Isoflurane potentiates metocurine via peripheral not central nervous system action

Inhalational anaesthetics potentiate neuromuscular blocking drugs. The exact sites are not known, but may include the central nervous system, the neuromuscular junction or muscle. Anaesthetic action in the brain could potentiate neuromuscular block directly, or indirectly by altering plasma catecholamine concentrations.

In 5 goats anaesthetised with fentanyl and pentobarbitone, an experimental preparation was used in which isoflurane (end-tidal/exhaust 1.2–1.3%) was selectively delivered to either the torso (via the lungs) or brain (via an oxygenator/roller pump) during a stable ≅60% metocurine blockade (≅= 4–8 μg/min). Bilateral evoked gastrocnemius muscle twitch was accomplished with electrical stimulation (0.1 Hz) of the sciatic nerves, one of which was cut proximal to the stimulation site; output from the force transducer was digitised and stored on a computer. Blood samples were taken for metocurine, noradrenaline and adrenaline analysis.

When isoflurane was added to the brain, % depression of the muscle twitch was unchanged at 64 ± 13% on the uncut side; the cut side was also unchanged. When isoflurane was added to the torso, % depression increased from 68 ± 14% to 82 ± 12% (P < 0.05) on the uncut side and from 68 ± 8% to 81 ± 5% on the cut side (P < 0.05). Metocurine concentration in the torso decreased slightly when isoflurane was added to the torso (133 ± 19 ng/ml to 121 ± 18 ng/ml, P < 0.05) and increased slightly when isoflurane was added to the head (116 ± 31 ng/ml to 136 ± 31 ng/ml, P < 0.05). There were no significant changes in noradrenaline or adrenaline concentrations.

These data suggest that the periphery (neuromuscular junction or muscle) is the important site where isoflurane potentiates metocurine-induced neuromuscular blockade.