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Canadian Association of Emergency Physicians Sepsis Guidelines: the optimal management of severe sepsis in Canadian emergency departments

Published online by Cambridge University Press:  21 May 2015

Robert S. Green ,
Dennis Djogovic ,
Sara Gray ,
Daniel Howes ,
Peter G. Brindley ,
Robert Stenstrom ,
Edward Patterson ,
David Easton  and
Jonathan S. Davidow
Robert S. Green*
Affiliation:
Department of Emergency Medicine and the Division of Critical Care Medicine, Department of Internal Medicine, Dalhousie University, Halifax, NS
Dennis Djogovic
Affiliation:
Department of Emergency Medicine, University of Alberta, Edmonton, Alta.
Sara Gray
Affiliation:
Division of Emergency Medicine, University of Toronto, and Emergency Medicine & Intensive Care Medicine, St. Michael's Hospital, Toronto, Ont.
Daniel Howes
Affiliation:
Emergency Medicine and Critical Care, Queen's University, and the Department of Emergency Medicine, Kingston General Hospital, Kingston, Ont.
Peter G. Brindley
Affiliation:
Department of Emergency Medicine, University of Alberta, Edmonton, Alta.
Robert Stenstrom
Affiliation:
Providence Health Care and the Department of Emergency Medicine, St. Paul's Hospital, Vancouver, BC
Edward Patterson
Affiliation:
Departments of Internal Medicine and Emergency Medicine, Regina Qu'Appelle Health Region and the University of Saskatchewan, Regina, Sask.
David Easton
Affiliation:
Department of Emergency Medicine, Health Sciences Centre, Winnipeg, Man.
Jonathan S. Davidow
Affiliation:
Department of Emergency Medicine, University of Alberta, Edmonton, Alta.
*
CAEP Critical Care Interest Group; 1278 Tower Rd., Rm. 349, Bethune Bldg., Halifax NS B3H 2Y9; greenrs@dal.ca

Abstract

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Introduction:

Optimal management of severe sepsis in the ED has evolved rapidly. The purpose of these guidelines is to review key management principles for Canadian emergency physicians, utilizing an evidence-based grading system.

Methods:

Key areas in the management of septic patents were determined by members of the CAEP Critical Care Interest Group (C4). Members of C4 were assigned a question to be answered after literature review, based on the Oxford grading system. After completion, each section underwent a secondary review by another member of C4. A tertiary review was conducted by additional external experts, and modifications were determined by consensus. Grading was based on peer-reviewed publications only, and where evidence was insufficient to address an important topic, a “practice point” was provided based on group opinion.

Results:

The project was initiated in 2005 and completed in December 2007. Key areas which were reviewed include the definition of sepsis, the use of invasive procedures, fluid resuscitation, vasopressor/inotrope use, the importance of culture acquisition in the ED, antimicrobial therapy and source control. Other areas reviewed included the use of corticosteroids, activated protein C, transfusions and mechanical ventilation.

Conclusion:

Early sepsis management in the ED is paramount for optimal patient outcomes. The CAEP Critical Care Interest Group Sepsis Position Statement provides a framework to improve the ED care of this patient population.

Keywords

sepsissevere sepsisseptic shockemergency medicineguidelinesresuscitation
Type
CAEP Update • Mise à jour de l’ACMU
Information
Canadian Journal of Emergency Medicine , Volume 10 , Issue 5 , September 2008 , pp. 443 - 459
Copyright
Copyright © Canadian Association of Emergency Physicians 2008

