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Published in: Intensive Care Medicine 11/2005

01-11-2005 | Brief Report

Rapid and beneficial hemodynamic effects of activated protein C in septic shock patients

Authors: X. Monnet, B. Lamia, N. Anguel, C. Richard, G. Bonmarchand, J. L. Teboul

Published in: Intensive Care Medicine | Issue 11/2005

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Abstract

Objective

Because recombinant human activated protein C (rhAPC) reduces NO production during sepsis, it could improve the vascular tone. We tested whether rhAPC reduces the dose of norepinephrine required to maintain mean arterial pressure (MAP) in septic shock patients.

Design and setting

Retrospective study in intensive care unit of two university hospitals.

Patients

Twenty-two septic shock patients with at least two organ failures were retrospectively investigated for MAP and the required dose of norepinephrine before and 24 h after rhAPC administration. A control group of 22 septic shock patients with at least two organ failures who did not receive rhAPC was matched on age, SAPS II, MAP, and norepinephrine dose at the time of the theoretical start of rhAPC.

Measurements and results

The MAP remained stable and similar in the two groups (86±16 vs. 89±9 mmHg at 24 h). The required dose of norepinephrine increased in the control group (+38%, from −41% to +38%) but decreased in the treated group (−33%, from −74% to +11%).

Conclusions

rhAPC rapidly improved the vascular tone in septic shock patients as assessed by a decrease in the norepinephrine dose required to maintain arterial pressure.
Literature
1.
go back to reference Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699–709CrossRefPubMed Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, Steingrub JS, Garber GE, Helterbrand JD, Ely EW, Fisher CJ Jr (2001) Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 344:699–709CrossRefPubMed
3.
go back to reference Vallet B (2003) Bench-to-bedside review: endothelial cell dysfunction in severe sepsis: a role in organ dysfunction? Crit Care 7:130–138CrossRefPubMed Vallet B (2003) Bench-to-bedside review: endothelial cell dysfunction in severe sepsis: a role in organ dysfunction? Crit Care 7:130–138CrossRefPubMed
4.
go back to reference Szabo C, Mitchell JA, Thiemermann C, Vane JR (1993) Nitric oxide-mediated hyporeactivity to noradrenaline precedes the induction of nitric oxide synthase in endotoxin shock. Br J Pharmacol 108:786–792PubMed Szabo C, Mitchell JA, Thiemermann C, Vane JR (1993) Nitric oxide-mediated hyporeactivity to noradrenaline precedes the induction of nitric oxide synthase in endotoxin shock. Br J Pharmacol 108:786–792PubMed
5.
go back to reference Isobe H, Okajima K, Uchiba M, Mizutani A, Harada N, Nagasaki A, Okabe K (2001) Activated protein C prevents endotoxin-induced hypotension in rats by inhibiting excessive production of nitric oxide. Circulation 104:1171–1175PubMed Isobe H, Okajima K, Uchiba M, Mizutani A, Harada N, Nagasaki A, Okabe K (2001) Activated protein C prevents endotoxin-induced hypotension in rats by inhibiting excessive production of nitric oxide. Circulation 104:1171–1175PubMed
6.
go back to reference Kalil AC, Coyle SM, Um JY, LaRosa SP, Turlo MA, Calvano SE, Sundin DP, Nelson DR, Lowry SF (2004) Effects of drotrecogin alfa (activated) in human endotoxemia. Shock 21:222–229CrossRefPubMed Kalil AC, Coyle SM, Um JY, LaRosa SP, Turlo MA, Calvano SE, Sundin DP, Nelson DR, Lowry SF (2004) Effects of drotrecogin alfa (activated) in human endotoxemia. Shock 21:222–229CrossRefPubMed
7.
go back to reference Derhaschnig U, Reiter R, Knobl P, Baumgartner M, Keen P, Jilma B (2003) Recombinant human activated protein C (rhAPC; drotrecogin alfa [activated]) has minimal effect on markers of coagulation, fibrinolysis, and inflammation in acute human endotoxemia. Blood 102:2093–2098CrossRefPubMed Derhaschnig U, Reiter R, Knobl P, Baumgartner M, Keen P, Jilma B (2003) Recombinant human activated protein C (rhAPC; drotrecogin alfa [activated]) has minimal effect on markers of coagulation, fibrinolysis, and inflammation in acute human endotoxemia. Blood 102:2093–2098CrossRefPubMed
8.
go back to reference Dhainaut JF, Laterre PF, Janes JM, Bernard GR, Artigas A, Bakker J, Riess H, Basson BR, Charpentier J, Utterback BG, Vincent JL (2003) Drotrecogin alfa (activated) in the treatment of severe sepsis patients with multiple-organ dysfunction: data from the PROWESS trial. Intensive Care Med 29:894–903PubMed Dhainaut JF, Laterre PF, Janes JM, Bernard GR, Artigas A, Bakker J, Riess H, Basson BR, Charpentier J, Utterback BG, Vincent JL (2003) Drotrecogin alfa (activated) in the treatment of severe sepsis patients with multiple-organ dysfunction: data from the PROWESS trial. Intensive Care Med 29:894–903PubMed
9.
go back to reference Vincent JL, Angus DC, Artigas A, Kalil A, Basson BR, Jamal HH, Johnson G, 3rd, Bernard GR (2003) Effects of drotrecogin alfa (activated) on organ dysfunction in the PROWESS trial. Crit Care Med 31:834–840CrossRefPubMed Vincent JL, Angus DC, Artigas A, Kalil A, Basson BR, Jamal HH, Johnson G, 3rd, Bernard GR (2003) Effects of drotrecogin alfa (activated) on organ dysfunction in the PROWESS trial. Crit Care Med 31:834–840CrossRefPubMed
10.
go back to reference Finigan JH, Dudek SM, Singleton PA, Chiang ET, Jacobson JR, Camp SM, Ye SQ, Garcia JG (2005) Activated protein C mediates novel lung endothelial barrier enhancement: role of sphingosine 1-phosphate receptor transactivation. J Biol Chem 280:17286–17293CrossRefPubMed Finigan JH, Dudek SM, Singleton PA, Chiang ET, Jacobson JR, Camp SM, Ye SQ, Garcia JG (2005) Activated protein C mediates novel lung endothelial barrier enhancement: role of sphingosine 1-phosphate receptor transactivation. J Biol Chem 280:17286–17293CrossRefPubMed
11.
go back to reference Bourgoin A, Leone M, Delmas A, Garnier F, Albanese J, Martin C (2005) Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function. Crit Care Med 33:780–786CrossRefPubMed Bourgoin A, Leone M, Delmas A, Garnier F, Albanese J, Martin C (2005) Increasing mean arterial pressure in patients with septic shock: effects on oxygen variables and renal function. Crit Care Med 33:780–786CrossRefPubMed
Metadata
Title
Rapid and beneficial hemodynamic effects of activated protein C in septic shock patients
Authors
X. Monnet
B. Lamia
N. Anguel
C. Richard
G. Bonmarchand
J. L. Teboul
Publication date
01-11-2005
Publisher
Springer-Verlag
Published in
Intensive Care Medicine / Issue 11/2005
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-005-2792-0

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