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O APACHE II é uma ferramenta útil para pesquisa clínica?

A população de pacientes admitidos na unidade de terapia intensiva (UTI) é bastante heterogênea. De forma geral, seu desfecho depende do local e da causa de admissão, além da idade e das comorbidades prévias, e das alterações fisiológicas agudas na admissão e nas primeiras horas de tratamento. A necessidade de se predizer a mortalidade hospitalar destes pacientes é muito importante, tanto para ser utilizada como critério de inclusão ou exclusão em ensaios clínicos, como para comparar a mortalidade observada com a mortalidade prevista pelo escore e estimar a razão de mortalidade padronizada em populações de pacientes críticos. Tal necessidade levou muitos investigadores a desenvolverem equações que calculassem a probabilidade de mortalidade associada. Embora escores sejam utilizados desde os anos 1950 (como o Apgar(11 Apgar V. A proposal for a new method of evaluation of the newborn infant. Curr Res Anesth Analg. 1953;32(4):260-7.) para recém-nascidos, desenvolvido por Virginia Apgar), só em 1985 seu uso foi consagrado em pacientes críticos, quando Knaus et al. publicaram a segunda versão do Acute Physiology and Chronic Health Evaluation (APACHE II),(22 Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818-29.) que rapidamente tornou-se o índice prognóstico mais utilizado em UTI e em estudos clínicos do mundo. A descrição original do APACHE II é até hoje o estudo mais citado da literatura em medicina intensiva.(33 Baltussen A, Kindler CH. Citation classics in critical care medicine. Intensive Care Med. 2004;30(5):902-10.)

A capacidade de um índice prognóstico prever um desfecho (no caso, mortalidade hospitalar) é avaliada de acordo com sua calibração e discriminação. A calibração refere-se à correspondência entre a mortalidade esperada pelo índice e a observada na população estudada. Normalmente, ela é avaliada pela comparação, em determinados grupos de risco predito (por exemplo, decis), entre a mortalidade observada e a predita naqueles grupos, o chamado teste de Hosmer-Lemeshow.(44 Hosmer DW, Lemeshow S. A goodness-of-fit test for the multiple logistic regression model. Commun Stat. 1980;9(10):1043-69.) A calibração de um modelo prognóstico costuma deteriorar-se ao longo dos anos devido às alterações nos critérios de admissão e alta das UTI, à evolução do suporte, e à disponibilidade e efetividade dos diferentes tratamentos para a condição cujo prognóstico ele tende a avaliar. Assim, as evoluções tecnológica e científica pelas quais a medicina intensiva passou nos últimos 30 anos fizeram com que o APACHE II se tornasse obsoleto. De forma geral, atualmente, ele tende a superestimar a mortalidade em muitos cenários em que é estudado. As versões seguintes, como o mais recente APACHE IV,(55 Zimmerman JE, Kramer AA, McNair DS, Malila FM. Acute Physiology and Chronic Health Evaluation (APACHE) IV: hospital mortality assessment for today's critically ill patients. Crit Care Med. 2006;34(5):1297-310.) vieram corrigir, ao menos em parte, este problema. Conforme descrito por Soares et al.,(66 Soares M, Dongelmans DA. Why should we not use APACHE II for performance measurement and benchmarking? Rev Bras Ter Intensiva. 2017;29(3):268-70.) o APACHE II não deve ser usado como ferramenta de benchmarking em UTI, uma vez que praticamente qualquer UTI atual poderia se considerar como de "alta performance" por ter uma mortalidade hospitalar encontrada bastante inferior àquela esperada em 1985.

A discriminação, por outro lado, avalia a habilidade do índice prognóstico em diferenciar os pacientes que sobrevivem dos que morrem. Sua avaliação é feita pela área sobre a curva Receiver Operating Characteristic (ROC).(77 Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143(1):29-36.) Quanto maior esta área, mais acurado é o índice (desde que, obviamente, a área seja superior a 0,5, valor em que a descriminação não é melhor que o acaso) (Tabela 1).

Tabela 1
Avaliação da discriminação de um índice prognóstico de acordo com sua área sobre a curva Receiver Operating Characteristic

Enquanto a calibração do APACHE II deteriorou-se ao longo do tempo, uma busca no MEDLINE dos estudos que se propuseram a avaliar seu desempenho nos últimos 2 anos mostra que, de forma geral, ele segue com discriminação boa ou muito boa nas diversas populações em que ele foi avaliado (Tabela 2).(88 Pérez Campos A, Bravo Paredes E, Prochazka Zarate R, Bussalleu A, Pinto Valdivia J, Valenzuela Granados V. [BISAP-O y APACHE-O: utility in predicting severity in acute pancreatitis in modified Atlanta classification]. Rev Gastroenterol Peru. 2015;35(1):15-24. Spanish.

