A Phase II Study of Moderate Hypothermia in Severe Brain Injury

Abstract

Forty-six patients with severe nonpenetrating brain injury [Glasgow Coma Scale (GCS) 4-7] were randomized to standard management at 37 degrees C (n = 22) and to standard management with systemic hypothermia to 32 to 33 degrees C (n = 24). The two groups were balanced in terms of age (Wilcoxon's rank sum test, p > 0.95), randomizing GCS (chi-square test, p = 0.54), and primary diagnosis. Cooling was begun within 6 h of injury by use of cooling blankets. Metocurine and morphine were given hourly during induction and maintenance of hypothermia. Rewarming was at a rate of 1 degree C per 4 h beginning 48 h after intravascular temperature had reached 33 degrees C. Muscle relaxants and sedation were continued until core temperature reached 35 degrees C. There were no cardiac or coagulopathy-related complications. Seizure incidence was lower in the hypothermia group (Fisher's exact text, p = 0.019). Sepsis was seen more commonly in the hypothermia group, but difference was not statistically significant (chi-square test). Mean Glasgow Outcome Scale (GOS) score at 3 months after injury showed an absolute increase of 16% (i.e., 36.4-52.2%) in the number of patients in the Good Recovery/Moderate Disability (GR/MD) category as compared with Severe Disability/Vegetative/Dead (SD/V/D) (chi-square test, p > 0.287). Based on evidence of improved neurologic outcome with minimal toxicity, we believe that phase III testing of moderate systemic hypothermia in patients with severe head injury is warranted.

Pathophysiology of Cerebral Ischemia and Brain Trauma: Similarities and Differences

“…and traumatic brain injuries has been obtained (Marion et al, 1997;Clifton et al, 1993;Polderman et al, 2002;Schwab et al, 1998), more experimental data are required to answer major scientific questions regarding therapeutic hypothermia, including therapeutic window, level and duration of hypothermia, rewarming phase, and gender considerations.…”

Neurotoxic Zinc Translocation into Hippocampal Neurons is Inhibited by Hypothermia and is Aggravated by Hyperthermia after Traumatic Brain Injury in Rats

“…Conversely, hyperthermia aggravates the neuronal death produced by those conditions (Dietrich, 1992;Dietrich et al, 1996;Lundgren et al, 1994;Minamisawa et al, 1990b). Hypothermia also has been associated with improved outcome after clinical TBI (Clifton et al, 1993;Marion et al, 1997), although recent data from a clinical trial suggest that therapeutic hypothermia might be ineffective (Clifton et al, 2001).…”

Keeping cool in acute liver failure: Rationale for the use of mild hypothermia

“…A higher rate of infection and worsening of coagulation have been reported in some clinical studies of hypothermia in neurotrauma [158], [159] and [160]. These complications, however, have not constituted a major problem in the majority of randomized studies [19], [20], [24] and [161], have been absent so far in ALF patients [80], [81], [119] and [120] and, importantly, they can be prevented and managed. New therapies, such as recombinant factor VIIa [162] or granulocyte colony-stimulating factor [163] could also be helpful.…”