Mivacurium Sensitivity at the Adductor Pollicis and Hand Grip Muscles: Differences Between Males and Females

Background: Males lose more handgrip strength (HGS) than females when adductor pollicis (AP) TOF ratio decreases. The reason is unclear. Objectives: The primary aim of this study was to explore gender-related differences in neuromuscular sensitivity to mivacurium. As a secondary aim, clearance of mivacurium was determined. Methods: In 10 healthy males and 10 healthy females, constant-rate infusions of mivacurium were administered to obtain three different levels of stable neuromuscular block (normalized acceleromyography AP TOF ratio 80, 60, and 40%) in each study subject. Arterial blood samples were collected to determine mivacurium plasma concentrations. The HGS was measured every five minutes. A Hill equation was fitted to data on mivacurium concentration versus normalized AP TOF ratio and HGS to determine drug concentrations associated with 50% maximum effect (C50 AP TOF ratio and C50 HGS). Differences within and between genders were tested with the parametric t-test. Clearance of mivacurium was calculated at each block level as the ratio between drug infusion  rate and concentration. Gender-related differences in relationships between AP TOF ratio and HGS, mivacurium infusion rates, and mivacurium plasma concentrations were determined with linear mixed-models. Results: The C50 AP TOF ratio was significantly greater than C50HGSin males, yet not in females. Mivacurium infusion rates, needed to maintain stable neuromuscular blocks, were significantly greater in males, while clearance was similar between genders. Males lost significantly more HGS with decreasing AP TOF ratio than females, both in absolute (kg) and relative (percentage of baseline) terms. Conclusions: In males, yet not in females, the AP was significantly less sensitive to the effect of mivacurium than the muscles involved in the handgrip function. Thisfindingexplainswhyhandgripstrength decreasesmorein males than females with decreasing AP TOF ratio during the mivacurium block