***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: BACKGROUND 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 . METHODS The study subjects were 392 patients 16 to 65 years of age with coma after sustaining closed head injuries who were r and omly 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 st and ard treatment . The primary outcome measure was functional status six months after the injury . RESULTS 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 r and omization 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 . CONCLUSIONS 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 BACKGROUND Cardiac arrest with widespread cerebral ischemia frequently leads to severe neurologic impairment . We studied whether mild systemic hypothermia increases the rate of neurologic recovery after resuscitation from cardiac arrest due to ventricular fibrillation . METHODS In this multicenter trial with blinded assessment of the outcome , patients who had been resuscitated after cardiac arrest due to ventricular fibrillation were r and omly assigned to undergo  therapeutic hypothermia ( target temperature , 32 degrees C to 34 degrees C , measured in the bladder ) over a period of 24 hours or to receive st and ard treatment with normothermia . The primary end point was a favorable neurologic outcome within six months after cardiac arrest ; secondary end points were mortality within six months and the rate of complications within seven days . RESULTS Seventy-five of the 136 patients in the hypothermia group for whom data were available ( 55 percent ) had a favorable neurologic outcome ( cerebral-performance category , 1 [ good recovery ] or 2 [ moderate disability ] ) , as compared with 54 of 137 ( 39 percent ) in the normothermia group ( risk ratio , 1.40 ; 95 percent confidence interval , 1.08 to 1.81 ) . Mortality at six months was 41 percent in the hypothermia group ( 56 of 137 patients died ) , as compared with 55 percent in the normothermia group ( 76 of 138 patients ; risk ratio , 0.74 ; 95 percent confidence interval , 0.58 to 0.95 ) . The complication rate did not differ significantly between the two groups . CONCLUSIONS In patients who have been successfully resuscitated after cardiac arrest due to ventricular fibrillation , therapeutic mild hypothermia increased the rate of a favorable neurologic outcome and reduced mortality Recent experimental studies have demonstrated that mild hypothermia at about 34 degrees C can be effective in the control of intracranial hypertension . A r and omized 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 Background Recent prospect i ve controlled trials of induced moderate hypothermia ( 32–34 ° C ) for relatively short periods ( 24–48 h ) in patients with severe head injury have suggested improvement in intracranial pressure control and outcome . It is possible that increased benefit might be achieved if hypothermia was maintained for more periods longer than 48 h , but there is little in the literature on the effects of prolonged moderate hypothermia in adults with severe head injury . We used moderate induced hypothermia ( 30–33 ° C ) in 43 patients with severe head injury for prolonged periods ( mean 8 days , range 2–19 days ) . Results Although nosocomial pneumonia ( defined in this study as both new chest radiograph changes and culture of a respiratory pathogen from tracheal aspirate ) was quite common ( 45 % ) , death from sepsis was rare ( 5 % ) . Other findings included hypokalaemia on induction of hypothermia and a decreasing total white cell and platelet count over 10 days . There were no major cardiac arrhythmias . There was a satisfactory neurological outcome in 20 out of 43 patients ( 47 % ) . Conclusion Moderate hypothermia may be induced for more prolonged periods , and is a relatively safe and feasible therapeutic option in the treatment of selected patients with severe traumatic brain injury . Thus , further prospect i ve controlled trials using induced hypothermia for longer periods than 48 h are warranted Forty-six patients with severe nonpenetrating brain injury [ Glasgow Coma Scale ( GCS ) 4 - 7 ] were r and omized to st and ard management at 37 degrees C ( n = 22 ) and to  st and ard 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 ) , r and omizing 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 BACKGROUND Cardiac arrest outside the hospital is common and has a poor outcome . Studies in laboratory animals suggest that hypothermia induced shortly after the restoration of spontaneous circulation may improve neurologic outcome , but there have been no conclusive studies in humans . In a r and omized , controlled trial , we compared the effects of moderate hypothermia and normothermia in patients who remained unconscious after resuscitation from out-of-hospital cardiac arrest . METHODS The study subjects were 77 patients who were r and omly assigned to treatment with hypothermia ( with the core body temperature reduced to 33 degrees C within 2 hours after the return of spontaneous circulation and maintained at that temperature for 12 hours ) or normothermia .  