Activated protein C and hospital mortality in septic shock: a propensity-matched analysis.
OBJECTIVE
Evidence regarding the efficacy and safety of human recombinant activated protein C in severe sepsis is limited, especially outside of clinical trials. We sought to compare the outcomes of patients with septic shock who received early treatment with activated protein C to those who did not.


METHODS
A retrospective cohort study at 404 U.S. hospitals. We studied 33,749 patients with sepsis who were admitted to intensive care and administered antibiotics and vasopressors within 2 days of admission.


RESULTS
Hospital mortality, intracranial and gastrointestinal hemorrhage, major transfusion. Compared to the entire cohort, the 1576 activated protein C-treated patients included in the matched analysis were younger (mean age, 61 vs. 67), more likely to be white (70% vs. 63%), and had fewer comorbidities. Treated patients were more likely to require mechanical ventilation (77% vs. 48%), to be administered two or more vasopressors (68% vs. 41%), to undergo pulmonary artery catheterization (9% vs. 4%), and to die in the hospital (40.7% vs. 38.1%). In a propensity-matched sample in which all covariates achieved balance, receipt of activated protein C was associated with reduced hospital mortality (40.7% vs. 46.6%; risk ratio, 0.87; 95% confidence interval, 0.80-0.95). This result was insensitive to a hypothetical unmeasured confounder. A similar pattern was observed across groups stratified by age and number of organ-supportive therapies. Four activated protein C-treated patients (0.25%) had hemorrhagic stroke, 107 (6.8%) had gastrointestinal bleeding, and five (0.3%) required major transfusion.


CONCLUSIONS
Among patients presenting with septic shock, early treatment with activated protein C may be associated with reduced hospital mortality.
Center for Quality of Care Research, Baystate Medical Center, Springfield, MA, USA. Peter.Lindenauer@bhs.org
Peter K
PK
Lindenauer
Michael B
MB
Rothberg
Brian H
BH
Nathanson
Penelope S
PS
Pekow
Jay S
JS
Steingrub
D000367:Age Factors; D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016009:Chi-Square Distribution; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D057216:Propensity Score; D011486:Protein C / Q000627:therapeutic use*; D012121:Respiration, Artificial; D012189:Retrospective Studies; D012737:Sex Factors; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality*; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D011486:Protein C; D014662:Vasoconstrictor Agents