9 Serpa Neto A, Assunção MS, Pardini A, Silva E. Feasibility of transitioning from APACHE II to SAPS III as prognostic model in a Brazilian general intensive care unit. A retrospective study. Sao Paulo Med J. 2015;133(3):199-205.

10 Que YA, Guessous I, Dupuis-Lozeron E, Alves de Oliveira CR, Ferreira Oliveir C, Graf R, et al. Prognostication of mortality in critically ill patients with severe infections. Chest. 2015;148(3):674-82.

11 Ariyaratnam P, Loubani M, Biddulph J, Moore J, Richards N, Chaudhry M, et al. Validation of the Intensive Care National Audit and Research Centre Scoring System in a UK Adult Cardiac Surgery Population. J Cardiothorac Vasc Anesth. 2015;29(3):565-9.

12 Williams JM, Greenslade JH, Chu K, Brown AF, Lipman J. Severity scores in emergency department patients with presumed infection: a prospective validation study. Crit Care Med. 2016;44(3):539-47.

13 Hashmi M, Asghar A, Shamim F, Khan FH. Validation of acute physiologic and chronic health evaluation II scoring system software developed at The Aga Khan University, Pakistan. Saudi J Anaesth. 2016;10(1):45-9.

14 Khwannimit B, Bhurayanontachai R, Vattanavanit V. Validation of the sepsis severity score compared with updated severity scores in predicting hospital mortality in sepsis patients. Shock. 2017;47(6):720-5.
-1515 Huang L, Li T, Xu L, Hu XM, Duan DW, Li ZB, et al. Performance of Multiple Risk Assessment Tools to Predict Mortality for Adult Respiratory Distress Syndrome with Extracorporeal Membrane Oxygenation Therapy: An External Validation Study Based on Chinese Single-center Data. Chin Med J (Engl). 2016;129(14):1688-95.) Ou seja, quanto maior a pontuação no APACHE II, maior a mortalidade hospitalar do grupo de indivíduos estudado.

Tabela 2
Estudos que se propuseram a avaliar o desempenho do APACHE II nos últimos 3 anos

Além da heterogeneidade da população de pacientes admitida em UTI, a atuação da medicina intensiva abrange síndromes que têm um espectro de apresentação igualmente amplo, como sepse, síndrome do desconforto respiratório agudo, delirium e pós-operatórios de cirurgias de grande porte. Assim, é necessária uma maneira para medir a gravidade destes pacientes. Tal necessidade aparece de forma especial em estudos clínicos, uma vez que a população representada neles deve ser representativa, para que seus achados possam ser extrapolados para a prática clínica. O APACHE II foi o primeiro índice a indicar, ou contraindicar, o uso de determinada terapêutica (no caso, a proteína C ativada em sepse),(1616 Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr; Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344(10):699-709.) um fato que se revelou errado e funesto.(1717 Ranieri VM, Thompson BT, Barie PS, Dhainaut JF, Douglas IS, Finfer S, Gårdlund B, Marshall JC, Rhodes A, Artigas A, Payen D, Tenhunen J, Al-Khalidi HR, Thompson V, Janes J, Macias WL, Vangerow B, Williams MD; PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012;366(22):2055-64.) Outra intervenção terapêutica, o uso de baixas doses de corticoide na sepse, mostrou-se benéfico em estudo que incluiu pacientes com maior gravidade (sendo usado, neste caso, outro escore, o Simplified Acute Physiology Score - SAPS - II),(1818 Annane D, Sébille V, Charpentier C, Bollaert PE, Francois B, Korach JM, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288(7):862-71.) mas não em outro com pacientes menos graves.(1919 Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J; CORTICUS Study Group. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008;358(2):111-24.) Esta diferença de achados fez com que a Sepsis Surviving Campaign recomendasse como opção o uso de hidrocortisona em pacientes com choque séptico que permanecessem instáveis após expansão volêmica e uso de vasopressor.(2020 Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017;43(3):304-77.)

