9. Hammarfjord O, Ekanayake K, Norton J, Stassen LF. Limited dissection and early primary closure of the tracheostomy stoma in head and neck oncology operations: a retrospective study of 158 cases. Int J Oral Maxillofac Surg. 2015;44(3):297-300. Coyle MJ, Shrimpton A, Perkins C, Fasanmade A, Godden D. First do no harm: should routine tracheostomy after oral and maxillofacial oncological operations be abandoned? Br J Oral Maxillofac Surg. 2012;50(8):732-5.

4.

5.

6.

Salgarelli AC, Collini M, Bellini P, Capparè P. Tracheostomy in maxillofacial surgery: a simple and safe technique for residents in training. J Craniofac Surg. 2011;22(1):243-6. Mogedas-Vegara A, Bescós-Atín C, GutiérrezSantamaría J, Masià-Gridilla J, Pamias-Romero J, Sáez-Barba M. Manejo de la vía aérea en oncología de cabeza y cuello. Rev Esp Cir Oral Maxilofac. 2014;36(4):164-8. Scott N, Bater M, Fardy M. Tracheostomy in head and neck oncology. Results of the 2014 Tracheostomy Survey of the BAOMS Oncology Specialist Interest Group. Br J Oral Maxillofac Surg. 2015;53(8):779-81.

Rev Col Bras Cir 45(4):e1744


Soares Elaboration of a tracheostomy conduct protocol in the Amazonas cancer reference hospital

7.

8.

9.

10.

11.

12.

13.

14. 15.

Mitchell R, Parker V, Giles M. An interprofessional team approach to tracheostomy care: a mixedmethod investigation into the mechanisms explaining tracheostomy team effectiveness. Int J Nurs Stud. 2013;50(4):536-42. Hasson F, Keeney S, McKenna H. Research guidelines for the Delphi survey technique. J Adv Nurs. 2000;32(4):1008-15. Hsu CC, Sandford B. The Delphi technique: making sense of consensus. Pract Assess Res Eval (Online). 2007;12(10):1-8. Mitchell RB, Hussey HM, Setzen G, Jacobs IN, Nussenbaum B, Dawson C, et al. Clinical consensus statement: tracheostomy care. Otolaryngol Head Neck Surg. 2013;148(1):6-20. Urrestarazu P, Varón J, Rodríguez A, Ton V, Vila F, Cipriani S, et al. Consenso sobre el cuidado del niño con traqueostomía. Arch Argentina Pediatr. 2016;114(1):89-95. Patel SA, Plowman EK, Halum S, Merati AL, Sardesai MG. Late tracheotomy is associated with higher morbidity and mortality in mechanically ventilated patients. Laryngoscope. 2015;125(9):2134-8. Liu CC, Livingstone D, Dixon E, Dort JC. Early versus late tracheostomy: a systematic review and meta-analysis. Otolaryngol Head Neck Surg. 2015;152(2):219-27. Scurry WC Jr, McGinn JD. Operative tracheotomy. Oper Tech Otolaryngol Head Neck Surg. 2007;18(2):85-9. Durbin CG Jr. Tracheostomy: why, when, and how? Respir Care. 2010;55(8):1056-68.

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16. Fraga JC, Souza JCK, Kruel J. Traqueostomia na criança. J Pediatr (Rio J). 2009;85(2):97-103. 17. Singapore. Ministry of Health. Moh Nursing Clinical Practice Guidelines 2/2010. Nursing Management of Adult Patients with Tracheostomy. Ministry of Health: Singapore, 2010. 18. Dawson D. Essential principles: tracheostomy care in the adult patient. Nurs Crit Care. 2014;19(2):63-72. 19. National Tracheostomy Safety Project Manual [Internet]. Manchester: National Tracheostomy Safety Project; 2013. Availbale from: www. tracheostomy.org.uk 20. McCormick ME, Ward E, Roberson DW, Shah RK, Stachler RJ, Brenner MJ. Life after tracheostomy: patient and family perspectives on teaching, transitions, and multidisciplinary teams. Otolaryngol Head Neck Surg. 2015;153(6):914-20. 21. Yelverton JC, Nguyen JH, Wan W, Kenerson MC, Schuman TA. Effectiveness of a standardized education process for tracheostomy care. Laryngoscope. 2015;125(2):342-7. Received in: 01/30/2018 Accepted for publication: 05/10/2018 Conflict of interest: none. Source of funding: none. Mailing address: Maria Carolina Coutinho Xavier Soares E-mail: mariaccxs@hotmail.com mcsoares@uea.edu.br

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Original Article

DOI: 10.1590/0100-6991e-20181861

Healing modulation in glaucoma surgery after application of subconjunctival triamcinolone acetate alone or combined with mitomycin C: an experimetal study Modulação da cicatrização na cirurgia do glaucoma após aplicação de acetato de triancinolona subconjuntival isolado ou em associação à mitomicina C: estudo experimental Hayana Marques do Aragão Rangel1,2; Hévila Tamar Rolim2,3; Paula Vidigal4; Ivana Duval de Araújo5; Sebastião Cronemberger1 A B S T R A C T Objective: to study the efficacy and safety of the use of subconjunctival triamcinolone acetate alone or in combination with mitomycin C as a modulator of trabeculectomy healing in rabbits. Methods: we submitted thirty male, albino, New Zealand rabbits to bilateral trabeculectomy. We divided the animals into four experimental groups with 15 eyes per group: control, mitomycin C, triamcinolone acetate and triamcinolone acetate + mitomycin C. We performed aplanation tonometry and clinical analysis of the bleb through the Moorfields Graduation System in the postoperative period. For the evaluation of healing, we carried out the quantitative analysis of the inflammatory infiltrate (polymorphonuclear) through Hematoxylin & Eosin staining, and vascular proliferation, through immunohistochemistry. Results: we observed a significant decrease in postoperative intraocular pressure in all groups compared with the preoperative pressure (p<0.001). However, there was no difference between groups (p=0.186). The triamcinolone + mitomycin C acetate group presented better indices as for the maximum bleb height and vascularization of the bleb central area (p=0.001); in addition, there was a lower inflammatory response (p=0.001) and lower vascular proliferation (p=0.001) in the intermediate phase of the study compared with the monotherapies. Conclusion: the combination of mitomycin C and triamcinolone acetate resulted in a synergistic action between these agents, with broader and more diffuse blebs, less inflammatory infiltrate and less vascular proliferation in the intermediate stages of follow-up in this animal model. Keywords: Glaucoma. Wound Healing. Antimitotic Agents. Trabeculectomy. Ophthalmologic Surgical Procedures.

INTRODUCTION

G

laucoma is an optic neuropathy that causes irreversible blindness if not treated properly. It is a public health problem, being the second largest cause of blindness in the population1. The objective

of its treatment is the reduction of intraocular pressure, through topical medications, laser and/or surgical procedures2,3. Since the first description, in 1968, trabeculectomy has become the standard procedure in the surgical treatment of glaucoma. It aims at forming a fistula that provides an alternative

route for the drainage of aqueous humor from the anterior chamber to the subconjunctival space, to reduce intraocular pressure (IOP)3,4. Unlike many types of surgery in which complete healing is the desirable outcome, trabeculectomy aims to achieve a partial healing response, to allow continuous drainage of the aqueous humor through the fistula4. Modulation of the healing response in glaucoma surgery is often necessary, to achieve adequate pressure, maximizing surgical success5. There are a variety of agents available that can modify this response.

1 - Federal University of Minas Gerais, Department of Ophthalmology, Belo Horizonte, MG, Brazil. 2 - Santa Casa de Misericórdia of Belo Horizonte, Glaucoma and Cataract Reference Center, Belo Horizonte, MG, Brazil. 3 - Federal University of Rondônia, Department of Medicine, Porto Velho, RO, Brazil. 4 - Federal University of Minas Gerais, Department of Pathology, Belo Horizonte, MG, Brazil. 5 - Federal University of Minas Gerais, Department of Surgery, Belo Horizonte, MG, Brazil. Rev Col Bras Cir 45(4):e1861


2

Rangel Healing modulation in glaucoma surgery after application of subconjunctival triamcinolone acetate alone or combined with mitomycin C: an experimetal study

In ophthalmologic practice, antimetabolites, 5-fluorouracil (5-FU) and mitomycin C (MMC), have revolutionized the history of glaucoma surgery and are therefore the drugs most used in modulating healing4,6. Although they have enhanced the surgical success rate in trabeculectomy, the non-specific mechanism of these agents may result in various ocular complications, such as corneal toxicity, avascular blebs, endophthalmitis, hypotonia and, in some cases, they are just ineffective7. Therefore, there is still a need for alternative strategies to prevent surgical failure secondary to over-healing. Anti-inflammatory agents are already part of the strategy to modulate inflammation and wound healing in the eye. Steroid hormones are the prototype4. Triamcinolone Acetate (TA) is a corticosteroid in the form of an injectable suspension already used for the treatment of neovascular, proliferative and edematous diseases in ophthalmology. Its anti-inflammatory potential is approximately five times that of cortisol8,9. The anti-inflammatory and antifibrotic action of TA is largely mediated by suppression of leukocyte concentration and functionality, as well as its effects on vascular permeability. This leads to less local inflammation, reduced release of growth factors, and production of clot and fibrin. As a result, there is a decrease in the fibroblast activity and in the cicatricial response8,10. Although there are already some studies evaluating the use of TA in glaucoma surgery, there is still a need to assess whether TA can be used in monotherapy or only in association with MMC. Therefore, in this research, the objective was to evaluate the efficacy and safety of the use of TA isolated or associated with MMC in trabeculectomy in rabbits.

METHODS Experimental model

We used thirty male, albino rabbits of the Oryctolagus caniculus species, New Zealand breed, weighing between 2kg and 3kg in the study. The Ethics Committee on Animals of the Federal University of Minas Gerais approved this research, and we treated all animals in accordance with the precepts of the Association for Research in Vision and Ophthalmology (ARVO) - protocol n# CEUA/ UFMG 149/2012. All animals underwent trabeculectomy in both eyes, under sterile conditions, by the same surgeon, using the same technique. General anesthesia was performed with ketamine 35mg/kg + Xylazine 5mg/kg + Acepromazine 0.75mg/kg. We made an upper corneal traction suture with 6-0 silk suture to expose the site to be operated. We prepared a fornix based conjunctival flap and a rectangular scleral flap (3mm x 3mm). Then we proceeded to sclerotomy and peripheral iridectomy. We closed the scleral and the conjunctiva with two 10-0 mononylon sutures. At the end of the procedure, we instilled a drop of 0.5% moxifloxacin and 0.1% dexamethasone. We distributed the animals in four experimental groups, with 15 eyes per group, since each animal underwent bilateral surgery and received different treatments in the right and left eyes. In the control group, we applied 0.2ml of saline solution through the sponge under the Tenon's capsule and under the scleral flap for two minutes. In the MMC group, we administered 0.4ml of 0.03% mitomycin C via sponge, below the Tenon's capsule and under the scleral flap for two minutes. In the TA group, we

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Rangel Healing modulation in glaucoma surgery after application of subconjunctival triamcinolone acetate alone or combined with mitomycin C: an experimetal study

administered 4mg of subconjunctival triamcinolone acetate superior to the bleb at the end of surgery. Finally, in the TA+MMC group, we administered 0.4ml of 0.03% MMC through sponge, below the Tenon's capsule and under scleral flap for two minutes, and, 4mg of subconjunctival triamcinolone acetate superior to the bleb at the end of surgery. Clinical analysis

We examined the animals preoperatively and on days one, three, seven, 14 and 30 after the surgical procedure. We performed applanation tonometry using the Perkins Tonometer (Haag-Streit, Koniz, Switzerland) by means of three IOP measurements, recording their mean. We studied the bleb trough the photographic evaluation of the surgical site and comparing them with the photos of the Moorfields bleb classification system11. Another examiner, unaware of the groups, performed this photographic analysis. Immunohistological analysis

With intravenous pentobarbital (150mg/ kg), we sacrificed five rabbits from each group and enucleated them on days three, 14 and 30 for evaluation of healing markers. We stained the material with Hematoxylin & Eosin (HE) for all animals and evaluated the region of the operated conjunctiva for polymorphonuclear counts. In the immunohistochemical analysis, we used the VEGF antibody (C-1): SC-7269 (Santa Cruz Biotechnology, California - USA) to investigate the expression of VEGF A in vascular endothelium, evaluating angiogenesis. From each slide, we took three photos in sequence of the area of interest, with a 400-fold increase, which were then evaluated by a pathologist who also did not know the groups.

3

Statistical analysis

We used the SPSS software, version 19.0. We applied non-parametric tests in the clinical analysis of the bleb. We performed the comparison between independent groups with the Kruskal-Wallis test. In the comparison between the phases, we used the Friedman test. To evaluate the influence of the groups and of the study phases on the intraocular pressure, we used the Variance Analysis based on a Repeated Measures planning. We carried out the evaluation of the influence of the group and the time of evaluation until death of the animals (phase) in the immunohistological variables, as well as the interaction between these two factors (group and phase) using the two-way Analysis of Variance. We considered the results significant for a probability of significance of less than 5% (p<0.05).

RESULTS There was no significant difference regarding the animals' initial weight between groups (p=0.910). As for intraocular pressure, in all groups the preoperative values ​​were higher than the values of the final postoperative period (p=0.001). However, there was a significant difference between groups only on the 30th postoperative day (POD): TA+MMC (8.9±0.9mmHg) and MMC (8.8±1.5mmHg) groups presented the lowest pressure indices, followed by the AT (9.9±1.1mmHg) and the control group (11.4±1.5mmHg) (p=0.043) (Figure 1). After the evaluation of the bleb by the Moorfields Bleb Graduation System, in the criteria bleb central area (p=0.002) and maximum area in the 30th POD, there were better results in the TA+MMC (2.8±0.4; 3.0±0.0) and MMC (2.8±0.4,

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Rangel Healing modulation in glaucoma surgery after application of subconjunctival triamcinolone acetate alone or combined with mitomycin C: an experimetal study

Figure 1. Comparison of the initial and final intraocular pressure.

3.0±0.0) groups. In the evaluation of maximum bleb height, the TA+MMC group (1.8±0.4) presented better rates than the other groups (p=0.001). As for the vascularization of the central area, there was a significant difference in the 14th POD, with better results in the TA+MMC group (2.4±0.9; p=0.001). For the vascularization of the maximum bleb area, on its turn, on the 14th POD the lowest indexes were similar in the TA+MMC (2.4±0.5) and MMC (2.4±0.9) groups (p=0.031) (Figure 2).

There were few complications during the study, with no significance for the results: two cases of subconjunctival whitish deposit (one case in the TA group and the other in the TA+MMC) that were reabsorbed at the end of the follow-up. In the quantitative analysis of polymorphonuclear cells throughout the study, the TA+MMC group (20.9±3.7 cells/field) had the lowest cell proliferation, followed by the TA group (22.1±2.3 cells/field; p=0.001). In the intermediate phase, the TA+MMC group (18.0±1.9 cells/field) remained with better results, followed by the MMC group (19.3±2.2 cells/field; p=0.001). At the end of the study, the TA+MMC (19.1±3.1 cells/field) and MMC (18.9±4.5 cells/field) groups presented lower inflammatory infiltrate and the TA group (24.9±4.5 cells/field) had the worst outcome (p=0.001) (Figures 3 and 4).

Figure 3. Polymorphonuclear count throughout the study; p1: comparison between groups in each phase; p2: comparison in each phase per group.

Figure 2. Photographs of the postoperative aspect of trabeculectomy in the seventh POD; Groups: Control (A), MMC (B), TA (C) and TA+MMC (D).

Angiogenesis, the process of growth of new blood vessels, is a key element of the healing proliferative phase. Its evaluation showed, in the initial phase, better results in the TA+MMC group

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Figure 4. Histological sections (HE) of the ocular globe in the conjunctival region of rabbits submitted to experimental surgery, showing the polymorphonuclear count in the 14th POD; Groups: Control (A); MMC (B); TA (C); TA+MMC (D).

(4.2±0.9 vessels marked/field), followed by the MMC group (5.4±1.1 vessels marked/field) (p=0.001). In the 14th POD, the TA+MMC group (3.4±1.0 labeled vessels/field) remained with the lower rates of vascular proliferation (p=0.001). However, at the end of the research, the group with the best results was the MMC one (4.1±1.2 vessels marked/field) (p=0.001) (Figures 5 and 6).

Figure 5. Results of vascular proliferation throughout the study; p1: comparison between groups in each phase; p2: comparison in each phase per group.

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Figure 6. Histological sections (immunohistochemical evaluation) of the conjunctiva of rabbits submitted to experimental surgery, showing the brown chromogen deposition in the vascular endothelium in the 14th POD; Groups: Control (A), MMC (B), TA (C) and TA+MMC (D).

