Influence of Hypothermia on Pharmacokinetics of Vecuronium in Rat Livers Investigated.Beaufort et al.(page 270)

Beaufort et al. used an isolated perfused rat liver model with a fairly constant perfusion rate to elucidate the influence of hypothermia on the uptake of vecuronium in the intact organ. The researchers divided each perfusion experiment into three phases: (1) a 950-μg bolus of vecuronium was administered, followed by a continuous infusion of vecuronium throughout the experiment; (2) temperature was reduced to 28°C; and (3) temperature was restored to 38°C. In control experiments, temperature was kept constant throughout the perfusion procedure. Concentrations of vecuronium and its metabolites were measured in the perfusion medium, in bile collected from the livers, and in liver homogenate.

The team found that hypothermia increased the amount of vecuronium in the perfusion medium and that, when normal temperatures were restored, this amount decreased. Although hypothermia reversibly reduced the net uptake of vecuronium to the liver, biliary excretion remained virtually intact. Hypothermia drastically reduced the biliary excretion rate of 3-desacetyl vecuronium in contrast to that of the parent compound. Researchers were able to measure metabolism of vecuronium in only one of three liver homogenate preparations, and they found in that case that hypothermia reduced the rate of conversion by a factor of 2. Pharmacokinetic analysis showed that the hypothermia-induced changes in the pharmacokinetics of vecuronium could be described adequately only by the combination of reduced hepatic net uptake and reduced metabolism. These results show the need for effective measurement of muscle relaxants during hypothermia to prevent overdosing.