***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 OBJECT 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 . METHODS 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 r and omly 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 . CONCLUSIONS 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 Animal research suggests that moderate therapeutic hypothermia may improve outcome after a severe head injury , but its efficacy has not been established in humans . The authors r and omly assigned 40 consecutively treated patients with a severe closed head injury ( Glasgow Coma Scale score 3 to 7 ) to either a  hypothermia or a normothermia group .  Using cooling blankets and cold saline gastric lavage , patients in the hypothermia group were cooled to 32 degrees to 33 degrees C ( brain temperature ) within a mean of 10 hours after injury , maintained at that temperature for 24 hours , and rewarmed to 37 degrees to 38 degrees C over 12 hours . Patients in the normothermia group were maintained at 37 degrees to 38 degrees C during this time . Deep-brain temperatures were monitored directly and used for all temperature determinations . Intracranial pressure ( ICP ) , cerebral blood flow ( CBF ) , and cerebral metabolic rate for oxygen ( CMRO2 ) were measured serially for all patients . Hypothermia significantly reduced ICP ( 40 % ) and CBF ( 26 % ) during the cooling period , and neither parameter showed a significant rebound increase after patients were rewarmed . Compared to the normothermia group , the mean CMRO2 in the hypothermia group was lower during cooling and higher 5 days after injury . Three months after injury , 12 of the 20 patients in the hypothermia group had moderate , mild , or no disabilities ; eight of the 20 patients in the normothermia group had improved to the same degree . Both groups had a similar incidence of systemic complications , including cardiac arrhythmias , coagulopathies , and pulmonary complications . It is concluded that therapeutic moderate hypothermia is safe and has sustained favorable effects on acute derangements of cerebral physiology and metabolism caused by severe closed head injury . The trend toward better outcome with hypothermia may indicate that its beneficial physiological and metabolic effects limit secondary brain injury Background Traumatic brain injury is a major cause of death and severe disability worldwide with 1,000,000 hospital admissions per annum throughout the European Union . Therapeutic hypothermia to reduce intracranial hypertension may improve patient outcome but key issues are length of hypothermia treatment and speed of re-warming . A recent meta- analysis showed improved outcome when hypothermia was continued for between 48 hours and 5 days and patients were re-warmed slowly ( 1 ° C/4 hours ) . Previous experience with cooling also appears to be important if complications , which may outweigh the benefits of hypothermia , are to be avoided . Methods / design This is a pragmatic , multi-centre r and omised controlled trial examining the effects of hypothermia 32 - 35 ° C , titrated to reduce intracranial pressure < 20 mmHg , on morbidity and mortality 6 months after traumatic brain injury . The study aims to recruit 1800 patients over 41 months . Enrolment started in April 2010 . Participants are r and omised to either st and ard care or st and ard care with titrated therapeutic hypothermia . Hypothermia is initiated with 20 - 30 ml/kg of intravenous , refrigerated 0.9 % saline and maintained using each centre 's usual cooling technique . There is a guideline for detection and treatment of shivering in the intervention group . Hypothermia is maintained for at least 48 hours in the treatment group and continued for as long as is necessary to maintain intracranial pressure < 20 mmHg . Intracranial hypertension is defined as an intracranial pressure > 20 mmHg in accordance with the Brain Trauma Foundation Guidelines , 2007 . Discussion The Eurotherm3235Trial is the most important clinical trial in critical care ever conceived by European intensive care medicine , because it was launched and funded by the European Society of Intensive Care Medicine and will be the largest non-commercial r and omised controlled trial due to the substantial number of centres required to deliver the target number of patients . It represents a new and fundamental step for intensive care medicine in Europe . Recruitment will continue until January 2013 and interested clinicians from intensive care units worldwide can still join this important collaboration by contacting the Trial Coordinating Team via the trial website http://www.eurotherm3235trial.eu . Trial registration Current Controlled Trials IS RCT Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more 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 prospect ively analysed 72 patients with severe head injury , r and omized 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 PURPOSE The study aim ed to investigate the association between blood glucose or lactate and the outcomes of severe traumatic brain injury ( TBI ) , and to evaluate the effect of mild hypothermia therapy on glucose and lactate levels . METHODS Eighty-one patients with TBI were r and omly divided into  normothermia ( n = 41 ) and mild hypothermia ( n = 40 ) group . Body temperature of hypothermia group was maintained at 32.7 ° C for 72 hours . Arterial blood glucose and lactic acid were determined before and after hypothermia therapy . Glasgow Outcome Scale ( GOS ) score was assessed 3 months after the treatment . RESULTS The mean glucose ( 7.04 ± 0.51 vs 9.71 ± 1.63 mmol/L , P < .05 ) in the hypothermia group was lower than in the normothermia group after hypothermia therapy . There were more patients with good neurologic function ( GOS 4 - 5 ) in the hypothermia group than in the normothermia group ( 75.0 % vs 51.2 % , P = .038 ) . Multivariate regression analysis showed that blood glucose greater than 10 mmol/L ( adjusted risk ratio , 5.7 ; 95 % confidence interval , 1.4 - 13.2 ; P < .05 ) was an independent predictor for poor neurologic outcomes in these patients , and hypothermia therapy was an independent predictor for favorable outcomes ( risk ratio , 4.9 ; 95 % confidence interval , 1.0 - 15.6 ; P < .05 ) . No significant association between lactate and GOS scores was identified in the multivariate analysis . CONCLUSION Hyperglycemia after TBI was associated with poor clinical outcomes , but the predictive value of blood lactate level requires further investigation . Hypothermia therapy improves neurologic outcomes in patients with severe TBI , and reduction in blood glucose may be partially responsible for the improved outcomes BACKGROUND 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 . METHODS In a r and omized , 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 . RESULTS 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 
    Output:
    
When the results of 18 trials that evaluated mortality as one of the outcomes were statistically aggregated , therapeutic hypothermia was associated with a significant reduction in mortality and a significant reduction in poor outcome .
There was a lack of statistical evidence for an association between use of therapeutic hypothermia and increased onset of new pneumonia .
Conclusions In contrast to previous review s , this systematic review found some evidence to suggest that therapeutic hypothermia may be of benefit in the treatment of traumatic brain injury .
Low quality trials may overestimate the effectiveness of hypothermia treatment versus st and ard care .