DISCUSSION The healing process is a physiological, complex, dynamic event that comprises a cascade of different processes closely linked and not yet fully understood5. For long-term success in glaucoma fistulating surgery, complete healing cannot occur. Therefore, the greatest limitation of trabeculectomy is the development of conjunctival and episclera fibrosis secondary to fibroblast proliferation and collagen deposition at the fistula site12. In this study, we evaluated the standard modulator, mitomycin C, and an alternative one, triamcinolone acetate, isolated or in combination, in an experimental model of rabbits. There were lower pressure rates at the end of the study in the TA+MMC and MMC groups, but with no difference between them. However, there was no pressure increase in the groups that used triamcinolone acetate. The use of this antiinflammatory in ophthalmology is associated with corticosteroid-induced increased intraocular pressure and its subconjunctival injection may cause

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Rangel Healing modulation in glaucoma surgery after application of subconjunctival triamcinolone acetate alone or combined with mitomycin C: an experimetal study

this increase for several months. It is believed that this occurs secondarily to the reduction in the ease of flow of the aqueous humor by the trabecular meshwork by deposition of drug particles in the trabecular meshwork9,13. The results of the present study are in agreement with the ones of Hogewind et al.8, who used 20mg of TA in their study, also without pressure increase, suggesting that the effect on the corticoid-induced pressure increase in the trabecular meshwork is compensated by the pressure decrease secondary to trabeculectomy. The first report of the use of TA as adjuvant in glaucoma surgery was made by Giangiacomo et al.14, in 1986, who reported 87.5% of surgical

without hypotensive medication and there were no complications (infection, hypotonia, conjunctival ulceration)16. Although they are only case reports, these results corroborate the positive effect of the association of these modulators on trabeculectomy. A prospective, randomized, controlled study evaluated the efficacy of subtenonian TA injection (20mg) on the success of trabeculectomies (with MMC) in secondary glaucoma. Complete success was 65.4% in the TA group and 63% in the control group (p=0.77). The fistula characteristics were similar in both groups (p>0.40) and there were no significant differences in the IOP at follow-up (p>0.05)17. The findings of this study

success and diffuse blebs at the end of follow-up, suggesting a positive effect of TA on healing modulation. In the present study, when we used TA as monotherapy, it did not demonstrate good results compared with TA+MMC and with isolated MMC, in disagreement with Hogewind, who presented similar surgical success rates between the groups in a five-year follow-up, suggesting that isolated TA could be used as adjuvant in fistulant surgery8. This difference in results is justified by the higher dosage used in the study. Most publications evaluated the use of the TA and MMC association. Tham et al.15, in a series of cases, injected TA (1.2mg) directly into the filtering ampules of three eyes submitted to facotrabeculectomy, of three undergoing trabeculectomy with MMC, and of five submitted to 5-FU trabeculectomy revision. They reported decreased IOP without the need of medication for up to three months and observed no signs of endothelial loss or progression of cataract. In 2009, another series of cases evaluated the use of retrobulbar TA (20mg) in trabeculectomies with MMC. There was a significant decrease in IOP at six months (p<0.001)

were similar, when TA was associated with MMC in trabeculectomies, to the recent retrospective series of cases that analyzed the administration of intracameral TA (0.1-0.3ml, 4mg/ml). Overall success was 68.4% in the study group and 52.4% in the control group, with partial success being 31.6% and 47.6%, respectively. There was also no increase in complications in the TA group (p>0.05)18. These results are in agreement with ours, that showed postoperative pressure decrease and good clinical aspect of trabeculectomy in the TA+MMC group, but with similar results to the group using MMC alone. We have not identified previous studies reporting the effect on the healing cascade of TA and TA+MMC in trabeculectomy in rabbits. In an experimental study that used another corticoid, dexamethasone, in the form of an intravitreal implant, as an adjuvant to trabeculectomy, there was less collagen deposition and longer surgery survival in relation to the control group, but the MMC group presented better results19. These findings, in association with the present ones, reinforce the positive action of corticosteroids in the modulation

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of wound healing in glaucoma surgery. However, both dexamethasone and triamcinolone acetate were not superior to the standard antifibrotic, MMC. Nonetheless, there was no evaluation of the association of adjuvants, as in the current study, which analyzed the association TA+MMC, showing a greater modulation of healing than these agents isolated in the initial and intermediate phases, both in relation to inflammatory infiltrate and vascular response. This is corroborated by reports that the topical use of corticosteroids postoperatively significantly increases surgical success by inhibiting wound healing as a result of suppression of fibroblast inflammation and proliferation20, as well as by screening in humans via culture of Tenon capsule fibroblasts, which showed that corticosteroids inhibit cell binding and proliferation21. However, the non-promising results of the isolated TA and the good ones with TA+MMC only up to the intermediate stage in this animal model can be justified by the low dosage of 4mg of this corticosteroid. This research did not directly evaluate the survival time of the filtering bleb, a criterion used in some experimental studies, defined by a healed, flat and vascularized appearance of the

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bleb. Nevertheless, the clinical evaluation using the Moorfields Bleb Graduation System analyzed the extent, height and degree of vascularization at the surgery site, and the poor score of these parameters, indirectly, would point to the survival criterion. Another limitation was the small number of eyes in the final phase of the study, but this number is similar to that of previous publications12,22. Because of the multifactorial nature of wound healing, it is likely that multiple agents, used simultaneously or sequentially, may be required for optimal modulation. The association of MMC with triamcinolone acetate in the current results points to a synergistic action among these agents, with diffuse and broader blebs, less inflammatory infiltrate and less vascular proliferation in the intermediate stage of follow-up in this animal model. The satisfactory results of the present study, as well as those already published, in relation to the use of TA as adjuvant to trabeculectomies should, however, be considered with caution. Long-term, multicenter, prospective clinical trials are required to assess the optimal dose and route of administration that produce the best surgical outcome with minimal side effects.

R E S U M O Objetivo: estudar a eficácia e segurança do uso de acetato de triancinolona subconjuntival isolado ou em associação à mitomicina C como modulador da cicatrização de trabeculectomias em coelhos. Métodos: trinta coelhos machos, albinos, raça Nova Zelândia foram submetidos à trabeculectomia bilateralmente. Os animais foram divididos em quatro grupos experimentais com 15 olhos por grupo: controle, mitomicina C, acetato de triancinolona e acetato de triancinolona + mitomicina C. Tonometria de aplanação e análise clínica da bolha através do Sistema de Graduação de Moorfields foram obtidas no pós-operatório. Para a avaliação da cicatrização, procedeu-se à análise quantitativa do infiltrado inflamatório (polimorfonucleares) através da coloração Hematoxilina & Eosina e da proliferação vascular por imuno-histoquímica. Resultados: foi observada em todos os grupos diminuição significativa da pressão intraocular pós-operatória em relação à pré-operatória (p<0,001). Contudo, não houve diferença entre os grupos (p=0,186). O grupo acetato de triancinolona + mitomicina C apresentou melhores índices na altura máxima da bolha e na vascularização da área central da bolha (p=0,001); além disso, houve menor resposta inflamatória (p=0,001) e menor proliferação vascular (p=0,001) na fase intermediária do estudo em relação às monoterapias. Conclusão: a associação da mitomicina C ao acetato de triancinolona resultou numa ação sinérgica entre esses agentes, com bolhas mais amplas e difusas e menor infiltrado inflamatório e menor proliferação vascular em estágio intermediário do acompanhamento neste modelo animal. Descritores: Glaucoma. Cicatrização. Antimitóticos. Trabeculectomia. Procedimentos Cirúrgicos Oftalmológicos.

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Rangel Healing modulation in glaucoma surgery after application of subconjunctival triamcinolone acetate alone or combined with mitomycin C: an experimetal study

REFERENCES 1.

Hennis A, Wu SY, Nemesure B, Honkanen R, Leske MC; Barbados Eyes Studies Group. Awareness of incident open-angle glaucoma in a population study: the Barbados Eye Studies. Ophthalmology. 2007;114(10):1816-21. 2. Harasymowycz P, Birt C, Gooi P, Heckler L, Hutnik C, Jinapriya D, et al. Medical management of glaucoma in the 21st century from a Canadian perspective. J Ophthalmol 2016;2016:6509809. 3. Razeghinejad MR, Fundemberg SJ, Spaeth GL. The changing conceptual basis of trabeculectomy: a review of past and current surgical techniques. Surv Ophthalmol. 2012;57(1):1-25. 4. Lama PJ, Fechtner RD. Antifibrotics and wound healing in glaucoma surgery. Surv Ophthalmol. 2003;48(3):314-46. 5. Cordeiro MF, Chang L, Lim KS, Daniels JT, Pleass RD, Siriwardena D, et al. Modulating conjuctival wound healing. Eye (Lond). 2000;14(Pt 3B):536-47. 6. Lockwood A, Brocchini S, Khaw PT. New developments in the pharmacological modulation of wound healing after glaucoma filtration surgery. Curr Opin Pharmacol. 2012;13(1):65-71. 7. Van Bergen T, Van de Velde S, Vandewalle E, Moons L, Stalmans I. Improving patient outcomes following glaucoma surgery: state of the art and future perspectives. Clin Ophthalmol. 2014;8:85767. 8. Hogewind BF, Pijl B, Hoyng CB, Theelen T. Purified triamcinolone acetonide as antifibrotic adjunct in glaucoma filtering surgery. Graefes Arch Clin Exp Ophthalmol. 2013;251(4):1213-8. 9. Kalina PH, Erie JC, Rosenbaum L. Biochemical quantification of triamcinolone in subconjunctival depots. Arch Ophthalmol. 1995;113(7):867-9. 10. Hosseini H, Mehryar M, Farvardin M. Focus on triamcinolone acetonide as an adjunct to glaucoma filtration surgery. Med Hypotheses. 2007;68(2):4013. 11. Wells AP, Crowston JG, Marks J, Kirwan JF, Smith G, Clarke JC, et al. A pilot study of a system for grading of drainage blebs after glaucoma surgery. J Glaucoma. 2004;13(6):454-60.

12. Memarzadeh F, Varma R, Lin LT, Parikh JG, Dustin L, Alcaraz A, et al. Postoperative use of bevacizumab as an antifibrotic agent in glaucoma filtration surgery in the rabbit. Invest Ophthalmol Vis Sci. 2009;50(7):3233-7. 13. Zaka-ur-Rab S, Mahmood S, Shukla M, Zakir SM, Khan BA, Owais M. Systemic absorption of triamcinolone acetonide after posterior sub-Tenon injection. Am J Ophthalmol. 2009;148(3):414-9. 14. Giangiacomo J, Dueker DK, Adelstein E. The effect of preoperative subconjunctival triamcinolone administration on glaucoma filtration. I. Trabeculectomy following subconjunctival triamcinolone. Arch Ophthalmol. 1986;104(6):83841. 15. Tham CC, Li FC, Leung DY, Kwong YY, Yick DW, Chi CC, et al. Intrableb triamcinolone acetonide injection after bleb-forming filtration surgery (trabeculectomy, phacotrabeculectomy, and trabeculectomy revision by needling): a pilot study. Eye (Lond). 2006;20(12):1484-6. 16. Kahook MY, Camejo L, Noecker RJ. Trabeculectomy with intraoperative retrobulbar triamcinolone acetonide. Clin Ophthalmol. 2009;3:29-31. 17. Yuki K, Shiba D, Kimura I, Ohtake Y, Tsubota K. Trabeculectomy with or without intraoperative sub-tenon injection of triamcinolone acetonide in treating secondary glaucoma. Am J Ophthalmol. 2009;147(6):1055-60. 18. Alagรถz N, Alagรถz C, Yildirim Y, Yesilkaya C, Altan ร‡, Bozkurt E, et al. The effect of adjuvant intracameral triamcinolone acetonide on the surgical results of trabeculectomy with mitomycin C. Turk J Ophthalmol. 2016;46(4):169-74. 19. Kiddee W, Orapiriyakul L, Kittigoonpaisan K,Tantisarasart T, Wangsupadilok B. Efficacy of adjunctive subconjunctival bevacizumab on the outcomes of primary trabeculectomy with mitomycin C: a prospective randomized placebocontrolled trial. J Glaucoma. 2015;24(8):600-6. 20. Araujo SV, Spaeth GL, Roth SM, Starita RJ. A tenyear follow-up on a prospective, randomized trial of postoperative corticosteroids after trabeculectomy. Ophthalmology. 1995;102(12):1753-9.

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Rangel Healing modulation in glaucoma surgery after application of subconjunctival triamcinolone acetate alone or combined with mitomycin C: an experimetal study

21. Nguyen KD, Lee DA. Effect of steroids and nonsteroidal anti-inflammatory agents on human ocular fibroblast. Invest Ophthalmol Vis Sci 1992;33(9):2693-701. 22. Cheng G, Xiang H, Yang G, Ma J, Zhao J. Bevacizumab inhibits angiogenesis and inflammation in rat filtration surgery model. Cell Biochem Biophys 2015;73(1):71-7.

Received in: 03/10/2018 Accepted for publication: 05/10/2018 Conflict of interest: none. Source of funding: none. Mailing address: Hayana Marques do AragĂŁo Rangel E-mail: hayanarangel@yahoo.com.br hevilarolim@unir.br

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Original Article

DOI: 10.1590/0100-6991e-20181715

Retrospective study of patients with cutaneous melanoma treated at the Federal University of São Paulo. Estudo retrospectivo dos pacientes portadores de melanoma cutâneo atendidos na Universidade Federal de São Paulo. Tácito Ferreira1; Ivan Dunshee de Abranches Oliveira Santos1; Andrea Fernandes Oliveira1; Lydia Masako Ferreira, TCBC-SP1 A B S T R A C T Objective: to evaluate the characteristics of the patients with cutaneous melanoma treated at the São Paulo Hospital UNIFESP. Methods: we conducted a retrospective study of 184 cases of cutaneous melanoma. We analyzed information on gender, age, tumor characteristics, histological characteristics and staging. Results: mean age at diagnosis was 58.7 years, with homogeneous age distribution between genders and predominance in white individuals (70.6%). There was a predominance of trunk involvement in men (36.7%) and lower limbs in women (42%). Sun exposure, with sunburns, was more common among males (31.2%) than among females (23.5%). There was an approximately three-fold increase in lymph node involvement when the mitotic index rose from zero (11.9%) to one or more mitosis per field (36.2%). In addition, the greater the Breslow thickness, the greater the lymph node involvement and poor the outcomes: 10.2% when less than 1mm and 59.2% when greater than 4mm. Conclusion: the characteristics of patients with cutaneous melanoma treated at Hospital São Paulo are similar to those found in the literature. Keywords: Melanoma. Skin Neoplasms. Mitosis. Risk Factors. Melanoma/epidemiology.

INTRODUCTION

S

kin cancer is the most common form of cancer, accounting for about 40-50% of all neoplasias diagnosed in the United States according to the World Health Organization1-3. Skin cancers are primarily classified as non-melanoma and melanoma (Figure 1). Melanoma represents a small percentage of skin cancers diagnosed annually (about 3%), but accounts for most of the deaths caused by skin tumors, reaching 65% per year4-6. The incidence of melanoma continues to increase progressively, with an approximate increase of 33% in men and 26% in women in the period from 2002 to 20067, and about 90,000 new cases and 10,000 deaths in the United States in 2017, according to the American Cancer Society statistics. The main risk factors related to the patient are skin phototype, personal and family history of

Figure 1. Malignant lentigo melanoma, a subtype of melanoma, on the left face of a patient with phototype I.

melanoma, presence of multiple atypical or dysplastic nevi and genetic factors. In addition, environmental factors such as intense or sporadic sun exposure,

1 - Federal University of São Paulo, Discipline of Plastic Surgery, São Paulo, SP, Brazil. Rev Col Bras Cir. 2018;45(4):e1715


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Ferreira Retrospective study of patients with cutaneous melanoma treated at the Federal University of São Paulo.

blistering, and UVB tanning play an important role in the development of melanoma8-19. Unfortunately, many patients receive diagnose at an advanced stage, or even experience disease progression, despite the established treatments. Melanoma evolves from several well-defined precursor lesions before it becomes invasive and metastatic20,21. Several studies have analyzed the predictive factors of prognosis related to melanoma, including tumorrelated, factors such as Breslow thickness, presence of ulceration and mitotic index, which were identified as the three most independent factors important in the analysis of patients' outcomes22-34. Therefore, knowledge of the epidemiology and risk factors of cutaneous melanoma is of interest to all those studying and working with melanoma, including surgeons, dermatologists, oncologists and primary care physicians, for the development of new prevention campaigns, expansion of existing knowledge and publication of data to reach professionals who are not yet familiar with the disease35. Numerous studies have investigated the characteristics of melanoma patients and their prognostic factors. However, records from Latin America and Brazil remain scarce36. Thus, through this study, we seek to better understand the epidemiological and pathological profile of patients with melanoma treated in Brazil and thus improve the strategies of care in our country.

METHODS We conducted a retrospective study of epidemiological data collected from the Department of Skin Tumors of the Discipline of Plastic Surgery of the University Hospital of the Federal University of São Paulo (UNIFESP). The study was approved by the Ethics and Research Committee of UNIFESP under number 0986/11. We performed an analysis of the hospital and outpatient records of 184 patients with

cutaneous melanoma treated at the Service from January 2005 to December 2010, based on a protocol that contained information about gender, color, age, occupation, sun exposure, tumor characteristics, location of the lesion, histological characteristics, staging and follow-up until the end of this work. Regarding the location of the lesions, we divided then into macroregions: head and neck, trunk, upper limbs, lower limbs or of unknown location. We submitted the collected data to statistical analysis, in which we used non-parametric tests. We set the level of rejection of the null hypothesis at 5%, considering a significant value of p=0.05. We then compared the results to national and international epidemiological studies.

RESULTS Of the 184 patients, 103 (66%) were female and 81 (44%), male. Regarding skin color, 130 (70.6%) were classified as whites and 51 (27.7%) were non-whites (brown, blacks and natives). Three (1.6%) patients had no information on skin color. The mean patient’s age was 58.7 years at the time of diagnosis. Of the patients analyzed, 49 (26.6%) worked exposed to the sun, 133 (72.2%) worked without sun exposure, and two (1.2%) did not report on their professions. Regarding the histological aspects, 116 (63.1%) had at least one mitosis per field (mitotic index), 42 (22.8%) had a mitotic index equal to zero and in 26 (14.1%) we did not have access to histopathological examination. Of the patients analyzed, 125 (67.9%) did not present lymph node metastases, 58 (31.5%) presented lymph node involvement; one (0.6%) patient’s record lacked this information. The analysis showed no significant difference between genders, with calculated X2 equal to 0.93 (p=0.6086). When we analyzed the

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affected region in relation to the gender, we found statistically significant differences. Head, neck and trunk involvement was more common in men, and the upper and lower limbs were more common and women: calculated X2 = 11.12 (p=0.0111) (Table 1). Table 1. Distribution of gender according to the regions involved.

Region Head and neck Trunk Upper limbs Lower limbs Total

Female N % 17 17.0 24 24.0 17 17.0 42 42.0 100 100

Male N 23 29 9 18 79

% 29.1 36.7 11.3 22.9 100

When comparing the exposure with the affected region, the results suggest a relation between the profession with sun exposure and the occurrence of head and neck melanoma, evidencing the role of sun exposure in the genesis of this neoplasm: calculated X2=8.821 (p=0.0318) (Table 2). We excluded seven patients (3.8%) with no information to make the comparison from this analysis. Table 2. Distribution of the exposure risk factor according to the regions involved.

Region Head and neck Trunk Upper limbs Lower limbs Total

Exposure Yes No 14 26 18 34 9 17 8 51 49 128

Total 40 52 26 59 177

% of Yes 35.0 34.6 34.6 13.6 27.6

When we compared the risk factor incidence of the sunburn with the affected region, the percentage of sunburn of the head and neck was significantly higher than in the other regions, and the presence of burns in patients with melanoma of the lower limbs was lower: calculated X2=12.59

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(p=0.0056) (Table 3). We excluded fifteen patients (8.2%) with no information to make the comparison from this analysis. Table 3. Distribution of the sunburn risk factor according to the regions involved.

