***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: The increasing use of shorter-acting hypnotic agents to control  intracranial pressure ( ICP ) following severe head injury has prompted a prospect i ve double-blind controlled trial comparing the efficacy of etomi date and Althesin , given by i.v . infusion . Over the dose ranges used , the two drugs appeared equipotent in decreasing ICP whilst preserving cerebral perfusion pressure . However , in two patients ( one in each group ) ICP did not respond to hypnotic infusion , a feature noted in other studies to occur in a minority of patients . With the cessation of Althesin manufacture and the discussion about the use of etomi date infusions , it is timely to document the effectiveness of etomi date in decreasing ICP 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 Background The current study investigates the effects of morphine and fentanyl upon intracranial pressure and cerebral blood flow estimated by cerebral arteriovenous oxygen content difference and transcranial Doppler sonography in 30 consecutive patients with severe head injury in whom cerebrovascular autoregulation previously had been assessed . Methods Patients received morphine ( 0.2 mg/kg ) and fentanyl ( 2 & mgr;g/kg ) intravenously over 1 min but 24 h apart in a r and omized fashion . Before study , carbon dioxide reactivity and autoregulation were assessed . Intracranial pressure , mean arterial blood pressure , and cerebral perfusion pressure were repeatedly monitored for 1 h after the administration of both opioids .  Cerebral blood flow was estimated from the reciprocal of arteriovenous oxygen content difference and middle cerebral artery mean flow velocity using transcranial Doppler sonography . Results Although carbon dioxide reactivity was preserved in all patients , 18 patients ( 56.7 % ) showed impaired or abolished autoregulation to hypertensive challenge , and only 12 ( 43.3 % ) had preserved autoregulation . Both morphine and fentanyl caused significant increases in intracranial pressure and decreases in mean arterial blood pressure and cerebral perfusion pressure , but estimated cerebral blood flow remain unchanged . In patients with preserved autoregulation , opioid-induced intracranial pressure increases were not different than in those with impaired autoregulation . Conclusions The authors conclude that both morphine and fentanyl moderately increase intracranial pressure and decrease mean arterial blood pressure and cerebral perfusion pressure but have no significant effect on arteriovenous oxygen content difference and middle cerebral artery mean flow velocity in patients with severe brain injury . No differences on intracranial pressure changes were found between patients with preserved and impaired autoregulation . Our results suggest that other mechanisms , besides the activation of the vasodilatory cascade , also could be implicated in the intracranial pressure increases seen after opioid administration OBJECT Sedation regimens for head-injured patients are quite variable . The short-acting sedative-anesthetic agent propofol is being increasingly used in such patients , yet little is known regarding its safety and efficacy . In this multicenter double-blind trial , a titratable infusion of 2 % propofol accompanied by low-dose morphine for analgesia was compared with a regimen of morphine sulfate in intubated head-injured patients . In both groups , other st and ard measures of controlling intracranial pressure ( ICP ) were also used . METHODS Forty-two patients from 11 centers were evaluated to assess both the safety and efficacy of propofol : 23 patients in the propofol group ( mean time of propofol usage 95+/-87 hours ) and 19 patients in the morphine group ( mean time of morphine usage 70+/-54 hours ) . There was a higher incidence of poor prognostic indicators in the propofol group than in the morphine group : patient age older than 55 years ( 30.4 % compared with 10.5 % , p < 0.05 ) , initial Glasgow Coma Scale scores of 3 to 5 ( 39.1 % compared with 15.8 % , p < 0.05 ) , compressed or absent cisterns on initial computerized tomography scanning ( 78.3 % compared with 57.9 % , p < 0.05 ) , early hypotension and /or hypoxia ( 26.1 % compared with 10.5 % , p = 0.07 ) . During treatment there was a trend toward greater use of vasopressors in the propofol group . However , the mean daily ICP and cerebral perfusion pressure were generally similar between groups and , on therapy Day 3 , ICP was lower in the propofol group compared with the morphine group ( p < 0.05 ) . Additionally , there was less use of neuromuscular blocking agents , benzodiazepines , pentobarbital , and cerebrospinal fluid drainage in the propofol group ( p < 0.05 ) . At 6 months postinjury , a favorable outcome ( good recovery or moderate disability ) was observed in 52.1 % of patients receiving propofol and in 47.4 % receiving morphine ; the mortality rates were 17.4 % and 21.1 % , respectively . Patients who received the highest doses of propofol for the longest duration tended to have the best