A major challenge of the KyberSept study was the “window” created to ensure enrollment of patients with severe sepsis within 6h after onset. Although the intention was to enroll patients early in their disease, the design of the study protocol made it possible to enroll patients who were in severe sepsis for longer than six hours. At our center, to ensure early enrollment, patients were evaluated for the study only if their ICU stay was less than 48 hours.
Enrollment criteria of the KyberSept protocol were used. Patients with severe sepsis (3 of the 4 SIRS criteria and organ failure present within a 6 hours window) were randomized to AT infusion (6000 U bolus and 250 U/h for 96 consecutive hours)(n=40) or placebo (n=41). The majority of our patients were enrolled early after the onset of sepsis (80% within 24 hours and 93% within 48 hours of ICU admission). Prophylactic low-dose heparin was administered to 90% of the patients. Fisher’s exact test was used to test binary data and student t-test was used to analyze continuous data.
There were no differences in demographics or APACHEII score values between groups. Baseline AT levels were not significantly different between groups (69%±18 for placebo and 65%±26, p=0.45). Fifteen of forty patients (38%) in the AT group died versus 21 of 41 (52%) in the placebo group (Absolute mortality reduction: 14% and relative reduction: 27%, Odds Ratio 0.57 with 95% CI 0.23-1.38). Total number of organ failures was significantly reduced in patients receiving AT on days 10 through 28. Six patients had significant bleeding in the AT group versus one patient in the placebo group (p=0.057). Other side effects were similar in both groups.
Administration of AT to patients with severe sepsis early after onset of their disease resulted in an absolute mortality reduction of 14%. The administration of heparin in prophylactic dosage did not diminish the benefit of AT.
AT appears to reduce mortality in severe sepsis.
A.A. Eid, None.