References

1.Phillips, B, Ball, C, Sackett, D, et al.Oxford Centre for Evidence-based Medicine levels of evidence (May 2001). Available: www.cebm.net/levels_of_evidence.asp (accessed March 2008).Google Scholar
2.Strehlow, MC, Emond, SD, Shapiro, NI, et al.National study of emergency department visits for sepsis, 1992 to 2001. Ann Emerg Med 2006;48:326–31, 331.e1–3.Google Scholar
3.Martin, GS, Mannino, DM, Eaton, S, et al.The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003 17;348:1546–54.Google Scholar
4.Angus, DC, Linde-Zwirble, WT, Lidicker, J, et al.Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 2001;29:1303–10.Google Scholar
5.Lambe, S, Washington, DL, Fink, A, et al.Trends in the use and capacity of california’s emergency departments, 1990–1999. Ann Emerg Med 2002;39:389–96.Google Scholar
6.Meggs, WJ, Czaplijski, T, Benson, N. Trends in emergency department utilization, 1988–1997. Acad Emerg Med 1999;6:1030–5.Google Scholar
7.Parkhe, M, Myles, PS, Leach, DS, et al.Outcome of emergency department patients with delayed admission to an intensive care unit. Emerg Med (Fremantle) 2002;14:50–7.CrossRefGoogle Scholar
8.Nelson, M, Waldrop, RD, Jones, J, et al.Critical care provided in an urban emergency department. Am J Emerg Med 1998;16:56–9.CrossRefGoogle Scholar
9.Varon, J, Fromm, RE Jr, Levine, RL. Emergency department procedures and length of stay for critically ill medical patients. Ann Emerg Med 1994;23:546–9.CrossRefGoogle ScholarPubMed
10.Svenson, J, Besinger, B, Stapczynski, JS. Critical care of medical and surgical patients in the ED: Length of stay and initiation of intensive care procedures. Am J Emerg Med 1997;15:654–7.CrossRefGoogle ScholarPubMed
11.Sampalis, JS, Denis, R, Lavoie, A, et al.Trauma care regionalization: a process-outcome evaluation. J Trauma 1999;46:565,79; discussion 579–81.Google Scholar
12.Rivers, E, Nguyen, B, Havstad, S, et al.Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368–77.Google Scholar
13.Cannon, CP, Gibson, CM, Lambrew, CT, et al.Relationship of symptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction. JAMA 2000;283:2941–7.CrossRefGoogle ScholarPubMed
14.Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995;333:1581–7.Google Scholar
15.Bernard, GR, Vincent, JL, Laterre, PF, et al.Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699–709.Google Scholar
16.Annane, D, Sebille, V, Charpentier, C, et al.Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862–71.Google Scholar
17.van den, BG, Wouters, P, Weekers, F, et al.Intensive insulin therapy in the critically ill patients. N Engl J Med 2001;345:1359–67.CrossRefGoogle Scholar
18.Bochud, PY, Bonten, M, Marchetti, O, et al.Antimicrobial therapy for patients with severe sepsis and septic shock: an evidence-based review. Crit Care Med 2004;32:S495–512.Google Scholar
19.Garnacho-Montero, J, Garcia-Garmendia, JL, Barrero-Almodovar, A, et al.Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis. Crit Care Med 2003;31:2742–51.Google Scholar
20.Leibovici, L, Shraga, I, Drucker, M, et al.The benefit of appropriate empirical antibiotic treatment in patients with bloodstream infection. J Intern Med 1998;244 :379–86.CrossRefGoogle ScholarPubMed
21.Leone, M, Bourgoin, A, Cambon, S, et al.Empirical antimicrobial therapy of septic shock patients: adequacy and impact on the outcome. Crit Care Med 2003;31:462–7.Google Scholar
22Levy, MM, Fink, MP, Marshall, JC, et al.2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31:1250–6.CrossRefGoogle ScholarPubMed
23.Hotchkiss, RS, Karl, IE. The pathophysiology and treatment of sepsis. N Engl J Med 2003;348:138–50.Google Scholar
24.Rivers, EP, McIntyre, L, Morro, DC, et al.Early and innovative interventions for severe sepsis and septic shock: taking advantage of a window of opportunity. CMAJ 2005;173:1054–65.CrossRefGoogle ScholarPubMed
25.Bone, RC, Balk, RA, Cerra, FB, et al.Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992;101:1644–55.Google Scholar
26.Rivers, E. The outcome of patients presenting to the emergency department with severe sepsis or septic shock. Crit Care 2006;10:154.Google Scholar
