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A Prospective Randomized Study to Evaluate the Antipyretic Effect of the Combination of Acetaminophen and Ibuprofen in Neurological ICU Patients
Mullins ME, Empey M, Jaramillo D, et al. Neurocrit Care 2011 15:375-378
Study question: Does the combination of ibuprofen (IBU) and acetaminophen (APAP) provide greater fever control than either agent alone in critically ill, febrile neurological and neurosurgical patients?
Methods: A prospective, randomized controlled study was conducted in a single neurology/neurosurgery ICU (NNICU) between 2003 and 2005. Adult patients were included with an oral temperature of ≥38°C after the first 24 hours of NNICU admission. Patients were randomized to a dose of APAP 975 mg, IBU 800 mg, or a combination of both. Oral temperatures were measured hourly for 6 hours following medication administration. The primary outcome was the difference in the AUC for ∆T over 6 hours.
Results: 79 patients were included, with 25 in the APAP, 28 in the IBU, and 26 in the APAP + IBU group. The difference in degree-hours when comparing APAP + IBU versus IBU alone did not reach statistical significance (-1.05°C-h, P = 0.09). Alternatively, the analysis of APAP + IBU versus APAP alone favored the combination group (-1.56°C-h, P = 0.03).
Conclusion: The combination of APAP + IBU was associated with a greater decrease in degree-hours over a 6-hour period when compared to APAP alone.
Perspective: This trial addresses an important clinical question, but small cohort sizes and single-dose evaluations in marginally febrile patients limit generalized conclusions. Ruling out other causes of fever was also not addressed. Despite the benefit of combination treatment over APAP alone in degree-hours, the absolute temperature difference of 0.2°C on average between hours 2-6 may not be clinically significant.