***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECT Deepening sedation is often needed in patients with intracranial hypertension . All widely used sedative and anesthetic agents ( opioids , benzodiazepines , propofol , and barbiturates ) decrease blood pressure and may therefore decrease cerebral perfusion pressure ( CPP ) .  Ketamine is a potent , safe , rapid-onset anesthetic agent that does not decrease blood pressure . However , ketamine 's use in patients with traumatic brain injury and intracranial hypertension is precluded because it is widely stated that it increases intracranial pressure ( ICP ) . Based on anecdotal clinical experience , the authors hypothesized that ketamine does not increase-but may rather decrease-ICP . METHODS The authors conducted a prospect i ve , controlled , clinical trial of data obtained in a pediatric intensive care unit of a regional trauma center . All patients were se date d and mechanically ventilated prior to inclusion in the study . Children with sustained , elevated ICP ( > 18 mm Hg ) resistant to first-tier therapies received a single ketamine dose ( 1 - 1.5 mg/kg ) either to prevent further ICP increase during a potentially distressing intervention ( Group 1 ) or as an additional measure to lower ICP ( Group 2 ) . Hemodynamic , ICP , and CPP values were recorded before ketamine administration , and repeated- measures analysis of variance was used to compare these values with those recorded every minute for 10 minutes following ketamine administration . RESULTS The results of 82 ketamine administrations in 30 patients were analyzed . Overall , following ketamine administration , ICP decreased by 30 % ( from 25.8 + /- 8.4 to 18.0 + /- 8.5 mm Hg ) ( p < 0.001 ) and CPP increased from 54.4 + /- 11.7 to 58.3 + /- 13.4 mm Hg ( p < 0.005 ) . In Group 1 , ICP decreased significantly following ketamine administration and increased by > 2 mm Hg during the distressing intervention in only 1 of 17 events . In Group 2 , when ketamine was administered to lower persistent intracranial hypertension , ICP decreased by 33 % ( from 26.0 + /- 9.1 to 17.5 + /- 9.1 mm Hg ) ( p < 0.0001 ) following ketamine administration . CONCLUSIONS In ventilation-treated patients with intracranial hypertension , ketamine effectively decreased ICP and prevented untoward ICP elevations during potentially distressing interventions , without lowering blood pressure and CPP . These results refute the notion that ketamine increases ICP .  Ketamine is a safe and effective drug for patients with traumatic brain injury and intracranial hypertension , and it can possibly be used safely in trauma emergency situations Objective : The manual injection of a bolus of opioid in patients with brain injury induces an increase in intracranial pressure related to a decrease in mean arterial pressure . Such an effect has not been observed with the use of ketamine . The use of target-controlled infusion would minimize or suppress this adverse effect of opioid . This study evaluated the effects of an increase in plasma concentrations of sufentanil or ketamine administered by target-controlled infusion on cerebral hemodynamics . Design : Prospect i ve , r and omized study . Setting : Intensive care unit in a trauma center . Patients : Thirty patients with severe traumatic brain injury . Interventions : Patients were assigned to receive sedation consisting of sufentanil-midazolam or ketamine-midazolam using target-controlled infusion . Twenty-four hours after the onset of sedation , the target concentrations of sufentanil or ketamine were doubled for 15 mins . Blood sample s were collected to determine the actual plasma concentration of sufentanil and ketamine , before and 15 mins after concentration change . Measurements and Main Results : The baseline values of intracranial pressure and cerebral perfusion pressure were similar in both groups . The two-fold increase in drug concentrations did not involve a significant change for intracranial pressure , cerebral perfusion pressure , and mean velocity of middle cerebral artery in both the ketamine and the sufentanil groups . The measured plasma concentrations of sufentanil and ketamine  were 0.4 ± 0.2 ng/mL and 2.6 ± 2.2 & mgr;g/mL , respectively , before the increase in concentrations and 0.7 ± 0.4 ng/mL and 5.5 ± 3.8 & mgr;g/mL after . Conclusions : The present study shows that the increase in sufentanil or ketamine plasma concentrations using a target-controlled infusion is not associated with adverse effects on cerebral hemodynamics in patients with severe brain injury . The use of target-controlled infusion could be of interest in the management of severely brain-injured patients . However , there is a need for specific pharmacokinetic models design ed for intensive care unit patients Traumatic brain injury ( TBI ) remains a major public health problem , and there is a great medical need for a pharmacological treatment that could improve long-term outcome . The excitatory neurotransmitter , glutamate , has been implicated in processes leading to neurodegeneration . Traxoprodil ( CP-101,606 ) is a novel and potent glutamate receptor antagonist that is highly selective for the NR2B subunit of the NMDA receptor ; it has been shown to be neuroprotective in animal models of brain injury and ischemia . A r and omized , double-blind , placebo-controlled study was therefore conducted to assess the efficacy and safety of a 72-h infusion of traxoprodil compared to placebo in subjects with computed tomography scan evidence of severe TBI ( GCS 4 - 8 ) . A total of 404 males and non-pregnant females , aged 16 - 70 , were treated within 8 h of injury . At baseline , subjects were stratified by motor score severity . The results showed that a greater proportion of the traxoprodil-treated subjects had a favorable outcome on the dichotomized Glasgow Outcome Scale ( dGOS ) at 6 months ( delta 5.5 % , OR 1.3 , p = 0.21 , 95 % CI:[0.85 , 2.06 ] ) and at last visit ( delta 7.5 % , OR 1.47 , p = 0.07 , 95 % CI:[0.97 , 2.25 ] ) . The mortality rate with traxoprodil treatment was 7 % less than with placebo treatment ( OR 1.45 , p = 0.08 , 95 % CI:[0.96 , 2.18 ] ) . Differences between treatment groups were more pronounced in the severest subset ( delta 11.8 % for the dGOS at last visit and delta 16.6 % for mortality ) . Traxoprodil was well tolerated . Although these results are intriguing , no definitive cl aim of efficacy can be made for traxoprodil for the treatment of severe TBI Summary Ketamine was supposed to be contra-indicated in head injured patients although it possesses numerous advantages over other commonly used analgosedative drugs . Referring to these potential advantages and the lack of definitive data about its effect upon ICP , CPP or neurological development , we conducted a prospect i ve study in which moderate or severely head injured patients ( n=35 ) were prospect ively allocated to receive treatment either with a combination of ketamine and midazolam or fentanyl and midazolam . The initial dose was 6.5 mg/kg/day midazolam , 65 mg/kg/day ketamine or 65 μg/kg/day fentanyl and was later adjusted due to clinical requirements for a period of 3 to 14 days . Comparably high dosages of detamine have been found necessary ( 104 mg/kg/day).Four patients from the ketamine group ( n=17 ) and 5 from the control group ( n=18 ) were withdrawn during treatment due to persistent ICP above 25 mm Hg , countermeasured by barbiturate coma . Two more patients were withdrawn due to development of cardiovascular arrest ( ketamine group ) and multi organ failure . A comparison of the remaining patients revealed a lower requirement of catecholamines ( significant on first day , p<0.05 ) , an on average 8 mm Hg higher cerebral perfusion pressure and a 2 mm Hg higher intracranial pressure in the fentanyl group . Enterai food intake was better in the study group . The outcome was comparable in both groups with or without inclusion of withdrawn patients OBJECT Excessive activity of excitatory amino acids released after head trauma has been demonstrated to contribute to progressive injury in animal models and human studies . Several pharmacological agents that act as antagonists to the glutamate receptor have shown promise in limiting this progression . The efficacy of the N-methyl-D-aspartate receptor antagonist Selfotel ( CGS 19755 ) was evaluated in two parallel studies of severely head injured patients , defined as patients with post resuscitation Glasgow Coma Scale scores of 4 to 8 . METHODS A total of 693 patients were prospect ively enrolled in two multicenter double-blind studies . Comparison between the treatment groups showed no