27.Hebert, PC, Drummond, AJ, Singer, J, et al.A simple multiple system organ failure scoring system predicts mortality of patients who have sepsis syndrome. Chest 1993;104:230–5.CrossRefGoogle ScholarPubMed
28.Nguyen, HB, Rivers, EP, Knoblich, BP, et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med 2004;32:1637–12.CrossRefGoogle Scholar
29.Pinsky, MR. Cardiovascular effects of ventilatory support and withdrawal. Anesth Analg 1994;79:567–76.Google Scholar
30.Sugerman, HJ, Diaco, JF, Pollock, TW, et al.Physiologic management of septicemic shock in man. Surg Forum 1971;22:3–5.Google Scholar
31.Turnaoglu, S, Tugrul, M, Camci, E, et al.Clinical applicability of the substitution of mixed venous oxygen saturation with central venous oxygen saturation. J Cardiothorac Vasc Anesth 2001;15:574–9.Google Scholar
32.Practice parameters for hemodynamic support of sepsis in adult patients in sepsis. Task Force of the American College of Critical Care Medicine, Society of Critical Care Medicine. Crit Care Med 1999;27:639–60.Google Scholar
33.Rackow, EC, Falk, JL, Fein, IA, et al.Fluid resuscitation in circulatory shock: a comparison of the cardiorespiratory effects of albumin, hetastarch, and saline solutions in patients with hypo-volemic and septic shock. Crit Care Med 1983;11:839–50.Google Scholar
34.Finfer, S, Norton, R, Bellomo, R, et al.The SAFE study: saline vs. albumin for fluid resuscitation in the critically ill. Vox Sang 2004;07(Suppl 2):123–31.CrossRefGoogle ScholarPubMed
35.Bunn, F, Alderson, P, Hawkins, V. Colloid solutions for fluid resuscitation. Cochrane Database Syst Rev 2003;(1):CD001319.Google Scholar
36.Roberts, I, Alderson, P, Bunn, F, et al.Colloids versus crystalloids for fluid resuscitation in critically ill patients. Cochrane Database Syst Rev. 2004;(4):CD000567Google Scholar
37.Alderson, P, Bunn, F, Lefebvre, C, et al.Human albumin solution for resuscitation and volume expansion in critically ill patients. Cochrane Database Syst Rev 2004;(4):CD001208.Google Scholar
38.Upadhyay, M, Singhi, S, Murlidharan, J, et al.Randomized evaluation of fluid resuscitation with crystalloid (saline) and colloid (polymer from degraded gelatin in saline) in pediatric septic shock. Indian Pediatr 2005 ;42:223–31.Google Scholar
39.Vincent, JL, Gerlach, H. Fluid resuscitation in severe sepsis and septic shock: an evidence-based review. Crit Care Med 2004;32:S451–4.Google Scholar
40.Brunkhorst, FM, Engel, C, Bloos, F, et al.Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008;358:125–39.Google Scholar
41.Holmes, CL. Vasoactive drugs in the intensive care unit. Curr Opin Crit Care 2005;11:413–7.Google Scholar
42.Holmes, CL, Walley, KR. The evaluation and management of shock. Clin Chest Med 2003;24:775–89.Google Scholar
43.Nguyen, HB, Rivers, EP, Abrahamian, FM, et al.Emergency Department Sepsis Education Program and Strategies to Improve Survival (ED-SEPSIS) Working Group. Severe sepsis and septic shock: review of the literature and emergency department man-agement guidelines. Ann Emerg Med 2006;48:28–54.Google Scholar
44.Dellinger, RP, Carlet, JM, Masur, H, et al.Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004;32:858–73.CrossRefGoogle ScholarPubMed
45.Kuhl, DA. Current strategies for managing the patient with sepsis. Am J Health Syst Pharm 2002;02/15(Suppl 1):S9–13.Google Scholar
46.Hollenberg, SM, Ahrens, TS, Annane, D, et al.Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update. Crit Care Med 2004;32:1928–48.Google Scholar
47.De Backer, D, Creteur, J, Silva, E, et al.Effects of dopamine, nor-epinephrine, and epinephrine on the splanchnic circulation in septic shock: Which is best? Crit Care Med 2003;31:1659–67.Google Scholar
48.Martin, C, Viviand, X, Leone, M, et al.Effect of norepinephrine on the outcome of septic shock. Crit Care Med 2000;28:2758–65.Google Scholar
49.Martin, C, Papazian, L, Perrin, G, et al.Norepinephrine or dopamine for the treatment of hyperdynamic septic shock? Chest 1993;103:1826–31.Google Scholar