Region Head and neck Trunk Upper limbs Lower limbs Total

Sunburn Yes No 20 19 20 31 9 17 9 44 58 111

Total

% of Yes

39 53 24 53 169

51.2 37.7 37.5 16.9 34

We noticed that the more cephalic the region the greater the rate of patients within it that present sunburn as a risk factor, evidencing the low influence of this risk factor on the genesis of melanomas in lower and less exposed regions. When comparing the presence of the risk factor "exposure" with the gender, we did not obtain a statistically significant difference: calculated X2=1.35 (p=0.2438) (Table 4). We excluded two patients (1.2%) who had no exposure information from this analysis. Table 4. Distribution of exposure risk factor according to gender.

Gender

Exposure

Total

% of Yes

55

80

31.2

24

78

102

23.5

49

133

182

30.2

Yes

No

Male

25

Female Total

When comparing the mitotic index of melanoma with lymph node involvement during follow-up, the analysis showed a significant association between the presence of one or more mitoses and the occurrence of lymph node metastasis, increasing the risk of metastases by 3.2 times: calculated X2=8.71 (p=0.0032) (Table 5).

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Table 5. Distribution of lymph node involvement according to the presence of mitosis.

Mitosis Present Absent Total

Lymph node Total Positive Negative 42 74 116 5 37 42 47 111 125

% positive 36.2 11.9 37.6

Breslow thickness obtained through anatomopathological study was significantly associated lymph node involvement during follow-up: calculated X2=38.56 (p<0.0001) (Table 6). Table 6. Distribution of lymph node involvement according to the Breslow thickness.

Breslow In situ (0) <1 1.01 to 2 2.01 to 4 >4 Total

Lymph node Total % positive Positive Negative 0 17 17 0.0 4 35 39 10.2 8 24 32 25.0 5 20 25 25.0 32 22 54 59.2 58 126 184 31.5

DISCUSSION It is important to note that the collection of data was hampered by the deficiency of the institution's records, as it usually occurs in Brazil36. We found a prevalence of women in relation to men, a situation commonly described for all skin diseases. The reasons for this disparity remain unknown, but it is probably multifactorial, including differences in the skin layers and their physiology, sex hormones, age, ethnicity, lifestyle, occupation, among others37-39. As with other data found in the literature, there was no significant difference between genders within the most affected age groups40-43. Regarding the age at diagnosis, we noticed a higher incidence in patients over 50 years.

When analyzing the known risk factors for the development of melanoma, 70.6% of the patients were considered white, of which 49.4% had skin type I or II and 27.1% had light hair and eyes colors, thus predisposed to melanoma due to their phenotype. The most prevalent risk factor was skin type I or II, followed by sunburn with blisters during life. When comparing the regions affected with the sunburn history, we observed that more exposed regions, such as head and neck and trunk, are more related to patients who presented burns compared with patients without them. As described by other authors20,44-46, the most affected regions were head and neck and trunk, accounting for 50.1%. We found that men are more affected in regions such as head, neck and trunk, which can be explained by a greater sun exposure in men's work in relation to women. In addition, we observed a statistical difference when we compared the presence of sun exposure with the affected area, evidencing the role of exposure in head and neck and trunk melanomas and its low relation with less exposed regions43. The most important information that the study detected in relation to the prognosis of the patients arose through the analysis of the relationship between the presence of mitoses and the Breslow thickness with the metastatic involvement of lymph nodes. We verified that the presence of only one mitosis per field in the histopathological evaluation is associated with lymph node metastasis, taking the patient to stage III, with poor prognosis. These patients have an indication of adjuvant treatment for the spread of the disease, in agreement with several international studies44-47. Likewise, when we compared Breslow thickness with lymph node involvement, we noticed that the larger

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the Breslow, the greater the risk of metastasis. Our study confirms this important information, published in the international review on prognostic factors and staging of cutaneous melanoma conducted by the American Joint Committee on Cancer48,49. In our study, we found plenty information that reaffirms the literature to date on risk factors more incident to the development of melanoma, such as light skin and eyes, sun exposure and

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sunburn, placing risk factors in two categories: phenotypic and non-preventable factors, and external factors, such as solar radiation, that can be prevented49,50. With this, we stimulate measures of melanoma prevention, such as campaigns to reduce sun exposure and encourage the use of sunscreens, as well as the identification of poor prognostic factors, to obtain better patient follow-up.

R E S U M O Objetivo: avaliar as características dos pacientes portadores de melanoma cutâneo atendidos no Hospital São Paulo UNIFESP. Métodos: estudo retrospectivo de 184 casos de melanoma cutâneo. Foram analisadas as informações sobre sexo, idade, características do tumor, características histológicas e estadiamento. Resultados: a média de idade ao diagnóstico foi de 58,7 anos, com distribuição etária homogênea entre os sexos e predominância em indivíduos brancos (70,6%). Observou-se acometimento predominante de tronco, em homens (36,7%), e de membros inferiores, em mulheres (42%). A exposição solar, com queimaduras, foi mais comum entre homens (31,2%) do que entre mulheres (23,5%). Houve aumento de aproximadamente três vezes no acometimento linfonodal quando o índice mitótico subia de zero (11,9%) para uma ou mais mitoses por campo (36,2%), e aumento progressivo do acometimento linfonodal e de desfechos ruins quanto maior a espessura de Breslow: 10,2% quando menor do que 1mm e 59,2% quando maior do que 4mm. Conclusão: as características dos pacientes portadores de melanoma cutâneo atendidos no Hospital São Paulo são semelhantes às encontradas na literatura. Descritores: Melanoma. Neoplasias Cutâneas. Mitose. Fatores de Risco. Melanoma/epidemiologia.

REFERENCES 1.

2.

3.

4.

5.

6.

World Health Organization. Cancer Research UK. World cancer factsheet. London: World Health Organ; 2014. Mariotto AB, Yabroff KR, Shao Y, Feuer EJ, Brown ML. Projections of the cost of cancer care in the United States: 2010-2020. J Natl Cancer Inst. 2011;103(2):117-28. Carpenter WR, Yeh WS, Wobker SE, Godley PA. Getting cancer prevalence right: using state cancer registry data to estimate cancer survivors. Cancer Causes Control. 2011;22(5):765-73. Dzwierzynski WW. Managing malignant melanoma. Plast Reconstr Surg. 2013;132(3):446e-60e. Erratum in. Plast Reconstr Surg. 2014;133(3):762. Siegel R, Ward E, Brawley O, Jemal A. Cancer Statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61(4):212-36.

Pavri SN, Clune J, Ariyan S, Narayan D. Malignant melanoma: beyond the basics. Plast Reconstr Surg. 2016;138(2):330e-40e. 7. Jemal A, Saraiya M, Patel P, Cherala SS, BarnholtzSloan J, Kim J, et al. Recent trends in cutaneous melanoma incidence and death rates in the United States, 1992-2006. J Am Acad Dermatol. 2011;65(5 Suppl 1):S17-25. e1-3. 8. Naeyaert JM, Brochez L. Clinical practice. Dysplastic nevi. N Engl J Med. 2003;349(23):223340. 9. Rigel DS, Rivers JK, Kopf AW, Friedman RJ, Vinokur AF, Heilman ER, et al. Dysplastic nevi. Markers for increased risk for melanoma. Cancer. 1989;63(2):386-9. 10. Evans RD, Kopf AW, Lew RA, Rigel DS, Bart RS, Friedman RJ, et al. Risk factors for the development of malignant melanoma--I: Review of case-control studies. J Dermatol Surg Oncol. 1988;14(4):393-408.

Rev Col Bras Cir. 2018;45(4):e1715


6

Ferreira Retrospective study of patients with cutaneous melanoma treated at the Federal University of São Paulo.

11. Góralska A, Blaszczyk J. Characteristics of risk factors for development of melanocytic naevi and melanoma in patients presented to a dermatologist to assess melanocytic lesions. Przegl Dermatol. 2013;100(1):86-95. 12. Williams ML, Sagebiel RW. Melanoma risk factors and atypical moles. West J Med. 1994;160(4):343-50. 13. Ivry GB, Ogle CA, Shim EK. Role of sun exposure in melanoma. Dermatol Surg. 2006;32(4):481-92. Erratum in: Dermatol Surg. 2006;32(6):preceding 773. 14. Colantonio S, Bracken MB, Beecker J. The association of indoor tanning and melanoma in adults: systematic review and meta-analysis. J Am Acad Dermatol. 2014;70(5):847-57. e1-18. 15. Lazovich D, Vogel RI, Berwick M, Weinstock MA, Anderson KE, Warshaw EM. Indoor tanning and risk of melanoma: a case-control study in a highly exposed population. Cancer Epidemiol Biomarkers Prev. 2010;19(6):1557-68. 16. Elliott F, Suppa M, Chan M, Leake S, Karpavicius B, Haynes S, et al. Relationship between sunbed use and melanoma risk in a large case-control study in the United Kingdom. Int J Cancer. 2012;130(12):3011-3. 17. Zhang M, Qureshi AA, Geller AC, Frazier L, Hunter DJ, Han J. Use of tanning beds and incidence of skin cancer. J Clin Oncol. 2012;30(14):1588-93. 18. Bentzen J, Krarup AF, Castberg IM, Jensen PD, Philip A. Determinants of sunbed use in a population of Danish adolescents. Eur J Cancer Prev. 2013;22(2):126-30. 19. Stapleton JL, Hillhouse J, Turrisi R, Robinson JK, Baker K, Manne SL, et al. Erythema and ultraviolet indoor tanning: findings from a diary study. Transl Behav Med. 2013;3(1):10-6. 20. Gordon D, Gillgren P, Eloranta S, Olsson H, Gordon M, Hansson J, et al. Time trends in incidence of cutaneous melanoma by detailed anatomical location and patterns of ultraviolet radiation exposure: a retrospective population-based study. Melanoma Res. 2015;25(4):348-56. 21. Shain AH, Yeh I, Kovalyshyn I, Sriharan A, Talevich E, Gagnon A, et al. The genetic evolution of melanoma from precursor lesions. N Engl J Med. 2015;373(20):1926-36. 22. Rozeman EA, Dekker TJA, Haanen JBAG, Blank CU. Advanced melanoma: current treatment options,

23. 24.

25.

26.

27.

28.

29.

30.

31.

32.

33.

biomarkers, and future perspectives. Am J Clin Dermatol. 2018;19(3):303-17. Shain AH, Bastian BC. From melanocytes to melanomas. Nat Rev Cancer. 2016;16(6):345-58. Svedman FC, Pillas D, Taylor A, Kaur M, Linder R, Hansson J. Stage-specific survival and recurrence in patients with cutaneous malignant melanoma in Europe - a systematic review of the literature. Clin Epidemiol. 2016;8:109-22. Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol. 2009;27(36):6199-206. National Comprehensive Cancer Network. NCCN Clinical practice guidelines in oncology. Melanoma. Fort Washington (PA): NCCN; 2016. Maurichi A, Miceli R, Camerini T, Mariani L, Patuzzo R, Ruggeri R, et al. Prediction of survival in patients with thin melanoma: results from a multi-institution study. J Clin Oncol. 2014;32(23):2479-85. Ericksson H, Frohm-Nilsson M, Järås J, KanterLewensohn L, Kjellman P, Månsson-Brahme E, et al. Prognostic factors in localized invasive primary cutaneous malignant melanoma: results of a large populationbased study. Br J Dermatol. 2015;172(1):175-86. Ransohoff KJ, Jaju PD, Tang JY, Carbone M, Leachman S, Sarin KY. Familial skin cancer syndromes: increased melanoma risk. J Am Acad Dermatol. 2016;74(3):423-34. Nikolaou V, Stratigos AJ. Emerging trends in the epidemiology of melanoma. Br J Dermatol. 2014;170(1):11-9. Aoude LG, Wadt KA, Pritchard AL, Hayward NK. Genetics of familial melanoma: 20 years after CDKN2A. Pigment Cell Melanoma Res. 2015;28(2):148-60. Edge SB, Carducci M, Byrd DR, eds. AJCC Cancer Staging Manual. 7th ed. New York: Springer-Verlag; 2009. Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Ding S, Byrd DR, et al. Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases. J Clin Oncol. 2010;28(14):2452-9.

Rev Col Bras Cir. 2018;45(4):e1715


Ferreira Retrospective study of patients with cutaneous melanoma treated at the Federal University of São Paulo.

34. Thompson JF, Soong SJ, Balch CM, Gershenwald JE, Ding S, Coit DG, et al. Prognostic significance of mitotic rate in localized primary cutaneous melanoma: an analysis of patients in the multi-institutional American Joint Committee on Cancer melanoma staging database. J Clin Oncol. 2011;29(16):2199205. Erratum in: J Clin Oncol. 2011;29(21):2949. 35. MacKie RM, Hauschild A, Eggermont AM. Epidemiology of invasive cutaneous melanoma. Ann Oncol. 2009;20 Suppl 6: vi1-7. 36. Vazquez Vde L, Silva TB, Vieira Mde A, de Oliveira AT, Lisboa MV, de Andrade DA, et al. Melanoma characteristics in Brazil: demographics, treatment, and survival analysis. BMC Res Notes. 2015;8:4. 37. Chen W, Mempel M, Traidl-Hofmann C, Al Khusaei S, Ring J. Gender aspects in skin diseases. J Eur Acad Dermatol Venereol. 2010;24(12):1378-85. 38. Pérez-Gómez B, Aragonés N, Gustavsson P, Lope V, López-Abente G, Pollán M. Do sex and site matter? Different age distribution in melanoma of the trunk among Swedish men and women. Br J Dermatol. 2008;158(4):766-72. 39. Lowe GC, Saavedra A, Reed KB, Velazquez AI, Dronca RS, Markovic SN, et al. Increasing incidence of melanoma among middle-aged adults: an epidemiologic study in Olmsted County, Minnesota. Mayo Clin Proc. 2014; 89(1):52-9. 40. Reed KB, Brewer JD, Lohse CM, Bringe KE, Pruitt CN, Gibson LE. Increasing incidence of melanoma among young adults: an epidemiological study in Olmsted County, Minnesota. Mayo Clin Proc. 2012;87(4):328-34. 41. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11-30. 42. Erdmann F, Lortet-Tieulent J, Schüz J, Zeeb H, Greinert R, Breitbart EW, et al. International trends in the incidence of malignant melanoma 19532008--are recent generations at higher or lower risk? Int J Cancer. 2013;132(2):385-400. 43. Ivry GB, Ogle CA, Shim EK. Role of sun exposure in melanoma. Dermatol Surg. 2006;32(4):481-92. 44. Colantonio S, Bracken MB, Beecker J. The association of indoor tanning and melanoma in adults: systematic review and meta-analysis. J Am Acad Dermatol. 2014;70(5):847-57.e1-18.

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45. Kirkland EB, Zitelli JA. Mitotic rate for thin melanomas: should a single mitotic figure warrant a sentinel lymph node biopsy? J Dermatol Surg. 2014;40(9):937-45. 46. Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV, Ross MI, Lazar AJ, Faries MB, Kirkwood JM, McArthur GA, Haydu LE, Eggermont AMM, Flaherty KT, Balch CM, Thompson JF; for members of the American Joint Committee on Cancer Melanoma Expert Panel and the International Melanoma Database and Discovery Platform. Melanoma Staging: Evidencebased changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(6):472-92. 47. Wat H, Senthilsenvan A, Salopek TG. A retrospective, multicenter analysis of the predictive value of mitotic rate for sentinel lymph node (SLN) positivity in thin melanomas. J Am Acad Dermatol. 2016;74(1):94101. 48. Kibrité A, Milot H, Douville P, Gagné ÉJ, Labonté S, Friede J, et al. Predictive factors for sentinel lymph nodes and non-sentinel lymph nodes metastatic involvement: a database study of 1,041 melanoma patients. Am J Surg. 2016;211(1):89-94. 49. Chhabra G, Ndiaye MA, Garcia-Peterson LM, Ahmad N. Melanoma chemoprevention: current status and future prospects. Photochem Photobiol. 2017;93(4):975-89. 50. Green AC, Williams GM, Logan V, Strutton GM. Reduced melanoma after regular sunscreen use: randomized trial follow-up. J Clin Oncol. 2011;29(3):257-63.

Received in: 01/08/2018 Accepted for publication: 05/17/2018 Conflict of interest: none. Source of funding: none. Mailing address: Tácito Ferreira E-mail: tacito.ferreira@hotmail.com dra.afo@gmail.com

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Original Article

DOI: 10.1590/0100-6991e-20181837

Experimental study of femoral vein reconstruction with sugarcane biopolymer tubular graft. Estudo experimental de reconstrução da veia femoral com enxerto tubular do bipolímero de cana-de-açúcar. Daniella Maria Souza Silva1; Esdras Marques Lins, TCBC-PE1; Sílvio Romero Barros Marques, TCBC-PE1; Amanda Vasconcelos Albuquerque1; José Lamartine Andrade Aguiar, TCBC-PE1 A B S T R A C T Objective: to evaluate, through Doppler flowmetry, venography, histology and clinical evolution, the use of sugarcane biopolymer (BP) tubular grafts in the reconstruction of femoral veins in dogs. Methods: we submitted eight adult dogs to femoral vein reconstruction, on the left with BP tubular graft and on the right with autologous vein. In the postoperative period, the animals underwent clinical evaluation and femoral vein Doppler flowmetry. After 360 days, we reoperated the dogs and submitted them to femoral vein phlebography with iodinated contrast. We removed the segments of the femoral veins containing the grafts and sent them for histopathological evaluation. Results: the dogs did not present hemorrhage, hematoma, surgical wound infection or operated limb edema. One animal had superficial venous dilatation in the left inguinal region. Phlebography performed 360 days after the first surgery showed that three (37.5%) BP grafts and seven (87.5%) grafts from the control group (C) were patent. In the histopathological evaluation, we found an inflammatory reaction, with neutrophils and lymphocytes on the external surface of both groups. In the intimal layer of the grafts and in the outer layer in the two groups, we observed fibrosis. Conclusion: based on the results obtained with the experimental model used, BP presents potential to be used as a tubular graft for venous revascularization. However, new research must be performed to confirm its efficacy in the revascularization of medium and large diameter veins, which could allow its use in clinical practice. Keywords: Vascular Grafting. Femoral Vein. Saccharum. Bioprosthesis. Vascular Surgical Procedures. Dogs.

INTRODUCTION

V

enous reconstruction surgery, especially when involving the use of vascular substitutes, poses a major challenge to the vascular surgeon, since the veins can easily lose their cylindrical shape. Currently, the most applied venous reconstructive surgical techniques use vascular substitutes in tubular form or as patches1-3. The vascular substitutes used in venous reconstruction may be autologous, biological or synthetic. Autologous substitutes are the most cost-effective, but have limited use by the availability of autologous veins in each patient. Synthetic substitutes, such as those of Dacron and e-PTFE are expensive, less resistant to infection, and are used in the reconstruction of large diameter veins4-10.

