Propofol in the treatment of moderate and severe head injury: a randomized, prospective double-blinded pilot trial

J Neurosurg. 1999 Jun;90(6):1042-52. doi: 10.3171/jns.1999.90.6.1042.


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 standard 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Pressure / physiology
  • Cause of Death
  • Cerebrovascular Circulation / physiology
  • Craniocerebral Trauma / drug therapy*
  • Craniocerebral Trauma / mortality
  • Craniocerebral Trauma / physiopathology*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Hypnotics and Sedatives / adverse effects
  • Hypnotics and Sedatives / therapeutic use*
  • Intracranial Pressure / physiology
  • Male
  • Middle Aged
  • Nervous System / physiopathology
  • Pilot Projects
  • Prognosis
  • Propofol / adverse effects
  • Propofol / therapeutic use*
  • Prospective Studies


  • Hypnotics and Sedatives
  • Propofol