title: The effect of infusions of adrenaline, noradrenaline and dopamine on cerebral autoregulation under propofol anaesthesia in an ovine model.
abstract: OBJECTIVE
  To compare the effects of infusions of adrenaline, noradrenaline and dopamine on cerebral autoregulation under steady-state propofol anaesthesia with the awake state.
  
  
  METHODS
  Prospective, randomised, interventional animal study.
  
  
  METHODS
  University laboratory.
  
  
  METHODS
  Six studies in two cohorts of adult ewes: awake and steady-state propofol anaesthesia (15 mg/min).
  
  
  METHODS
  In random order, each animal received ramped infusions of adrenaline, noradrenaline (0-40 microg/min) and dopamine (0-40 microg/kg per min).
  
  
  RESULTS
  Cerebral blood flow (CBF) was measured continuously from changes in Doppler velocities in the sagittal sinus and normalised to a PaCO(2) 35 mmHg. Propofol decreased CBF by 55% relative to pre-anaesthesia values (p=0.0001). All three catecholamines significantly and equivalently increased mean arterial pressure (MAP) from baseline in a dose-dependent manner in both awake and propofol cohorts. Adrenaline significantly increased CBF from baseline in both awake sheep (p<0.01) and during propofol anaesthesia (p<0.001); noradrenaline and dopamine did not statistically increase CBF. When comparing the effects of individual catecholamines with each other within each cohort, no statistically significant difference between the catecholamines was demonstrated. (p>0.05). Using linear regression analysis, normalised CBF was correlated against associated changes in MAP. No significant differences were demonstrated between the slopes of regression lines for adrenaline, noradrenaline and dopamine in either cohort (ANCOVA). There was a statistically significant difference between the intercepts of the awake and propofol cohorts (p<0.0001), but no difference between the slopes (p=0.69).
  
  
  CONCLUSIONS
  Over a specific dose range, catecholamine-induced hypertension caused increased CBF during steady-state propofol anaesthesia. This effect was offset by an associated reduction in CBF caused by propofol. The concomitant administration of propofol and catecholamines was not associated with altered autoregulatory function compared to the awake state.
authors.affiliation: Department of Anaesthesia and Intensive Care, University of Adelaide and Royal Adelaide Hospital, 5000 Adelaide, Australia. j.myburgh@unsw.edu.au
authors.forename: John A
authors.initials: JA
authors.lastname: Myburgh
authors.forename: Richard N
authors.initials: RN
authors.lastname: Upton
authors.forename: Cliff
authors.initials: C
authors.lastname: Grant
authors.forename: Allison
authors.initials: A
authors.lastname: Martinez
mesh_terms: D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006706:Homeostasis / Q000187:drug effects*; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D015742:Propofol; D012756:Sheep
chemical_list: D018686:Anesthetics, Intravenous; D004298:Dopamine; D009638:Norepinephrine; D015742:Propofol; D004837:Epinephrine