outcomes . There were no significant differences between groups in terms of adverse events . CONCLUSIONS Despite a higher incidence of poor prognostic indicators in the propofol group , ICP therapy was less intensive , ICP was lower on therapy Day 3 , and long-term outcome was similar to that of the morphine group . These results suggest that a propofol-based sedation and an ICP control regimen is a safe , acceptable , and , possibly , desirable alternative to an opiate-based sedation regimen in intubated head-injured patients 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 BACKGROUND Midazolam and propofol are sedative agents commonly administered to patients with brain injury . We compared plasma concentrations of glial cell S100beta protein and nitric oxide ( NO ) between patients who received midazolam and those who received propofol sedation after severe brain injury , and investigated the association between S100beta and NO concentrations and neurological outcome . DESIGN 28 patients with severe head injury ( Glasgow Coma Score < 9 ) who required sedation and ventilation were r and omly assigned to receive midazolam ( n = 15 ) or propofol ( n = 13 ) based sedation . Blood sample s were drawn daily for 5 days for estimation of S100beta and NO concentrations . Neurological outcome was assessed 3 months later as good ( Glasgow Outcome Score [ GOS ] , 4 - 5 ) or poor ( GOS , 1 - 3 ) . RESULTS A good neurological outcome was observed in 8/15 patients ( 53 % ) in the midazolam group and 7/13 patients ( 54 % ) in the propofol group . Patients with a poor outcome had higher serum S100beta concentrations on ICU admission and on Days 1 - 4 in the ICU than those with a good outcome ( mean [ SD ] on Day 1 , 0.99 [ 0.81 ] v 0.41 [ 0.4 ] microg/L ; Day 2 , 0.80 [ 0.81 ] v 0.41 [ 0.24 ] microg/L ; Day 3 , 0.52 [ 0.55 ] v 0.24 [ 0.25 ] microg/L ; and Day 4 , 0.54 [ 0.43 ] v 0.24 [ 0.35 ] microg/L ; P<0.05 ) . There was no significant difference on Day 5 . Plasma NO concentrations were not associated with outcome . In subgroup analysis , there was no difference in S100beta and NO concentrations between patients with a good outcome versus those with a poor outcome in either the midazolam or propofol group . CONCLUSIONS Plasma concentrations of markers of neurological injury in patients with severe head injury were similar in those who received midazolam sedation and those who received propofol . Patients who had a poor neurological outcome at 3 months had consistently higher serum S100beta concentrations during the initial 4 days after injury than patients who had a good outcome OBJECTIVE We proposed to compare the efficacy and safety of midazolam and propofol in its new preparation ( 2 % propofol ) when used for prolonged , deep sedation in traumatized , critically ill patients . We also retrospectively compared 2 % propofol with its original preparation , 1 % propofol , used in a previous study in a similar and contemporary set of patients . DESIGN A prospect i ve , r and omized , unblinded trial ( midazolam and 2 % propofol ) and a retrospective , contemporary trial ( 2 % propofol and 1 % propofol ) . SETTING S A trauma intensive care unit in a tertiary university hospital . PATIENTS A total of 63 consecutive trauma patients , admitted within a period of 5 months and requiring mechanical ventilatory support for > 48 hrs , 43 of whom ( 73 % ) suffered severe head trauma . We also retrospectively compared the 2 % propofol group with a series of patients in whom 1 % propofol was used . INTERVENTIONS For the prospect i ve trial , we r and omized two groups -- a midazolam group with continuous administration of midazolam at dosages 0.1 - 0.35 mg/kg/hr , and a 2 % propofol group with continuous infusion at dosages 1.5 - 6 mg/kg/hr . Equal dosages of analgesics were administered . Similar management protocol s were applied in the 1 % propofol group , used in the retrospective analysis with 2 % propofol . MEASUREMENTS AND MAIN RESULTS Epidemiologic and efficacy variables were recorded . Hemodynamic and biochemical variables were also monitored on a regular basis . Neuromonitoring was also performed on those patients with head trauma .  Sedation adequacy was similar and patient behavior after drug discontinuation was not different in either prospect i ve group ( midazolam and 2 % propofol ) . Hemodynamic or neur 
    Output:
    
Although their effects are likely transient , bolus doses of opioids may increase intracranial pressure and decrease cerebral perfusion pressure .
Trials of propofol vs. midazolam and ketamine vs. sufentanil found no difference between agents in intracranial pressure and cerebral perfusion pressure .
This systematic review found no convincing evidence that one sedative agent is more efficacious than another for improvement of patient-centered outcomes , intracranial pressure , or cerebral perfusion pressure in critically ill adults with severe traumatic brain injury .
High bolus doses of opioids , however , have potentially deleterious effects on intracranial pressure and cerebral perfusion pressure .