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: 3.74). 02/2009; 110(6):1256-64. DOI: 10.3171/2009.1.JNS081320
Source: PubMed


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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    • "The difficulty of cooling deeper regions of the brain can be explained by the anatomic changes that occur with depth and the rapid heat dissipation that is facilitated by robust cerebral blood flow. The results of our experiments involving direct brain cooling agree with those of a previous theoretical simulation and with several clinical trials of localized external head cooling in patients with traumatic brain injuries (Zhu and Diao, 2001; Wang et al., 2004; Forte et al., 2009; Harris et al., 2009). In those trials, external cooling was applied with cooling helmets or ice packs to achieve a comparable change in temperature within the brain of about 2°C. "
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    ABSTRACT: Focal cortical cooling inhibits seizures and prevents acquired epileptogenesis in rodents. To investigate the potential clinical utility of this treatment modality, we examined the thermal characteristics of canine and human brain undergoing active and passive surface cooling in intraoperative settings. Four patients with intractable epilepsy were treated in a standard manner. Before the resection of a neocortical epileptogenic focus, multiple intraoperative studies of active (custom-made cooled irrigation-perfused grid) and passive (stainless steel probe) cooling were performed. We also actively cooled the neocortices of two dogs with perfused grids implanted for 2 hours. Focal surface cooling of the human brain causes predictable depth-dependent cooling of the underlying brain tissue. Cooling of 0.6-2°C was achieved both actively and passively to a depth of 10-15 mm from the cortical surface. The perfused grid permitted comparable and persistent cooling of canine neocortex when the craniotomy was closed. Thus, the human cortex can easily be cooled with the use of simple devices such as a cooling grid or a small passive probe. These techniques provide pilot data for the design of a permanently implantable device to control intractable epilepsy.
    04/2015; 5(2). DOI:10.1089/ther.2014.0025
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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: Traumatic brain injury (TBI) is a major worldwide healthcare problem. Despite promising outcomes from many preclinical studies, the failure of several clinical studies to identify effective therapeutic and pharmacological approaches for TBI suggests that methods to improve the translational potential of preclinical studies are highly desirable. Rodent models of TBI are increasingly in demand for preclinical research, particularly for closed head injury (CHI), which mimics the most common type of TBI observed clinically. Although seemingly simple to establish, CHI models are particularly prone to experimental variability. Promisingly, bioengineering-oriented research has advanced our understanding of the nature of the mechanical forces and resulting head and brain motion during TBI. However, many neuroscience-oriented laboratories lack guidance with respect to fundamental biomechanical principles of TBI. Here, we review key historical and current literature that is relevant to the investigation of TBI from clinical, physiological and biomechanical perspectives, and comment on how the current challenges associated with rodent TBI models, particularly those involving CHI, could be improved.
    Disease Models and Mechanisms 09/2013; 6(6). DOI:10.1242/dmm.011320 · 4.97 Impact Factor
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    ABSTRACT: Twenty-two randomised controlled trials involving 1409 patients with traumatic head injury were included in this review. In each trial, the patients were randomly divided into two groups: one group remained at normal body temperature, and the other group was cooled to a maximum of 35 degrees Celsius for at least 12 hours. Cooling could be of the whole body (e.g. with a blanket with circulating cold water), or just the head (e.g. with a helmet with circulating cold water). Information on death, disability, and pneumonia was evaluated for each trial. The review authors found that fewer people died or became severely disabled if they were treated with hypothermia, but this finding may be due to the play of chance. It was also found that patients given hypothermia were more likely to develop pneumonia, and some patients died from pneumonia, but the increased risk of pneumonia could also be due to the play of chance. Some of the trials included in the review were of low methodological quality. Low quality trials have a tendency to overestimate the effect of a treatment. In this review, the lower quality trials showed hypothermia treatment to be effective in reducing death and disability among head injured patients. However, the good quality trials showed less benefit for hypothermia treatment and a lower chance of pneumonia. The review authors conclude that hypothermia might reduce death and disability in traumatic head injured patients, but it may also increase the risk of pneumonia. These effects may be due to the play of chance. Due to uncertainties in its effects, hypothermia should only be given to patients taking part in good quality randomised controlled trials.
    Cochrane database of systematic reviews (Online) 02/2009; 2(2):CD001048. DOI:10.1002/14651858.CD001048.pub4 · 6.03 Impact Factor
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