50.Marik, PE, Mohedin, M. The contrasting effects of dopamine and norepinephrine on systemic and splanchnic oxygen utilization in hyperdynamic sepsis. JAMA 1994;272:1354–7.Google Scholar
51.Redl-Wenzl, EM, Armbruster, C, Edelmann, G, et al.The effects of norepinephrine on hemodynamics and renal function in severe septic shock states. Intensive Care Med 1993;19:151–4.Google Scholar
52.Levy, B, Bollaert, PE, Charpentier, C, et al.Comparison of nor-epinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study. Intensive Care Med 1997;23:282–7.CrossRefGoogle Scholar
53.Desjars, P, Pinaud, M, Potel, G, et al.A reappraisal of norepinephrine therapy in human septic shock. Crit Care Med 1987;15:134–7.Google Scholar
54.Meadows, D, Edwards, JD, Wilkins, RG, et al.Reversal of intractable septic shock with norepinephrine therapy. Crit Care Med 1988;16:663–6.CrossRefGoogle ScholarPubMed
55.Desjars, P, Pinaud, M, Bugnon, D, et al.Norepinephrine therapy has no deleterious renal effects in human septic shock. Crit Care Med 1989;17:426–9.CrossRefGoogle ScholarPubMed
56.Hesselvik, JF, Brodin, B. Low dose norepinephrine in patients with septic shock and oliguria: effects on afterload, urine flow, and oxygen transport. Crit Care Med 1989;17:179–80.Google Scholar
57.Marin, C, Eon, B, Saux, P, et al.Renal effects of norepinephrine used to treat septic shock patients. Crit Care Med 1990;18:282–5.Google Scholar
58.Bellomo, R, Chapman, M, Finfer, S, et al.Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 2000;356:2139–43.Google ScholarPubMed
59.Kellum, JA, Decker, M. Use of dopamine in acute renal failure: a meta-analysis. Crit Care Med 2001;29:1526–31.Google Scholar
60.Olson, D, Pohlman, A, Hall, JB. Administration of low-dose dopamine to nonoliguric patients with sepsis syndrome does not raise intramucosal gastric pH nor improve creatinine clearance. Am J Respir Crit Care Med 1996;154:1664–70.CrossRefGoogle Scholar
61.Patel, BM, Chittock, DR, Russell, JA, et al.Beneficial effects of short-term vasopressin infusion during severe septic shock. Anesthesiology 2002;96:576–82.Google Scholar
62.Malay, MB, Ashton, RC Jr, Landry, DW, et al.Low-dose vasopressin in the treatment of vasodilatory septic shock. J Trauma 1999;47:699–703.CrossRefGoogle ScholarPubMed
63.Holmes, CL, Walley, KR, Chittock, DR, et al.The effects of vasopressin on hemodynamics and renal function in severe septic shock: a case series. Intensive Care Med 2001;27:1416–21.Google Scholar
64.Dufresne, RG Jr. Skin necrosis from intravenously infused materials. Cutis 1987;39:197–8.Google ScholarPubMed
65.Greenwald, RA, Rheingold, OJ, Chiprut, RO, et al.Local gangrene: a complication of peripheral pitressin therapy for bleeding esophageal varices. Gastroenterology 1978;74:744–6.Google Scholar
66.Kahn, JM, Kress, JP, Hall, JB. Skin necrosis after extravasation of low-dose vasopressin administered for septic shock. Crit Care Med 2002;30:1899–901.CrossRefGoogle ScholarPubMed
67.Korenberg, RJ, Landau-Price, D, Penneys, NS. Vasopressin-induced bullous disease and cutaneous necrosis. J Am Acad Dermatol 1986;15:393–8.Google Scholar
68.Rudis, MI, Basha, MA, Zarowitz, BJ. Is it time to reposition vasopressors and inotropes in sepsis? Crit Care Med 1996;24:525–37.CrossRefGoogle ScholarPubMed
69.Cohen, J, Brun-Buisson, C, Torres, A, et al.Diagnosis of infection in sepsis: an evidence-based review. Crit Care Med 2004;32:S466–94.CrossRefGoogle ScholarPubMed
70.Smith-Elekes, S, Weinstein, MP. Blood cultures. Infect Dis Clin North Am 1993;7:221–34.Google Scholar
71.Reimer, LG, Wilson, ML, Weinstein, MP. Update on detection of bacteremia and fungemia. Clin Microbiol Rev 1997;10:444–65.Google Scholar
72.Wilson, ML. General principles of specimen collection and transport. Clin Infect Dis 1996;22:766–77.CrossRefGoogle ScholarPubMed
73.Broder, G, Weil, MH. Excess lactate: an index of reversibility of shock in human patients. Science 1964;143:1457–9.Google Scholar
74.Bernardin, G, Pradier, C, Tiger, F, et al.Blood pressure and arterial lactate level are early indicators of short-term survival in human septic shock. Intensive Care Med 1996 ;22:17–25.Google Scholar
