Changes of evoked potentials and evaluation of mild hypothermia for treatment of severe brain injury. A multicenter prospective randomized controlled trial of the efficacy of mild hypothermia for severely head injured patients with low intracranial pressure. Mild Hypothermia Study Group in Japan. The influence of mild hypothermia on ICP, CPP and outcome in patients with primary and secondary brain injury. Effect of long-term mild hypothermia therapy in patients with severe traumatic brain injury: 1-year follow-up review of 87 cases. Thyroid hormone response to moderate hypothermia in severe brain injury. Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury. Phase II clinical trial of moderate hypothermia after severe traumatic brain injury in children. Little benefit from mild hypothermia therapy for severely head injured patients with low intracranial pressure. A phase II study of moderate hypothermia in severe brain injury. Systemic hypothermia in treatment of brain injury. Moderate hypothermia improves imbalances of thromboxane A2 and prostaglandin I2 production after traumatic brain injury in humans. Treatment of acute traumatic brain injury in children with moderate hypothermia improves intracranial hypertension. Effects of therapeutic mild hypothermia on patients with severe traumatic brain injury after craniotomy. Hypothermia therapy after traumatic brain injury in children. Mild hypothermia reduces expression of heat shock protein 60 in leukocytes from severely head-injured patients. Lack of effect of induction of hypothermia after acute brain injury. Treatment of traumatic brain injury with moderate hypothermia.
To observe the changes of evoked potentials after severe brain injury and the effect of mild hypothermia on acute severe brain injury.
                A total of 44 patients with severe closed head injury (GCS 3-8, admitted within 10 hours from injury) admitted from May 1998 to March 1999 were selected for this study. All patients were admitted into the intensive care unit and divided into 2 groups, Group A (GCS 3-5) and Group B (GCS 6-8). Patients were also randomly assigned to either normothermia or hypothermia subgroups. Patients in the hypothermia group were cooled to 32-34 degrees C. Median nerve short-latency somatosensory evoked potentials (SLSEP) and brain stem auditory evoked potentials (BAEP) were recorded before cooling and 4, 24, 48, 72, 96 and 120 hours, respectively after cooling and temperature resuming. SLSEP and BAEP were measured at the same time in the normothermia group (control group). The changes of evoked potentials (EP) were analyzed by statistical methods.
                In the Group B, N(20) amplitudes in SLSEP and I/V amplitudes in BAEP after mild hypothermia treatment in the hypothermia group differed significantly from those in the control group (P<0.05). However, in the Group A, no significant difference in all parameters was found.
                These results demonstrate that mild hypothermia treatment (32-34 degrees C) in the Group B has a significant neuroelectrophysiological effect on severe brain injury. Nevertheless, the effect of mild hypothermia in the Group A is not apparent and needs further studying. The criteria for the use of mild hypothermia (34 degrees C) in severely head injured patients have not been standardized. A prospective randomized controlled trial was conducted to determine whether mild hypothermia is essential in the treatment of severely head injured patients with low intracranial pressure (ICP).
                At 11 medical centers, 91 severely head injured patients with an admission Glasgow Coma Scale score of 8 or less in whom ICP could be maintained below 25 mm Hg by conventional therapies were divided randomly into two groups: the mild hypothermia group (HT group, 45 patients) and the normothermia group (NT group, 46 patients). Patients in the HT group were exposed to mild hypothermia (34 degrees C) for 48 hours, followed by rewarming at 1 degrees C per day for 3 days, whereas patients in the NT group were exposed to normothermia (37 degrees C) for 5 days. The two groups were similar with respect to prognostic factors, and there was no difference in clinical outcome at 3 months postinjury. During treatment, there was a significantly greater use of neuromuscular blocking agents in the HT group (p = 0.011). During the initial 2 weeks postinjury, the incidences of pneumonia, meningitis, leukocytopenia, thrombocytopenia, hypernatremia, hypokalemia, and hyperamylasemia were significantly higher in the HT than in the NT group (p < 0.05).
