The effect of midazolam on end-tidal concentration of isoflurane necessary to prevent movements in dogs

Objective To determine the possible additive effect of midazolam, a GABAA agonist, on the end-tidal concentration of isoflurane that prevents movement (MACNM) in response to noxious stimulation. Study design Randomized crossover experimental study. Animals Six, healthy, adult intact male, mixed-breed dogs. Methods After baseline isoflurane MACNM (MACNM-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 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). MACNM was re-determined after each dose in each series (MACNM-T). Results The median MACNM-B was 1.42. MACNM-B did not differ among groups (p > 0.05). Percentage reduction in MACNM 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 MACNM 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 MACNM. However, doses greater than 10 μg kg-1 minute-1 did not further decrease MACNM indicating a ceiling effect.