***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 High  intracranial pressure ( HICP ) may be a very early event after traumatic brain injury ( TBI ) , but in most cases , especially when contusions and edema develop over time , HICP will worsen over succeeding days . This study describes the incidence and severity of elevated intracranial pressure ( ICP ) after TBI and attempts to document its time course . In this prospect i ve study , 201 TBI patients in whom ICP was monitored for more than 12 h were evaluated .  ICP  was measured , digitalized , and analyzed after manual filtering . The number of episodes of HICP and the mean ICP value for every 12-h interval were calculated . When monitoring was concluded , the highest mean ICP collected in every patient was identified . A total of 21,000 h of ICP monitoring were recorded . Active treatment to prevent or reduce HICP  was used in 200 patients . HICP was documented in 155 cases . Half of the patients had their highest mean ICP during the first 3 days after injury , but many showed delayed ICP elevation , with 25 % showing highest mean ICP after day 5 . In these cases , HICP was significantly worse and required more intense therapies 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 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 Moderate hypothermia may reduce subsequent neuronal damage after traumatic brain injury .  Interleukin (IL)-6 may have a role in the pathogenesis of traumatic neuronal damage or repair . Using the enzyme-linked immunological sorbent assay ( ELISA ) , we serially measured IL-6 levels in plasma obtained from the radial artery ( systemic ) and internal jugular vein ( regional ) in 13 cerebral trauma patients who underwent hypothermia of 32 - 33 degrees C ranged from 4 - 9 days postinjury and 10 head-injured patients who were maintained at normothermic levels ( 36 - 37 degrees C ) . In both patient population s , surface cooling was used since even in the normothermic group , cooling was needed to maintain patient temperature in the normothermic range . All patients were mechanically ventilated after injection of midazolam and vecuronium . The administration of these agents were continued until the end of the study . Hypothermia was typically maintained for four days , however , in some cases based upon CT findings and /or intra-cranial pressure change , the duration was prolonged . No significant differences were found between the two groups in age , gender and Glasgow Coma Scale upon admission . Further , no differences were found in terms of the classification of computed tomography findings or the occurrence of pupillary abnormalities on admission . The patients in this study had not sustained either abdominal or thoracic trauma . Before inducing hypothermia , IL-6 levels in the arterial and internal jugular venous blood exceeded the normal range . Specifically , the internal jugular plasma levels were significantly higher than those in the arterial plasma . While IL-6 levels in the normothermic group did not decrease even at 4 days postinjury , the plasma cytokine levels fell at both sites sharply after moderate hypothermia . The cytokine suppression found in the hypothermic group continued even after rewarming in these patients showing an improved clinical course , but not in those whose condition worsened . In addition to these changes in cytokine levels , the Glasgow Outcome Scale at 6 months postinjury was significantly higher in the hypothermic group than in the normothermia group . Based on the above , this clinical study with its small patient sample size suggests the need for further prospect i ve r and omized studies to examine the role of cytokine suppression in the beneficial effects of moderate hypothermia in patients with traumatic brain injury Abstract Objective . Therapeutic hypothermia may improve outcome in patients with severe head injury , but clinical studies have produced conflicting results . We hypothesised that the severe side effects of artificial cooling might have masked the positive effects in earlier studies , and we treated a large group of patients with severe head injury with hypothermia using a strict protocol to prevent the occurrence of cooling-induced side effects . Design . Prospect i ve clinical trial . Setting . University teaching hospital . Patients . Hundred thirty-six consecutive patients admitted to our hospital with severe head injury ( Glasgow Coma Scale ( GCS ) ≤8 ) . Measurements and results . Patients included are the 136 patients with a GCS of 8 or less on admission in whom intracranial pressure ( ICP ) remained above 20 mmHg in spite of therapy according to a step-up protocol . Those who responded to the last step of our protocol ( barbiturate coma ) constituted the control group ( n=72 ) . Those who did not respond to barbiturate coma ( n=64 ) were treated with moderate hypothermia ( 32–34 ° C ) . Average APACHE II scores were higher ( 28.9±14.4 vs 25.2±12.1 , p<0.01 ) and average GCS at admission slightly lower ( 5.37±1.8 vs 5.9±2.1 , p<0.05 ) in the hypothermia group , indicating greater severity of illness and more severe neurological injury . Predicted mortality was 86 % for the hypothermia group versus 80 % in controls ( p<0.01 ) . Actual mortality rates were significantly lower : 62 % versus 72 % ; the difference in mortality between hypothermic patients and controls was significant ( p<0.05 ) . The number of patients with good neurological outcome was also higher in the hypothermia group : 15.7 % versus 9.7 % for hypothermic patients versus controls , respectively ( p<0.02 ) . These differences were explained almost entirely by the subgroup of patients with GCS of 5 or 6 at admission ( mortality 52 % vs 76 % , p<0.01 ; good neurological outcome 29 % vs 8 % , p<0.01 ) . Conclusions . Artificial cooling can significantly improve survival and neurological outcome in patients with severe head injury when used in a protocol with great attention to the prevention of side effects . Because there is likely to have been bias against the hypothermia group in this study , the positive effects of hypothermia might even have been underestimated . In addition , our results confirm the value of therapeutic hypothermia in treating refractory intracranial hypertension 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 To compare the effect of long-term mild hypothermia versus short-term mild hypothermia on the outcome of 215 severe traumatic brain injured patients with cerebral contusion and intracranial hypertension . At three medical centers , 215 patients aged 18 to 45 years old with an admission Glasgow Coma Scale ⩽ 8 within 4 h after injury were r and omly divided into two groups : long-term mild hypothermia group ( n = 108 ) for 5 ± 1.3 
    Output:
    
The best available evidence to date supports the use of early prophylactic mild-to-moderate hypothermia in patients with severe TBI ( Glasgow Coma Scale score < or = 8) to decrease mortality and improve rates of good neurologic recovery .
Most studies report using a temperature of 32 degrees -34 degrees C. The maximal benefit occurred with a long-term or goal -directed cooling protocol , in which cooling was continued for at least 72 hours and /or until stable normalization of intracranial pressure for at least 24 hours was achieved .