A special class of material produced from substances synthesized by different types of microorganisms has been recently studied. These microorganisms exhibit organic tissue characteristics, such as flexibility and resistance to rupture. An example of this type of material is an extracellular polysaccharide, produced through bacterial synthesis from sugarcane molasses, developed at the Biopolymers Laboratory of the Sugarcane Experiment Station of the Federal Rural University of Pernambuco. The Sugarcane Biopolymer (BP) presents flexibility, resistance to rupture, besides being biocompatible and presenting low cytotoxicity11-17. Recently the BP membrane has been successfully used as a patch in arterioplasties and venoplasties in the femoral vessels of dogs, with no reported cases of thrombosis, rupture or rejection16,17.

1 - Federal University of Pernambuco, Surgery Department, Recife, PE, Brazil. Rev Col Bras Cir. 2018;45(4):e1837


Silva Experimental study of femoral vein reconstruction with sugarcane biopolymer tubular graft.

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The development in the production and technological innovation of BP materials resulted in the creation of tubes, which can be applied, at low cost, in the area of vascular surgery as tubular venous grafts. The purpose of this study was to evaluate, through Doppler flowmetry, venography, histology and clinical evolution, the use of BP tubular grafts in the reconstruction of femoral veins in dogs.

METHODS We used eight adult dogs, six males, with a mean weight of 16.8kg in this study. We kept the animals at the Experimental Surgery Nucleus of the Center of Health Sciences of the Federal University of Pernambuco (NCE-CCS-UFPE). This research was approved by the Animal Experimentation Ethics Committee of the Center of Biological Sciences of the Federal University of Pernambuco (CEEA-UFPE), under the procedure 23076.000105/2012-22. It is in accordance with the norms in force in Brazil, especially Law n# 11,749, of 2008, regulated by Decree n# 6899, of July 15, 2009, which deals with animal use for scientific purposes. Prior

to

undergoing

any

surgical

procedure, all animals received: 1) Duramune Max 10ÂŽ for immunization against the distemper virus, coronavirus type 2, adenovirus and parvovirus CPV2b, parainfluenza virus, and against Leptospira (L. canicola, L. icterohaemorrhagiae, L. grippotyphosa and L. Pomona); 2) antirabic vaccine. As vermicide, the dogs were given subcutaneous AncilexÂŽ at a dosage of 1ml/5kg, for hookworm, spirocercosis and toxocariasis. They remained in the vivarium under surveillance for a period of 21 days before being submitted to the experimental procedure. Preoperatively and throughout the experiment period, they were fed daily with water and 6kg of chow specific for adult dogs. The study design used was the randomized controlled trial.

We divided the experiment into two groups: one control group consisting of eight right femoral veins with autologous femoral vein graft, and the experimental group, consisting of eight left femoral veins with the BP tubular graft. In this research, each animal was its own control. During the study period, the animals were conducted by trained technicians and veterinarians following international standards for animal research. Before surgery, the animals fasted for 12 hours. Anesthesia was performed with thiopental sodium (12.5mg/kg), ketamine hydrochloride (2.5mg/kg) and pancuronium bromide (0.2mg/kg). Each animal was then placed in dorsal decubitus and submitted to orotracheal intubation. Next, trichotomy and antisepsis of the inguinal regions were performed, and the femoral veins were accessed through a 5cm long longitudinal inguinal incision. After exposure of the femoral veins, we resected a 10mm-long segment from the left femoral vein, which we then reconstructed with the BP tubular graft through continuous, terminal-terminal, proximal and distal sutures with cardiovascular 7.0 polypropylene suture. We performed the same procedure in the right femoral vein, but we made its reconstruction with a 10mm venous segment taken from the left femoral vein. The dogs were followed for 360 days after surgery through clinical evaluation and doppler flowmetry. In the first week, the animals received daily clinical evaluation, and from the eighth day on, the evaluation was weekly until the 30th postoperative day. Thereafter, we evaluated the animals monthly until the end of the evaluation period. After 360 days monitoring, we reoperated the dogs following the same conditions of anesthesia and access of the femoral veins of the first surgery. After exposure of the femoral veins and puncture of the internal saphenous veins, right and left, we performed a phlebography. After the phlebography, we sacrificed

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Silva Experimental study of femoral vein reconstruction with sugarcane biopolymer tubular graft.

the animals with a toxic dose of the anesthetic and removed the left and right femoral vein segments containing the BP and control grafts. For the histological evaluation, the removed venous segments were fixed in 10% neutral formalin. The material was then stained with hematoxylin and eosin and Masson's trichrome for microscopic study. The specimens were processed in the Laboratory of Histopathology Research of the Post-Graduation in Pathological Anatomy of the Federal University of Pernambuco. For data analysis, we computed absolute and percentage distributions of the statistical measures, mean, median, standard deviation, variation coefficient and minimum and maximum values

(descriptive

statistics

techniques),

frequency percentages and the respective variants distributions. We applied the chi-square test for homogeneity to assess whether the distribution of variables differed between groups. In cases where the assumptions of the chi-square test were not satisfied, we used the Fisher's exact test. We considered the significance level of 5% in all the conclusions. We entered the data in an Excel spreadsheet and analyzed it using the Statistical

3

Package for Social Sciences (SPSS) software, version 18.

RESULTS All eight animals survived the established 360-day period for clinical observation and second surgery. During the observation period, the dogs had no clinical signs of hemorrhage or hematoma in the operative wound. There were also no signs of wound infection or edema in the operated limbs in both groups. One dog presented dilation of the superficial veins in the limb and left inguinal region (BP) (Table 1). The postoperative Doppler flow measurement showed the presence of phasic flow with the respiration in the femoral veins in all dogs evaluated on the first postoperative (POD). The flow pattern changed, losing the characteristic of being phasic with breathing and becoming continuous in the BP group as follows: in the eighth POD, one dog presented continuous flow, in the 30th POD, two dogs, and 360 days after the surgery, five dogs. In the control group, we observed that in the eighth and thirtieth day the dogs maintained the phasic flow with respiration, but 360 days after surgery one dog presented continuous pattern flow (Table 1).

Table 1. Distribution of Doppler flow, edema and superficial venous dilatation at different moments of the evaluation.

1stday BP Control Phasic Flow   Yes 8 (100%) 8 (100%)    No 0 (0%) 0 (0%)    p-value* -** Edema    Yes 0 (0%) 0 (0%)    No 8 (100%) 8 (100%)    p-value* -** Superficial Venous Dilatation    Yes 0 (0%) 0 (0%)    No 8 (100%) 8 (100%)    p-value* -**

8thday BP Control 7 (87.5%) 8 (100%) 1 (12.5%) 0 (0%) 1,000

30thday BP Control

360thday BP Control

6 (75%) 8 (100%) 3 (37.5%) 7 (87.5%) 2 (25%) 0 (0%) 5 (62.5%) 1 (12.5%) 0467 0119

0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 8 (100%) 8 (100%) 8 (100%) 8 (100%) 8 (100%) 8 (100%) -** -** -** 0 (0%) 0 (0%) 0 (0%) 0 (0%) 1 (12.5%) 0 (0%) 8 (100%) 8 (100%) 8 (100%) 8 (100%) 7 (87.5%) 8 (100%) -** -** 1.000

* p-value of Fisher's exact test (if p-value <0.05, the distribution of the factor under study is homogeneous between the moments of analysis); ** Could not be calculated, therefore, the absence/presence was constant at the moments evaluated.

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Silva Experimental study of femoral vein reconstruction with sugarcane biopolymer tubular graft.

Phlebography performed 360 days after the first surgery showed that three (37.5%) BP and seven (87.5%) grafts of the control group were patent (Figure 1).

The implants of the control group were also externally coated by a layer of inflammatory cells, but these occurred less than in the experimental group, demonstrating a mild inflammatory reaction. In the control group, the inflammatory cell layer was also coated externally by a thick layer of fibrous tissue. We found no foci of degenerative process or areas of calcification.

Figure 1. Phlebography after 360 days: radiopaque needles highlight the grafts.

At the macroscopic evaluation, the femoral veins in both groups were externally lined by a thick layer of loose connective tissue

Figure 2. Femoral vein appearance in the BP group after 360 days.

and showed scarring adherence to neighboring tissues. We observed no change in staining or consistency of the BP graft (Figure 2). Histological evaluation of the venous segments showed that the inner layer of the grafts was continuous with the intima layer of the recipient femoral vein and formed by a thick layer of fibrous tissue firmly adhered to the internal surface of the grafts (Figure 3). The external surface of the grafts in the BP group was surrounded by a layer of connective tissue rich in lymphocytes, neutrophils and rare macrophages firmly adhered to the grafts. This layer with inflammatory cells was coated externally by a thick layer of fibrous tissue.

Figure 3. Internal surface of the BP graft. Vv- vasa-vasorum; E- endothelium; CT- connective tissue.

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Silva Experimental study of femoral vein reconstruction with sugarcane biopolymer tubular graft.

DISCUSSION Dogs have been used as experimental models in several scientific studies. Some authors describe that the behavior of vascular prostheses in dogs is what most resembles humans. This explains their preference as an animal model commonly used for evaluation of vascular grafts16-21. Due to both the simplicity of the access and diameter, we chose the femoral veins for the accomplishment of these experiments. In femoral vein exposure there is no trauma to the abdominal musculature, which is often related to pain and limitation of movements in the postoperative period, and there is no manipulation of the intra-abdominal organs, as occurs in surgery on the inferior vena cava. There is a lower risk of severe hemodynamic changes and, in addition, the extensive network of collateral veins in this region ensures, in most cases, limb drainage when femoral vein thrombosis occurs16,17,20. Although the BP graft presented some properties different from those of an autologous vein, such as minor elasticity, there was no difficulty in performing the suture. This feature has already been demonstrated in other studies that used the BP membrane as a patch in angioplasties of the femoral arteries and veins of dogs 16,17. Another aspect of the present study is that the control group comprised the femoral veins contralateral to that of the BP graft implants. This allowed a smaller number of animals to be used in the study, and consequently sacrificed, which is

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in accordance with current bioethical principles. In addition, the fact that each animal is its own control made the groups more homogeneous, as well as in other studies that used the same principle, as in the cases of biopolymer patches in veins and femoral arteries of dogs, and in the use of latex as prosthesis in the femoral artery also of dogs16,17. The observation time of the groups was 360 days. This period is in agreement with the observed in several experimental works that evaluate the use of vascular substitutes in animal models. This occurs because the healing process of the vascular grafts, which involves its incorporation by the adjacent organic tissues, occurs between 180 and 360 days after the implant3,20,21. The complementary exams used in this study for the evaluation of the venous grafts were Doppler flowmetry and ascending phlebography. Doppler flowmetry is a noninvasive test that uses ultrasound principles to assess venous flow, but does not provide information on vein morphology. Several experimental studies have shown that Doppler flowmetry can be used in postoperative evaluations in reconstructive vascular surgery. Phlebography is an invasive examination that uses iodinated contrast and allows studying both venous physiology and morphology, so it is considered the gold standard for the evaluation of the venous system and has been widely used in experimental models that use animals to test vascular substitutes16,17. The association between clinical evaluation, Doppler flowmetry and phlebography allowed a high sensitivity in the diagnosis of thrombosis and venous graft patency.

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Silva Experimental study of femoral vein reconstruction with sugarcane biopolymer tubular graft.

The use of these exams in association has been described in other experimental studies evaluating venous grafts16,17. The main complications resulting from the use of tubular venous grafts are thrombosis, rupture and infection of the surgical wound. Several authors have reported the occurrence of these complications. The rate of thrombosis found in the literature with reconstructions using synthetic vena cava substitutes varies from 20 to 30% after one year of surgery. In the reconstruction of the iliac veins in humans, which present a smaller caliber than the vena cava using synthetic e-PTFE prosthesis, the one-year thrombosis rate is about 50%, while in endovascular reconstructions, also of the iliac veins, the rate of thrombosis after one year ranges from 70 to 80%7-10. Greca's study, which used a patch with a biological graft in the vena cava of dogs, revealed that after 40 days, only one of the 16 studied dogs had partial thrombosis, and anticoagulation was performed in the transoperative period3. In the present study, we used no anticoagulation, which may have contributed to the higher rate of thrombosis in the BP group. We identified no cases of infection or hemorrhage in the operative wound in both groups, findings that have been reported in other experimental studies16,17. The development of chronic inflammatory reaction on the external surface and the presence of fibrosis on the internal surface were observed in all cases of the control group and in the experimental group, similar to that found in the literature16,17.

The healing process of the BP grafts occurred in a similar way to that of the autologous vein grafts with regard to the presence of inflammatory cells on their external surface and fibrosis on both surfaces, but in the experimental group there was a more important inflammatory reaction than in the control one. We found no phagocytic cells in the inflammatory reaction of the external surface of the grafts of either group. The absence of these inflammatory cells confirms the low antigenic content of both grafts, since the presence of phagocytic cells has the objective of defending the organism against an aggressive agent. We observed no foci of calcification in the biopolymer prosthesis, as observed in heterologous grafts20-23. The inflammatory reaction observed in this study was concentrated in the periphery of the implants, both in the autologous graft and in the BP prosthesis. We also observed that the intima and adventitia layers were firmly adhered, respectively, to the inner and outer faces of the biopolymer prosthesis. This aspect has already been described in previous studies that used BP membrane patches in arterioplasties and femoral venoplasties in dogs10,11. Advances in the surgical treatment of chronic acute venous lesions have been slowly evolving. The results obtained in this study represent a perspective for venous reconstruction surgery in humans. Due to its low cost, the use of BP grafts may bring new possibilities for the treatment of several venous diseases. New research must be carried out to confirm and improve the results found.

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Silva Experimental study of femoral vein reconstruction with sugarcane biopolymer tubular graft.

7

R E S U M O Objetivo: avaliar, através de dopplerfluxometria, de venografia, de histologia e de evolução clínica, o uso de enxertos tubulares de biopolímero de cana-de-açúcar (BP) na reconstrução de veias femorais em cães. Métodos: oito cães adultos foram submetidos à reconstrução de veia femoral, à esquerda com enxerto tubular de BP e à direita com veia autóloga. No período pós-operatório, os animais foram submetidos à avaliação clínica e dopplerfluxometria das veias femorais. Após 360 dias, os cães foram reoperados e submetidos à flebografia das veias femorais com contraste iodado. Os segmentos das veias femorais contendo os enxertos foram retirados e enviados para avaliação histopatológica. Resultados: os cães não apresentaram hemorragia, hematoma, infecção da ferida operatória ou edema dos membros operados. Um animal apresentou dilatação venosa superficial na região inguinal esquerda. A flebografia realizada 360 dias após a primeira cirurgia demonstrou que três (37,5%) enxertos de BP e sete (87,5%) do grupo controle (C) estavam pérvios. Na avaliação histopatológica foi encontrada uma reação inflamatória com neutrófilos e linfócitos na superfície externa de ambos os grupos. Na camada íntima de revestimento dos enxertos e na camada externa nos dois grupos, foi encontrada fibrose. Conclusão: com base nos resultados obtidos com o modelo experimental utilizado, conclui-se que a BP apresenta potencial para ser utilizado como enxerto tubular para revascularização venosa, porém novas pesquisas precisam ser realizadas para confirmar a sua eficácia na revascularização de veias de médio e grande calibre, o que poderia permitir o seu uso na prática clínica. Descritores: Enxerto Vascular. Veia Femoral. Saccharum. Bioprótese. Procedimentos Cirúrgicos Vasculares. Cães.

REFERENCES 1.

2.

3.

4. 5.

6.

7.

8.

J Vasc Surg Venous Lymphat Disord. 2018;6(2):173-

Lantz GC, Badylak SF, Coffey AC, Geddes LA, Sandusky GE. Small intestinal submucosa as a superior vena cava graft in the dog. J Surg Res. 1992;53(2):175-81. D'Andrilli A, Ciccone AM, Ibrahim M, Venuta F, Rendina EA. A new technique for prosthetic reconstruction of the superior vena cava. J Thorac Cardiovasc Surg. 2006;132(1):192-4. Greca FH, Noronha L, Costa FDA, Souza Filho ZA, Soccol AT, Feres NA, et al. Estudo comparativo da biocompatibilidade da submucosa intestinal porcina e pericárdio bovino como enxertos na veia cava de cães. Acta Cir Bras. 2005;20(4):317-22. Eberhardt RT, Raffetto JD. Chronic venous insufficiency. Circulation. 2014;130(4):333-46. Daenens K, Fourneau I, Nevelsteen A. Ten-year experience in autogenous reconstruction with the femoral vein in the treatment of aortofemoral prosthetic infection. Eur J Vasc Endovasc Surg. 2003;25(3):240-5. Florek HJ, Brunkwall J, Orend KH, Handley I, Pribble J, Dieck R. Results from a First-in-Human trial of a novel vascular sealant. Front Surg. 2015;2:29. Caroll S, Moll S. Inferior vena cava filters, MayThurner syndrome, and veins stents. Circulation. 2016;133(6):e383-7. Erben Y, Bjarnason H, Oladottir GL, McBane RD, Gloviczki P. Endovascular recanalization for nonmalignant obstruction of the inferior vena cava.

9.

10.

11.

12.

13.

14.

15.

82. Sfyroeras GS, Antonopoulos CN, Mantas G, Moulakakis KG, Kakisis JD, Brountzos E, et al. A review of open and endovascular treatment of superior vena cava syndrome of benign aetiology. Eur J Vasc Endovas Surg. 2017;53(2):238-54. Campbell CD, Goldfarb D, Roe R. A small arterial substitute: expanded microporous polytetrafluoroethylene: patency versus porosity. Ann Surg. 1975;182(2):138-43. Xue L, Greisler HP. Biomaterials in the development and future of vascular grafts. J Vasc Surg. 2003;37(2):472-80. Daghighi S, Sjollema J, van der Mei HC, Busscher HJ, Rochford ET. Infection resistance of degradable versus non-degradable biomaterials: an assessment of the potential mechanisms. Biomaterials. 2013;34(33):8013-7. Fernandes Teixeira FM, Figueiredo Pereira M, Gomes Ferreira NL, Miranda GM, Andrade Aguiar JL. Spongy film of cellulosic polysaccharide as a dressing for aphthous stomatitis treatment in rabbits. Acta Cir Bras. 2014;29(4):231-6. Paterson-Beedle M, Kennedy JF, Melo FAD, Lloyd LL, Medeiros V. A cellulosic exopolysaccharide produced from sugarcane molasses by a Zoogloea sp. Carbohydr Polym. 2000;42(4):375-83. Martins AG, Lima SV, Araújo LA, Vilar FO, Cavalcante NT. A wet dressing for hypospadias surgery. Int Braz J Urol. 2013;39(3):408-13.

