Reducing mortality in sepsis: new directions

Jean-Louis Vincent, Edward Abraham, Djillali Annane, Gordon Bernard, Emanuel Rivers, Greet Van den Berghe, Jean-Louis Vincent, Edward Abraham, Djillali Annane, Gordon Bernard, Emanuel Rivers, Greet Van den Berghe

Abstract

Considerable progress has been made in the past few years in the development of therapeutic interventions that can reduce mortality in sepsis. However, encouraging physicians to put the results of new studies into practice is not always simple. A roundtable was thus convened to provide guidance for clinicians on the integration and implementation of new interventions into the intensive care unit (ICU). Five topics were selected that have been shown in randomized, controlled trials to reduce mortality: limiting the tidal volume in acute lung injury or acute respiratory distress syndrome, early goal-directed therapy, use of drotrecogin alfa (activated), use of moderate doses of steroids, and tight control of blood sugar. One of the principal investigators for each study was invited to participate in the roundtable. The discussions and questions that followed the presentation of data by each panel member enabled a consensus recommendation to be derived regarding when each intervention should be used. Each new intervention has a place in the management of patients with sepsis. Furthermore, and importantly, the therapies are not mutually exclusive; many patients will need a combination of several approaches--an "ICU package". The present article provides guidelines from experts in the field on optimal patient selection and timing for each intervention, and provides advice on how to integrate new therapies into ICU practice, including protocol development, so that mortality rates from this disease process can be reduced.

Figures

Figure 1
Figure 1
Mortality prior to hospital discharge in patients receiving a tidal volume of 6 and 12 ml/kg ideal body weight.
Figure 2
Figure 2
Proportion of patients alive and off the ventilator having been ventilated with a tidal volume of 6 and 12 ml/kg ideal body weight.
Figure 3
Figure 3
Median number of ventilator-free days in patients receiving a tidal volume of 6 and 12 ml/kg ideal body weight.
Figure 4
Figure 4
Twenty-eight-day survival in patients treated with drotrecogin alfa (activated) or placebo: all-cause mortality.
Figure 5
Figure 5
Most important effects on morbidity [46]. CVVH, continuous venovenous hemofiltration; ICU, intensive care unit; NNT, number needed to treat; RRR, relative risk reduction.