                Mild hypothermia should not be used for the treatment of severely head injured patients with low ICP because this therapy conveys no advantage over normothermia in such patients. Aim of this study was to examine the hypothesis that only a subgroup of patients with lesser primary brain damage after severe head injury may benefit from therapeutic hypothermia. We prospectively analysed 72 patients with severe head injury, randomized into groups with (n = 37) and without (n = 35) hypothermia of 34 degrees C maintained for 72 hours. The influence of hypothermia on ICP, CPP and neurological outcome was analysed in the context of the extent of primary brain damage. Patients with normothermia and primary lesions (n = 17) values: GCS on admission 5 (median), ICP 18.9 (mean), CPP 73 (mean), GOS 4 (median). Patients with normothermia and extracerebral hematomas (n = 20): GCS 4, ICP 16, CPP 71, GOS 3. Patients with hypothermia and primary lesions (n = 21): GCS 4,62, ICP 10, 81, CPP 78,1, GOS 4. Patients with hypothermia and extracerebral hematomas (n = 14): GCS 5, ICP 13.2, CPP 78, GOS 5. Hypothermia decreased ICP and increased CPP regardless of the type of brain injury. Hypothermia was not able to improve outcome in patients with primary brain lesions but this pilot study suggests that it significantly improves outcome in patients with extracerebral hematomas. The goal of this study was to investigate the protective effects of long-term (3-14 days) mild hypothermia therapy (33-35 degrees C) on outcome in 87 patients with severe traumatic brain injury (TBI) (Glasgow Coma Scale score < or = 8).
                In 43 patients assigned to a mild hypothermia group, body temperatures were cooled to 33 to 35 degrees C a mean of 15 hours after injury and kept at 33 to 35 degrees C for 3 to 14 days. Rewarming commenced when the individual patient's intracranial pressure (ICP) returned to the normal level. Body temperatures in 44 patients assigned to a normothermia group were maintained at 37 to 38 degrees C. Each patient's outcome was evaluated 1 year later by using the Glasgow Outcome Scale. One year after TBI, the mortality rate was 25.58% (11 of 43 patients) and the rate of favorable outcome (good recovery or moderate disability) was 46.51% (20 of 43 patients) in the mild hypothermia group. In the normothermia group, the mortality rate was 45.45% (20 of 44 patients) and the rate of favorable outcome was 27.27% (12 of 44 patients) (p < 0.05). Induced mild hypothermia also markedly reduced ICP (p < 0.01) and inhibited hyperglycemia (p < 0.05). The rates of complication were not significantly different between the two groups.
                The data produced by this study demonstrate that long-term mild hypothermia therapy significantly improves outcomes in patients with severe TBI. To examine the effect of controlled moderate hypothermia on thyroid response in head-injured patients.
                Prospective, controlled, randomized study.
                University hospital intensive care unit (ICU).
                Twenty-eight patients with severe blunt head injury (Glasgow Coma Scale < or =9).
                Patients were randomly assigned to a hypothermia or a normothermia group. Hypothermia (32-33 degrees C) was induced within 8 h after trauma and maintained for a mean of 36 h. All patients were sedated and mechanically ventilated.
                Thyroid-stimulating hormone( TSH), free and total triiodothyronine (FT3/TT3), reverse triiodothyronine (RT3) and thyroxine (FT4/TT4) were measured during the hypothermia or corresponding normothermia period, after regaining normothermia and 4-6 days later. Of 28 patients included in the study, 11 subjects were treated with hypothermia and 13 patients with normothermia. Four patients had to be excluded. In both groups, serum concentrations of TT3 and FT3 were just below the lower normal range whereas RT3 serum concentrations were near the upper limit of the normal range. TSH serum concentrations were not increased. No statistically significant intra- or inter-group differences were observed.
                Thyroid hormone patterns during moderate hypothermia in head-injured patients did not differ from the well known "low T3 state" which is observed in other forms of severe illness. Recent experimental studies have demonstrated that mild hypothermia at about 34 degrees C can be effective in the control of intracranial hypertension. A randomized controlled study of mild hypothermia was carried out in 33 severely head-injured patients. All patients fulfilled the following criteria: 1) persistent intracranial pressure (ICP) greater than 20 mm Hg despite fluid restriction, hyperventilation, and high-dose barbiturate therapy; 2) an ICP lower than the mean arterial blood pressure; and 3) a Glasgow Coma Scale score of 8 or less. The patients were divided into two groups: one received mild hypothermia (16 patients) and one served as a control group (17 patients). Mild hypothermia significantly reduced the ICP and increased the cerebral perfusion pressure. Eight patients (50%) in the hypothermia group and three (18%) in the control group survived (p < 0.05), while five (31%) in the hypothermia group and 12 (71%) in the control group died of uncontrollable intracranial hypertension (p < 0.05). In five patients in the hypothermia group, cerebral blood flow was measured by the hydrogen clearance method and arteriojugular venous oxygen difference was evaluated before and during mild hypothermia. Mild hypothermia significantly decreased the cerebral blood flow, arteriojugular venous oxygen difference, and cerebral metabolic rate of oxygen (p < 0.01). The results of this preliminary investigation suggest that mild hypothermia is a safe and effective method to control traumatic intracranial hypertension and to improve mortality and morbidity rates. To determine whether moderate hypothermia (HYPO) (32-33 degrees C) begun in the early period after severe traumatic brain injury (TBI) and maintained for 48 hours is safe compared with normothermia (NORM) (36.5-37.5 degrees C).
                After severe (Glasgow Coma Scale score < or =8) nonpenetrating TBI, 48 children less than 13 years of age admitted within 6 hours of injury were randomized after stratification by age to moderate HYPO (32-33 degrees C) treatment in conjunction with standardized head injury management versus NORM in a multicenter trial. An additional 27 patients were entered into a parallel single-institution trial of excluded patients because of late transfer or consent (delayed in transfer >6 h but within 24 h of admission), unknown time of injury (e.g., child abuse), and adolescence (e.g., aged 13-18 yr). Assessments of safety included mortality, infection, coagulopathy, arrhythmias, and hemorrhage as well as ability to maintain target temperature, mean intracranial pressure (ICP), and percent time of ICP less than 20 mm Hg during the cooling and subsequent rewarming phases. Additionally, assessments of neurocognitive outcomes were obtained at 3 and 6 months of follow-up.
                Moderate HYPO after severe TBI in children was found to be safe relative to standard management and NORM in children of all ages and in children with delay of initiation of treatment up to 24 hours. Although there was decreased mortality in HYPO in both studies, there was an increased potential for arrhythmias with HYPO, although they were manageable with fluid administration or rewarming. Additionally, there was a reduction in mean ICP during the first 72 hours after injury in both studies, although rebound ICP elevations in HYPO compared with those in NORM were noted for up to 10 to 12 hours after rewarming. Although functional outcome at 3 or 6 months did not differ between treatment groups, functional outcome tended to improve from the 3- to 6-month cognitive assessment in HYPO compared with NORM, although the sample size was too small for any definitive conclusions.
                HYPO is likely a safe therapeutic intervention for children after severe TBI up to 24 hours after injury. Further studies are necessary and warranted to determine its effect on functional outcome and intracranial hypertension. This study was performed to determine whether mild hypothermia therapy is essential for the treatment of severely head injured patients in whom intracranial pressure (ICP) can be maintained below 20 mm Hg by using conventional therapies.
                Sixteen consecutive severely head injured patients fulfilled the following criteria: the patient's ICP was maintained below 20 mm Hg by using fluid restriction, hyperventilation, and high-dose barbiturate therapy; and the patient had a Glasgow Coma Scale score of 8 or less on admission. After conventional therapies had been applied, the patients were divided randomly into two groups: the mild hypothermia group (HT group; eight patients) and the normothermia group (NT group; eight patients). The HT group received mild hypothermia (intracranial temperature 34 degrees C) therapy for 48 hours followed by rewarming at 1 degree C per day for 3 days, whereas the NT group received normothermia (intracranial temperature 37 degrees C) therapy for 5 days. Specimens of cerebrospinal fluid (CSF) taken from an intraventricular catheter every 24 hours were analyzed for the presence of excitatory amino acids ([EAAs] glutamate, aspartate, and glycine) and cytokines (tumor necrosis factor-alpha, interleukin [IL]-1beta, IL-6, IL-8, and IL-10). The two groups did not differ significantly in patient age, neurological status, or level of ICP. There were no significant differences in daily changes in CSF concentrations of EAAs and cytokines between the two groups. The incidence of pneumonia was slightly higher in the HT group compared with the NT group (p = 0.059). The incidence of diabetes insipidus associated with hypernatremia was significantly higher in the HT group compared with that in the NT group (p < 0.01). The two groups did not differ with respect to their clinical outcomes.