Rev Col Bras Cir. 2018;45(4):e1837


Silva Experimental study of femoral vein reconstruction with sugarcane biopolymer tubular graft.

8

16. Aguiar JL, Lins EM, Marques SR, Coelho AR, Rossiter

de

of autogenous canine fascia lata, Gore-Tex, lyophilized human fascia lata, and autogenous canine vein for vascular patch graft material in a canine arteriotomy model. Neurosurgery. 1992;31(1):108-13.

Albuquerque MC, de Andrade-Aguiar JL. Sugarcane

22. Douglas JF, Gaughran ER, Henderson J, Lord GH,

biopolymer patch in femoral vein angioplasty on

Rosenberg N. The use of arterial implants prepared

dogs. J Vasc Surg. 2012;55(2):517-21.

by enzymatic modification of arterial heterografts: II.

RO, Melo RJ. Surgarcane biopolymer patch in femoral artery angioplasty on dogs. Acta Cir Bras. 2007;22 Suppl 1:77-81. 17. de

Barros-Marques

SR,

Marques-Lins

E,

18. Berenstein A, Song JK, Tsumoto T, Namba K, Niimi

The physical properties of the elastica and collagen

Y. Treatment of experimental aneurysms with an

components of the arterial wall. AMA Arch Surg.

embolic-containing device and liquid embolic agent:

1957;74(1):89-95.

feasibility and angiographic and histological results.

23. Robotin-Johnson MC, Swanson PE, Johnson DC, Schuessler RB, Cox JL. An experimental model of small

Neurosurgery. 2009;64(2):367-73. 19. Divakov MG. Revascularization of avascular spongy bone and head of the femur in transplantation of

intestinal submucosa as a growing vascular graft. J Thorac Cardiovasc Surg. 1998;116(5):805-11.

vascular bundle (An experimental and clinical study). Received in: 01/04/2018

Acta Chir Plast. 1991;33(2):114-25. 20. Teijeira FJ, Marois Y, Aguiar L, Guidoin R, Bauset

Accepted for publication: 05/17/2018

R, Lamoureux G, et al. Comparison of processed

Conflict of interest: none.

bovine internal mammary arteries and autologous

Source of funding: none.

veins as arterial femoral substitutes in dogs: blood compatibility and pathological characteristics. Can J Surg. 1989;32(3):180-7. 21. Benzel EC, McMillan R, Fowler MR, Landreneau MD, Kesterson L, Payne DL. Histological comparison

Mailing address: Esdras Marques Lins E-mail: esdraslins@uol.com.br esdraslins39@gmail.com

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Original Article

DOI: 10.1590/0100-6991e-20181912

Surgical treatment of extravasation injuries: experience of the Hospital das Clínicas, Faculty of Medicine, University of São Paulo. Opções de tratamento cirúrgico em lesões cutâneas por extravasamento acidental de drogas: experiência do Hospital das Clínicas da Faculdade de Medicina da USP. Dimas André Milcheski1; Wellington Menezes Motta1; Rodolfo Costa Lobato1; Araldo Ayres Monteiro Júnior1; Rolf Gemperli, TCBC-SP1 A B S T R A C T Objective: to report the experience of the Division of Plastic Surgery of the Hospital das Clínicas of the Medical School of the University of São Paulo in the treatment of cutaneous lesions due to accidental extravasation of drugs. Methods: we included patients with lesions due to extravasation of drugs over a period of 18 months. We retrospectively evaluated the following parameters: age, diagnoses during hospitalization and comorbidities, serum levels of albumin and hemoglobin, place of hospitalization, drug involved, anatomic segment affected, therapeutic management and death during hospitalization. Results: we followed-up 14 patients. The main drug involved was noradrenaline (21%). All patients underwent debridement of tissue necrosis. Three patients were submitted to flaps after preparation of the wound bed with negative pressure therapy, with good results. Seven patients had no definitive treatment of their lesions due to lack of clinical conditions. Conclusion: in patients with favorable clinical conditions, the definitive treatment with flaps was adequate for cases of wounds due to extravasation of drugs in the subcutaneous tissue when there was exposure of noble structures. Keywords: Iatrogenic Disease. Extravasation of Diagnostic and Therapeutic Materials. Ischemia. Necrosis. Surgical Flaps. Surgery. Plastic.

INTRODUCTION

I

njury due to extravasation of drugs is the major cause of iatrogenic morbidity in the hospital

environment1. The incidence of this event in the

literature from varies 0.1% to 6% in adult patients and from 11% to 70%, in children2,3. Patients at extremes of age, neonates and the elderly, are at greater risk of injury by extravasation, in addition to individuals with altered levels of consciousness or sedated, who are unable to express pain4. This is an event that generates a high cost for the health system, involving expenses of around US$.66,000.00 due to lawsuits in the United States5. In up to 25% of cases of injury due to extravasation of drugs, the morbidity resulting from it is more serious than the underlying cause of the patient's hospitalization. This is due to pain, difficulty in

mobility, limitation of daily activities, permanent nerve damage, loss of limbs and, in some cases, death1. The occurrence of such lesions can be avoided with preventive measures. However, when they occur, they need rapid recognition of the event and immediate appropriate treatment to prevent progression. The delay in recognition of the lesion can lead to catastrophic consequences, from unsightly scars, contractures, cellulitis, need for skin grafts and flaps, neurovascular injury, limb shortening, amputations and even death6. This paper aims to report the experience of the Division of Plastic Surgery of the Hospital das Clínicas of the Medical School of the University of São Paulo (HC-FMUSP) in the treatment of cutaneous lesions due to accidental extravasation of drugs.

1 - Faculty of Medicine, University of São Paulo, Discipline of Plastic Surgery, Hospital das Clínicas, São Paulo, SP, Brazil.

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Milcheski Surgical treatment of extravasation injuries: experience of the Hospital das ClĂ­nicas, Faculty of Medicine, University of SĂŁo Paulo.

METHODS This is a retrospective, descriptive case series, in which we evaluated all the referrals for the wounds group of the Plastic Surgery Division of the HC-FMUSP from January 2016 to June 2017 (18 months). We included in the study all patients who presented with an injury resulting from inadvertent extravascular extravasation of medication during that period. We analyzed the following parameters: age of the patient at the time of the event; diagnoses during hospitalization and comorbidities; serum levels of albumin and hemoglobin; place of hospitalization - intensive care unit or ward; drug involved; anatomical segment involved; therapeutic treatment for the wound; occurrence of death during hospitalization. We performed descriptive data analysis with the Statistical Package for the Social Sciences, version 18.0 (SPSS Inc., Chicago, IL, USA). We described the categorical variables as percentages, and the continuous ones, as mean and standard deviation of the mean, if their distribution was normal, or as median and interquartile range, in case of non-normal distribution. This work was approved by the Institutional Ethics Committee with the following reference number 76201617.6.0000.0068.

RESULTS In the study period, 830 referrals for evaluation of wounds in the complex of the HC-FMUSP were analyzed by the Plastic Surgery Service, totaling 14 patients with injuries resulting from extravascular extravasation of drugs, with incidence in our sample of 1.6%

of wounds accompanied by the Plastic Surgery Wound Group. The mean age of the patients was 44.4Âą30.2 years, ranging from one month to 69. All the patients studied had at least two associated comorbidities, which can be observed in table 1. The most involved anatomical location was the hand dorsum (50%), with cutaneous lesions of total thickness and without the presence of infectious signs. Patients were treated in the intensive care unit in most cases (78.5%) and 57.1% died during hospitalization due to clinical worsening of comorbidities. In no case was the death due to wound complications. The main drug responsible for the incidents was noradrenaline (21%) administered in peripheral veins in two cases. In six cases, it was not possible to identify the medication involved. The main treatment applied was debridement of necrotic tissue of the wound bed and daily dressings associated with chemical debridant with 10% calcium alginate or papain in 11 cases (78.5%), due to hemodynamic conditions that prevented the performance of surgical procedures. Of these, eight died without definitive skin coverage. The other three that survived and did not receive skin flaps were pediatric patients, who presented good evolution and wound healing with conservative treatment with established dressings (Table 2). Three patients underwent wound closure by skin flaps. All had hemodynamic stability and were debrided in the operating room with wound bed preparation with negative pressure therapy, in addition to nutritional improvement, accompanied by an increase in serum albumin levels. One patient had an large hand and forearm lesion due

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Milcheski Surgical treatment of extravasation injuries: experience of the Hospital das Clínicas, Faculty of Medicine, University of São Paulo.

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Table 1. Patients’ clinical characteristics and lesion etiology.

Patient

Age (years)

Drug

Location

1

54

50% glucose

Right foot

2

1 month

Bicarbonate

Right hand

3

85

4

8 months

Unknown

Right hand

5 6

51 1 month

Unknown Bicarbonate

Right hand Right hand

7

65

Unknown

Right hand

8

51

9

59

Unknown

Left forearm

10

65

50% glucose

Left foot

11

56

Noradrenaline

Right groin

12

3 months

Unknown

Right forearm

13

69

Unknown

Right hand

66

Iron III hydroxide saccharate.

Right hand and forearm

14

Noradrenaline Left forearm

Noradrenaline Left forearm

Comorbidities Surgery for brain stem tumor + ischemic stroke + urinary septic shock + BCP ARF-peritoneal dialysis + congenital cardiopathy + CHF CHF + cardiogenic shock + ARF Fallot’s tetralogy + imperforate anus Crf + pacemaker + ischemic colitis Premature Post renal transplant + urinary sepsis Spinal cord injury + urinary sepsis + ARF Pelvic abscess + septic shock Post liver transplantation + ischemic cholangitis + pulmonary sepsis + transplant rejection CRF + isquemica cardiomyopathy + DM + AH Fallot’s tetralogy + endocarditis + ischemic stroke CRF + post renal transplant + AH + urinary sepsis CRF + post renal transplant + pancytopenia + active infection by parvovirus and cytomegalovirus

In-hospital Death unit ICU

Yes

ICU

Yes

ICU

Yes

Ward

U

ICU ICU

Yes No

ICU

Yes

ICU

Yes

ICU

Yes

ICU

Yes

ICU

No

ICU

No

Ward

No

Ward

No

BCP: Bronchopneumonia; ICU: Intensive Care Unit; ARF: Acute Renal Failure; CHF: Congestive Heart Failure; CRF: Chronic Renal Failure; DM: Diabetes Mellitus; AH: Arterial Hypertension.

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Milcheski Surgical treatment of extravasation injuries: experience of the Hospital das Clínicas, Faculty of Medicine, University of São Paulo.

Table 2. Type of treatment and patients’ nutritional parameters (levels of albumin and hemoglobin).

Patient 1 2 3 4 5 6 7 8 9 10 11 12 13 14

Albumin Hemoglobin (g/dl) (g/dl)

Treatment Debridement in bed + dressing (papain 10%) Debridement in bed + dressing (calcium and sodium alginate hydrogel®) ➜ healing Dressings (emollients) Debridement in bed + dressing (calcium and sodium alginate hydrogel®) ➜ healing Debridement in bed + dressing (papain 10%) Debridement in bed + dressing (calcium and sodium alginate hydrogel®) ➜ healing Soft silicone dressing with silver (mepilex ag®) Debridement in bed + dressing (papain 10%) Debridement in bed + dressing (papain 10%) Debridement in bed + dressing (papain 10%) Debridement + negative pressure therapy for ➜ tensor fascia lata flap Debridement in bed + dressing (calcium and sodium alginate - hydrogel®) ➜ healing Debridement + local rhomboid flap Debridement + negative pressure therapy ➜ groin flap to hand + forearm grafting

2.6

8.6

3

12.7

2.9

13.7

3.1

13.6

1.5

8.8

3.3

11.6

2.7 1.6 1.6 1.6 3

11.7 9.2 7 6.3 7.7

5.7

14.2

2.3

7.8

2.6

10.2

to iron III hydroxide saccharate (Figure 1). The treatment initially adopted was surgical debridement and negative pressure therapy, with evolution to an adequate bed. At that time, we applied a pediculated groin flap based on the superficial iliac circumflex artery to cover the back of the right hand (Figure 2) and grafting on the forearm, obtaining an excellent esthetic and functional result (Figure 3). The second case, due to noradrenaline extravasation in the right inguinal region, was resolved by means of a tensor fascia lata flap, due to the presence of noble structures in the inguinal region, after seven days of negative pressure

Figura 1. Injury to the back of the hand and forearm: extensive initial lesion with exposure of extensor tendons, requiring cutaneous coverage through a flap.

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Milcheski Surgical treatment of extravasation injuries: experience of the Hospital das ClĂ­nicas, Faculty of Medicine, University of SĂŁo Paulo.

Figura 2. Patient submitted to a pediculated groin flap with adequate coverage of the back of the hand, without tendon or other noble structures exposure.

Figura 3. Aesthetic and functional result after six months of the groin flap to the back of the right hand and partial skin graft in the forearm.

therapy (Figure 4). The patient evolved without complications in the surgical wound and without limitations of limb mobilization. The third case in which a flap was necessary was due to unidentified extravasation on the back of the right hand, receiving a local rhomboid flap following a week of negative pressure therapy (Figure 5). The cutaneous cover was satisfactory for the coverage of the tendons of the back of the hand, without limitations.

5

Figura 4. Tensor fascia lata flap to cover the right inguinal region, previously submitted to debridement and negative pressure therapy, requiring a small partial skin graft in the flap donor area.

Figura 5. Rhomboid local flap (Limberg) on the back of right hand. In the upper left corner, initial ulcerated lesion, treated with debridement and vacuum dressing, allowing the local flap to be carried out, with good wound coverage.

DISCUSSION The incidence of drug extravasations in the literature is underestimated, as most are not reported7,8. Most of these events occur at night, going unnoticed, and the risk is increased when inexperienced individuals are manipulating intravenous accesses, especially when cytotoxic drugs are used8. Possibly, the number of events

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Milcheski Surgical treatment of extravasation injuries: experience of the Hospital das ClĂ­nicas, Faculty of Medicine, University of SĂŁo Paulo.

occurred in our Hospital is greater than the observed, considering that only one of the cases did not require surgical debridement for the removal of necrotic tissue. Thus, probably the evaluation of the Plastic Surgery was requested only for the most serious cases. The sites most frequently involved in cases of drug extravasation are the back of the hand and foot, ankle, antecubital fossa, near joints or joint spaces, areas with little subcutaneous tissue to protect underlying structures8,9. In the presented series, the main agent responsible for the lesions due to extravasation was noradrenaline, and in two of the three cases, it was being administered in a peripheral vein. The main risk factors for necrosis due to extravasation of vasopressor drugs are the presence of vascular diseases, hypotension, diabetic neuropathy, Raynauld's disease, coagulopathy, advanced age and altered mental status10. In addition, another important risk factor is administration to small, peripheral or slow-circulation veins, such as the antecubital fossa and the saphenous vein. The rate of cutaneous necrosis resulting from peripheral administration of noradrenaline amounts to 46-60%. The rapid recognition of the adverse event is essential for the initial measures to be taken. Early diagnosis is critical to reduce the extent of the lesion and the first symptoms are pain, erythema and local edema, followed by pallor, flicten and cutaneous dyschromia. The presence of pain is the most important symptom to alert the team about the occurrence of extravasation, and its duration, referred by the patients, indicates the severity of the event8,11. After recognition of the lesion by extravasation, the infusion of the drug should be immediately interrupted, and its aspiration, attempted through the existing access. There are a range of acceptable options, such as immobilization

and continuous observation, topical and injectable antidotes when available, subcutaneous irrigation techniques, and early surgical debridement and fasciotomy, when there are signs of compartment syndrome12. Surgical intervention of extravasation lesions may be immediate or late. The best timing and type of surgical intervention required in extravasation lesions remains controversial in view of the variety of agents causing the lesions and the characteristics of the patients in the studies3,13,14. Although some authors advocate early surgical intervention within 24 hours after the event to avoid ulceration, necrosis and secondary infection, most recommend a conservative initial management14,15. However, surgical treatment may be necessary early and its indication can be classified into three situations: emergency (neurovascular involvement or suspicion of compartment syndrome); urgency (persistent pain, total plane necrosis and cutaneous sepsis focus) and elective (ulceration, nonadherence to treatment with dressings, delayed treatment of the underlying disease and delayed healing)3,16. We agree that, initially, all cases of extravasation identified should be treated through frequent observation and conservative methods. Such measures include elevation of the affected limb, emollient, anti-inflammatory and analgesic agents, cold dressings (or heated if caused by catecholamines or vinca-derived alkaloids), surgery being reserved to the situations previously mentioned, and whenever there is delimitation of the necrotic tissue, a period that varies between 24 hours and 14 days7. Thus, we based our definitive surgical management on two main conditions: the presence of necrosis and the patient's clinical and nutritional conditions (Figure 6). In general, we prefer to perform definitive surgical treatment in patients with hemoglobin levels above 10g/dl and albumin above 3.0g/dl.

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Milcheski Surgical treatment of extravasation injuries: experience of the Hospital das ClĂ­nicas, Faculty of Medicine, University of SĂŁo Paulo.

Figura 6. Flowchart of conduct after injury by drug extravasation, based on the presence or absence of necrosis and on the patient's clinical conditions.