References

    1. Hoyert DL, Arias E, Smith BL, Murphy SL, Kochanek KD. National Vital Statistics Reports [serial online], 21 September 2001. 1 October 2002.
    1. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–1310. doi: 10.1097/00003246-200107000-00002.
    1. The task force on the management of acute myocardial infarction of the European Society of Cardiology. Eur Heart J. 1996;17:43–63.
    1. Angus DC, Wax RS. Epidemiology of sepsis: an update. Crit Care Med. 2001;29:S109–S116. doi: 10.1097/00003246-200107001-00035.
    1. Balk RA. Severe sepsis and septic shock. Definitions, epidemiology, and clinical manifestations. Crit Care Clin. 2000;16:179–192.
    1. Bone RC. Gram-negative sepsis: a dilemma of modern medicine. Clin Microbiol Rev. 1993;6:57–68.
    1. Vincent JL. Sepsis definitions. Lancet Infect Dis. 2002;2:135. doi: 10.1016/S1473-3099(02)00232-3.
    1. Vincent JL, de Mendonça A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Crit Care Med. 1998;26:1793–1800.
    1. Milberg JA, Davis DR, Steinberg KP, Hudson LD. Improved survival of patients with Acute Respiratory Distress Syndrome (ARDS): 1983–1993 [Concepts in Emergency and Critical Care]. JAMA. 1995;273:306–309. doi: 10.1001/jama.273.4.306.
    1. Ziegler EJ, Fisher CJ, Sprung CL, Straube RC, Sadoff JC, Foulke GE, Wortel CH, Fink MP, Dellinger RP, Teng NN. The HA-1A Sepsis Study Group. Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. N Engl J Med. 1991;324:429–436.
    1. Ziegler EJ, McCutchan JA, Fierer J, Glauser MP, Sadoff JC, Douglas H, Braude AI. Treatment of gram-negative bacteremia and shock with human antiserum to a mutant Escherichia coli. N Engl J Med. 1982;307:1225–1230.
    1. Abraham E, Wunderink R, Silverman H, Perl TM, Nasraway S, Levy H, Bone R, Wenzel RP, Balk R, Allred R. The TNFα MAb Sepsis Study Group: monoclonal antibody to human tumor necrosis factor alpha (TNFα MAb): efficacy and safety in patients with the sepsis syndrome. JAMA. 1995;273:934–941. doi: 10.1001/jama.273.12.934.
    1. Abraham E, Reynaert M, Lew D, Pingleton S, Butler T, Dugernier T, Margolis B, Kudsk K, Zimmerli W, Anderson P, Reynaert M, Lew D, Lesslauer W, Passe S, Cooper P, Burdeska A, Modi M, Leighton A, Salgo M, Van der Auwera P. Lenercept Study Group. Lenercept (p55-Tumor Necrosis Factor Receptor Fusion Protein, Ro 45–2081, Tenefuse) patients with severe sepsis or early septic shock. A randomized double-blind placebo-controlled multicenter phase III trial with 1342 patients. Crit Care Med. 2001;29:503–510. doi: 10.1097/00003246-200103000-00006.
    1. 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;344:699–709. doi: 10.1056/NEJM200103083441001.
    1. Wheeler AP, Bernard GR. Current concepts: treating patients with severe sepsis. N Engl J Med. 1999;340:207–214. doi: 10.1056/NEJM199901213400307.
    1. Vincent JL. Need for intensivists in intensive care units [commentary]. Lancet. 2000;356:695–696. doi: 10.1016/S0140-6736(00)02622-2.
    1. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet. 1988;2:349–360.
    1. Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky AS. Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model. J Clin Invest. 1997;99:944–952.
    1. Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS. Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA. 1999;282:54–61. doi: 10.1001/jama.282.1.54.
    1. Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998;338:347–354. doi: 10.1056/NEJM199802053380602.
    1. 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;342:1301–1308. doi: 10.1056/NEJM200005043421801.
    1. Martin GS, Bernard GR. Airway and lung in sepsis. Intensive Care Med. 2001;27:S63–S79.
    1. Hayes TA, Timmins AC, Yau EH, Palazzo M, Hinds CJ, Watson D. Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med. 1994;330:1717–1722. doi: 10.1056/NEJM199406163302404.
    1. Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A, Fumagalli R. A trial of goal-oriented hemodynamic therapy in critically ill patients. SvO2 Collaborative Group. N Engl J Med. 1995;333:1025–1032. doi: 10.1056/NEJM199510193331601.
    1. Rivers E, Nguyen B, Havstad S, Ressler J, Muzzin A, Knoblich B, Peterson E, Tomlanovich M. Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368–1377. doi: 10.1056/NEJMoa010307.
    1. Task Force of the American College of Critical Care Medicine Society of Critical Care Medicine. Practice parameters for hemodynamic support of sepsis in adult patients in sepsis. Crit Care Med. 1999;27:639–660.
    1. Nguyen HB, Rivers EP, Havstad S, Knoblich B, Ressler JA, Muzzin AM, Tomlanovich MC. Critical care in the emergency department: a physiologic assessment and outcome evaluation. Acad EmergMed. 2000;7:1354–1361.
    1. Nelson M, Waldrop RD, Jones J, Randall Z. Critical care provided in an urban emergency department. Am J Emerg Med. 1998;16:56–59. doi: 10.1016/S0735-6757(98)90066-3.