                The authors recommend normothermia therapy for the treatment of severely head injured patients in whom ICP can be maintained at lower than 20 mm Hg by using conventional therapies, because mild hypothermia therapy does not convey any advantage over normothermia therapy in such patients. 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. An extensive literature suggests that there are minimal complications of systemic hypothermia in humans at and above 30 degrees C for periods of several days. Intracranial hemorrhage has been found to complicate profound hypothermia (10-15 degrees C), and ventricular arrhythmias occur at temperatures below 30 degrees C. Our initial clinical studies were with 21 patients undergoing elective craniotomy cooled to 30-32 degrees C for 1-8 h (mean 4 h). Hypothermia was induced by surface cooling with water blankets. No complications were found. Among 11 patients with severe brain injury, cooling to levels below 32 degrees C was associated with ventricular arrhythmias in 1 patient and atrioventricular block in 1 patient. Asymptomatic hypokalemia was found routinely and treated with potassium replacement. No intracranial hemorrhage or other complications were found. With surface cooling, intravascular temperature dropped at 1.6 degrees C/h. Based on the safety of surface cooling to a core temperature of 32 degrees C for 48 h, we are conducting a randomized study of this level of hypothermia in patients with severe brain injury, cooled within 6 h of injury. To examine the levels of thromboxane B2 (TXB2) and 6-keto prostaglandin F1alpha (6-keto PGF1alpha) production in arterial and internal jugular bulb sera in patients with traumatic brain injury (TBI). TBI is associated with arachidonate release and may be associated with an imbalance of vasoconstricting and vasodilating cyclooxygenase metabolites.
                A prospective, randomized study.
                The intensive care unit of a medical university hospital.
                Twenty-six ventilated TBI patents (Glasgow Coma Scale score on admission, < or = 8 points) were divided randomly into two groups: a hypothermic group (n = 15), in which the patients were cooled to 32 to 33 degrees C after being giving vecuronium, midazolam, and buprenorphine; and a normothermic group (n = 11), in which the patients' body temperature was controlled at 36 to 37 degrees C by surface cooling using the same treatment as the hypothermic group. Body temperature control including normothermia was started 3 to 4 hrs after injury. The duration of hypothermia usually lasted for 3 to 4 days, after which the patients were rewarmed at a rate of approximately 1 C per day.
                Blood sampling for TXB2 and 6-keto PGF1alpha was started shortly after admission in both groups. Arterial TXB2 levels on admission in both groups were elevated remarkably, but not 6-keto PGF1alpha, thereby causing an imbalance of the prostanoids after injury. In the normothermic group, TXB2 decreased transiently, but this prostanoid increased again 3 days after the injury. In the hypothermic group, such prostanoid differences disappeared shortly after therapy, and the condition was sustained for 10 days. Hypothermia attenuated differences in TXB2 levels between arterial and internal jugular bulb sera, which may reflect reduced cerebral prostanoid production. The Glasgow Outcome Scale score 6 months after the insult in the hypothermic group was significantly higher than that in the normothermic group (p = .04).
                The current results from a limited number of patients suggest that moderate hypothermia may reduce prostanoid production after TBI, thereby attenuating an imbalance of thromboxane A2 and prostaglandin I2. However, it must be clarified whether the changes in the prostanoid after moderate hypothermia are a secondary effect of other mediator changes or whether they simply represent an epiphenomenon that is mechanistically unrelated to damage in TBI. nan We investigated the effects of therapeutic mild hypothermia on patients with severe traumatic brain injury after craniotomy (TBI).
                Eighty patients with severe TBI after unilateral craniotomy were randomized into a therapeutic hypothermia group with the brain temperature maintained at 33 degrees C to 35 degrees C for 4 days, and a normothermia control group in the intensive care unit. Vital signs, intracranial pressure, serum superoxide dismutase level, Glasgow Outcome Scale scores, and complications were prospectively analyzed.
