What are the best sedatives for patients with traumatic brain injury? A systematic review found no evidence that one sedative agent is better than another for improvement of neurologic outcome or mortality in critically ill adults with severe TBI. Thirteen randomised trials including around 380 patients were reviewed.
Why sedate brain injured patients anyway? Reasons include:

• minimise noxious stimuli
• improve patient comfort
• reduce metabolic requirements of the injured brain to avoid ischemic progression of the traumatic lesion in presence of increased ICP
• facilitate mechanical ventilation to control PaCo2
• avoid ICP rises due to airway instrumentation such as those induced by coughing

Sedation generally improved intracranial pressure (ICP) and cerebral perfusion pressure (CPP) vs. baseline in most trials.
Interestingly boluses or short infusions of opioids resulted in (often transient) increases in ICP and decreases in MAP and CPP in three RCTs. An accompanying editorial suggests this may be due to large opioid doses (up to 3 μg/kg of fentanyl) and consequent hypotension; hypotension itself may trigger autoregulatory cerebral vasodilatation and increase ICP and decrease CPP. Although opioids have been linked with increased ICP through decreased cerebrovascular resistance, increased cerebral blood flow or Paco2, and disturbed cerebral autoregulation, they state that in studies in which hypotension after opioid administration was prevented, an ICP increasing effect was not seen. It is important to note the small sample sizes studied and the long time period of studies included, dating back some decades.
Importantly, ketamine did not result in the increase in ICP purported by older literature.

OBJECTIVES: 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.

DATA SOURCES: PubMed, MEDLINE, EMBASE, the Cochrane Database, Google Scholar, two clinical trials registries, personal files, and reference lists of included articles.

STUDY SELECTION: 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.

DATA EXTRACTION: In duplicate and independently, two investigators extracted data and evaluated methodologic quality and results.

DATA SYNTHESIS: 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.

Sedation for critically ill adults with severe traumatic brain injury: A systematic review of randomized controlled trials
Crit Care Med. 2011 Dec;39(12):2743-51