Acetaminophen drip of little benefit in critically ill sepsis patients

Giving intravenous acetaminophen to critically ill patients with sepsis is safe but falls short of improving survival outcomes, according to a phase IIb study.

A total of 447 adults (mean age 64 years, 51 percent female) with sepsis and respiratory or circulatory organ dysfunction (mean Sequential Organ Failure Assessment [SOFA] score 5.4) who were admitted to the emergency department or intensive care unit were included in the study.

The patients were randomly assigned to receive acetaminophen 1 g in 100 mL diluent (or 15 mg/kg if actual body weight was <50 kg; n=227) or an identical appearing intravenous infusion of 100 mL of 5% dextrose in water (placebo; n=220). Treatment was given intravenously every 6 hours for 5 days (20 doses).

Acetaminophen was safe, with no meaningful changes seen in liver enzymes, blood pressure, or fluid balance.

However, the primary endpoint of days alive and free of organ support (mechanical ventilation, vasopressors, and kidney replacement therapy) to day 28 did not significantly differ between the acetaminophen group and the placebo group (20.2 vs 19.6 days; p=0.56).

Secondary outcomes including total, respiratory, and coagulation SOFA scores were significantly lower on days 2 through 4 in the acetaminophen group than in the placebo group, as was the rate of development of acute respiratory distress syndrome within 7 days (2.2 percent vs 8.5 percent; p=0.01; difference, −6.3, 95 percent confidence interval, −10.8 to −1.8).

No evidence of significant interaction between cell-free haemoglobin levels and acetaminophen was detected.