title: Interaction between thiopental and fentanyl in mice is different between hypnotic and lethal doses.
abstract: Much is known about the interaction of intravenous anesthetics and opioids at the therapeutic level, but less is known regarding their combined lethal effect, leaving some uncertainty regarding the window of safety for their clinical use. We set out to document the type of interaction between thiopental and fentanyl for both the hypnotic effect (loss of righting reflex) and lethal effect in mice. Hypnotic and lethal dose-response curves were constructed for thiopenthal alone and in combination with fentanyl (0.8 microg/kg, each based on five to seven subgroups of six to ten ICR mice. The dose of fentanyl was that needed to double the lag time to tail flick following a noxious stimulus (the equivalent of human analgesia). While fentanyl did not change the median effective hypnotic dose of thiopental (8.9 mg/kg [95% confidence interval {CI} 8.0-9.9 mg/kg] alone versus 7.8 mg/kg [95% CI 6.7-8.7 mg/kg] in combination), it significantly reduced its median lethal dose from 71.8 mg/kg (95% CI 68.3-74.8 mg/kg) to 64.5 mg/kg (95% CI 63.7-65.2 mg/kg). Most remarkably, it increased the slope of the curve from 0.17 (95% CI 0.10-0.36) to 0.61 (95% CI 0.24-1.10), virtually eliminating the difference between the non-lethal and lethal ranges. We conclude that the type of interaction between thiopental and fentanyl is stronger for the lethal effect than for the hypnotic effect. This may become relevant to clinical situations in humans when higher doses of thiopental are used.
authors.affiliation: Department of Anesthesiology, HaEmek Medical Center, Afula, Israel.
authors.forename: Ori
authors.initials: O
authors.lastname: Hadash
authors.forename: Izhar
authors.initials: I
authors.lastname: Ben-Shlomo
authors.forename: Ron
authors.initials: R
authors.lastname: Ben-Abraham
authors.forename: Yeshayahu
authors.initials: Y
authors.lastname: Katz
mesh_terms: D018686:Anesthetics, Intravenous / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005283:Fentanyl / Q000009:adverse effects / Q000494:pharmacology*; D006323:Heart Arrest / Q000139:chemically induced; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000494:pharmacology*; D007928:Lethal Dose 50; D051379:Mice; D008813:Mice, Inbred ICR; D013874:Thiopental / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D013874:Thiopental; D005283:Fentanyl