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Interaction of a subanaesthetic concentration of isoflurane with midazolam: effects on responsiveness, learning and
M M Ghoneim1, R I Block, V J Dhanaraj
1Department of Anesthesia, College of Medicine, University of Iowa, Iowa City 52242, USA.
Abstract:
There are situations in which "light" anaesthesia combined with neuromuscular block is the only anaesthetic regimen that can be tolerated safely by the patient. Benzodiazepines have hypnotic and specific amnesic effects. Therefore, we have examined the interaction of midazolam with a subanaesthetic dose of isoflurane (0.2% end-expired concentration) in 28 healthy volunteers. Thereafter, 15 subjects received midazolam 0.03 mg kg-1 i.v. and 13 subjects received midazolam 0.06 mg kg-1 in a random, double-blind manner. Word lists were administered and response to commands was tested before and after administration of midazolam. After 1 h of recovery, memory for word lists was tested by word completion, free recall and forced choice recognition tasks. After administration of midazolam, recall and, to a lesser degree, implicit memory were absent. Recognition was also absent after administration of midazolam 0.06 mg kg-1 and at the 3-min and 15-min assessments after administration of midazolam 0.03 mg kg-1. Responsiveness was more frequent with midazolam 0.03 mg kg-1 than with 0.06 mg kg-1 and increased over time. We conclude that a larger dose of midazolam or isoflurane, or both, may be necessary to abolish responsiveness.
Insights
Midazolam, a benzodiazepine, combined with light anesthesia (isoflurane) impaired memory recall and recognition. Higher midazolam doses reduced responsiveness more effectively, suggesting potential for deeper anesthesia.
Area of Science:
- Anesthesiology
- Pharmacology
- Neuroscience
Background:
- Light anesthesia with neuromuscular blockade is sometimes the only safe option.
- Benzodiazepines offer hypnotic and amnesic effects, valuable in anesthesia.
Purpose of the Study:
- To investigate the interaction between midazolam and a subanesthetic dose of isoflurane.
- To assess the effects on memory and responsiveness in healthy volunteers.
Main Methods:
- 28 healthy volunteers received midazolam (0.03 or 0.06 mg kg-1 IV) and 0.2% end-expired isoflurane.
- Memory (recall, recognition) and responsiveness were tested before and after midazolam administration, with memory re-tested after 1 hour recovery.
Main Results:
- Midazolam administration resulted in absent recall and reduced implicit memory.
- Recognition was impaired, particularly at the higher midazolam dose (0.06 mg kg-1).
- Responsiveness was more frequent with the lower midazolam dose (0.03 mg kg-1) and increased over time.
Conclusions:
- Midazolam significantly impacts memory functions, including recall and recognition.
- Higher doses of midazolam, potentially combined with increased isoflurane, may be needed to fully abolish responsiveness.
- This interaction highlights the dose-dependent effects of midazolam on cognitive function during light anesthesia.