The primary outcome measure was survival to hospital discharge with sufficiently good neurologic function to be discharged to home or to a rehabilitation facility . RESULTS The demographic characteristics of the patients were similar in the hypothermia and normothermia groups . Twenty-one of the 43 patients treated with hypothermia ( 49 percent ) survived and had a good outcome --that is , they were discharged home or to a rehabilitation facility -- as compared with 9 of the 34 treated with normothermia ( 26 percent , P=0.046 ) . After adjustment for base-line differences in age and time from collapse to the return of spontaneous circulation , the odds ratio for a good outcome with hypothermia as compared with normothermia was 5.25 ( 95 percent confidence interval , 1.47 to 18.76 ; P=0.011 ) . Hypothermia was associated with a lower cardiac index , higher systemic vascular resistance , and hyperglycemia . There was no difference in the frequency of adverse events . CONCLUSIONS Our preliminary observations suggest that treatment with moderate hypothermia appears to improve outcomes in patients with coma after resuscitation from out-of-hospital cardiac arrest OBJECT In a recently conducted trial of hypothermia in patients with severe brain injury , differences were found in the effects of hypothermia treatment among various centers . This analysis explores the reasons for such differences . METHODS The authors review ed data obtained in 392 patients treated for severe brain injury . Prer and omization variables , critical physiological variables , treatment variables , and accrual method ologies were investigated among various centers . Hypothermia was found to be detrimental in patients older than the age of 45 years , beneficial in patients younger than 45 years of age in whom hypothermia was present on admission , and without effect in those in whom normothermia was documented on admission . Marginally significant differences ( p < 0.054 ) in the intercenter outcomes of  hypothermia-treated  patients were likely the result of wide differences in the percentage of patients older than 45 years of age and in the percentage of patients in whom hypothermia was present on admission among centers . The trial sensitivity was likely diminished by significant differences in the incidence of mean arterial blood pressure ( MABP ) less than 70 mm Hg ( p < 0.001 ) and cerebral perfusion pressure ( CPP ) less than 50 mm Hg ( p < 0.05 ) but not intracranial pressure ( ICP ) greater than 25 mm Hg ( not significant ) among patients in the various centers . Hours of vasopressor usage ( p < 0.03 ) and morphine dose ( p < 0.001 ) and the percentage of dehydrated patients varied significantly among centers ( p < 0.001 ) . The participation of small centers increased intercenter variance and diminished the quality of data . CONCLUSIONS For Phase III clinical trials we recommend : 1 ) a detailed protocol specifying fluid and MABP , ICP , and CPP management : 2 ) continuous monitoring of protocol compliance ; 3 ) a run-in period for new centers to test accrual and protocol adherence ; and 4 ) inclusion of only centers in which patients are regularly r and omized OBJECT The criteria for the use of mild hypothermia ( 34 degrees C ) in severely head injured patients have not been st and ardized . A prospect i ve r and omized controlled trial was conducted to determine whether mild hypothermia is essential in the treatment of severely head injured patients with low intracranial pressure ( ICP ) . METHODS 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 r and omly 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 , leukocytopen 
    Output:
    
Hypothermia to a target temperature between 32 degrees C and 33 degrees C , a duration of 24 hours , and rewarming within 24 hours were all associated with reduced risks of poor neurologic outcome compared with normothermia .
Therapeutic hypothermia may reduce the risks of mortality and poor neurologic outcome in adults with TBI .
Outcomes were influenced , however , by depth and duration of hypothermia as well as rate of rewarming ( < or=24 hours ) after discontinuation of hypothermia .