Firat et al.7 studied 22 cases of drug extravasation in a two-year period, with involvement of the upper limb in most cases (68%), more specifically the back of the hand. The majority of the cases required surgical resolution and were resolved with skin grafts (36.4%) and flaps (27.3%). The closure of the wound by second intention occurred in five cases, and conservative treatment, in three cases. The author believes that surgical management should be reserved for cases of cutaneous necrosis in which there is indication of a surgical procedure, not intervening early in extravasation cases. In general, surgical procedures are required in about one-third of initially conservatively managed extravasation lesions17. Surgical debridement should be radical and remove all non-viable tissue, keeping only the non-affected and well-perfused tissue observed by active bleeding in the wound bed after surgical cleaning8. Often, multiple debridements are required in the weeks following the occurrence of extravasation to remove necrosis and infectious foci. In such cases, debridement sequences are necessary until a suitable bed is obtained for definitive closure of the wound through skin grafting or flaps, increasing the length of hospital stay and treatment costs15,18. In our surgical cases with a definitive closure proposal, we used negative pressure therapy, which has the capacity to reduce wound size, remove fluid and bacteria, decrease the local inflammatory process

7

and stimulate granulation tissue, collaborating with the improvement of the wound bed19,20. Immediate or late reconstructive surgery can be performed with similar results21. Once indicated, the surgical procedure should be performed as soon as possible to reduce morbidity and not to delay treatment for the patient's primary condition. Cedidi et al.22 compared early and late surgical treatment of extravasation lesions and found that all 18 patients who were referred late (on average 22 days after the event) required debridement and temporary and definitive wound coverage by means of grafts and flaps. This author concludes that early referral to a plastic surgeon is necessary to reduce the need for complex surgical procedures, risk of infection, treatment time and consequently costs. Murphy et al. 2 evaluated 43 cases of drug extravasation lesions over 18 months in an Australian pediatric hospital and referred immediately after the event identification to the Plastic Surgery team. They observed the need for subcutaneous tissue irrigation in five patients (11%) and only three (7%) developed cutaneous necrosis. These lesions were debrided and treated satisfactorily by dressing with silver in their composition, without the need for reconstructive surgeries, but with increased morbidity and prolonged hospitalization. This finding corroborates the expectant behavior regarding the lesions treated conservatively in the three cases presented here in pediatric patients. The use of well-established initial care protocols after the occurrence of extravasation and the use of measures such as skin infiltration with saline solution may contribute to the reduction of the number of cases that evolve with tissue necrosis23. D'Andrea et al.24 evaluated drug extravasation in a period of 12 years, finding 240 cases. Of these,

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Milcheski Surgical treatment of extravasation injuries: experience of the Hospital das Clínicas, Faculty of Medicine, University of São Paulo.

only 11 evolved with necrosis and ulceration, requiring definitive coverage. All lesions were on the back of the hands and were treated by grafting in one case, local flap in four cases, radial flap in other four cases, and serratus myocutaneous microsurgical flap in two. Another option for patients sustaining wounds with exposure of noble

structures after surgical debridement is the use of dermal substitutes, when available. It was observed that the definitive treatment skin flaps was adequate for the cases of wounds by extravasation of drugs in the subcutaneous tissue when there is exposure of deep structures in patients with favorable clinical conditions.

R E S U M O Objetivo: relatar a experiência da Divisão de Cirurgia Plástica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo no tratamento de lesões cutâneas por extravasamento acidental de drogas. Métodos: foram incluídos os pacientes com lesões por extravasamento de drogas num período de 18 meses. Os seguintes parâmetros foram avaliados retrospectivamente: idade, diagnósticos durante internação e comorbidades, níveis séricos de albumina e hemoglobina, local de internação, droga envolvida, segmento anatômico acometido, conduta terapêutica e óbito durante internação. Resultados: foram acompanhados 14 pacientes. A principal droga envolvida foi a noradrenalina (21%). Todos os pacientes foram submetidos a desbridamento da necrose tecidual. Três pacientes foram submetidos a retalhos após preparo do leito com terapia por pressão negativa, com bons resultados. Sete pacientes não tiveram tratamento definitivo de suas lesões por falta de condições clínicas. Conclusão: o tratamento definitivo por meio de retalhos se mostrou adequado para os casos de feridas por extravasamento de drogas em tecido subcutâneo, quando há exposição de estruturas nobres, em pacientes com condições clínicas favoráveis. Descritores: Doença iatrogênica. Extravasamento de Materiais Terapêuticos e Diagnósticos. Isquemia. Necrose. Retalhos Cirúrgicos. Cirurgia Plástica.

REFERENCES 1.

2.

3. 4. 5.

6.

7.

Reynolds PM, MacLaren R, Mueller SW, Fish DN, Kiser TH. Management of extravasation injuries: a focused evaluation of noncytotoxic medications. Pharmacotherapy. 2014;34(6):617-32. Murphy AD, Gilmour RF, Coombs CJ. Extravasation injury in a paediatric population. ANZ J Surg. 2017 Jul 6. doi: 10.1111/ans. Goutos I, Cogswell LK, Giele H. Extravasation injuries: a review. J Hand Surg Eur Vol. 2014;39(8):808-18. Tong R. Preventing extravasation injuries in neonates. Paediatr Nurs. 2007;19(8):22-5. Bhananker SM, Liau DW, Kooner PK, Posner KL, Caplan RA, Domino KB. Liability related to peripheral venous and arterial catheterization: a closed claims analysis. Anesth Analg. 2009;109(1):124-9. Le A, Patel S. Extravasation of noncytotoxic drugs: a review of the literature. Ann Pharmacother. 2014;48(7):870-86.

Firat C, Erbatur S, Aytekin AH. Management of extravasation injuries: a retrospective study. J Plast Surg Hand Surg. 2013;47(1):60-5.

8.

Al-Benna S, O'Boyle C, Holley J. Extravasation injuries in adults. ISRN Dermatol. 2013;2013:856541.

9.

Garden AL, Laussen PC. An unending supply of 'unusual' complications from central venous catheters. Paediatr Anaesth. 2004;14(11):905-9.

10. Chen JL, O'Shea M. Extravasation injury associated with low-dose dopamine. Ann Pharmacother. 1998;32(5):545-8. 11. Heckler FR. Current thoughts on extravasation injuries. Clin Plast Surg. 1989;16(3):557-63. 12. Hannon MG, Lee SK. Extravasation injuries. J Hand Surg Am. 2011;36(12):2060-5. 13. Wickham R, Engelking C, Sauerland C, Corbi D. Vesicant extravasation part II: Evidence-based management and continuing controversies. Oncol Nurs Forum. 2006;33(6):1143-50.

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Milcheski Surgical treatment of extravasation injuries: experience of the Hospital das Clínicas, Faculty of Medicine, University of São Paulo.

14. Boulanger J, Ducharme A, Dufour A, Fortier S, Almanric K; Comité de l'évolution de la pratique des soins pharmaceutiques (CEPSP); Comité de l'évolution des pratiques en oncologie (CEPO). Management of the extravasation of anti-neoplastic agents. Support Care Cancer. 2015;23(5):1459-71. 15. Schulmeister L. Extravasation management: clinical update. Semin Oncol Nurs. 2011;27(1):82-90. 16. Fallscheer P, Kammer E, Roeren T, Meuli-Simmen C. Injury to the upper extremity caused by extravasation of contrast medium: a true emergency. Scand J Plast Reconstr Surg Hand Surg. 2007;41(1):26-32. 17. Kassner E. Evaluation and treatment of chemotherapy extravasation injuries. J Pediatr Oncol Nurs. 2000;17(3):135-48. 18. Ener RA, Meglathery SB, Styler M. Extravasation of systemic hemato-oncological therapies. Ann Oncol. 2004;15(6):858-62. 19. Anghel EL, Kim PJ. Negative-pressure wound therapy: a comprehensive review of the evidence. Plast Reconstr Surg. 2016;138(3 Suppl):129S-37S. 20. Milcheski DA, Ferreira MC, Nakamoto HA, Pereira DD, Batista BN, Tuma P Jr. Subatmospheric pressure therapy in the treatment of traumatic soft tissue injuries. Rev Col Bras Cir. 2013;40(5):392-6.

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21. Shenaq SM, Abbase EH, Friedman JD. Softtissue reconstruction following extravasation of chemotherapeutic agents. Surg Oncol Clin N Am. 1996;5(4):825-45. 22. Cedidi C, Hierner R, Berger A. Plastic surgical management in tissue extravasation of cytotoxic agents in the upper extremity. Eur J Med Res. 2001;6(7):309-14. 23. Napoli P, Corradino B, Badalamenti G, Tripoli M, Vieni S, Furfaro MF, et al. Surgical treatment of extravasation injuries. J Surg Oncol. 2005;91(4):264-8. 24. D'Andrea F, Onesti MG, Nicoletti GF, Grella E, Renzi LF, Spalvieri C, et al. Surgical treatment of ulcers caused by extravasation of cytotoxic drugs. Scand J Plast Reconstr Surg Hand Surg. 2004;38(5):288-92. Received in: 05/15/2018 Accepted for publication: 05/29/2018 Conflict of interest: none. Source of funding: none. Mailing address: Dimas André Milcheski E-mail: dimas.milcheski@hc.fm.usp.br drdimasandre@gmail.com

Rev Col Bras Cir. 2018;45(4):e1912


Review Article

DOI: 10.1590/0100-6991e-20181885

Anesthetic therapy for acute pain relief after laparoscopic cholecystectomy: systematic review. Terapêutica anestésica para o alívio da dor aguda pós-colecistectomia videolaparoscópica: revisão sistemática. Renato Ribeiro de Jesus1; Adebaldo Maia Leite1; Simone Soares Leite1; Márcio Carneiro Vieira1; Nivaldo Ribeiro Villela1,2 A B S T R A C T Inappropriate therapy of postoperative pain in laparoscopic cholecystectomy may lead to late mobilization, patient dissatisfaction, delayed hospital discharge, and chronic pain development. Our objective was to identify the best therapeutic strategy available to the anesthesiologist for the acute postoperative pain of patients submitted to elective laparoscopic cholecystectomy. This is a systematic review that included 36 complete articles indexed in the Medline, Scopus, Web of Science and LILACS databases, with a five-year time cut (2012 to 2016), resulting from controlled and randomized studies that were submitted to qualitative analysis. In a proposal for multimodal analgesia, it is important to consider the contraindications, adverse effects, dose and optimal timing of interventions. Non-opioid drugs, such as non-steroidal anti-inflammatory drugs (NSAIDs)/cyclooxygenase-2 (COX-2) inhibitors, gabapentin/pregabalin, N-methylD-aspartate (NMDA) receptor antagonists, and others. Opioids may be used at low doses associated with multimodal therapy or are restricted to cases where non-opioid multimodal analgesia is insufficient. We conclude that there is no consensus as to the best analgesic strategy to be implemented in the acute postoperative pain of laparoscopic cholecystectomy, which requires its applicability in an individualized way, based on the scientific evidence found in the literature. As contribution to medical learning and practice, we point out the theoretical enrichment of the analgesic drug options available for the therapy of postoperative pain in patients submitted to elective laparoscopic cholecystectomy, and alert the team to consider the adverse effects of the interventions implemented. Keywords: Pain, Postoperative. Cholecystectomy, Laparoscopic. Analgesia. Review.

INTRODUCTION

intraperitoneal bupivacaine in the establishment

T

he inadequate treatment of postoperative pain in laparoscopic cholecystectomy (LC) can lead to

negative consequences, such as late mobilization, with consequent delay in discharge, development of chronic pain and increased treatment costs1.

In recent years, multimodal analgesia has been recommended to combine additive and synergistic effects of different analgesics, with less adverse effects and more effective analgesia1-3. Systematic reviews of the literature conducted in 2006 and in 2011 highlighted multimodal interventions to relieve pain in LC. One study focused on the preoperative administration of intravenous (IV)

dexamethasone

(8mg),

non-steroidal

anti-inflammatory or COX-2 inhibitors and topical bupivacaine, intraoperative use of antiemetic and

of pneumoperitoneum and drains4. The other study recommended a single preoperative dose of dexamethasone, local anesthetics in the incisions (at the beginning or at the end of the surgery, depending on the anesthesiologist's preference), and continued treatment with non-steroidal antiinflammatory drugs (NSAIDs)/COX-2 during the first three to four days, reserving the opioids for when other analgesic techniques fail5. The objective was to identify the best therapeutic strategy available to the anesthesiologist for treatment of acute postoperative pain of patients submitted to elective laparoscopic cholecystectomy.

METHODS We carried out the study in June and July 2016 by the main investigator plus one independent

1 - Federal University of Rio de Janeiro, Department of Surgery, Anesthesiology Service, Rio de Janeiro, RJ, Brazil. 2 - State University of Rio de Janeiro, Department of General Surgery, Anesthesiology Service, Center for Teaching and Training in Pain, Rio de Janeiro, RJ, Brazil. Rev Col Bras Cir 45(4):e1885


2

Jesus Anesthetic therapy for acute pain relief after laparoscopic cholecystectomy: systematic review.

reviewer, following the steps for the design of a systematic review6. For the search of the scientific productions, we used the following combination of “Descritores em Ciências da Saúde” (DeCS) and Medical Subject Headings (MeSH) terms, in English, Portuguese and Spanish: “postoperative pain” (“dor pós-operatória”, “dolor postoperatorio”) AND “laparoscopic cholecystectomy” (“colecistectomia laparoscópica”, “colecistectomía laparoscópica”) AND analgesia. The inclusion criteria were papers indexed in the Medical Literature Analysis and Retrieval System Online (Medline), Scopus, Web of Science and Latin American and Caribbean Literature in Health Sciences (LILACS) databases, in the 2012 to 2016 five-year interval, published in Portuguese, English or Spanish, resulting from randomized controlled studies. In addition, we chose studies with adults/elders between 18 and 65 years of age, non-pregnant, submitted to elective laparoscopic cholecystectomy. We excluded works on surgical considerations (instillation of local anesthetics, amount of infused carbon dioxide, etc.), open cholecystectomy, literature reviews, and case reports. There were 800 articles, 136 in Medline, 306 in Scopus, 349 in Web of Science and nine in LILACS. We performed the search in unpublished, in progress and gray literature data sources through a research in the Clinical Trials website and in the Brazilian Registry of Clinical Trials. We used the terms "postoperative pain" AND "laparoscopic cholecystectomy" and "analgesia", with 46 articles found in Clinical Trials and none in the Brazilian Registry of Clinical Trials. After the search, we sent all references to EndNote® online for organization of study and deletion of duplicates.

There were 846 articles, of which 173 were duplicates, remaining 673 in the first selection. We then read the title and Abstract, prioritizing the sensitivity in detriment of the specificity in order to make a selection of these references6. This was done by a pair of reviewers, independently. The article was considered when at least one of the reviewers judged it as eligible. This process resulted in 145 articles that could be submitted to a complete reading. If there was disagreement between the reviewers, these were resolved either by consensus between the reviewers or by consulting a third reviewer. There were 109 rejected articles and 36 were accepted to compose the definitive set (Figure 1). All articles that met the eligibility criteria for the systematic review had their methodological quality evaluated individually, minimizing biases and maximizing internal and external validity6. To that end, we assessed adequate randomization (allocation sequence generation), guaranteed allocation, blinding scheme (participants, team involved in conducting the study, outcome assessors), intention-to-treat analysis, loss of followup, as well as other sources of bias, such as early termination of the study due to benefit.

Figure 1. Flowchart illustrating the article search strategy.

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Jesus Anesthetic therapy for acute pain relief after laparoscopic cholecystectomy: systematic review.

We organized the articles1-3,7-38 included in this systematic review and described in table 1. Through the convergence of the findings that answered the question of the study, we grouped the evidence according to the available therapeutic strategies for the control of acute pain after elective LC with the necessary comments to the discussion.

RESULTS AND DISCUSSION

In total, we identified 36 controlled and randomized clinical trials, including 2526 patients (Table 1).

3

NSAIDs/COX-2 inhibitors

Many studies have been done evaluating the risk-benefit of several NSAIDs/COX-2 inhibitors. The majority of the studies reviewed showed a reduction in the acute pain scores and the need for opioids in the postoperative period of LC, with adverse effects not found and/or not analyzed. There is no substantial superiority between the NSAIDs/COX-2 inhibitors available, and it is up to the anesthesiologist to decide which medication to use, according to the options available. However, their use is recommended as a key element within a

Table 1. Interventions, evaluation of acute pain, need for postoperative opioid and adverse effects in the included studies.

Number of patients/groups

First author/year

Intervention

Effects Adverse Acute Need for effects Pain opioids

NSAIDs/COX inhibitor Anil et al., 20161

60/2

Fleckenstein et al., 20157

103/2

Shuying et al., 20148

120/3

Gautam et al., 20149

120/4

Kouroukli et al., 2013

180/3

Gousheh et al., 201311

30/2

Ureña-Frausto et al., 201312

56/4

Ekmekci et al., 201213

40/2

10

NMDA receptor antagonist Ozhan et al., 201514 Yadav et al., 201515 Kocman et al., 201316 Leal et al., 201317 Karcioglu et al., 201318

60/2 66/2 60/3 40/2 40/2

Dexketoprofen trometamol (vs. diclofenac) Etoricoxib (vs. placebo) Parecoxib before anesthetic induction (vs. parecoxib after gallbladder removal or vs. placebo) Etoricoxib with methylprednisolone/etoricoxib/ methylprednisolone (vs. placebo) Lornoxicam/parecoxib (vs. placebo) Paracetamol (vs. placebo) Ketoprofen and tramadol (vs. ketorolac) Tramadol and dexketoprofen (vs. tramadol) Ketamine (vs. placebo) Flupirtine (vs. placebo) Magnesium sulfate (vs. placebo) Ketamine (vs. placebo) Ketamine (vs. placebo)

Rev Col Bras Cir 45(4):e1885

ǂ

§

ǂ

ǂ

ǂ

ǂ

+

§

ǂ

+

+

ǂ

+

ǂ drugs/ § vs. placebo ǂ

-

+

§

ǂ

+

§

ǂ

ǂ + + ǂ

§ ǂ ǂ ǂ

+ + ǂ ǂ

+

§

+

+

ǂ


Jesus Anesthetic therapy for acute pain relief after laparoscopic cholecystectomy: systematic review.

