title: The effects of large-dose propofol on cerebrovascular pressure autoregulation in head-injured patients.
abstract: In healthy individuals, cerebrovascular pressure autoregulation is preserved or even improved when propofol is infused. We examined the effect of an increase in propofol plasma concentration on pressure autoregulation in 10 head-injured patients. Using target-controlled infusions, the static rate of autoregulation was determined at a moderate (2.3 +/- 0.4 microg/mL) and a large (4.3 +/- 0.04 microg/mL) plasma target concentration of propofol. Using norepinephrine to control cerebral perfusion pressure, transcranial Doppler measurements from the middle cerebral artery were made at a cerebral perfusion pressure of 70 and 85 mm Hg at each propofol concentration. Middle cerebral artery flow velocities at the large propofol concentration were significantly lower than at the moderate concentration, without any concurrent increase in arterio-jugular difference in oxygen content, a finding compatible with maintained flow-metabolism coupling. Despite this, static rate of autoregulation decreased significantly from 54% +/- 36% to 28% +/- 35% (P = 0.029). Our data suggest that after head injury, the cerebrovascular effects of propofol are different from those observed in healthy individuals. We propose that large doses of propofol should be used cautiously in head-injured patients, because there is the potential to increase the injured brain's vulnerability to secondary insults.
  
  
  CONCLUSIONS
  Propofol is used for sedation and control of intracranial pressure in head-injured patients. In contrast to previous data from healthy individuals, we show a deterioration of cerebrovascular pressure autoregulation with fast propofol infusion rates after head injury. Large propofol doses may increase the injured brain's vulnerability to secondary insults.
authors.affiliation: *Academic Neurosurgery, †University Department of Anaesthesia, and ‡Wolfson Brain Imaging Centre, Addenbrooke's Hospital, Cambridge, United Kingdom.
authors.forename: Luzius A
authors.initials: LA
authors.lastname: Steiner
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Johnston
authors.forename: Doris A
authors.initials: DA
authors.lastname: Chatfield
authors.forename: Marek
authors.initials: M
authors.lastname: Czosnyka
authors.forename: Martin R
authors.initials: MR
authors.lastname: Coleman
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Coles
authors.forename: Arun K
authors.initials: AK
authors.lastname: Gupta
authors.forename: John D
authors.initials: JD
authors.lastname: Pickard
authors.forename: David K
authors.initials: DK
authors.lastname: Menon
mesh_terms: D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D001930:Brain Injuries / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D007427:Intracranial Pressure / Q000187:drug effects; D008297:Male; D015742:Propofol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D006993:Hypnotics and Sedatives; D015742:Propofol