Continuous low dose diclofenac sodium infusion to control fever in neurosurgical critical care

Introduction: Aim of this randomized prospective clinical trial is to compare two methods of antipyretics and evaluate their efficacy in controlling fever during the acute phase of brain damage. Methods: Twenty-two febrile comatose patients: 12 severe traumatic brain injury and 10 subarachnoid hemorrhage divided in 2 groups: Diclofenac low-dose infusion (10 patients) and extemporaneous boluses of NSAIDs (CTRL, 12 patients). The primary outcome measure was length of time with temperature > 38 degrees C. Secondary outcome measures were: 1) to assess the effects of each antipyretic strategy on intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial pressure (MAP) and heart rate; 2) to monitor adverse effects of each antipyretic strategy. The baseline characteristics in the two treatment groups were similar. Results: Primary findings: percentage of time per patient with temperature > 38 degrees C was significantly lower (P < 0.0001) in the DCF group, 4% (0-22%), vs. 34% (8-56%) in CTRL group. In addition, mean T degrees, max T degrees were lower in DCF than in CTRL (P < 0.05). Secondary findings: CPP and MAP were significantly higher in DCF group (P < 0.05) while ICP was not different (NS). However, if ICP pre randomization was < 25 mmHg, CTRL suffered a worst ICP (24 +/- 11 vs. +/- 16 +/- 7 P = 0.01), MAP (89 +/- 10 vs. 104 +/- 10 P = 0.01) and CPP (75 +/- 10 vs. 94 +/- 17 P = 0.01) compared to DCF. No differences between the two treatment were recorded when ICP +/- 25 mmHg before randomization. There was no gastrointestinal or intracranial bleeding. Conclusions: Low dose DCF infusion is a potential useful strategy for a successful control temperature better than intermittent NSAIDs dosing, minimizing potentially brain-damaging effects of fever.