4

First author/year

Number of patients/groups

Singh et al., 201319

80/4

Nesek-Adam et al., 201220

80/2

Olgun et al., 201221 Gabapentin/Pregabalin

60/2

Gurunathan et al., 201522

100/4

Bekawi et al., 201423

90/3

Sarakatsianou et al., 201324 Balaban et al., 201225 Miscellaneous

50/3 90/3

Bakan et al., 20152

80/2

Dereli et al., 201526 Delfino et al., 201527

60/4 50/2

Akelma et al., 201428

48/3

Ortiz et al., 20143

80/4

Lee et al., 201329

90/3

Park et al., 201230

42/2

Lopez-Alvarez et al., 201231

60/2

Peripheral blockades Elamin et al., 201532 Basaran, 201533

80/2 76/2

Pandey et al., 201534

60/2

Bathia et al., 201435

60/3

Petersen et al., 201236

80/2

Opioids Choi et al., 201537 Hwang et al., 201438

54/2 81/2

Intervention Ketamine (vs. placebo) Ketamine and diclofenac (vs. placebo) Magnesium sulfate (vs. placebo) Pregabalin/celecoxib/pregabalin and celecoxib (vs. placebo) Pregabalin (vs. Gabapentin or vs. placebo) Pregabalin (vs. placebo) Pregabalin (vs. diclofenac) Dexmedetomidine and lidocaine (vs. remifentanyl) Esmolol (vs. placebo) Phenylephrine (vs. placebo) Esmolol/ lidocaine (vs. remifentanyl) Propofol (vs. isoflurane, vs. desflurane and vs. sevoflurane) Nefopam and fentanyl (vs. fentanyl) Dexmedetomidine (vs. placebo) Esmolol (vs. ketamine and remifentanyl) TAP block (vs. no blockade) TAP block (vs. no blockade) Epidural blockade with levobupivacaine and clonidine (vs. ropivacaine and clonidine) Subcostal TAP block (vs. posterior TAP block) TAP block with ropivacaine (vs. placebo TAP block) Oxycodone (vs. fentanyl) Oxycodone (vs. fentanyl)

Effects Adverse Acute Need for effects Pain opioids + § + +

ǂ

ǂ

+

§

+

ǂ

ǂ

+

+

§

+

+ +

§ §

+ +

+

ǂ

+

+ ǂ

§ §

+ ǂ

+

§

ǂ

ǂ

ǂ

-

+

ǂ

-

+

ǂ

-

+

§

ǂ

+ +

ǂ §

ǂ ǂ

+

ǂ

+

+

§

ǂ

+

§

ǂ

+ +

ǂ ǂ

ǂ +

Legends: - Not investigated; + Significant effect in the treated group; ǂ Non-significant effect in the treated group; § Opioid reduction in the postoperative period. Studies of degree of recommendation A - level of evidence 1B.

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Jesus Anesthetic therapy for acute pain relief after laparoscopic cholecystectomy: systematic review.

multimodal therapy, mainly because of its analgesic benefits and the rarity and low importance of its adverse effects. Some options are presented in the text and serve as a scientific basis for conduct. Intravenous (IV) parecoxib 40mg used 30-45 minutes prior to anesthetic induction was associated with less postoperative pain and opioid consumption when compared with its administration after gallbladder removal or with placebo8. The use of oral (VO) lornoxicam 8mg showed analgesic efficacy similar to parecoxib 40mg IV and better than placebo when given in three doses (30 minutes before surgery and 12 and 24 hours after). The need for opioids in the postoperative period was similar between lornoxicam and parecoxib10. The administration of methylprednisolone 125mg IV and etoricoxib 120mg VO one hour before surgery was more effective in reducing the consumption of opioids, without a higher incidence of adverse effects. However, only the associated use showed better postoperative pain scores9. The use of etoricoxib 120mg VO on the morning of surgery and for three days after surgery did not show superiority to placebo in reducing the cumulative dose of opioid after LC or in perioperative pain scores7. Ketorolac 1mg/kg IV on induction bolus showed worse scores of acute pain and greater need for rescue opioids compared with groups in which drugs were given 60 minutes before surgery in continuous infusion. These groups were ketoprofen 100mg IV followed by 2mg/kg/24h; ketoprofen 50mg IV associated with tramadol 50mg IV, followed by 1mg/kg/24h and 0.1mg/kg/h, respectively, in addition to one group using twice the dose of attack and maintenance of the previous group. The latter group receiving ketoprofen 100mg IV associated with tramadol 100mg IV with maintenance of 2mg/ kg/24h and 0.2mg/kg/h, respectively, needed less opioids in the postoperative period in relation to the other groups12.

5

Single dose administration of dexcetoprofen trometamol 50mg IV 30 minutes before the end of surgery presented postoperative pain scores similar to the use of diclofenac sodium 75mg IV in patients submitted to LC. However, opioid consumption was higher in the dexketoprofen trometamol group compared with the diclofenac sodium group. There was no increase in adverse effects1. The use of dexcetoprofen trometamol 100mg IV associated with tramadol 600mg IV, via patient controlled analgesia, when used in physiological solution 0.9% of 100ml with 3ml bolus, interval between doses of 15 minutes and 15ml limit in four hours, showed lower analgesic consumption in the postoperative period without increase in adverse effects when compared with the use of tramadol 600mg IV13. The administration of paracetamol 1g IV immediately after induction of anesthesia reduced pain significantly compared with placebo, but without reduction in opioid consumption after LC procedures11. NMDA receptor antagonists (N-methyl-D-aspartate)

Regarding NMDA receptor antagonists, a large part of the studies reported lower scores of acute pain and opioid need in the postoperative period of LC. However, they indicated significant adverse effects depending on the intervention used. The anesthesiologist should take this into consideration when opting for its use within the multimodal therapy, since it will influence the anesthetic and perioperative dynamics. The use of ketamine 1mg/kg IV on induction bolus, followed by 25mcg/kg/min IV until the end of surgery, used as supplementary form to propofol and alfentanyl in total venous anesthesia, produces lower postoperative pain scores and decreases opioid consumption compared with placebo. However, there was longer time to extubation and discharge from the post-anesthetic recovery room18. When

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6

Jesus Anesthetic therapy for acute pain relief after laparoscopic cholecystectomy: systematic review.

administered at a dose of 5mcg/kg/min IV, with changes in its dosage according to hemodynamic parameters, at the time of induction until the end of surgery, it did not alter the intensity of postoperative pain and the need for opioid in the LC postoperative period17. At the 0.25mg/kg IV bolus dose two minutes before induction, it reduced postoperative acute pain and opioid need scores over placebo. However, Aldrete scores were lower, with higher sedation due to Ramsay scores, as well as loss of verbal response and orientation after extubation14. Ketamine at the dose of 0.5-1mg/kg IV given 30 minutes before induction was effective in controlling acute pain and opioid need in the postoperative period of LC compared with placebo. As a side effect, increased heart rate (HR) and presence of hallucinations were observed19. At a dose of 0.15mg/kg before the surgical incision, associated with diclofenac sodium 1mg/kg IV 20 minutes before induction of anesthesia, it reduced postoperative pain scores, but not opioid consumption. However, the individual use of ketamine did not display these findings and the isolated use of diclofenac sodium did not spare opioid postoperatively20. The administration of magnesium sulphate 40mg/kg IV before induction, followed by intraoperative 10mg/kg/h, showed lower pain scores and opioid requirement in the postoperative period. Nevertheless, it led to inadequate breathing and delayed recovery, as demonstrated by a decreased Aldrete score21. Its administration prior to anesthetic induction of 5.0mg/kg and 7.5mg/kg reduced postoperative acute pain after LC compared with placebo. However, 7.5mg/kg were more effective. There was no difference in postoperative adverse effects and opioid consumption16. The use of flupirtine 200mg VO two hours before surgery was superior to placebo for acute postoperative pain, but there was no difference in opioid consumption. Nonetheless, there was a higher incidence of sedation in the group studied15.

Gabapentin/Pregabalin

In

general,

the

use

of

gabapentin/

pregabalin in patients undergoing LC also showed lower scores of acute pain and need for opioid in the postoperative period, but several studies have shown adverse effects that may limit their use, such as sedation, delayed extubation and dizziness. Administration of pregabalin 150mg or 300 mg VO an hour before surgery decreased pain intensity and opioid consumption after LC compared with placebo. There was a higher degree of sedation on the Ramsay scale in the 300mg pregabalin group25. This dose, on the night before surgery and one hour before surgery, when compared with placebo, also obtained these positive analgesic results, albeit associated with delayed extubation time, as well as with increased incidence of post- operative dizziness24. The isolated use of pregabalin 150mg VO or in combination with celecoxib 400mg one hour before surgery did not provide lower pain scores or need for opioid when compared with placebo. The pregabalin group presented more dizziness and somnolence22. The use of gabapentin 1200mg VO two hours before surgery, followed by the same dose 12 hours postoperatively and every eight hours for two days, and pregabalin 150mg VO in the same administration scheme, reduced the need for opioids in patients undergoing LC when compared with placebo. The pregabalin group showed lower pain scores when compared with the other groups. Non-placebo interventions resulted in a greater degree of dizziness and drowsiness23. Miscellaneous

Interventions that could not be amassed in the previous groups were considered miscellaneous. These showed satisfactory results in the fight against acute pain and opioid need in the postoperative period of LC. However, several of their adverse

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Jesus Anesthetic therapy for acute pain relief after laparoscopic cholecystectomy: systematic review.

7

effects were not highlighted in the studies or were not evaluated. In conducting the case, the anesthesiologist should always consider the risk-benefit of such interventions.

recovery room. The use of esmolol resulted in a decrease in the use of opioids extending up to 24 hours postoperatively. There was no reduction in postoperative pain scores28.

The infusion of dexmedetomidine 1mg/

The use of intravenous phenylephrine

kg/min IV before induction followed by 0.5mcg/

to maintain SBP 20-30% above baseline reduced

kg/h showed a reduction in postoperative pain

opioid consumption and pain scores after LC when

scores only in the first hour compared with placebo.

compared with maintenance of SBP 20-30% below

There was no difference in the need for opioid in

baseline. There was no change in postoperative

the postoperative period. The intervention group

hemodynamic parameters. In this study, according to

showed lower values o â&#x20AC;&#x2039;â&#x20AC;&#x2039; f bispectral index (BIS), systolic

the author, it was not possible to distinguish whether

blood pressure (SBP) and heart rate (HR) .

this analgesic effect resulted from the increase in

30

Opioid-free

total

venous

anesthesia

with propofol, dexmedetomidine 0.6mcg/kg IV

SBP or from the direct effect of phenylephrine as a pain modulator27.

followed by 0.3mcg/kg/h and lidocaine 1.5mg/kg

Administration of nefopam 20mg or

IV and 2mg/kg/h intraoperatively is associated with

40mg IV with fentanyl 50mcg IV at the end of

lower opioid consumption and postoperative pain

surgery reduced postoperative pain and side effects

scores compared with total venous anesthesia with

of opioid when compared with the single use of

remifentanyl and propofol. Greater hypertensive

fentanyl. There was no evaluation of the need for

events and longer recovery time were observed in

opioid in the postoperative period29. Maintaining

the opioid-free group2.

general anesthesia with propofol compared with

The use of esmolol 1mg/kg followed by

isoflurane, desflurane or sevoflurane did not result

10mcg/kg/min IV after induction of anesthesia

in minor pain scores and opioid consumption after

until the end of surgery, whether associated with

LC. No adverse effects of the medications used were

propofol and remifentanyl or with desflurane

evaluated27.

and remifentanyl, decreased the need for opioid and postoperative pain when compared with its non-use. As adverse effects, there was a greater reduction in HR, but the mean arterial pressure remained the same26. Esmolol 0.5mcg/kg IV, when used at induction followed by 5-15mcg/kg/min until the end of surgery, reduced the need for opioid and improved postoperative analgesia when compared with the group receiving ketamine 0.5mg/kg IV at induction31. The infusion of esmolol 1mg/kg IV before induction followed by 50mcg/kg/min until the end of surgery and/or lidocaine 2mg/kg/min, followed by 2mg/kg/min in the same manner, showed lower opioid consumption in the post-anesthetic

Peripheral blockade

In the majority of studies, the use of peripheral blockade in the analgesia of patients submitted to LC reduced the postoperative acute pain and opioid need scores. However, some studies have discouraged its routine use because of adverse effects, which, although rare, do not justify its use in this type of surgery. It is up to the professional anesthesiologist to know the anesthetic options available in the hospital in question and suited to be used in the patient to assemble his/her analgesic arsenal. Patients who received ultrasound-guided transverse abdominal plane block (TAP block) after

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8

Jesus Anesthetic therapy for acute pain relief after laparoscopic cholecystectomy: systematic review.

LC had reduced pain scores when coughing, but not at rest, when compared with those who did not receive the block. Postoperative opioid consumption was lower36. Another similar study showed reduction of postoperative acute pain, but the reduction in the need for opioids in the postoperative period was not evaluated32. An oblique subcostal approach in the use of a single-injection TAP block was effective in the control of LC postoperative pain and decreased opioid consumption33. This block showed lower postoperative pain and opioid need scores in comparison to the posterior TAP block or no blockade35. When two groups undergoing epidural block were compared in a LC surgery, the associated use of clonidine with levobupivacaine resulted in less analgesic need in the treatment of shoulder pain compared with clonidine with ropivacaine, but both groups had a high decline in blood pressure, requiring vasopressors34. Opioids

Opioids are the best option for analgesia. However, due to their potential for chemical dependence and adverse effects, several other drugs appear on the market every day. Currently, the combination of drugs is recommended to approximate the analgesic quality of opioids, a therapy known as multimodal. Researches involving opioids aim for greater efficacy with the fewest possible adverse effects. In this sense, the use of oxycodone has been shown to be promising in patients submitted to LC37. Oxycodone 0.08mg/kg IV 20 minutes before the end of surgery relieved immediate postoperative pain when compared with fentanyl

1mcg/kg, and was not associated with an increase in side effects in patients submitted to LC. The need for additional doses was similar between groups37. Regarding its use by patient-controlled analgesia, oxycodone 1mg IV per bolus showed similar effects for pain relief compared with fentanyl 10mcg IV, but showed a higher incidence of postoperative nausea and vomiting38. Despite the viability of the various strategies for acute pain relief in patients undergoing LC, some studies have not investigated the adverse effects of interventions, only efficacy in postoperative analgesia and the need for opioids. This can be explained by the rarity of their occurrences, difficulty in evaluation, or because they were not the objective of these studies4. The heterogeneity of the review studies may have led to weaknesses in the discussion. Nevertheless, this systematic review of the literature has contributed to teaching and professional practice with the theoretical enrichment of the analgesic tools available for LC therapy, as well as to alert the team to consider the adverse effects of the implemented interventions. Our study did not consider surgical strategies in the treatment of acute pain relief of patients undergoing LC, but these should be valued in the search for a better analgesic strategy.

CONCLUSION There is no consensus as to the best analgesic strategy to be implemented in the acute postoperative pain of laparoscopic cholecystectomy, which requires its applicability in an individualized way, based on the scientific evidence found in the literature.

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9

R E S U M O A terapêutica inadequada da dor pós-operatória em colecistectomia videolaparoscópica pode levar a mobilização tardia, insatisfação do paciente, atraso na alta hospitalar e desenvolvimento de dor crônica. Objetivou-se identificar qual a melhor estratégia terapêutica disponível ao anestesiologista na terapia da dor aguda pós-operatória de pacientes submetidos à colecistectomia videolaparoscópica eletiva. Trata-se de revisão sistemática que incluiu 36 artigos completos indexados nas bases de dados Medline, Scopus, Web of Science e LILACS, com recorte temporal de cinco anos (2012 a 2016), resultantes de estudos controlados e randomizados que foram submetidos à análise qualitativa. Em uma proposta de analgesia multimodal, é importante considerar as contraindicações, os efeitos adversos, a dose e o momento ideal das intervenções. Utiliza-se fármacos não opioides, como anti-inflamatórios não esteroides (AINES)/inibidores da ciclo-oxigenase-2 (COX-2), gabapentina/pregabalina, antagonistas dos receptores N-methyl-D-aspartato (NMDA), entre outras. Os opioides podem ser utilizados em doses baixas associadas ou não a terapia multimodal e/ou ficarem restritos aos casos em que a analgesia multimodal não opioide for insuficiente. Conclui-se que não há consenso sobre qual a melhor estratégia analgésica a ser implementada na dor aguda pós-operatória da colecistectomia videolaparoscópica, o que requer sua aplicabilidade de forma individualizada, com base nas evidências científicas encontradas na literatura. Aponta-se como contribuições para o ensino e a prática profissional o enriquecimento teórico das opções medicamentosas analgésicas disponíveis para a terapêutica da dor pós-operatória de pacientes submetidos à colecistectomia videolaparoscópica eletiva, além de alertar a equipe para considerar os efeitos adversos das intervenções implementadas. Descritores: Dor Pós-Operatória. Colecistectomia Laparoscópica. Analgesia. Revisão.

REFERENCES 1.

2.

3.

4.

5.

6.

7.

Anil A, Kaya FN, Yavascaoglu B, Mercanoğlu Efe E, Türker G, Demirci A. Comparison of postoperative analgesic efficacy of intraoperative single-dose intravenous administration of dexketoprofen trometamol and diclofenac sodium in laparoscopic cholecystectomy. J Clin Anesth. 2016;32:127-33. Bakan M, Umutoglu T, Topuz U, Uysal H, Bayram M, Kadioglu H, et al. Opioid-free total intravenous anesthesia with propofol, dexmedetomidine and lidocaine infusions for laparoscopic cholecystectomy: a prospective, randomized, double-blinded study. Rev Bras Anestesiol. 2015;65(3):191-9. Portuguese. Ortiz J, Chang LC, Tolpin DA, Minard CG, Scott BG, Rivers JM. Randomized, controlled trial comparing the effects of anesthesia with propofol, isoflurane, desflurane and sevoflurane on pain after laparoscopic cholecystectomy. Rev Braz Anesthesiol. 2014;64(3):145-51. Ahn Y, Woods J, Connor S. A systematic review of interventions to facilitate ambulatory laparoscopic cholecystectomy. HPB (Oxford). 2011;13(10):677-86. Bisgaard T. Analgesic treatment after laparoscopic cholecystectomy: a critical assessment of the evidence. Anesthesiology. 2006;104(4):835-46. Galvão TF, Pansani TSA, Harrad D. Principais itens para relatar revisões sistemáticas e meta-análises: a recomendação PRISMA. Epidemiol Serv Saúde. 2015;24(2):335-42.

Fleckenstein J, Kohls N, Evtouchenko E, Lehmeyer L, Kramer S, Lang PM, et al. No effect of the cyclooxygenase-2 inhibitor etoricoxib on preemptive and post-operative analgesia in visceral surgery: results of a randomized controlled trial. Eur J Pain. 2016;20(2):186-95. 8. Shuying L, Xiao W, Peng L, Tao Z, Ziying L, Liang Z. Preoperative intravenous parecoxib reduces length of stay on ambulatory laparoscopic cholecystectomy. Int J Surg. 2014;12(5):464-8. 9. Gautam S, Agarwal A, Das PK, Agarwal A, Kumar S, Khuba S. Evaluation of the efficacy of methylprednisolone, etoricoxib and a combination of the two substances to attenuate postoperative pain and PONV in patients undergoing laparoscopic cholecystectomy: a prospective, randomized, placebo-controlled trial. Korean J Pain. 2014;27(3):278-84. 10. Kouroukli I, Zompolas V, Tsekoura V, Papazoglou I, Louizos A, Panaretou V. Comparison between lornoxicam quick-release and parecoxib for post-operative analgesia after laparoscopic cholecystectomy: a prospective randomized, placebo-controlled trial. J Anaesthesiol Clin Pharmacol. 2013;29(4):485-90. 11. Gousheh SM, Nesioonpour S, Javaher Foroosh F, Akhondzadeh R, Sahafi SA, Alizadeh Z. Intravenous paracetamol for postoperative analgesia in laparoscopic cholecystectomy. Anesth Pain Med. 2013;3(1):214-8.