75.Shapiro, NI, Howell, MD, Talmor, D, et al.Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med 2005;45:524–8.Google Scholar
76.Trzeciak, S, Dellinger, RP, Chansky, ME, et al.Serum lactate as a predictor of mortality in patients with infection. Intensive Care Med 2007;33:970–7.Google Scholar
77.Aduen, J, Bernstein, WK, Khastgir, T, et al.The use and clinical importance of a substrate-specific electrode for rapid determination of blood lactate concentrations. JAMA 1994;272:1678–85.CrossRefGoogle ScholarPubMed
78.Shapiro, N, Howell, MD, Bates, DW, et al.The association of sepsis syndrome and organ dysfunction with mortality in emergency department patients with suspected infection. Ann Emerg Med 2006;48:583,90, 590.Google Scholar
79.Kumar, A, Haery, C, Paladugu, B, et al.The duration of hypotension before the initiation of antibiotic treatment is a critical determinant of survival in a murine model of escherichia coli septic shock: association with serum lactate and inflammatory cytokine levels. J Infect Dis 2006;193:251–8.CrossRefGoogle Scholar
80.Miner, JR, Heegaard, W, Mapes, A, et al.Presentation, time to antibiotics, and mortality of patients with bacterial meningitis at an urban county medical center. J Emerg Med 2001;21:387–92.Google Scholar
81.Houck, PM, Bratzler, DW, Nsa, W, et al.Timing of antibiotic administration and outcomes for medicare patients hospitalized with community-acquired pneumonia. Arch Intern Med 2004; 164:637–44.CrossRefGoogle ScholarPubMed
82.Kumar, A, Roberts, D, Wood, KE, et al.Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006;34:1589–96.Google Scholar
83.Bochud, PY, Glauser, MP, Calandra, T. Antibiotics in sepsis. Intensive Care Med 2001;27(Suppl 1):S33–48.Google Scholar
84.Simon, D, Trenholme, G. Antibiotic selection for patients with septic shock. Crit Care Clin 2000;16:215–31.Google Scholar
85.Hughes, WT, Armstrong, D, Bodey, GP, et al.2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 2002 ;34:730–51.Google Scholar
86.Marshall, JC, Maier, RV, Jimenez, M, et al.Source control in the management of severe sepsis and septic shock: an evidence-based review. Crit Care Med 2004;32:S513–26.Google Scholar
87.Moss, RL, Musemeche, CA, Kosloske, AM. Necrotizing fasciitis in children: Prompt recognition and aggressive therapy improve survival. J Pediatr Surg 1996;31:1142–6.Google Scholar
88.Feistritzer, C, Wiedermann, CJ. Effects of anticoagulant strategies on activation of inflammation and coagulation. Expert Opin Biol Ther 2007;7:855–70.CrossRefGoogle ScholarPubMed
89.Baillie, JK. Activated protein C: Controversy and hope in the treatment of sepsis. Curr Opin Investig Drugs 2007;8:933–8.Google ScholarPubMed
90.Abraham, E, Laterre, PF, Garg, R, et al.Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med 2005 ;353:1332–41.CrossRefGoogle Scholar
91.Bernard, GR, Margolis, BD, Shanies, HM, et al.Extended Evaluation of Recombinant Human Activated Protein C United States Trial (ENHANCE US): a single-arm, phase 3B, multicenter study of drotrecogin alfa (activated) in severe sepsis. Chest 2004;125:2206–16.Google Scholar
92.Yildiz, O, Doganay, M, Aygen, B, et al.Physiological-dose steroid therapy in sepsis [ISRCTN36253388]. Crit Care 2002;6:251–9.Google Scholar
93.Briegel, J, Forst, H, Haller, M, et al.Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med 1999;27:723–32.Google Scholar
94.Bollaert, PE, Charpentier, C, Levy, B, et al.Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med 1998;26:645–50. Google Scholar
95.Keh, D, Boehnke, T, Weber-Cartens, S, et al.Immunologic and hemodynamic effects of “low-dose” hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study. Am J Respir Crit Care Med 2003 02/15;167(4):512–20.Google Scholar
96.Minneci, PC, Deans, KJ, Banks, SM, et al.Meta-analysis: the effect of steroids on survival and shock during sepsis depends on the dose. Ann Intern Med 2004;141:47–56.Google Scholar
97.Annane, D, Bellissant, E, Bollaert, PE, et al.Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis. BMJ 2004;329:480.Google Scholar
