Fever Control Management Is Preferable to Mild Therapeutic Hypothermia in Traumatic Brain Injury Patients with Abbreviated Injury Scale 3-4: A Multi-Center, Randomized Controlled Trial

Abstract

In our prospective, multi-center, randomized controlled trial (RCT)-the Brain Hypothermia (B-HYPO) study-we could not show any difference on neurological outcomes in patients probably because of the heterogeneity in the severity of their traumatic condition. We therefore aimed to clarify and compare the effectiveness of the two therapeutic temperature management regimens in severe (Abbreviated Injury Scale [AIS] 3-4) or critical trauma patients (AIS 5). In the present post hoc B-HYPO study, we re-evaluated data based on the severity of trauma as AIS 3-4 or AIS 5 and compared Glasgow Outcome Scale score and mortality at 6 months by per-protocol analyses. Consequently, 135 patients were enrolled. Finally, 129 patients, that is, 47 and 31 patients with AIS 3-4 and 36 and 15 patients with AIS 5 were allocated to the mild therapeutic hypothermia (MTH) and fever control groups, respectively. No significant intergroup differences were observed with regard to age, gender, scores on head computed tomography (CT) scans, and surgical operation for traumatic brain injury (TBI), except for Injury Severity Score (ISS) in AIS 5. The fever control group demonstrated a significant reduction of TBI-related mortality compared with the MTH group (9.7% vs. 34.0%, p = 0.02) and an increase of favorable neurological outcomes (64.5% vs. 51.1%, p = 0.26) in patients with AIS 3-4, although the latter was not statistically significant. There was no difference in mortality or favorable outcome in patients with AIS 5. Fever control may be considered instead of MTH in patients with TBI (AIS 3-4).

Keywords: Abbreviated Injury Scale; heterogeneous pathophysiology; multi-center randomized controlled trial; therapeutic hypothermia; traumatic brain injury.

FIG. 1.

Alterations of platelet counts between MTH (32°C–34°C) and fever control group (35 · 5°C–37°C) in AIS 3–4 and 5. (A) Comparisons of platelet counts between MTH and fever control group in AIS 3–4. (B) Comparisons of platelet counts between MTH and fever control group in AIS 5. Patients who received MTH at 32°C–34°C are indicated in gray, and those who received fever control at 35 · 5°C–37°C are indicated in white. The boxes are the 25th to 75th percentile and the whiskers are the 5th to 95th percentiles. p < 0.05 compared with data between MTH group and fever control group. AIS, Abbreviated Injury Scale; MTH, mild therapeutic hypothermia.