The Effects of Large-Dose Propofol on Cerebrovascular Pressure Autoregulation in Head-Injured Patients Luzius A. Steiner, MD, DEAA*†, Andrew J. Johnston, FRCA†, Doris A. Chatfield, BA‡, Marek Czosnyka, PhD, DSc*, Martin R. Coleman, PhD‡, Jonathan P. Coles, FRCA†, Arun K. Gupta, FRCA†, John D. Pickard, MChir, FRCS, FMedSci*, and David K. Menon, MD, PhD, FRCP, FRCA, FMedSci† *Academic Neurosurgery, †University Department of Anaesthesia, and ‡Wolfson Brain Imaging Centre, Addenbrooke’s Hospital, Cambridge, United Kingdom In healthy individuals, cerebrovascular pressure auto- regulation is preserved or even improved when propo- fol is infused. We examined the effect of an increase in propofol plasma concentration on pressure autoregula- tion in 10 head-injured patients. Using target- controlled infusions, the static rate of autoregulation was determined at a moderate (2.3  0.4 g/mL) and a large (4.3  0.04 g/mL) plasma target concentration of propofol. Using norepinephrine to control cerebral per- fusion 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 oxy- gen 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. (Anesth Analg 2003;97:572–6) P ropofol is frequently used for sedation and con- trol of increased intracranial pressure (ICP) in head-injured patients (1). The literature suggests that in healthy individuals propofol improves cerebro- vascular pressure autoregulation (2), i.e., the brain’s ability to keep cerebral blood flow (CBF) relatively constant despite changes in cerebral perfusion pres- sure (CPP). Propofol has also been shown to restore impaired pressure autoregulation in patients during cardiopulmonary bypass (3). Even large doses of this drug, leading to a burst-suppression pattern on the electroencephalogram (EEG), do not lead to a deteri- oration of pressure autoregulation (4). This is possibly explained by the cerebral vasoconstrictor effect of this drug, because vasoconstrictors are generally expected to increase vascular smooth muscle tone and therefore to improve pressure autoregulation (5). After head injury, pressure autoregulation is an im- portant prognostic factor with a strong association be- tween dysautoregulation and impaired outcome (6 – 8). This may be because intact pressure autoregulation is a powerful mechanism that protects the injured brain against secondary physiological insults related to unsta- ble perfusion pressure. Consequently, interventions that improve pressure autoregulation may provide benefit in this patient population. This study was designed to test the hypothesis that increasing the dose of propofol im- proves pressure autoregulation in head-injured patients initially sedated with a moderate dose of this drug. LAS is supported by a Myron B. Laver Grant (Department of Anaesthesia, University of Basel, Switzerland), a grant from the Margarete und Walter Lichtenstein-Stiftung (Basel, Switzerland), by the Swiss National Science Foundation, and is recipient of an Over- seas Research Student Award (Committee of Vice-Chancellors and Principals of the Universities of the United Kingdom). AJJ is recip- ient of a grant from Codman. JPC is funded by a Wellcome Research Training Fellowship and by a Beverley and Raymond Sackler Stu- dentship Award. This work was further supported by the MRC Acute Brain Injury Programme Grant G9439390 ID 56833. MC is on leave from the Warsaw University of Technology, Poland. Accepted for publication March 20, 2003. Address correspondence and reprint requests to Luzius A. Steiner, MD, DEAA, Academic Neurosurgery, Box 167, Addenbro- oke’s Hospital, Cambridge CB2 2QQ, UK. Address e-mail to las30@cam.ac.uk. DOI: 10.1213/01.ANE.0000070234.17226.B0 ©2003 by the International Anesthesia Research Society 572 Anesth Analg 2003;97:572–6 0003-2999/03