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The anesthetic efficacy of midazolam in the enflurane-anesthetized dog
R I Hall1, I M Schwieger, C C Hug
1Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia.
Abstract:
This study determined the anesthetic efficacy of midazolam (MID) in terms of its ability to reduce enflurane MAC (EMAC). Control EMAC was determined by the tail-clamp method in 15 mongrel dogs. Each animal then received at least three incremental infusion rates of MID from among the following: 0.48, 2.4, 9.6, 19.2, 28.8, 48, or 151.2 micrograms.kg-1.min-1. MAC was determined during each infusion rate following a 1-h observation period, during which time MID concentration in plasma [( MID]) stabilized. [MID] was measured every 15 min beginning 45 min from the start of each new infusion rate. There was a linear relationship between MID infusion rates and the resulting [MID] (r = 0.995). In the range of [MID] from 14 to 14,118 ng/ml, there was a linear relationship between the log [MID] and the percent EMAC reduction. The slope of the line was very shallow, and the [MID] required to reduce EMAC by more than 50% exceeded the [MID] likely to be employed clinically in humans (750 ng/ml). Also, the 73 +/- 4% (mean +/- SEM) EMAC reduction produced by [MID] = 9,763 +/- 1213 ng/ml was not significantly greater than the 60 +/- 3% EMAC reduction achieved by [MID] = 1,464 +/- 293 ng/ml, a finding which suggests a ceiling effect to the anesthetic efficacy of midazolam. The authors conclude that, within the dose range of MID likely to be employed in humans, MID produced a concentration-dependent reduction of enflurane MAC in the dog. In doses above those likely to be employed clinically, a ceiling effect to the anesthetic efficacy of MID may become evident.
Insights
Midazolam (MID) reduces enflurane MAC (EMAC) in dogs in a dose-dependent manner. However, higher MID doses may show a ceiling effect, limiting anesthetic efficacy.
Area of Science:
- Veterinary Anesthesiology
- Pharmacology
Background:
- Anesthetic efficacy is crucial for patient safety during surgical procedures.
- Midazolam (MID) is a common sedative and anesthetic agent.
- Understanding its interaction with other anesthetics like enflurane is important.
Purpose of the Study:
- To determine the anesthetic efficacy of midazolam (MID) by measuring its effect on enflurane MAC (EMAC) in dogs.
- To establish the relationship between MID plasma concentration and EMAC reduction.
Main Methods:
- Enflurane MAC (EMAC) was determined using the tail-clamp method in 15 mongrel dogs.
- Dogs received incremental infusion rates of MID (0.48 to 151.2 µg.kg-1.min-1).
- Plasma MID concentrations ([MID]) were measured after stabilization, and EMAC was re-determined.
Main Results:
- A linear relationship was observed between MID infusion rates and plasma [MID] (r=0.995).
- A linear correlation existed between log [MID] and percent EMAC reduction within a specific range.
- Significant EMAC reduction (>50%) required [MID] levels potentially higher than clinical use in humans; a ceiling effect was suggested at higher doses.
Conclusions:
- Midazolam (MID) demonstrated a concentration-dependent reduction of enflurane MAC (EMAC) in dogs within clinically relevant doses.
- Anesthetic efficacy of MID may plateau at higher concentrations, indicating a potential ceiling effect.