title: Cerebral pharmacodynamics of anaesthetic and subanaesthetic doses of ketamine in the normoventilated pig.
abstract: There are still divergent opinions regarding the pharmacodynamic effects of ketamine on the brain. In this study, the cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2) and electroencephalographic (EEG) activity were sequentially assessed over 80 min in 17 normoventilated pigs following rapid i.v. infusions of anaesthetic (10.0 mg.kg-1; n = 7) or subanaesthetic (2.0 mg.kg-1; n = 7) doses of ketamine or of its major metabolite norketamine (10.0 mg.kg-1; n = 3). The animals were continuously anaesthetized with fentanyl, nitrous oxide and pancuronium. CBF was determined by the intra-arterial 133Xe technique. Ketamine (10.0 mg.kg-1) induced an instant, gradually reverting decrease in CBF, amounting to -26% (P < 0.01) at 1 min and -13% (P < 0.05) at 10 min, a delayed increase in CMRO2 by 42% (P < 0.01) at 10 min and a sustained rise in low- and intermediate-frequency EEG voltage by 87% at 1 and 97% at 10 min (P < 0.0001). It is concluded that metabolically formed norketamine does not contribute to these effects. Considering the dissociation of CBF from CMRO2 found 10-20 min after ketamine (10.0 mg.kg-1) administration, it is suggested that ketamine should be used with caution for anaesthesia in patients with suspected cerebral ischaemia in order not to increase the vulnerability of brain tissue to hypoxic injury. Ketamine (2.0 mg.kg-1) had no significant effects on CBF, CMRO2 or EEG. It therefore seems that up to one fifth of the minimal anaesthetic i.v. dose can be used safely for analgesia, provided that normocapnaemia is preserved.
authors.affiliation: Department of Anaesthesia and Intensive Care, Malmö General Hospital, Lund University, Malmö, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Akeson
authors.forename: S
authors.initials: S
authors.lastname: Björkman
authors.forename: K
authors.initials: K
authors.lastname: Messeter
authors.forename: I
authors.initials: I
authors.lastname: Rosén
authors.forename: M
authors.initials: M
authors.lastname: Helfer
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004569:Electroencephalography / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D007262:Infusions, Intravenous; D007649:Ketamine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects*; D012119:Respiration; D013552:Swine; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D002245:Carbon Dioxide; D007649:Ketamine; D010100:Oxygen; C033419:norketamine