Discrete cerebral hypothermia in the management of traumatic brain injury: a randomized controlled trial Clinical article
ABSTRACT Hypothermia has been extensively evaluated in the management of traumatic brain injury (TBI), but no consensus as to its effectiveness has yet been reached. Explanatory hypotheses include a possible confounding effect of the neuroprotective benefits by adverse systemic effects. To minimize the systemic effects, the authors evaluated a selective cerebral cooling system, the CoolSystem Discrete Cerebral Hypothermia System (a "cooling cap"), in the management of TBI.
A prospective randomized controlled clinical trial was conducted at Grady Memorial Hospital, a Level I trauma center. Adults admitted with severe TBI (Glasgow Coma Scale [GCS] score < or = 8) were eligible. Patients assigned to the treatment group received the cooling cap, while those in the control group did not. Patients in the treatment group were treated with selective cerebral hypothermia for 24 hours, then rewarmed over 24 hours. Their intracranial and bladder temperatures, cranial-bladder temperature gradient, Glasgow Outcome Scale (GOS) and Functional Independence Measure (FIM) scores, and mortality rates were evaluated. The primary outcome was to establish a cranial-bladder temperature gradient in those patients with the cooling cap. The secondary outcomes were mortality and morbidity per GOS and FIM scores.
The cohort comprised 25 patients (12 in the treatment group, 13 controls). There was no significant intergroup difference in demographic data or median GCS score at enrollment (treatment group 3.0, controls 3.0; p = 0.7). After the third hour of the study, the mean intracranial temperature of the treatment group was significantly lower than that of the controls at all time points except Hours 4 (p = 0.08) and 6 (p = 0.08). However, the target intracranial temperature of 33 degrees C was achieved in only 2 patients in the treatment group. The mean intracranial-bladder temperature gradient was not significant for the treatment group (p = 0.07) or the controls (p = 0.67). Six (50.0%) of 12 patients in the treatment group and 4 (30.8%) of 13 in the control group died (p = 0.43). The medians of the maximum change in GOS and FIM scores during the study period (28 days) for both groups were 0. There was no significant difference in complications between the groups (p value range 0.20-1.0).
The cooling cap was not effective in establishing a statistically significant cranial-bladder temperature gradient or in reaching the target intracranial temperature in the majority of patients. No significant difference was achieved in mortality or morbidity between the 2 groups. As the technology currently stands, the Discrete Cerebral Hypothermia System cooling cap is not beneficial for the management of TBI. Further refinement of the equipment available for the delivery of selective cranial cooling will be needed before any definite conclusions regarding the efficacy of discrete cerebral hypothermia can be reached.
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ABSTRACT: Abstract Objectives: To evaluate the effect of moderate hypothermia treatment (MHT) in severe traumatic brain injury (sTBI) compared to normothermia management. Methods: PubMed, Medline, Springer, Elsevier Science Direct, Cochrane Library and Google scholar were searched up to December 2012. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) for the mortality and clinical neurological outcome of the adult patients with sTBI were collected and calculated in a fixed-effects model or a random-effects model. Summary effect estimates were stratified by study design and ethnicity. Egger's regression asymmetry tests were utilized for detecting the publication bias. Results: The overall estimates showed that MHT could reduce the mortality (hypothermia vs. normothermia, RR = 0.86, 95% CI = 0.73-1.01, p = 0.06) and unfavourable clinical neurological outcomes (RR = 1.21, 95% CI = 0.95-1.53, p = 0.12) for traumatic brain injured patients without statistical significance. Moreover, the further stratification sub-group analysis indicated that MHT presented a significant reduction (RR = 0.60, 95% CI = 0.44-0.83, p = 0.002) of mortality compared to the normothermia management in an Asian population. Surprisingly, American patients treated with moderate hypothermia showed an increasing mortality (RR = 1.07, 95% CI = 0.83-1.39, p = 0.61). Conclusions: MHT may be effective in reducing death and unfavourable clinical neurological outcomes, but this finding is not statistically significant, except for decreasing the mortality in Asian patients.Brain Injury 07/2014; 28(8):1036-1041. DOI:10.3109/02699052.2014.910609 · 1.86 Impact Factor
Cochrane database of systematic reviews (Online) 01/2015; 1:CD006638. DOI:10.1002/14651858.CD006638.pub3 · 5.94 Impact Factor
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ABSTRACT: Great expectations have been raised about neuroprotection of therapeutic hypothermia in patients with traumatic brain injury (TBI) by analogy with its effects after heart arrest, neonatal asphyxia, and drowning in cold water. The aim of this study is to review our present knowledge of the effect of therapeutic hypothermia on outcome in children and adults with severe TBI. A literature search for relevant articles in English published from year 2000 up to December 2013 found 19 studies. No signs of improvement in outcome from hypothermia were seen in the five pediatric studies. Varied results were reported in 14 studies on adult patients, 2 of which reported a tendency of higher mortality and worse neurological outcome, 4 reported lower mortality, and 9 reported favorable neurological outcome with hypothermia. The quality of several trials was low. The best-performed randomized studies showed no improvement in outcome by hypothermia-some even indicated worse outcome. TBI patients may suffer from hypothermia-induced pulmonary and coagulation side effects, from side effects of vasopressors when re-establishing the hypothermia-induced lowered blood pressure, and from a rebound increase in intracranial pressure (ICP) during and after rewarming. The difference between body temperature and temperature set by the biological thermostat may cause stress-induced worsening of the circulation and oxygenation in injured areas of the brain. These mechanisms may counteract neuroprotective effects of therapeutic hypothermia. We conclude that we still lack scientific support as a first-tier therapy for the use of therapeutic hypothermia in TBI patients for both adults and children, but it may still be an option as a second-tier therapy for refractory intracranial hypertension.03/2014; 4(1):10-20. DOI:10.1089/ther.2013.0024