Por sua continuada capacidade de discriminação, o APACHE II permanece como um índice bastante usado para descrever a gravidade de populações de pacientes críticos que participam de estudos clínicos. Em 2016, foram publicados 12 ensaios clínicos em pacientes críticos nas três revistas médicas de maior impacto.(2121 Gaudry S, Hajage D, Schortgen F, Martin-Lefevre L, Pons B, Boulet E, Boyer A, Chevrel G, Lerolle N, Carpentier D, de Prost N, Lautrette A, Bretagnol A, Mayaux J, Nseir S, Megarbane B, Thirion M, Forel JM, Maizel J, Yonis H, Markowicz P, Thiery G, Tubach F, Ricard JD, Dreyfuss D; AKIKI Study Group. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med. 2016;375(2):122-33.

22 Gordon AC, Perkins GD, Singer M, McAuley DF, Orme RM, Santhakumaran S, et al. Levosimendan for the prevention of acute organ dysfunction in sepsis. N Engl J Med. 2016;375(17):1638-48.

23 Legriel S, Lemiale V, Schenck M, Chelly J, Laurent V, Daviaud F, Srairi M, Hamdi A, Geri G, Rossignol T, Hilly-Ginoux J, Boisramé-Helms J, Louart B, Malissin I, Mongardon N, Planquette B, Thirion M, Merceron S, Canet E, Pico F, Tran-Dinh YR, Bedos JP, Azoulay E, Resche-Rigon M, Cariou A; HYBERNATUS Study Group. Hypothermia for neuroprotection in convulsive status epilepticus. N Engl J Med. 2016;375(25):2457-67.

24 Schaller SJ, Anstey M, Blobner M, Edrich T, Grabitz SD, Gradwohl-Matis Heim M, Houle T, Kurth T, Latronico N, Lee J, Meyer MJ, Peponis T, Talmor D, Velmahos GC, Waak K, Walz JM, Zafonte R, Eikermann M; International Early SOMS-guided Mobilization Research Initiative. Early, goal-directed mobilisation in the surgical intensive care unit: a randomised controlled trial. Lancet. 2016;388(10052):1377-88.

25 Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX, et al. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet. 2016;388(10054):1893-902.

26 Walsh TS, Kydonaki K, Antonelli J, Stephen J, Lee RJ, Everingham K, Hanley J, Phillips EC, Uutela K, Peltola P, Cole S, Quasim T, Ruddy J, McDougall M, Davidson A, Rutherford J, Richards J, Weir CJ; Development and Evaluation of Strategies to Improve Sedation Practice in Intensive Care (DESIST) study investigators. Staff education, regular sedation and analgesia quality feedback, and a sedation monitoring technology for improving sedation and analgesia quality for critically ill, mechanically ventilated patients: a cluster randomised trial. Lancet Respir Med. 2016;4(10):807-17.

27 Girardis M, Busani S, Damiani E, Donati A, Rinaldi L, Marudi A, et al. Effect of conservative vs conventional oxygen therapy on mortality among patients in an intensive care unit: the oxygen-ICU randomized clinical trial. JAMA. 2016;316(15):1583-9.

28 Gordon AC, Mason AJ, Thirunavukkarasu N, Perkins GD, Cecconi M, Cepkova M, Pogson DG, Aya HD, Anjum A, Frazier GJ, Santhakumaran S, Ashby D, Brett SJ; VANISH Investigators. Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the VANISH randomized clinical trial. JAMA. 2016;316(5):509-18.

29 Hernández G, Vaquero C, Colinas L, Cuena R, González P, Canabal A, et al. Effect of postextubation high-flow nasal cannula vs noninvasive ventilation on reintubation and postextubation respiratory failure in high-risk patients: a randomized clinical trial. JAMA. 2016;316(15):1565-74.

30 Keh D, Trips E, Marx G, Wirtz SP, Abduljawwad E, Bercker S, Bogatsch H, Briegel J, Engel C, Gerlach H, Goldmann A, Kuhn SO, Hüter L, Meier-Hellmann A, Nierhaus A, Kluge S, Lehmke J, Loeffler M, Oppert M, Resener K, Schädler D, Schuerholz T, Simon P, Weiler N, Weyland A, Reinhart K, Brunkhorst FM; SepNet-Critical Care Trials Group. Effect of Hydrocortisone on development of shock among patients with severe sepsis: the HYPRESS randomized clinical trial. JAMA. 2016;316(17):1775-85.