                The mean intracranial pressure values of the therapeutic hypothermia group at 24, 48, and 72 hours after injury were much lower than those of the control group (23.49 +/- 2.38, 24.68 +/- 1.71, and 22.51 +/- 2.44 vs 25.87 +/- 2.18, 25.90 +/- 1.86, and 24.57 +/- 3.95 mm Hg; P = .000, .000, and .003, respectively). The mean serum superoxide dismutase levels of the therapeutic hypothermia group at days 3 and 7 were much higher than those of the control group at the same time point (533.0 +/- 103.4 and 600.5 +/- 82.9 vs 458.7 +/- 68.1 and 497.0 +/- 57.3 mug/L, respectively; P = .000). The percentage of favorable neurologic outcome 1 year after injury was 70.0% and 47.5%, respectively (P = .041). Complications, including pulmonary infections (57.5% in the therapeutic hypothermia group vs 32.5% in the control group; P = .025) were managed without severe sequelae.
                Therapeutic mild hypothermia provides a promising way in the intensive care unit for patients with severe TBI after craniotomy. Hypothermia therapy improves survival and the neurologic outcome in animal models of traumatic brain injury. However, the effect of hypothermia therapy on the neurologic outcome and mortality among children who have severe traumatic brain injury is unknown.
                In a multicenter, international trial, we randomly assigned children with severe traumatic brain injury to either hypothermia therapy (32.5 degrees C for 24 hours) initiated within 8 hours after injury or to normothermia (37.0 degrees C). The primary outcome was the proportion of children who had an unfavorable outcome (i.e., severe disability, persistent vegetative state, or death), as assessed on the basis of the Pediatric Cerebral Performance Category score at 6 months.
                A total of 225 children were randomly assigned to the hypothermia group or the normothermia group; the mean temperatures achieved in the two groups were 33.1+/-1.2 degrees C and 36.9+/-0.5 degrees C, respectively. At 6 months, 31% of the patients in the hypothermia group, as compared with 22% of the patients in the normothermia group, had an unfavorable outcome (relative risk, 1.41; 95% confidence interval [CI], 0.89 to 2.22; P=0.14). There were 23 deaths (21%) in the hypothermia group and 14 deaths (12%) in the normothermia group (relative risk, 1.40; 95% CI, 0.90 to 2.27; P=0.06). There was more hypotension (P=0.047) and more vasoactive agents were administered (P<0.001) in the hypothermia group during the rewarming period than in the normothermia group. Lengths of stay in the intensive care unit and in the hospital and other adverse events were similar in the two groups.
                In children with severe traumatic brain injury, hypothermia therapy that is initiated within 8 hours after injury and continued for 24 hours does not improve the neurologic outcome and may increase mortality. (Current Controlled Trials number, ISRCTN77393684 [controlled-trials.com].).
                Copyright 2008 Massachusetts Medical Society. Infectious complications are among the most serious problems that occur in severely head-injured patients treated with mild hypothermia. The mechanism underlying the susceptibility to infection has not been clarified. Heat shock protein (HSP) 60 has been reported to play an essential role in innate immunity. Thus, we conducted a study to clarify the impact of mild hypothermia on the expression of HSPs in polymorphonuclear leukocytes (PMNLs) in severely head-injured patients.
                Between September 1997 and November 1999, 17 severely head-injured patients with a Glasgow Coma Scale score of 8 or less at admission in whom intracranial pressure could be maintained below 20 mm Hg by conventional therapy were randomly assigned to two treatment groups: a mild hypothermia group (HT group, nine patients) and a normothermia group (NT group, eight patients). The HT group was subjected to mild hypothermia (intracranial temperature, 34 degrees C) for 48 hours followed by rewarming at a rate of 1 degrees C per day for 3 days, whereas the NT group was subjected to normothermia (intracranial temperature, 37 degrees C) for 5 days. Blood samples were serially obtained at three time points; days 0 to 1, days 2 to 5, and days 6 to 14 after head injury. We measured the expression of HSP27, HSP60, HSP70, and HSP90 by flow cytometry.