98.Annane, D, Sebille, V, Troche, G, et al.A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA 2000;283:1038–45.CrossRefGoogle ScholarPubMed
99.Sprung, CL, Annane, D, Keh, D, et al.Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008;358:111–24.CrossRefGoogle ScholarPubMed
100.Marik, PE, Zaloga, GP. Adrenal insufficiency during septic shock. Crit Care Med 2003;31:141–5.Google Scholar
101.Bourne, RS, Webber, SJ, Hutchinson, SP. Adrenal axis testing and corticosteroid replacement therapy in septic shock patients-local and national perspectives. Anaesthesia 2003;58:591–6.Google Scholar
102.Bouachour, G, Tirot, P, Gouello, JP, et al.Adrenocortical function during septic shock. Intensive Care Med 1995;21:57–62.Google Scholar
103.Rothwell, PM, Udwadia, ZF, Lawler, PG. Cortisol response to corticotropin and survival in septic shock. Lancet 1991;337:582–3.Google Scholar
104.Goodman, S, Sprung, CL, Ziegler, D, et al.Cortisol changes among patients with septic shock and the relationship to ICU and hospital stay. Intensive Care Med 2005;31:1362–9.Google Scholar
105.Keh, D, Sprung, CL. Use of corticosteroid therapy in patients with sepsis and septic shock: an evidence-based review. Crit Care Med 2004;32:S527–33.Google Scholar
106.Hebert, PC, Wells, G, Blajchman, MA, et al.A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. transfusion requirements in critical care investigators, canadian critical care trials group. N Engl J Med 1999;340:409–17.Google Scholar
107.Fan, E, Needham, DM, Stewart, TE. Ventilatory management of acute lung injury and acute respiratory distress syndrome. JAMA 2005;294:2889–96.Google Scholar
108.Kallet, RH. Evidence-based management of acute lung injury and acute respiratory distress syndrome. Respir Care 2004;49:793–809.Google Scholar
109.Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The acute respiratory distress syndrome network. N Engl J Med 2000;342:1301–8.Google Scholar
110.Kollef, MH, Schuster, DP. The acute respiratory distress syndrome. N Engl J Med 1995;332:27–37.CrossRefGoogle ScholarPubMed
111.Bernard, GR, Artigas, A, Brigham, KL, et al.The American-European consensus conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994;149:818–24.Google Scholar
112.Hickling, KG, Walsh, J, Henderson, S, et al.Low mortality rate in adult respiratory distress syndrome using low-volume, pressure-limited ventilation with permissive hypercapnia: a prospective study. Crit Care Med 1994;22:1568–78.CrossRefGoogle ScholarPubMed
113.Amato, MB, Barbas, CS, Medeiros, DM, et al.Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med 1998;338:347–54.CrossRefGoogle ScholarPubMed
114.Stewart, TE, Meade, MO, Cook, DJ, et al.Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. pressure- and volume-limited ventilation strategy group. N Engl J Med 1998;338:355–61.Google Scholar
115.Bidani, A, Tzouanakis, AE, Cardenas, VJ Jr, et al.Permissive hy-percapnia in acute respiratory failure. JAMA 1994;272:957–62.CrossRefGoogle ScholarPubMed
116.Stocker, R, Neff, T, Stein, S, et al.Prone positioning and low-volume pressure-limited ventilation improve survival in patients with severe ARDS. Chest 1997;111:1008–17.Google Scholar
117.Jolliet, P, Bulpa, P, Chevrolet, JC. Effects of the prone position on gas exchange and hemodynamics in severe acute respiratory distress syndrome. Crit Care Med 1998;26:1977–85.Google Scholar
118.Gattinoni, L, Tognoni, G, Pesenti, A, et al.Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med 2001;345:568–73.CrossRefGoogle ScholarPubMed
119.Papazian, L, Gainnier, M, Marin, V, et al.Comparison of prone positioning and high-frequency oscillatory ventilation in patients with acute respiratory distress syndrome. Crit Care Med 2005;33:2162–71.Google Scholar
120.Van den Berghe, G, Wilmer, A, Hermans, G, et al.Intensive insulin therapy in the medical ICU. N Engl J Med 2006;354:449–61.Google Scholar
121.Malhotra, A. Intensive insulin in intensive care. N Engl J Med 2006;354:516–8.CrossRefGoogle ScholarPubMed