Effect of extended intravenous diclofenac infusions on brain tissue oxygenation in patients with acute brain injury.

Abstract

Background: Fever is associated with worse outcomes in patients with acute brain injury. Diclofenac, a non-steroidal anti-inflammatory drug, is commonly used as antipyretic therapy. As evidence emerged that short diclofenac infusions (< 1 h) decrease brain tissue oxygen (PtO2) and cerebral perfusion pressure (CPP), clinical practice has shifted to extended infusions (12 h). The purpose of this study was to investigate the effects of extended diclofenac infusion for the treatment of fever on cerebral perfusion and tissue oxygenation after acute brain injury.

Results: We conducted a retrospective study of prospectively collected data from a cohort of 18 patients with acute brain injury and PtO2 monitoring admitted between November 2018 and April 2024. The hour before and the 12 h during an extended diclofenac infusion were compared. Additionally, we compared the 12 h prior and 12 h during the diclofenac infusion. Cerebral autoregulation and metabolites obtained by microdialysis were assessed in a subgroup of patients. Thirty-nine interventions were analyzed. Core temperature decreased from 38.1°C in the hour before to 37.4 °C during an extended diclofenac infusion (p < 0.0001). ICP (11.0 vs 10.0 mmHg, p < 0.0001) and heart rate (84 vs. 77 bpm, p < 0.0001) decreased. CPP and PaCO2 did not vary significantly. PtO2 decreased from 23.1 mmHg (IQR 19.0-31.4) during fever peak to 21.7 mmHg (IQR 17.8-27.2) (p < 0.0001). Median PtO2 during the 12 h before diclofenac was 23.3 mmHg (IQR 18.9-30.5). In a multivariable analysis the effect of treatment was significantly influenced by heart rate and temperature (p < 0.0001).

Conclusions: Extended diclofenac infusions for the treatment of fever in patients with acute brain injury achieve a clinically significant reduction in temperature but are associated with a small decrease in PtO2, even in the setting of maintained CPP.