31 Patel BK, Wolfe KS, Pohlman AS, Hall JB, Kress JP. Effect of noninvasive ventilation delivered by helmet vs face mask on the rate of endotracheal intubation in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA. 2016;315(22):2435-41.
-3232 Reade MC, Eastwood GM, Bellomo R, Bailey M, Bersten A, Cheung B, Davies A, Delaney A, Ghosh A, van Haren F, Harley N, Knight D, McGuiness S, Mulder J, O'Donoghue S, Simpson N, Young P; DahLIA Investigators; Australian and New Zealand Intensive Care Society ClinicalTrials Group. Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium: a randomized clinical trial. JAMA. 2016;315(14):1460-8.) O APACHE II foi o índice mais usado para descrever a gravidade dos pacientes incluídos nestes estudos, aparecendo em 9 dos 12 estudos (Figura 1).

Figura 1
Índices prognósticos usados para descrever a gravidade de pacientes incluídos em 12 ensaios clínicos realizados em terapia intensiva e publicados nos periódicos New England Journal of Medicine, Lancet e JAMA em 2016.(2121 Gaudry S, Hajage D, Schortgen F, Martin-Lefevre L, Pons B, Boulet E, Boyer A, Chevrel G, Lerolle N, Carpentier D, de Prost N, Lautrette A, Bretagnol A, Mayaux J, Nseir S, Megarbane B, Thirion M, Forel JM, Maizel J, Yonis H, Markowicz P, Thiery G, Tubach F, Ricard JD, Dreyfuss D; AKIKI Study Group. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med. 2016;375(2):122-33.

22 Gordon AC, Perkins GD, Singer M, McAuley DF, Orme RM, Santhakumaran S, et al. Levosimendan for the prevention of acute organ dysfunction in sepsis. N Engl J Med. 2016;375(17):1638-48.

23 Legriel S, Lemiale V, Schenck M, Chelly J, Laurent V, Daviaud F, Srairi M, Hamdi A, Geri G, Rossignol T, Hilly-Ginoux J, Boisramé-Helms J, Louart B, Malissin I, Mongardon N, Planquette B, Thirion M, Merceron S, Canet E, Pico F, Tran-Dinh YR, Bedos JP, Azoulay E, Resche-Rigon M, Cariou A; HYBERNATUS Study Group. Hypothermia for neuroprotection in convulsive status epilepticus. N Engl J Med. 2016;375(25):2457-67.

24 Schaller SJ, Anstey M, Blobner M, Edrich T, Grabitz SD, Gradwohl-Matis Heim M, Houle T, Kurth T, Latronico N, Lee J, Meyer MJ, Peponis T, Talmor D, Velmahos GC, Waak K, Walz JM, Zafonte R, Eikermann M; International Early SOMS-guided Mobilization Research Initiative. Early, goal-directed mobilisation in the surgical intensive care unit: a randomised controlled trial. Lancet. 2016;388(10052):1377-88.

25 Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX, et al. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet. 2016;388(10054):1893-902.

26 Walsh TS, Kydonaki K, Antonelli J, Stephen J, Lee RJ, Everingham K, Hanley J, Phillips EC, Uutela K, Peltola P, Cole S, Quasim T, Ruddy J, McDougall M, Davidson A, Rutherford J, Richards J, Weir CJ; Development and Evaluation of Strategies to Improve Sedation Practice in Intensive Care (DESIST) study investigators. Staff education, regular sedation and analgesia quality feedback, and a sedation monitoring technology for improving sedation and analgesia quality for critically ill, mechanically ventilated patients: a cluster randomised trial. Lancet Respir Med. 2016;4(10):807-17.

27 Girardis M, Busani S, Damiani E, Donati A, Rinaldi L, Marudi A, et al. Effect of conservative vs conventional oxygen therapy on mortality among patients in an intensive care unit: the oxygen-ICU randomized clinical trial. JAMA. 2016;316(15):1583-9.

28 Gordon AC, Mason AJ, Thirunavukkarasu N, Perkins GD, Cecconi M, Cepkova M, Pogson DG, Aya HD, Anjum A, Frazier GJ, Santhakumaran S, Ashby D, Brett SJ; VANISH Investigators. Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the VANISH randomized clinical trial. JAMA. 2016;316(5):509-18.

29 Hernández G, Vaquero C, Colinas L, Cuena R, González P, Canabal A, et al. Effect of postextubation high-flow nasal cannula vs noninvasive ventilation on reintubation and postextubation respiratory failure in high-risk patients: a randomized clinical trial. JAMA. 2016;316(15):1565-74.

