A prospective randomized study to evaluate the antipyretic effect of the combination of acetaminophen and ibuprofen in neurological ICU patients.

Background: To compare the antipyretic effect of simultaneously administered acetaminophen (APAP) plus ibuprofen (IBU) to either APAP or IBU alone in critically ill febrile neurological and neurosurgical patients.

Methods: This is a prospective, three-armed, randomized controlled trial of 79 patients in the neurology/neurosurgery intensive care unit (NNICU) of a tertiary care academic hospital. Eligible patients who developed a temperature ≥38°C were randomized to receive either a single dose of APAP 975 mg, a single dose of IBU 800 mg, or a combination of both (APAP + IBU). Oral temperatures were measured hourly for 6 h following medication administration.

Results: All three treatments decreased temperature over the 6-h period. The area under the curve (AUC) for ΔT for APAP was -3.55°C-h (95% CI -4.75 to -2.34°C-h); for IBU was -4.05°C-h (95% CI -5.16 to -2.94°C-h); and for the combination of APAP and IBU was -5.10°C-h (95% CI -6.20 to -4.01°C-h). The differences in AUC between the groups were as follows: IBU versus APAP = -0.50°C-h (P = 0.28), APAP + IBU versus IBU = -1.05°C-h (P = 0.09), and APAP + IBU versus APAP = -1.56°C-h (P = 0.03).

Conclusion: The combination of IBU and APAP produces significantly greater fever control than APAP alone, with trends favoring the combination over IBU alone and IBU over APAP alone.