                The two groups were similar with respect to prognostic factors, and there was no difference in clinical outcome. The expression of PMNL HSP60 in the HT group was significantly lower in all three time periods compared with that in the NT group (p < 0.05), whereas expression of the other HSPs did not differ significantly between the groups. The incidence of infectious complications was significantly increased in the HT group over that in the NT group (p < 0.05). In in vitro studies, PMNLs from 10 healthy volunteers were incubated at 37 degrees C, 34 degrees C, or 26 degrees C for 1 hour with sodium arsenite (100 micromol/L), an HSP inducer. The expression of HSP60 at 26 degrees C and 34 degrees C was significantly lower than that at 37 degrees C (p < 0.05), whereas expression of the other HSPs did not differ significantly at 26 degrees C, 34 degrees C, or 37 degrees C.
                Mild hypothermia reduces the expression of HSP60 in PMNLs from severely head-injured patients. Thus, mild hypothermia may suppress innate immunity. Induction of hypothermia in patients with brain injury was shown to improve outcomes in small clinical studies, but the results were not definitive. To study this issue, we conducted a multicenter trial comparing the effects of hypothermia with those of normothermia in patients with acute brain injury.
                The study subjects were 392 patients 16 to 65 years of age with coma after sustaining closed head injuries who were randomly assigned to be treated with hypothermia (body temperature, 33 degrees C), which was initiated within 6 hours after injury and maintained for 48 hours by means of surface cooling, or normothermia. All patients otherwise received standard treatment. The primary outcome measure was functional status six months after the injury.
                The mean age of the patients and the type and severity of injury in the two treatment groups were similar. The mean (+/-SD) time from injury to randomization was 4.3+/-1.1 hours in the hypothermia group and 4.1+/-1.2 hours in the normothermia group, and the mean time from injury to the achievement of the target temperature of 33 degrees C in the hypothermia group was 8.4+/-3.0 hours. The outcome was poor (defined as severe disability, a vegetative state, or death) in 57 percent of the patients in both groups. Mortality was 28 percent in the hypothermia group and 27 percent in the normothermia group (P=0.79). The patients in the hypothermia group had more hospital days with complications than the patients in the normothermia group. Fewer patients in the hypothermia group had high intracranial pressure than in the normothermia group.
                Treatment with hypothermia, with the body temperature reaching 33 degrees C within eight hours after injury, is not effective in improving outcomes in patients with severe brain injury. Traumatic brain injury initiates several metabolic processes that can exacerbate the injury. There is evidence that hypothermia may limit some of these deleterious metabolic responses.
                In a randomized, controlled trial, we compared the effects of moderate hypothermia and normothermia in 82 patients with severe closed head injuries (a score of 3 to 7 on the Glasgow Coma Scale). The patients assigned to hypothermia were cooled to 33 degrees C a mean of 10 hours after injury, kept at 32 degrees to 33 degrees C for 24 hours, and then rewarmed. A specialist in physical medicine and rehabilitation who was unaware of the treatment assignments evaluated the patients 3, 6, and 12 months later with the use of the Glasgow Outcome Scale.
                The demographic characteristics and causes and severity of injury were similar in the hypothermia and normothermia groups. At 12 months, 62 percent of the patients in the hypothermia group and 38 percent of those in the normothermia group had good outcomes (moderate, mild, or no disabilities). The adjusted risk ratio for a bad outcome in the hypothermia group was 0.5 (95 percent confidence interval, 0.2 to 1.2). Hypothermia did not improve the outcomes in the patients with coma scores of 3 or 4 on admission. Among the patients with scores of 5 to 7, hypothermia was associated with significantly improved outcomes at 3 and 6 months (adjusted risk ratio for a bad outcome, 0.2; 95 percent confidence interval, 0.1 to 0.9 at both intervals), although not at 12 months (risk ratio, 0.3; 95 percent confidence interval, 0.1 to 1.0).
                Treatment with moderate hypothermia for 24 hours in patients with severe traumatic brain injury and coma scores of 5 to 7 on admission hastened neurologic recovery and may have improved the outcome.
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.