30 Keh D, Trips E, Marx G, Wirtz SP, Abduljawwad E, Bercker S, Bogatsch H, Briegel J, Engel C, Gerlach H, Goldmann A, Kuhn SO, Hüter L, Meier-Hellmann A, Nierhaus A, Kluge S, Lehmke J, Loeffler M, Oppert M, Resener K, Schädler D, Schuerholz T, Simon P, Weiler N, Weyland A, Reinhart K, Brunkhorst FM; SepNet-Critical Care Trials Group. Effect of Hydrocortisone on development of shock among patients with severe sepsis: the HYPRESS randomized clinical trial. JAMA. 2016;316(17):1775-85.

31 Patel BK, Wolfe KS, Pohlman AS, Hall JB, Kress JP. Effect of noninvasive ventilation delivered by helmet vs face mask on the rate of endotracheal intubation in patients with acute respiratory distress syndrome: a randomized clinical trial. JAMA. 2016;315(22):2435-41.
-3232 Reade MC, Eastwood GM, Bellomo R, Bailey M, Bersten A, Cheung B, Davies A, Delaney A, Ghosh A, van Haren F, Harley N, Knight D, McGuiness S, Mulder J, O'Donoghue S, Simpson N, Young P; DahLIA Investigators; Australian and New Zealand Intensive Care Society ClinicalTrials Group. Effect of dexmedetomidine added to standard care on ventilator-free time in patients with agitated delirium: a randomized clinical trial. JAMA. 2016;315(14):1460-8.) O total é maior que 12 porque alguns estudos usaram mais de um índice prognóstico.

APACHE - Acute Physiology and Chronic Health Evaluation; SOFA - Sequential Organ Failure Assessment; SAPS - Simplified Acute Physiology Score.


Uma crítica recorrente ao APACHE II e às suas versões posteriores é o fato de todos terem sido desenvolvidos a partir de um banco de dados exclusivamente norte-americano. Este fato introduz um viés muito grande, devido à disponibilidade de diferentes tecnologias(3333 Bastos PG, Knaus WA, Zimmerman JE, Magalhães A Jr, Sun X, Wagner DP. The importance of technology for achieving superior outcomes from intensive care. Brazil APACHE III Study Group. Intensive Care Med. 1996;22(7):664-9.) e às diferentes características dos pacientes,(3434 Moreno R, Apolone G, Miranda DR. Evaluation of the uniformity of fit of general outcome prediction models. Intensive Care Med. 1998;24(1):40-7.) fatos que mesmo a modificação das equações não permite corrigir corretamente.(3535 Moreno R, Apolone G, Fidler V, Reis Miranda D. The impact of first level customization on the uniformity of fit of SAPS II [abstract]. Intensive Care Med. 1996;22(Suppl 3):S267.) Atualmente, outros escores apresentam melhor calibração e devem ser utilizados na avaliação da mortalidade prevista,(3636 Moreno RP, Metnitz PG, Almeida E, Jordan B, Bauer P, Campos RA, Iapichino G, Edbrooke D, Capuzzo M, Le Gall JR; SAPS 3 Investigators. SAPS 3--From evaluation of the patient to evaluation of the intensive care unit. Part 2: Development of a prognostic model for hospital mortality at ICU admission. Intensive Care Med. 2005;31(10):1345-55. Erratum in: Intensive Care Med. 2006;32(5):796.) sendo uma opção para expressar a gravidade de pacientes incluídos em estudos clínicos.

De qualquer forma, como o APACHE II continua a ser um índice que determina bem a gravidade de um grupo de pacientes (embora não possa - e nem deva - ser utilizado em pacientes individuais), seu uso em pesquisa clínica pode eventualmente permanecer justificado, ao contrário do que ocorre na avaliação do desempenho de UTI ou na avaliação prognóstica de grupos de pacientes. Nestes casos, o APACHE II deve retornar às bibliotecas e merece apenas o respeito de quem foi pioneiro no campo da avaliação prognóstica na UTI.

