Clinical pharmacokinetics of neuromuscular relaxants in pregnancy

Abstract

Despite an increased in bodyweight, plasma volume by 45% and blood volume by 35% that might influence the volume of distribution of polar drugs, the apparent volume of distribution at steady state (Vss), volume of distribution (Vd) and the apparent volume of the central compartment (Vc) of atracurium, vecuronium and pancuronium are unchanged during pregnancy. With an elimination that is independent of renal, hepatic and enzymatic functions, the clearance of atracurium is also unchanged. This is corroborated by an unchanged clinical duration of atracurium during pregnancy. The clearance of pancuronium is increased by 27% during caesarean section. This may be explained by the increased glomerular filtration rate reported in pregnant women. The clinical duration of vecuronium in term and postpartum women is twice that reported in nonpregnant women. On the other hand, an increase in the clearance clearance of vecuronium during cesarean sections has been reported. The umbilical/maternal vein concentration ratio (UV/MV) of nondepolarising neuromuscular relaxants varies from 7 to 26% and clinical doses of these drugs may induce partial residual curarisation in neonates. Fetal concentrations of non-depolarising neuromuscular relaxants are proportional to the maternal dose injected as demonstrated for pancuronium and vecuronium. Increasing UV/MV with longer drug injection to delivery intervals have been demonstrated for drugs with a high molecular weight, such as atracurium, but not for those with a low molecular weight, such as vecuronium, while conflicting results have been reported for pancuronium. Despite decreased plasma pseudocholinesterases, the clinical duration of succinylcholine 1 mg/kg is unchanged in pregnant women, and only is slightly increased in postpartum women. On the other hand, larger doses of succinylcholine have induced prolonged apnoea and phase II block. The use of a pretreatment dose of a nondepolarising neuromuscular relaxant to decrease fasciculations and subsequent postoperative muscle pain is not only unnecessary in pregnant women but may be hazardous, since it may produce unexpected significant curarisation with respiratory distress. At clinical doses, transplacental passage of succinylcholine is insufficient to produce curarisation of neonates except in those born to mothers with abnormal plasma pseudocholinesterases. Magnesium sulfate, used in the treatment of pre-eclampsia, will enhance the blocking effects of nondepolarising neuromuscular relaxants but will have no effects on the characteristics of paralysis of succinylcholine. Histamine type 2 antagonists used to decrease the risk of aspiration during induction of anaesthesia do not influence the blocking properties of neuromuscular relaxants, while metoclopramide prolongs the block of succinylcholine.