Early intravenous unfractionated heparin and mortality in septic shock.
BACKGROUND
Sepsis and septic shock represent a systemic inflammatory state with substantial pro-coagulant elements. Unfractionated heparin is a known anticoagulant, which also possesses anti-inflammatory properties. Unfractionated heparin has been shown to increase survival in experimental models of septic shock.


OBJECTIVE
To evaluate the impact of intravenous therapeutic dose unfractionated heparin in a cohort of patients diagnosed with septic shock.


METHODS
Retrospective, propensity matched, multicenter, cohort study.


METHODS
Regional intensive care units in Winnipeg, Canada between 1989 and 2005.


METHODS
Two thousand three hundred fifty-six patients diagnosed with septic shock, of which 722 received intravenous therapeutic dose heparin.


RESULTS
The primary outcome of study was 28-day mortality, and mortality stratified by severity of illness (Acute Physiologic and Chronic Health Evaluation II quartile). Safety was assessed by comparing rates of gastrointestinal hemorrhage, intracranial hemorrhage, and the need for transfusion. By using a Cox proportional hazards model, systemic heparin therapy was associated with decreased 28-day mortality (307 of 695 [44.2%] vs. 279 of 695 [40.1%]; hazard ratio 0.85 [confidence interval (CI) 95% 0.73-1.00]; p = 0.05). In the highest quartile of severity of illness (Acute Physiologic and Chronic Health Evaluation II score 29-53), heparin administration was associated with a clinically and statistically significant reduction in 28-day mortality [127 of 184 (69.0%) vs. 94 of 168 (56.0%); hazard ratio 0.70 (CI 95% 0.54-0.92); p = 0.01]. The use of intravenous unfractionated heparin was associated with successful liberation from mechanical ventilation [odds ratio of 1.42 (CI 95% 1.13-1.80); p = 0.003], and successful discontinuation of vasopressor/inotropic support [odds ratio of 1.34 (CI 95% 1.06-1.71); p = 0.01]. No significant differences in the rates of major hemorrhage or need for transfusion were identified.


CONCLUSIONS
Early administration of intravenous therapeutic dose unfractionated heparin may be associated with decreased mortality when administered to patients diagnosed with septic shock, especially in patients with higher severity of illness. Prospective randomized trials are needed to further define the role of this agent in sepsis and septic shock.
Zarychanski
Ryan
R
Section of Critical Care Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Doucette
Steven
S
Fergusson
Dean
D
Roberts
Daniel
D
Houston
Donald S
DS
Sharma
Satendra
S
Gulati
Harlena
H
Kumar
Anand
A
D000925:Anticoagulants / Q000008:administration & dosage*; D001803:Blood Transfusion; D002543:Cerebral Hemorrhage / Q000209:etiology; D015331:Cohort Studies; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000209:etiology; D006493:Heparin / Q000008:administration & dosage*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality*
D000925:Anticoagulants; D006493:Heparin