Biochemical properties of plasma cholinesterase of significance to the anaesthetist are reviewed. The role of the genetic variants of the enzyme in suxamethonium sensitivity and hyperthermia are discussed with emphasis on the pregnant patient. Altered gene frequencies of the enzyme variants in some mental disorders is commented upon.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2044.1980.tb03800.x

Plasma cholinesterase variants and the anaesthetist.

Most anesthetic and analgesic agents in current use traverse the placental barrier in varying degrees, but are well tolerated by the fetus if judiciously administered. For labor analgesia, many options are available. Systemic administration of opioids and sedatives is one such option. Repeated maternal administration of opioids such as pethidine (meperidine) results in significant fetal exposure and neonatal respiratory depression. Patient-controlled analgesia with synthetic opioids such as fentanyl, alfentanil, and the new ultra-short-acting remifentanil may be used for labor analgesia in selected patients. Other options for labor analgesia include epidural and combined spinal-epidural techniques. With such techniques, neonatal exposure to opioids and sedatives can be minimized or totally avoided. While limiting the fetal exposure to the harmful effects of depressant drugs, epidural anesthesia and/or analgesia improves placental perfusion and oxygenation of the fetus, which is beneficial, especially in conditions such as pregnancy-induced hypertension. Regional blocks are also administered for the majority of cesarean deliveries because of the overwhelming and unequivocal evidence of maternal and fetal safety compared with general anesthesia for this indication. However, in some instances, administration of general anesthesia is unavoidable. Neonatal respiratory depression with low Apgar scores, and umbilical arterial and venous pH associated with general anesthesia, is often transient. A properly administered anesthetic, whether regional or general, has no significant adverse fetal or neonatal effects.

Effects of obstetric analgesics and anesthetics on the neonate : a review.

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.

Clinical pharmacokinetics of neuromuscular relaxants in pregnancy.

The treatment of pregnant and lactating women with psychopharmacologic agents requires skilled decision making on the part of the psychiatric consultant. The physician must consider the benefits of pharmacotherapy compared to the risks it involves not only for the mother but also for the developing fetus. In assigning weights to the factors that enter the risk/benefit equation, the physician must be aware of data from the literature regarding medication administration during pregnancy. The objective of this chapter is to provide an overview of currently available data with respect to pharmacologic treatment during pregnancy and lactation for the major classes of medications used in psychiatric practice: antipsychotics, antidepressants, lithium, and antianxiety agents. Information on the use of electroconvulsive therapy (ECT) during pregnancy will also be reviewed.

Psychopharmacologic Agents and Electroconvulsive Therapy during Pregnancy and the Puerperium

The Placenta: Anatomy, Physiology, and Transfer of Drugs

Analysis of maternal and neonatal blood samples for cholinesterase-activity determination revealed a case of hypoventilation in the newborn to be apparently secondary to succinylcholine administration to the mother during obstetric anesthesia.

William D. Owens

Papers

Hypoventilation in a newborn following administration of succinylcholine to the mother: a case report.