    1. Donnino M, Nguyen B, Rivers E. A hemodynamic comparison of early and late phase severe sepsis and septic shock. Chest. 2002;122:5S. doi: 10.1378/chest.122.1.5.
    1. Yan SB, Helterbrand JD, Hartman DL, Wright TJ, Bernard GR. Low levels of protein C are associated with poor outcomes in severe sepsis. Chest. 2001;120:915–922. doi: 10.1378/chest.120.3.915.
    1. Hesselvik JF, Malm J, Dahlback B, Blomback M. Protein C, protein S, C4b-binding protein in severe infection and septic shock. Thomb Haemost. 1991;65:126–129.
    1. Mesters RM, Helterbrand J, Utterback BG, Yan B, Chao YB, Fernandez JA, Griffin JH, Hartman DL. Prognostic value of protein C concentrations in neutropenic patients at high risk of severe septic complications. Crit Care Med. 2000;28:2209–2216. doi: 10.1097/00003246-200007000-00005.
    1. Leclerc F, Hazelzet J, Jude B, Hofhuis W, Hue V, Martinot A, Van der Voort E. Protein C and S deficiency in severe infectious purpura of children: a collaborative study of 40 cases. Intensive Care Med. 1992;18:202–205. doi: 10.1007/BF01709832.
    1. Powars D, Larsen R, Johnson J, Hulbert T, Sun T, Patch MJ, Francis R, Chan L. Epidemic meningioccemia and purpura fulminans with induced protein C deficiency. Clin Infect Dis. 1993;17:254–261.
    1. Taylor FB Jr, Chang A, Esmon CT, D'Angelo A, Vigano-D'Angelo S, Blick KE. Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. J Clin Invest. 1987;79:918–925.
    1. Taylor Jr FB, Stearns-Kurosawa DJ, Kurosawa S, Ferrell G, Chang AC, Laszik Z, Kosanke S, Peer G, Esmon CT. The endothelial cell protein C receptor aids in host defense against Escherichia coli sepsis. Blood. 2000;95:1680–1686.
    1. Cronin L, Cook DJ, Carlet J, Heyland DK, King D, Lansang MA, Fisher CJ Jr. Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature. Crit Care Med. 1995;23:1430–1439. doi: 10.1097/00003246-199508000-00019.
    1. Lefering R, Neugebauer EA. Steroid controversy in sepsis and septic shock: a meta-analysis. Crit Care Med. 1995;23:1294–1303. doi: 10.1097/00003246-199507000-00021.
    1. Annane D, Sébille V, Troché G, Raphael JC, Gajdos P, Bellissant E. A 3-level prognostic classification in septic shock based on cortisol levels and cortisol response to corticotropin. JAMA. 2000;283:1038–1045. doi: 10.1001/jama.283.8.1038.
    1. Briegel J, Forst H, Haller M, Schelling G, Kilger E, Kuprat G, Hemmer B, Hummel T, Lenhart A, Heyduck M, Stoll C, Peter K. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blinded, single-center study. Crit Care Med. 1999;27:723–732. doi: 10.1097/00003246-199904000-00025.
    1. Meduri GU, Tolley EA, Chrousos GP, Stentz F. Prolonged methylprednisolone treatment suppresses systemic inflammation in patients with unresolving acute respiratory distress syndrome: evidence for inadequate endogenous glucocorticoid secretion and inflammation-induced immune cell resistance to glucocorticoids. Am J Respir Crit Care Med. 2002;165:983–991.
    1. Beishuizen A, Thijs LG, Vermes I. Patterns of corticosteroid-binding globulin and the free cortisol index during septic shock and multitrauma. Intensive Care Med. 2001;27:1584–1591. doi: 10.1007/s001340101073.
    1. Koo DJ, Jackman D, Chaudry IH, Wang P. Adrenal insufficiency during the late stage of polymicrobial sepsis. Crit Care Med. 2001;29:618–622. doi: 10.1097/00003246-200103000-00026.
    1. Bollaert PE, Charpentier C, Levy B, Debouverie M, Audibert G, Larcan A. Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med. 1998;26:645–650. doi: 10.1097/00003246-199804000-00010.
    1. Annane D, Sébille V, Charpentier C, Bollaert PE, Francois B, Korach JM, Capellier G, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellissant E. Effect of a treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288:862–971. doi: 10.1001/jama.288.7.862.
    1. Van den Berghe G, Wouters P, Weekers F, Mohan S, Baxter RC, Veldhuis JD, Bowers CY, Bouillon R. Reactivation of pituitary hormone release and metabolic improvement by infusion of growth hormone-releasing peptide and thyrotropin-releasing hormone in patients with protracted critical illness. J Clin Endocrinol Metab. 1999;84:1311–1323. doi: 10.1210/jc.84.4.1311.
    1. Van den Berghe G, Baxter RC, Weekers F, Wouters P, Bowers CY, Veldhuis JD. A paradoxical gender dissociation within the growth hormone/insulin-like growth factor I axis during protracted critical illness. J Clin Endocrinol Metab. 2000;85:183–192. doi: 10.1210/jc.85.1.183.
    1. Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345:1359–1367. doi: 10.1056/NEJMoa011300.
    1. Morris AH. Decision support and safety of clinical environments. Qual Saf Health Care. 2002;11:69–75. doi: 10.1136/qhc.11.1.69.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever