title: Sedation for critically ill adults with severe traumatic brain injury: a systematic review of randomized controlled trials.
abstract: OBJECTIVE
  To summarize randomized controlled trials on the effects of sedative agents on neurologic outcome, mortality, intracranial pressure, cerebral perfusion pressure, and adverse drug events in critically ill adults with severe traumatic brain injury.
  
  
  METHODS
  PubMed, MEDLINE, EMBASE, the Cochrane Database, Google Scholar, two clinical trials registries, personal files, and reference lists of included articles.
  
  
  METHODS
  Randomized controlled trials of propofol, ketamine, etomidate, and agents from the opioid, benzodiazepine, α-2 agonist, and antipsychotic drug classes for management of adult intensive care unit patients with severe traumatic brain injury.
  
  
  METHODS
  In duplicate and independently, two investigators extracted data and evaluated methodologic quality and results.
  
  
  RESULTS
  Among 1,892 citations, 13 randomized controlled trials enrolling 380 patients met inclusion criteria. Long-term sedation (≥24 hrs) was addressed in six studies, whereas a bolus dose, short infusion, or doubling of plasma drug concentration was investigated in remaining trials. Most trials did not describe baseline traumatic brain injury prognostic factors or important cointerventions. Eight trials possibly or definitely concealed allocation and six were blinded. Insufficient data exist regarding the effects of sedative agents on neurologic outcome or mortality. Although their effects are likely transient, bolus doses of opioids may increase intracranial pressure and decrease cerebral perfusion pressure. In one study, a long-term infusion of propofol vs. morphine was associated with a reduced requirement for intracranial pressure-lowering cointerventions and a lower intracranial pressure on the third day. Trials of propofol vs. midazolam and ketamine vs. sufentanil found no difference between agents in intracranial pressure and cerebral perfusion pressure.
  
  
  CONCLUSIONS
  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. Adequately powered, high-quality, randomized controlled trials are urgently warranted.
authors.affiliation: Department of Surgery, University of Calgary and the Foothills Medical Centre, Calgary, Alberta, Canada.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Roberts
authors.forename: Richard I
authors.initials: RI
authors.lastname: Hall
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Kramer
authors.forename: Helen Lee
authors.initials: HL
authors.lastname: Robertson
authors.forename: Clare N
authors.initials: CN
authors.lastname: Gallagher
authors.forename: David A
authors.initials: DA
authors.lastname: Zygun
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use; D001569:Benzodiazepines / Q000627:therapeutic use; D001930:Brain Injuries / Q000188:drug therapy*; D005045:Etomidate / Q000627:therapeutic use; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D007649:Ketamine / Q000627:therapeutic use; D015742:Propofol / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D001569:Benzodiazepines; D007649:Ketamine; D015742:Propofol; D005045:Etomidate