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Jesus Anesthetic therapy for acute pain relief after laparoscopic cholecystectomy: systematic review.

12. Ureña-Frausto CA, Plancarte-Sánchez R, ReyesTorres JI, Ramírez-Aranda JM. Infusional therapy: an alternative for shouder pain post-laparoscopy. Cir Cir. 2013;81(3):187-95. Spanish. 13. Ekmekçi P, Kazak Bengisun Z, Kazbek BK, Özis SE, Tastan H, Süer AH. The efficacy of adding dexketoprofen trometamol to tramadol with patient controlled analgesia technique in postlaparoscopic cholecystectomy pain treatment. Agri. 2012;24(2):63-8. 14. Ozhan Y, Bakan N, Karaoren GY, Tomruk SG, Topaç Z. Effects of subanesthetic ketamine on pain and cognitive functions in TIVA. J Clin Anal Med. 2015;6(4):452-7. 15. Yadav G, Behera SS, Das SK, Jain G, Choupoo S, Raj J. Role of flupirtine as a preemptive analgesic in patients undergoing laparoscopic cholecystectomy. J Anaesthesiol Clin Pharmacol. 2015;31(2):169-73. 16. Kocman IB, Krobot R, Premuzić J, Kocman I, Stare R, Katalinić L, et al. The effect of preemptive intravenous low-dose magnesium sulfate on early postoperative pain after laparoscopic cholecystectomy. Acta Clin Croat. 2013;52(3):289-94. 17. Leal PC, Sakata RK, Salomão R, Sadatsune EJ, Issy AM. Assessment of the effect of ketamine in combination with remifentanil on postoperative pain. Braz J Anesthesiol. 2013;63(2):178-82. 18. Karcioglu M, Davarci I, Tuzcu K, Bozdogan YB, Turhanoglu S, Aydogan A, et al. Addition of ketamine to propofol-alfentanil anesthesia may reduce postoperative pain in laparoscopic cholecystectomy. Surg Laparosc Endosc Percutan Tech. 2013;23(2):197-202. 19. Singh H, Kundra S, Singh RM, Grewal A, Kaul TK, Sood D. Preemptive analgesia with Ketamine for Laparoscopic cholecystectomy. J Anaesthesiol Clin Pharmacol. 2013;29(4):478-84. 20. Nesek-Adam V, Grizelj-Stojčić E, Mršić V, Rašić Z, Schwarz D. Preemptive use of diclofenac in combination with ketamine in patients undergoing laparoscopic cholecystectomy: a randomized, double-blind, placebo-controlled study. Surg Laparosc Endosc Percutan Tech. 2012;22(3):232-8. 21. Olgun B, Oguz G, Kaya M, Savli S, Eskiçirak HE, Güney I, et al. The effects of magnesium

22.

23.

24.

25.

26.

27.

28.

29.

30.

sulphate on desflurane requirement, early recovery and postoperative analgesia in laparascopic cholecystectomy. Magnes Res. 2012;25(2):72-8. Gurunathan U, Rapchuk IL, King G, Barnett AG, Fraser JF. The effect of pregabalin and celecoxib on the analgesic requirements after laparoscopic cholecystectomy: a randomized controlled trial. J Anesth. 2016;30(1):64-71. Bekawi MS, El Wakeel LM, Al Taher WM, Mageed WM. Clinical study evaluating pregabalin efficacy and tolerability for pain management in patients undergoing laparoscopic cholecystectomy. Clin J Pain. 2014;30(11):944-52. Sarakatsianou C, Theodorou E, Georgopoulou S, Stamatiou G, Tzovaras G. Effect of pre-emptive pregabalin on pain intensity and postoperative morphine consumption after laparoscopic cholecystectomy. Surg Endosc. 2013;27(7):2504-11. Balaban F, Yagar S, Özgök A, Koç M, Güllapoglu H. A randomized, placebo-controlled study of pregabalin for postoperative pain intensity after laparoscopic cholecystectomy. J Clin Anesth. 2012;24(3):175-8. Dereli N, Tutal ZB, Babayigit M, Kurtay A, Sahap M, Horasanli E. Effect of intraoperative esmolol infusion on anesthetic, analgesic requirements and postoperative nausea-vomitting in a group of laparoscopic cholecystectomy patients. Rev Bras Anestesiol. 2015;65(2):141-6. Portuguese. Delfino AE, de la Fuente N, Echevarría GC, Altermatt FR, Cortinez LI. Effect of acute arterial hypertension on morphine requirements and postsurgical pain. J Clin Anesth. 2015;27(3):226-32. Akelma FK, Ergil J, Özkan D, Akinci M, Özmen M, Gümüs J. A comparison of the effects of intraoperative esmolol and lidocaine infusions on postoperative analgesia. Anestezi Dergisi. 2014;22(1):25-31. Lee JH, Kim JH, Cheong YK. The analgesic effect of nefopam with fentanyl at the end of laparoscopic cholecystectomy. Korean J Pain. 2013;26(4):361-7. Park JK, Cheong SH, Lee KM, Lim SH, Lee JH, Cho K, et al. Does dexmedetomidine reduce postoperative pain after laparoscopic cholecystectomy with multimodal analgesia? Korean J Anesthesiol. 2012;63(5):436-40.

Rev Col Bras Cir 45(4):e1885


Jesus Anesthetic therapy for acute pain relief after laparoscopic cholecystectomy: systematic review.

31. Lรณpez-รlvarez S, Mayo-Moldes M, Zaballos M, Iglesias BG, Blanco-Dรกvila R. Esmolol versus ketamine-remifentanil combination for early postoperative analgesia after laparoscopic cholecystectomy: a randomized controlled trial. Can J Anaesth. 2012;59(5):442-8. 32. Elamin G, Waters PS, Hamid H, O'Keeffe HM, Waldron RM, Duggan M, et al. Efficacy of a laparoscopically delivered transversus abdominis plane block technique during elective laparoscopic cholecystectomy: a prospective, double-blind randomized trial. J Am Coll Surg. 2015;221(2):335-44. 33. Basaran B, Basaran A, Kozanhan B, Kasdogan E, Eryilmaz MA, Ozmen S. Analgesia and respiratory function after laparoscopic cholecystectomy in patients receiving ultrasound-guided bilateral oblique subcostal transversus abdominis plane block: a randomized

36. Petersen PL, Stjernholm P, Kristiansen VB, Torup H, Hansen EG, Mitchell AU, et al. The beneficial effect of transversus abdominis plane block after laparoscopic cholecystectomy in day-case surgery: a randomized clinical trial. Anesth Analg. 2012;115(3):527-33. 37. Choi YJ, Park SW, Kwon HJ, Choi JM, Lee YM. Efficacy of early intravenous bolus oxycodone or fentanyl in emergence from general anaesthesia and postoperative analgesia following laparoscopic cholecystectomy: a randomized trial. J Int Med Res. 2015;43(6):809-18. 38. Hwang BY, Kwon JY, Kim E, Lee DW, Kim TK, Kim HK. Oxycodone vs. fentanyl patient-controlled analgesia after laparoscopic cholecystectomy. Int J Med Sci. 2014;11(7):658-62.

double-blind study. Med Sci Monit. 2015;21:1304-12. 34. Pandey A, Kumar R, Kang CLS, Agarwal M. Comparative study between levobupivacaine with clonidine and ropivacaine with clonidine in thoracic epidural block for laparoscopic cholecystectomy. J Evolution Med Dent Sci. 2015;4(9):1457-65. 35. Bhatia N, Arora S, Jyotsna W, Kaur G. Comparison of

posterior

and

ultrasound-guided

subcostal

transverse

approach

abdominis

Received in: 04/02/2018 Accepted for publication: 05/17/2018 Conflict of interest: none. Source of funding: none.

to

plane

block for postoperative analgesia in laparoscopic cholecystectomy. J Clin Anesth. 2014;26(4):294-9.

11

Mailing address: Renato Ribeiro de Jesus E-mail: renatordejesus@gmail.com ok.renato@hotmail.com

Rev Col Bras Cir 45(4):e1885


INSTRUCTIONS FOR AUTHORS SCOPE AND POLITICS The Journal of the Brazilian College of Surgeons (CBC), an official division of the CBC, is published bimonthly in one annual volume, and proposes the dissemination of articles of all surgical specialties, contributing to its teaching, development and national integration. Articles published in the Journal of the Brazilian College of Surgeons follow the uniform requirements recommended by the International Committee of Medical Journals Editors (ICMJE – www.icmje.org), and are submitted to a double blind peer review. The journal of the Brazilian College of surgeons supports the policies for registration of clinical trials of the World Health Organization (WHO) and the ICMJE, recognizing the importance of these initiatives for the record and international dissemination of information on clinical studies in open access. Thus, it will only accept for publication the clinical research articles that have received an identification number on a clinical trial registry validated by the criteria established by WHO and ICMJE. The identification number must be registered at the end of the abstract. Between three and five members of the Editorial Board, anonymous to the authors, receive the texts, also anonymously, and decide for their publication. In the event of conflict of opinions, the Director of publications will evaluate the need for a new appraisal. Rejected articles are returned to authors. Only the works within the journal’s publication standards will be submitted to evaluation. Approved articles may sustain editorial-type alterations, provided that they do not alter the merit of the work. GENERAL INFORMATION The Journal of the Brazilian College of Surgeons evaluates articles for publication in Portuguese (Brazilian authors) and English (foreign authors) that follow the rules for manuscripts submitted to biomedical journals prepared and published by the International Committee of Medical Journal Editors (ICMJE – www.icmje.org) [CIERM Rev Col Bras Cir. 2008; 35 (6): 425-41, or article on the website of the journal (www.revistadocbc.org.br)] with the following characteristics: • Editorial: Is the initial article of an issue, generally about a current subject, requested by the Editor to the author of recognized technical and scientific capacity. • Original Article: Is the full account of clinical or experimental research, with positive or negative results. It must consist of Abstract, Introduction, Methods, Results, Discussion and References, the latter limited to a maximum of 35, aiming to the inclusion, whenever possible, of articles from national authors and national journals. The title should be written in Portuguese and English, and should contain the maximum of information with the minimum of words, without abbreviations. It must be accompanied by the complete name(s) of author(s) followed by the name(s) of the institution(s) where the work was performed. If multicenter, Arabic numerals must indicate the provenance of each of the authors in relation to the listed institutions. Authors should send along with their names only one title and one that best represents their academic activity. The Abstract should have a maximum of 250 words and be structured as follows: objective, methods, results, conclusions and keywords in the form referred to by DeCS (http://decs.bvs.br ). • Review article: The Editorial Board encourages the publication of matters of great interest to the surgical specialties containing synthetic analysis and relevant criticism and not merely a chronological description of literature. I must contain an introduction with description of the reasons that led to the writing of the article, the search criteria, followed by text ordered in titles and subheadings according to the complexity of the subject, and unstructured abstract. When applicable, at the end there may be conclusions and opinions of authors summarizing the review contents. • Letters to the Editor: Scientific Comments or controversy regarding articles published in the journal of the CBC. In general, such letters are sent to the principal author of the article to response and both letters are published in the same journal issue, no replica being allowed. • Scientific Communication: Content that deals with the form of presentation of scientific communication, investigating the problems and proposing solutions. Due to its features, this section can be multidisciplinary, receiving contributions from doctors, surgeons and non-surgeons and other professionals from various areas. It must have an unstructured Abstract, Keywords and free text. • Technical Note: Information about a particular operation or procedure of importance in surgical practice. The original must not exceed six pages including pictures and references if necessary. It must have an unstructured Abstract, Keywords and free text. • Education: Freeform content that addresses the teaching of surgery, both in graduate and post-graduate levels. Unstructured abstract. • Bioethics in surgery: Discussion of bioethical aspects in surgery. The content should address bioethical dilemmas in the performance of surgical activity. Freeform. Unstructured abstract. • Case reports: May be submitted for evaluation and the approved reports will be published, mainly in electronic journal of case reports, the Journal of Case Reports of the Brazilian College of Surgeons which can be accessed through the Brazilian College of Surgeons’ website (www.cbc.org.br) or directly at www.relatosdocbc.org.br. ARTICLE SUBMISSION Sending articles for the Journal of the Brazilian College of Surgeons can only be done through the online platform for submission of scientific papers, which can be accessed through the Brazilian College of Surgeons’ website (www.cbc.org.br) or directly at www.rcbc.gnpapers.com.br.

FORM AND STYLE • Text: Manuscripts submitted for review by the Journal of the Brazilian College of Surgeons must be unpublished and should not be evaluated in whole or in part by another scientific journal. Images should be forwarded separately from the text, and in accordance with the instructions on the online submission platform. Articles should be concise, not exceeding 2500 words. The abbreviations should be as few as possible, limited to the terms mentioned repetitively, as long as they do not hinder the understanding of the text, and should be defined from the first use. • References: Must be predominantly of works published in the last five years, restricted to those cited in the text, in order of citation, numbered consecutively and presented according to the Vancouver format (rules for manuscripts submitted to Biomedical Journals ICMJE- www.icmje.org – CIERM Rev Col Bras Cir. 2008; 35 (6): 425-41-www. revistadocbc.org.br). Annals of congresses and personal communications will not be accepted as references. Citations of books and theses should be discouraged. The authors of the article are responsible for the accuracy of the references. • Acknowledgements: Should be made to people who importantly contributed to the work’s realization. TABLES (maximum of six) Tables should be numbered with Arabic numerals, with captions on the top containing one or two sentences, and explanations of symbols at the bottom. Cite the tables in the text in numerical order including only information necessary for understanding of important points of the text. The data presented should not be repeated in graphs. Tables should follow the above-mentioned Vancouver standards. Tables must be typed in the body of the text, and never sent as figures. FIGURES (maximum of six) Figures are all the photos, graphics, paintings and drawings. All figures must be referred to in the text, being numbered consecutively by Arabic numbers and accompanied by descriptive captions. Histological images should contain in the legends the histological technique used and the degree of magnification. All figures should be submitted separately at the end of the manuscript.

MANDATORY CONDITIONS (READ CAREFULLY) It is expressed that, with the electronic submission, the author (s) agree (s) with the following assumptions: 1) that there is no conflict of interests, compliant with the Brazilian Federal Council of Medicine (CFM) resolution No. 1595/2000 that prevents the publication of works and materials with promotional purposes of products and/or medical devices; 2) that one must cite the funding source, if any; 3) that the work was submitted to the respective Ethics in Research Committee which approved it, providing the aproval number in the text; 4) that all authors authorize that the article suffer changes in the submitted text to be standardized in the language format of the Journal, which can result in removal of redundancies, as well as tables and/ or figures that are deemed unnecessary to understanding the text, provided that it does not change its meaning. If there are disagreements of the authors about these assumptions, they should write a letter leaving explicit the point at which they disagree, which will be appraised by the Editor, who will decide whether the article can be forwarded for publication or returned to the authors. 5) that the authors are allowed to hold the copyright of their published work without restrictions. 6) that if there is conflict of interest, it should be quoted with the text: “the author (s) (provide names) received financial support of the private company (provide name) for this study”. When there is a research foment funding source, it must also be cited. 7) that the responsibility for concepts or statements issued on articles and announcements published in the Journal of the Brazilian College of Surgeons is entirely up to the author (s) and advertisers. 8) that works already published or simultaneously submitted for evaluation in other periodicals will not be accepted. 9) that each approved article will have a cost of R$ 1,000.00 (one thousand reais) for the authors. If the lead author is a member of the Brazilian College of Surgeons, there will be a 50% discount on the article’s fee. Case Reports, approved for publication in the Journal of Case Reports of the Brazilian College of Surgeons are exempt from charges.

CONTACT: 2016-Brazilian College of Surgeons Rua Visconde de Silva, 52-3the floor 22271-090-Rio de Janeiro-RJ-Brazil Tel: + 55 21 2138-0659 Fax: + 55 21-2286 2595 Address for submission of manuscripts: E-mail: revistacbc@cbc.org.br


ABOUT THE JOURNAL Basic information Objectives: To disseminate scientific works of the surgical area of medicine that contribute to its teaching and development. History: The publication and dissemination of scientific activities of its members is one of the aims of medical societies. The Brazilian College of Surgeons (Colégio Brasileiro de Cirurgiões – CBC), founded in 1929, already in its first statute provided for the issuance of the “Bulletin of the Brazilian College of Surgeons” as its official division, whose starting number was published in January 1930. In 1967, the National Directory of CBC changed its name to “Journal of the Brazilian College of Surgeons”. From 1974 on, the journal began to be published bi-monthly, on a regular basis, to the present day. The abbreviation for its title is Rev Col Bras Cir, which should be used in bibliographies, footnotes and in references and bibliographic legends.

Creative Commons The journal of the Brazilian College of Surgeons is licensed with a 4.0 International , non-commercial, Creative Commons Attribution. This license lets others remix, adapt and create from your work, for non-commercial purposes. Although the new works have to assign proper credit and may not be used for commercial purposes, users do not have to license these derivative works under the same terms.

Free access policy This journal provides free and immediate access to its content, following the principle that providing free scientific knowledge to the public provides greater democratization of world knowledge.

About APC (Article Processing Charges) In view of the high costs for publication of the journal, from the issue 1/2017 on, every approved article started to have a cost of R$ 1000.00 (1000 reais) for the authors. Articles in which the lead author is a member of the CBC will have a discount of 50% of the publication fee.

Anti-Plagiarism Policy The Journal of the Brazilian College of Surgeons uses the iThenticate program to identify plagiarism in articles submitted for publication.

Indexing sources · · · · · · ·

Latindex LILACS Scopus DOAJ Free Medical Journals MEDLINE/PUBMED SciELO

Intellectual property All journal content, except where otherwise stated, is licensed under a Creative Commons License of type CC-BY attribution.

Sponsors The Journal of the Brazilian College of Surgeons is sponsored by CBC through: · Annuity of its associated members · Money from advertisers · Article publication fee


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Revista do CBC v45n4 - Inglês  

Revista do CBC v45n4 - Inglês

Revista do CBC v45n4 - Inglês  

Revista do CBC v45n4 - Inglês