Top

Intensive Care Medicine

Published in:

01-07-2009 | Original

Reversal of refractory septic shock with drotrecogin alpha (activated)

Authors: A. Vieillard-Baron, V. Caille, C. Charron, G. Belliard, P. Aegerter, B. Page, F. Jardin

Published in: Intensive Care Medicine | Issue 7/2009

Abstract

Objective

We previously reported that early continuous veno-venous hemodiafiltration (CVVHDF) enables rapid identification of a subgroup of patients with “refractory” septic shock and a 100% risk of death. The objective of this study was to investigate whether early administration of drotrecogin alpha (activated) (DrotAA) to this selected subgroup of septic patients at extremely high risk of death would significantly improve prognosis.

Method

Prospective observational study in a medical intensive-care unit of a University Hospital. Twenty-three patients with refractory septic shock were included. “Refractory” shock was defined as persistent circulatory failure despite adequate circulatory support, associated with persisting lactic acidosis despite early CVVHDF. Response to CVVDHF was assessed after 6 h of this continuous procedure. Patients selected by this strategy received DrotAA infusion for four days.

Results

The 28-day mortality rate of the 23 patients was 39%. No difference was observed at inclusion between survivors and nonsurvivors. In patients who finally survived, 12 h of DrotAA infusion was associated with a significant decrease in lactic acidosis and in norepinephrine dose.

Conclusion

DrotAA therapy was associated with unexpectedly high 28-day survival in patients with “refractory” septic shock.

Bernard G, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ, Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699–709PubMedCrossRef

Vincent JL, Bernard G, Beale R, Doig C, Putensen C, Dhainaut JF, Artigas A, Fumagalli R, Macias W, Wright T, Wong K, Sundin DP, Turlo MA, Janes J (2005) Drotrecogin alfa (activated) treatment in severe sepsis from the global open-label trial ENHANCE: further evidence for survival and safety and implication for early treatment. Crit Care Med 33:2266–2277PubMedCrossRef

Eichacker P, Natanson C (2006) Surviving sepsis-practice guidelines, marketing campaigns, and Eli Lilly. N Engl J Med 19:1640–1642CrossRef

Abraham E, Laterre PF, Garg R, Levy H, Talwar D, Trzaskoma BL, François B, Guy JS, Brückmann M, Rea-Neto A, Rossaint R, Perrotin D, Sablotzki A, Arkins N, Utterback BG, Macias WL (2005) Drotrecogin alfa (activated) treatment for adults with severe sepsis and a low risk of death. N Engl J Med 353:1332–1341PubMedCrossRef

Dellinger P (2006) Recombinant activated protein C: decisions for administration. Crit Care Med 34:530–531PubMedCrossRef

Page B, Vieillard-Baron A, Beauchet A, Aegerter P, Prin S, Jardin F (2005) Early veno-venous hemodiafiltration for sepsis-related multiple organ failure. Crit Care 9:R755–R763PubMedCrossRef

Carlet J (2006) Prescribing indications based on successful clinical trials in sepsis: a difficult exercise. Crit Care Med 34:525–531PubMedCrossRef

Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ (1992) Definition for sepsis and organ failure and guideline for the use of innovative therapies in sepsis. Chest 101:1644–1655PubMedCrossRef

Le Gall JR, Lemeshow S, Saulnier F (1993) A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study. JAMA 270:2957–2963PubMedCrossRef

10.

Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, Reinhart C, Suter P, Thijs L (1996) The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. Intensive Care Med 22:707–710PubMedCrossRef

11.

McCabe R, Jackson G (1962) Gram-negative bacteremia: I. Etiology and ecology. Ann Intern Med 110:847–855

12.

Vieillard-Baron A, Prin S, Chergui K, Dubourg O, Jardin F (2003) Hemodynamic instability in sepsis: bedside assessment by Doppler echocardiography. Am J Respir Crit Care Med 168:1270–1276PubMedCrossRef

13.

Vieillard-Baron A, Caille V, Charron C, Belliard G, Page B, Jardin F (2008) Actual incidence of global left ventricular hypokinesia in adult septic shock. Crit Care Med 36:1701–1706PubMedCrossRef

14.

Annane D, Sebille V, Charpentier C, Bollaert P, François B, Korach J, Cappello M, Cohen Y, Azoulay E, Troche G, Chaumet-Riffaut P, Bellissant E (2002) Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862–871PubMedCrossRef

15.

Dellinger R, Levy MM, Carlet J, International Surviving Sepsis Campaign guidelines committee (2008) Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock. Crit Care Med 36:296–327PubMedCrossRef

16.

Page B, Vieillard-Baron A, Beauchet A, Aegeter Ph, Prin S, Jardin F (2003) Low stretch ventilator strategy in acute respiratory distress syndrome: eight years of clinical experience in a single center. Crit Care Med 31:765–769PubMedCrossRef

17.

