Effects of sufentanil or ketamine administered in target-controlled infusion on the cerebral hemodynamics of severely brain-injured patients

Crit Care Med. 2005 May;33(5):1109-13. doi: 10.1097/01.ccm.0000162491.26292.98.


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: Prospective, randomized 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 samples 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 mug/mL, respectively, before the increase in concentrations and 0.7 +/- 0.4 ng/mL and 5.5 +/- 3.8 mug/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 designed for intensive care unit patients.

Publication types

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

MeSH terms

  • Adult
  • Analgesics / administration & dosage
  • Analgesics / blood
  • Analgesics / pharmacology*
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / blood
  • Analgesics, Opioid / pharmacology*
  • Brain Injuries / metabolism
  • Brain Injuries / therapy*
  • Drug Delivery Systems
  • Humans
  • Infusions, Intravenous
  • Intensive Care Units
  • Intracranial Pressure / drug effects*
  • Ketamine / administration & dosage
  • Ketamine / blood
  • Ketamine / pharmacology*
  • Sufentanil / administration & dosage
  • Sufentanil / blood
  • Sufentanil / pharmacology*


  • Analgesics
  • Analgesics, Opioid
  • Ketamine
  • Sufentanil