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Low‐dose midazolam antagonizes cerebral metabolic stimulation by ketamine in the pig
Author(s) -
ÅKESON J.,
BJÖRKMAN S.,
MESSETER K.,
ROSÉN I.
Publication year - 1993
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.1399-6576.1993.tb03759.x
Subject(s) - ketamine , midazolam , medicine , anesthesia , cerebral blood flow , ketamine hydrochloride , anesthetic , blood pressure , diazepam , fentanyl , pharmacology , sedation
In order to test the hypothesis that low‐dose midazolam reduces excitatory cerebral symptoms by attenuating ketamine‐induced increases in the cerebral metabolic rate for oxygen (CMRo 2 ), we compared the cerebral effects of a combination of an anaesthetic dose of ketamine hydrochloride (10.0 mg‐kg 1 i.v.) and a subanaesthetic dose of midazolam maleate (0.25 mg‐ kg ‐1 i.v., n = 6; or 0.10 mg‐kg ‐1 i.v., n = 6) with results recently obtained with ketamine (10.0 mg‐kg ‐1 i.v.) in normoventilated pigs anaesthetized with fentanyl, nitrous oxide and pancuronium. Cerebral blood flow (CBF) was measured with the intra‐arterial 133 Xe clearance technique, and CMRo 2 was calculated from CBF and the cerebral arteriovenous oxygen content difference (Cavo 2 ). The CMRo 2 did not increase significantly. In contrast, the maximal increase in cerebral Cavo 2 (by 56–59% at 10 min; P < 0.01) was similar to that induced by ketamine, since CBF was more depressed (by 35–45% at 1 min: P < 0.001) by ketamine‐midazolam than by ketamine only. Midazolam was found to increase CVR ( P < 0.01) and further depress CBF ( P < 0.01), and to antagonize the ketamineinduced increase in CMRo 2 ( P < 0.05). Ketamine‐induced effects on mean arterial pressure (MAP) and spectral electroencephalographic (EEG) voltage were not significantly altered by midazolam. The pharmacokinetics of ketamine, as measured during an 80‐min period, were not affected by the concomitant administration of midazolam. We propose that a ketamine‐midazolam combination comprising a low‐dose fraction (1/ 100‐1/40) of midazolam is superior to ketamine alone for anaesthetic use.