Hypothermia Improves Neurologic Outcome After Head Injury
Hypothermia Improves Neurologic Outcome After Head Injury
ABSTRACT & COMMENTARY
Synopsis: Mild hypothermia for the first 24 hours following head injury is associated with improved clinical function three, six, and 12 months later.
Source: Marion DW, et al. N Engl J Med 1997;336: 540-546.
Aggressive resuscitation and treatment of traumatized patients with closed head injury has resulted in improved survival. Unfortunately, this has produced many individuals with severe disabilities. Hypothermia has been suggested as a way to further improve survival and possibly improve functional outcome in these patients. A recently completed, prospective, randomized, long-term study of one-day, moderate hypothermia suggests that improved function is possible.
Marion and colleagues randomized 82 adult patients with severe head trauma (Glasgow Coma Scale [GCS] of 3-7) seen within six hours of injury to receive sedation, paralysis, and mechanical ventilation with or without 24 hours of hypothermia (rectal temperature 32-33° C). Patients were block assigned to assure equal proportions of patients with GCS of 3-4 and 5-7 in each treatment group. Functional outcome was assessed at three, six, and 12 months by physical medicine and rehabilitation physicians having no knowledge of the treatment.
All patients received standardized, conventional treatment including: ventriculostomy monitoring of ICP, normocapnic ventilation, and hemodynamic monitoring and treatment to preserve cerebral perfusion pressure of greater than 70 torr. No patients received steroids. Intracranial hypertension was treated with CSF drainage, mannitol, hyperventilation, and barbiturates if necessary. CSF was analyzed for aspartate, glutamate, and interlukin 1-b. The hypothermic patients were passively cooled over 12 hours to a rectal temperature of 32° C; 24 hours later they were rewarmed.
Survival and acute complications were identical in the two groups. However, 68% of the hypothermic patients were assessed to have a good functional outcome (moderate, mild, or no disability) at six months, as compared to only 38% of the normothermic patients.
Nine of the 40 hypothermic, and 10 of the 42 normothermic patients had expired by 12 months (P = 0.18). In the less severely injured patients (GCS 5-7), the mortality difference reached statistical significance between the groups: two of 22 in those with hypothermia vs. six of 26 in those with normothermia (P = 0.04). Functional status was better in the patients treated with hypothermia at all follow-up intervals. The normothermic patients had slightly worse CT scan grades; however, in a multifactorial analysis, treatment with hypothermia was independently associated with improved function at all follow-up intervals. Average glutamate and interlukin 1-b levels were lower in the less severely injured hypothermic patients, implying that less secondary inflammatory response may be the reason for the improved outcome.
COMMENT BY CHARLES G. DURBIN, Jr., MD, FCCM
Over the years, hypothermia for brain protection has been advocated and then abandoned. This latest reported study indicates that significant improvement in functional outcome may be possible with moderate hypothermia maintained for a short period of time in selected patients. Twenty-four hours of hypothermia in patients with GCS between 5-7 produced a remarkable improvement in patient outcome in this study. This protocol should be continued to include more patients and expanded to other institutions to confirm these encouraging preliminary results.
Although the presented data are impressive, the study details are not completely reported in this paper. Infectious complications were stated not to be different between the groups, although the actual details were not given. Lethal pneumonia and sepsis were frequently seen in children treated with profound hypothermia in the past, and this observation lead to abandonment of this approach. More information about serious infections must be reviewed to conclude that hypothermia is safe.
Details about and frequency of ICP treatments between the groups are not provided. On average, ICP was lower in the hypothermic group during the treatment period (15.4 vs 19.7 mmHg) and was slightly higher after the treatment period (19.2 vs 17.4 mmHg). Was hypocapnia more often used in the normothermic control group? A recent study implicates hyperventilation as a risk factor for worse outcomes in moderately severe head injury (Wolf AL, et al. J Neurosurg 1993;78:54-59). If this were more frequent in the control patients, it could account for the outcome difference reported. The frequencies of use of barbiturates and mannitol are also not reported in this paper. Differences in the use of these agents may contribute to the outcome seen. More complete data reporting is necessary before acceptance of these promising results can be advocated.
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