significant difference with regard to demographic data , previous incidence of hypotension , and severity of injury . As the study progressed , the Safety and Monitoring Committee became concerned about possible increased deaths and serious brain-related adverse events in the treatment arm of the two head injury trials , as well as deaths in the two stroke trials being monitored concurrently . The Selfotel trials were stopped prematurely because of this concern and because an interim efficacy analysis indicated that the likelihood of demonstrating success with the agent if the studies had been completed was almost nil . CONCLUSIONS Subsequently , more complete data analysis revealed no statistically significant difference in mortality rates in all cases between the two treatment groups in the head injury trials . In this report the authors examine the studies in detail and discuss the potential application of the data to future trial design Background : The potential adverse effects of ketamine in neurosurgical anesthesia have been well established and involve increased intracranial pressure ( ICP ) and cerebral blood flow . However , reexamination of ketamine is warranted because data regarding the effects of ketamine on cerebral hemodynamics are conflicting . Methods : Eight patients with traumatic brain injury were studied . In all patients , ICP monitoring was instituted before the study . Control of ICP ( less than 25 mmHg ) , hemodynamic values , and blood gas tension ( partial pressure of carbon dioxide in arterial blood between 35–38 mmHg ) was obtained with propofol infusion ( 3 mg [ center dot ] kg sup ‐1 [ center dot ] h sup ‐1 ) and mechanical ventilation . The effects of three doses of ketamine , 1.5 , 3 , and 5 mg/ kg , respectively , on ICP , cerebral perfusion pressure , jugular vein bulb oxygen saturation , middle cerebral artery blood flow velocity , and electric activity of the brain ( EEG ) were measured . The three doses were administered intravenously at 6‐h intervals over 30 s through a central venous line . Systemic and cerebral hemodynamics and end‐tidal carbon dioxide were continuously monitored and recorded at 1‐min intervals throughout the 30‐min study periods . Results : Ketamine , in all three doses studied ( 1.5 , 3 , and 5 mg/kg ) was associated with a significant decrease in ICP ( mean + /‐ SD : 2 + /‐ 0.5 mmHg [ P < 0.05 ] , 4 + /‐ 1 mmHg [ P < 0.05 ] , and 5 + /‐ 2 mmHg [ P < 0.05 ] ) among the study patients regardless of the ketamine dose used . There were no significant differences in cerebral perfusion pressure , jugular vein bulb oxygen saturation , and middle cerebral artery blood flow velocity . Ketamine induced a low‐amplitude fast‐activity electroencephalogram , with marked depression , such as burst suppression . Conclusions : These results suggest that ketamine may not adversely alter cerebral hemodynamics of mechanically ventilated head‐trauma patients se date d with propofol . These encouraging results should be confirmed in larger groups of similar patients Objective The aim of the study was to compare the safety concerning cerebral hemodynamics of ketamine and sufentanil used for sedation of severe head injury patients , both drugs being used in combination with midazolam . Design Prospect i ve , r and omized , double-blind study . Setting Intensive care unit in a trauma center . Patients Twenty-five patients with severe head injury . Interventions Twelve patients received sedation with a continuous infusion of ketamine-midazolam and 13 with a continuous infusion of sufentanil-midazolam . All patients were mechanically ventilated with moderate hyperventilation . Measurements and Main Results Prognostic indicators ( age , Glasgow Coma Scale scores , computed tomography diagnosis , and Injury Severity Scale score ) were similar in the two groups at study entry . Measurements were carried out during the first 4 days of sedation . The average infusion rates during this time were 82 ± 25 & mgr;g·kg−1·min−1 ketamine and 1.64 ± 0.5 & mgr;g·kg−1·min−1 midazolam in the ketamine group and 0.008 ± 0.002 & mgr;g·kg−1·min−1 sufent 
    Output:
    
There currently exists Oxford level 2b , GRADE C evidence to support that ketamine does not increase ICP in severe TBI patients that are se date d and ventilated , and in fact may lower it in selected cases