  • Editor responsável: Jorge Ibrain Figueira Salluh

REFERÊNCIAS

  • 1
    Apgar V. A proposal for a new method of evaluation of the newborn infant. Curr Res Anesth Analg. 1953;32(4):260-7.
  • 2
    Knaus WA, Draper EA, Wagner DP, Zimmerman JE. APACHE II: a severity of disease classification system. Crit Care Med. 1985;13(10):818-29.
  • 3
    Baltussen A, Kindler CH. Citation classics in critical care medicine. Intensive Care Med. 2004;30(5):902-10.
  • 4
    Hosmer DW, Lemeshow S. A goodness-of-fit test for the multiple logistic regression model. Commun Stat. 1980;9(10):1043-69.
  • 5
    Zimmerman JE, Kramer AA, McNair DS, Malila FM. Acute Physiology and Chronic Health Evaluation (APACHE) IV: hospital mortality assessment for today's critically ill patients. Crit Care Med. 2006;34(5):1297-310.
  • 6
    Soares M, Dongelmans DA. Why should we not use APACHE II for performance measurement and benchmarking? Rev Bras Ter Intensiva. 2017;29(3):268-70.
  • 7
    Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143(1):29-36.
  • 8
    Pérez Campos A, Bravo Paredes E, Prochazka Zarate R, Bussalleu A, Pinto Valdivia J, Valenzuela Granados V. [BISAP-O y APACHE-O: utility in predicting severity in acute pancreatitis in modified Atlanta classification]. Rev Gastroenterol Peru. 2015;35(1):15-24. Spanish.
  • 9
    Serpa Neto A, Assunção MS, Pardini A, Silva E. Feasibility of transitioning from APACHE II to SAPS III as prognostic model in a Brazilian general intensive care unit. A retrospective study. Sao Paulo Med J. 2015;133(3):199-205.
  • 10
    Que YA, Guessous I, Dupuis-Lozeron E, Alves de Oliveira CR, Ferreira Oliveir C, Graf R, et al. Prognostication of mortality in critically ill patients with severe infections. Chest. 2015;148(3):674-82.
  • 11
    Ariyaratnam P, Loubani M, Biddulph J, Moore J, Richards N, Chaudhry M, et al. Validation of the Intensive Care National Audit and Research Centre Scoring System in a UK Adult Cardiac Surgery Population. J Cardiothorac Vasc Anesth. 2015;29(3):565-9.
  • 12
    Williams JM, Greenslade JH, Chu K, Brown AF, Lipman J. Severity scores in emergency department patients with presumed infection: a prospective validation study. Crit Care Med. 2016;44(3):539-47.
  • 13
    Hashmi M, Asghar A, Shamim F, Khan FH. Validation of acute physiologic and chronic health evaluation II scoring system software developed at The Aga Khan University, Pakistan. Saudi J Anaesth. 2016;10(1):45-9.
  • 14
    Khwannimit B, Bhurayanontachai R, Vattanavanit V. Validation of the sepsis severity score compared with updated severity scores in predicting hospital mortality in sepsis patients. Shock. 2017;47(6):720-5.
  • 15
    Huang L, Li T, Xu L, Hu XM, Duan DW, Li ZB, et al. Performance of Multiple Risk Assessment Tools to Predict Mortality for Adult Respiratory Distress Syndrome with Extracorporeal Membrane Oxygenation Therapy: An External Validation Study Based on Chinese Single-center Data. Chin Med J (Engl). 2016;129(14):1688-95.
  • 16
    Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr; Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344(10):699-709.
  • 17
    Ranieri VM, Thompson BT, Barie PS, Dhainaut JF, Douglas IS, Finfer S, Gårdlund B, Marshall JC, Rhodes A, Artigas A, Payen D, Tenhunen J, Al-Khalidi HR, Thompson V, Janes J, Macias WL, Vangerow B, Williams MD; PROWESS-SHOCK Study Group. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012;366(22):2055-64.
  • 18
    Annane D, Sébille V, Charpentier C, Bollaert PE, Francois B, Korach JM, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288(7):862-71.
  • 19
    Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, Weiss YG, Benbenishty J, Kalenka A, Forst H, Laterre PF, Reinhart K, Cuthbertson BH, Payen D, Briegel J; CORTICUS Study Group. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008;358(2):111-24.
  • 20
    Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017;43(3):304-77.
  • 21
    Gaudry S, Hajage D, Schortgen F, Martin-Lefevre L, Pons B, Boulet E, Boyer A, Chevrel G, Lerolle N, Carpentier D, de Prost N, Lautrette A, Bretagnol A, Mayaux J, Nseir S, Megarbane B, Thirion M, Forel JM, Maizel J, Yonis H, Markowicz P, Thiery G, Tubach F, Ricard JD, Dreyfuss D; AKIKI Study Group. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med. 2016;375(2):122-33.
  • 22
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Datas de Publicação

  • Publicação nesta coleção
    Jul-Sep 2017

Histórico

  • Recebido
    21 Fev 2017
  • Aceito
    22 Fev 2017
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