Discrete cerebral hypothermia in the management of traumatic brain injury: A randomized controlled trial - Clinical article

Departments of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia, USA.
Journal of Neurosurgery (Impact Factor: 3.23). 02/2009; 110(6):1256-64. DOI: 10.3171/2009.1.JNS081320
Source: PubMed

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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    • "Furthermore, many interventions that were tested across multiple trials led to mixed results. For example, decompressive craniotomy, hyperosmotic therapy and hypothermia have shown inconsistent effects, with studies reporting positive (Cruz et al., 2001; Cruz et al., 2002; Zhi et al., 2003; Jiang et al., 2005; Qiu et al., 2005; Jiang et al., 2006; Qiu et al., 2007), negative (Cooper et al., 2011) or no (Smith et al., 1986; Marion et al., 1997; Shiozaki et al., 2001; Clifton et al., 2002; Lü et al., 2003; Cooper et al., 2004; Harris et al., 2009; Clifton et al., 2011) effect on outcomes. A single trial of hyperventilation to reduce ICP also revealed an adverse effect (Muizelaar et al., 1991). "
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    ABSTRACT: Hypothermia has been used in the treatment of head injury for many years. Encouraging results from small trials and laboratory studies led to renewed interest in the area and some larger trials. To estimate the effect of mild hypothermia for traumatic head injury on mortality and long-term functional outcome complications. We searched the Injuries Group Specialised Register, Current Controlled Trials MetaRegister of trials, Zetoc, ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED) and Conference Proceedings Citation Index-Science (CPCI-S), CENTRAL (The Cochrane Library), MEDLINE and EMBASE. We handsearched conference proceedings and checked reference lists of all relevant articles. The search was last updated in January 2009. Randomised controlled trials of hypothermia to a maximum of 35 degrees C for at least 12 consecutive hours versus control in patients with any closed traumatic head injury requiring hospitalisation. Two authors independently assessed all trials. Data on death, Glasgow Outcome Scale and pneumonia were sought and extracted, either from published material or by contacting the investigators. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each trial on an intention-to-treat basis. We found 23 trials with a total of 1614 randomised patients. Twenty-one trials involving 1587 patients reported deaths. There were fewer deaths in patients treated with hypothermia than in the control group (OR 0.84, 95% CI 0.67 to 1.05). Nine trials with good allocation concealment showed no decrease in the likelihood of death compared with the control group, and this result was not statistically significant (OR 1.08, 95% CI 0.79 to 1.47). Twenty-one trials involving 1587 patients reported data on unfavourable outcomes (death, vegetative state or severe disability). Patients treated with hypothermia were less likely to have an unfavourable outcome than those in the control group (OR 0.76, 95% CI 0.61 to 0.93). Nine trials with good allocation concealment showed patients treated with hypothermia were less likely to have an unfavourable outcome than those in the control group, but the reduction was small and non-significant (OR 0.91, 95% CI 0.69 to 1.20). Hypothermia treatment was associated with a slight increase in the odds of pneumonia (OR 1.31, 95% CI 0.93 to 1.86) but there was a reduction in pneumonia for trials with good allocation concealment (4 trials analysed separately, 294 patients, OR 0.79, 95% CI 0.49 to 1.27) although in both cases the results are not statistically significant. There is no evidence that hypothermia is beneficial in the treatment of head injury. Hypothermia may be effective in reducing death and unfavourable outcomes for traumatic head injured patients, but significant benefit was only found in low quality trials. Low quality trials have a tendency to overestimate the treatment effect. The high quality trials found no decrease in the likelihood of death with hypothermia, but this finding was not statistically significant and could be due to the play of chance. Hypothermia should not be used except in the context of a high quality randomised controlled trial with good allocation concealment.
    Cochrane database of systematic reviews (Online) 02/2009; 2(2):CD001048. DOI:10.1002/14651858.CD001048.pub4 · 5.94 Impact Factor
  • Journal of Neurosurgery 04/2009; 110(6). DOI:10.3171/2009.1.JNS081320a · 3.23 Impact Factor
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