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Low-dose midazolam antagonizes cerebral metabolic stimulation by ketamine in the pig

Åkeson, Jonas LU ; Björkman, S; Messeter, K and Rosén, I (1993) In Acta Anaesthesiologica Scandinavica 37(6). p.525-531
Abstract
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 (CMRO2), we compared the cerebral effects of a combination of an anesthetic 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 133Xe clearance technique, and CMRo2 was calculated from CBF and the cerebral arteriovenous oxygen content difference (CaVO2). The... (More)
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 (CMRO2), we compared the cerebral effects of a combination of an anesthetic 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 133Xe clearance technique, and CMRo2 was calculated from CBF and the cerebral arteriovenous oxygen content difference (CaVO2). The CMRO2 did not increase significantly. In contrast, the maximal increase in cerebral CaVo2 (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 ketamine-induced increase in CMRO2 (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. (Less)
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organization
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Contribution to journal
publication status
published
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in
Acta Anaesthesiologica Scandinavica
volume
37
issue
6
pages
525 - 531
publisher
Wiley-Blackwell
external identifiers
  • pmid:8213014
  • scopus:0027234044
ISSN
0001-5172
language
English
LU publication?
yes
id
bfc5a9b9-2f24-453c-8bae-41a852f21b2c (old id 1107373)
date added to LUP
2008-07-30 17:02:52
date last changed
2017-02-19 03:24:01
@article{bfc5a9b9-2f24-453c-8bae-41a852f21b2c,
  abstract     = {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 (CMRO2), we compared the cerebral effects of a combination of an anesthetic 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 133Xe clearance technique, and CMRo2 was calculated from CBF and the cerebral arteriovenous oxygen content difference (CaVO2). The CMRO2 did not increase significantly. In contrast, the maximal increase in cerebral CaVo2 (by 56-59% at 10 min; P &lt; 0.01) was similar to that induced by ketamine, since CBF was more depressed (by 35-45% at 1 min: P &lt; 0.001) by ketamine-midazolam than by ketamine only. Midazolam was found to increase CVR (P &lt; 0.01) and further depress CBF (P &lt; 0.01), and to antagonize the ketamine-induced increase in CMRO2 (P &lt; 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.},
  author       = {Åkeson, Jonas and Björkman, S and Messeter, K and Rosén, I},
  issn         = {0001-5172},
  language     = {eng},
  number       = {6},
  pages        = {525--531},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Anaesthesiologica Scandinavica},
  title        = {Low-dose midazolam antagonizes cerebral metabolic stimulation by ketamine in the pig},
  volume       = {37},
  year         = {1993},
}