Bellomo R, Kellum J, Ronco C (2001) Acute renal failure: time for consensus. Intensive Care Med 27:1685–1688PubMedCrossRef

18.

Ely W, Laterre PF, Angus D, Helterbrand J, Levy H, Dhainaut JF, Vincent JL, Macias W, Bernard G, for the PROWESS investigators (2003) Drotrecogin alfa (activated) administration across clinically important subgroups of patients with a severe sepsis. Crit Care Med 31:12–19PubMedCrossRef

19.

Honore PM, Jamez J, Wauthier M, Lee PA, Dugernier T, Pirenne B, Hanique G, Matson JR (2000) Prospective evaluation of short-term, high-volume isovolemic hemofiltration on the hemodynamic course and outcome in patients with intractable circulatory failure resulting from septic shock. Crit Care Med 28:3581–3587PubMedCrossRef

20.

Piccinni P, Dan M, Barbacini S, Carraro R, Lieta E, Marafon S, Zamperetti N, Brendolan A, D’Intini V, Tetta C, Bellomo R, Ronco C (2006) Early isovolemic hemofiltration in oliguric patients with septic shock. Intensive Care Med 32:80–86PubMedCrossRef

21.

Cornejo R, Downey P, Castro R, Romero C, Regueira T, Vega J, Castillo L, Andresen M, Dougnac A, Bugedo G, Hernandez G (2006) High-volume haemofiltration as salvage therapy in severe hyperdynamic septic shock. Intensive Care Med 32:713–722PubMedCrossRef

22.

Vincent JL, O’Brien J Jr, Wheeler A, Wittebole X, Garg R, Trzaskoma BL, Sundin DP (2006) Use of an integrated clinical trial database to evaluate the effect of timing of drotrecogin alfa (activated) treatment in severe sepsis. Crit Care 10:R74PubMedCrossRef

23.

Monnet X, Lamia B, Anguel N, Richard C, Bonmarchand G, Teboul JL (2005) Rapid and beneficial hemodynamic effects of activated protein C in septic shock patients. Intensive Care Med 31:1573–1576PubMedCrossRef

24.

Legall JR, Klar J, Lemeshow S, Saulnier F, Alberti C, Artigas A, Teres D (1996) The logistic organ dysfunction score. JAMA 275:802–810CrossRef

25.

Angus D, Linde-Zwirble W, Lidicker J, Clermont G, Carcillo J, Pinsky M (2001) Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med 29:1303–1310PubMedCrossRef

26.

Padkin A, Goldfrad C, Brady A, Young D, Black N, Rowan K (2003) Epidemiology of severe sepsis occurring in the first 24 h in intensive-care units in England, Walles, and Northern Ireland. Crit Care Med 31:2332–2338PubMedCrossRef

27.

Vincent JL, Sakf V, Sprung C, Ranieri M, Reinhart K, Gerlach H, Moreno R, Carlet J, Le Gall JR, Payen D (2006) Sepsis in European intensive-care units: results of the SOAP study. Crit Care Med 34:344–353PubMedCrossRef

28.

Annane D, Aegerter Ph, Jars-Guincestre MC, Guidet B (2003) Current epidemiology of septic shock. The CUB-Rea network. Am J Respir Crit Care Med 168:165–172PubMedCrossRef

29.

The EPISEPSIS Study Group (2004) EPISEPSIS/a reappraisal of the epidemiology and outcome of severe sepsis in French intensive-care units. Intensive Care Med 30:580–588CrossRef

30.

Abid O, Akça S, Haji-Michael P, Vincent JL (2000) Strong vasopressor support may be futile in the intensive-care unit patient with multiple organ failure. Crit Care Med 55:947–949CrossRef

31.

Martin C, Viviand X, Leone M, Thirion X (2000) Effect of norepinephrine on the outcome of septic shock. Crit Care Med 28:2758–2765PubMedCrossRef

Title: Reversal of refractory septic shock with drotrecogin alpha (activated)
Authors: A. Vieillard-Baron
V. Caille
C. Charron
G. Belliard
P. Aegerter
B. Page
F. Jardin
Publication date: 01-07-2009
Publisher: Springer-Verlag
Published in: Intensive Care Medicine / Issue 7/2009
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI: https://doi.org/10.1007/s00134-009-1538-9

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Reversal of refractory septic shock with drotrecogin alpha (activated)

Abstract

Objective

Method

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objective

Method

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 7/2009

Total brain failure: a new contribution by the President’s Council on Bioethics to the definition of death according to the neurological standard

Short-term evaluation of sedation with sevoflurane administered by the anesthetic conserving device in critically ill patients

Comprehensive safety analysis of concomitant drotrecogin alfa (activated) and prophylactic heparin use in patients with severe sepsis

Sepsis care bundles and clinicians

Using midazolam to monitor changes in hepatic drug metabolism in critically ill patients

Reduction of ventilator-associated pneumonia: active versus passive guideline implementation