OBJECTIVE: To determine the possible additive effect of midazolam, a GABA(A) agonist, on the end-tidal concentration of isoflurane that prevents movement (MAC(NM) ) in response to noxious stimulation. STUDY DESIGN: Randomized cross-over experimental study. ANIMALS: Six healthy, adult intact male, mixed-breed dogs. METHODS: After baseline isoflurane MAC(NM) (MAC(NM-B) ) determination, midazolam was administered as a low (LDS), medium (MDS) or high (HDS) dose series of midazolam. Each series consisted of two dose levels, low and high. The LDS was a loading dose (Ld) of 0.2 mg kg(-1) and constant rate infusion (CRI) (2.5 μg kg(-1) minute(-1)) (LDL), followed by an Ld (0.4 mg kg(-1)) and CRI (5 μg kg(-1) minute(-1)) (LDH). The MDS was an Ld (0.8 mg kg(-1)) and CRI (10 μg kg(-1) minute(-1)) (MDL) followed by an Ld (1.6 mg kg(-1)) and CRI (20 μg kg(-1) minute(-1)) (MDH). The HDS was an Ld (3.2 mg kg(-1)) and CRI (40 μg kg(-1) minute(-1)) (HDL) followed by an Ld (6.4 mg kg(-1)) and CRI (80 μg kg(-1) minute(-1)) (HDH). MAC(NM) was re-determined after each dose in each series (MAC(NM-T)). RESULTS: The median MAC(NM-B) was 1.42. MAC(NM-B) did not differ among groups (p > 0.05). Percentage reduction in MAC(NM) was significantly less in the LDS (11 ± 5%) compared with MDS (30 ± 5%) and HDS (32 ± 5%). There was a weak correlation between the plasma midazolam concentration and percentage MAC(NM) reduction (r = 0.36). CONCLUSION AND CLINICAL RELEVANCE: Midazolam doses in the range of 10-80 μg kg(-1) minute(-1) significantly reduced the isoflurane MAC(NM) . However, doses greater than 10 μg kg(-1) minute(-1) did not further decrease MAC(NM) indicating a ceiling effect.
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