Chapter 19
Anaesthesia for obstetrics
Clinical significance of changes during pregnancy and parturition
Intravenous anaesthetics; neuromuscular blockers
Anaesthesia for caesarean section
Introduction
There is no one anaesthetic agent or technique that is ideal for all parturient animals. In veterinary practice, the choice of anaesthetic methods and drugs is often influenced by whether the fetus(es) are alive and wanted, unwanted, or dead due to obstetrical problems. In any case, the choice must be such as to ensure the safety of the mother and any living fetus(es), comfort of the mother during parturition or hysterotomy and convenience of the obstetrician/ surgeon. To make a rational choice, the anaesthetist must be familiar with physiological alterations induced by pregnancy and labour, the pharmacology of the agents used, and significance of obstetric complications necessitating assisted delivery of the newborn. Most studies have been carried out in ewes, but physiological alterations are broadly comparable in other species of animal even if their magnitude differs. The following brief account of changes in physiology and in actions of drugs administered during pregnancy and parturition is a summary of many published papers and accounts in standard textbooks and should apply to all species of domestic animals. A referenced review of this topic has been published by Pascoe and Moon (2001).
The state of pregnancy
Physiological and anatomical alterations occur in many organ systems during pregnancy and delivery of the fetuses. Early in pregnancy changes are due, at least in part, to metabolic demands of the fetus(es), placenta and uterus, due largely to increasing levels of progesterone and oestrogen. Later changes starting around mid-pregnancy are anatomical in nature and are caused by mechanical pressure from the enlarging uterus.
Circulatory changes
Circulatory changes develop primarily to meet increased metabolic demands of the mother and fetus(es) (Table 19.1). Blood volume increases progressively, most of the added volume being accommodated in the increased capacity of vessels in the uterus, mammary glands, renal, striated muscle and cutaneous tissues so that there is no evidence of circulatory overload in healthy pregnant animals. Increase in plasma volume is relatively greater than that of red cells, resulting in haemodilution with decreased haemoglobin content and haematocrit. The purpose of this increase in blood volume is usually assumed to be twofold. First, it increases placental exchanges of respiratory gases, nutrients and waste metabolites. Secondly, it acts as a reserve if there is any abnormal maternal blood loss at parturition so that increased autotransfusion of blood can occur from the involuting uterus. Cardiac output increases in pregnancy to a similar degree as blood volume and there is an additional increase in cardiac output during all stages of labour. In 3rd stage labour it probably results from blood being expelled from the involuting uterus into the general circulation. Peripheral vascular resistance usually decreases during pregnancy so that mean arterial pressure (MAP) does not change. A serious decrease in venous return due to compression of the vena cava and aorta by the enlarged uterus and its contents can occur if the animal is restrained or positioned in dorsal recumbency. This decrease in venous return will, of course, cause a fall in cardiac output for the heart cannot pump more blood than is being returned to it. Cardiac work is increased during pregnancy so that at parturition cardiac reserve is reduced and pulmonary congestion and heart failure may occur in animals that had previously well compensated cardiac disease.
Table 19.1
Physiological changes with pregnancy and impact on anaesthesia
| Physiological changes | Significance for anaesthesia |
| Central nervous system | |
| Decreased requirement for anaesthetic agents | Risk of deep anaesthesia |
| Respiratory system | |
| Increased volume of ventilation Increased oxygen consumption and decreased functional residual capacity | Uptake of inhalation agents more rapid PaO2 decreases more rapidly during decreased ventilation; onset of hypoxia more rapid during apnoea |
| Cardiovascular system | |
| Blood volume increases to accommodate uterus and fetus(es) Heart rate increases but blood pressure remains unchanged Cardiac output increases | Factors decreasing blood volume and cardiac output decrease blood pressure; maternal hypotension decreases uterine blood flow and causes fetal metabolic acidosis |
| Gastrointestinal tract | |
| Gastric emptying slowed | Retention of gastric contents increases risk for aspiration pneumonia in dogs and cats |
| Reproductive tract | |
| Enlarged uterus | Uterus compresses diaphragm and decreases ventilation during anaesthesia; uterus may compress caudal vena cava during dorsal recumbency and cause hypotension |
Respiratory system changes
During pregnancy, the sensitivity of the respiratory centre to carbon dioxide is increased, presumably due to changes in hormone levels, so that PaCO2 and serum bicarbonate decrease, although arterial pH is maintained due to long-term renal compensation. Oxygen consumption is increased by the demands of the developing fetus(es), placenta, uterine muscle and mammary glands. During labour, ventilation may be further increased by apprehension or anxiety. Airway conductance is increased and total pulmonary resistance is decreased, apparently from hormone-induced relaxation of bronchial smooth muscle. Cranial displacement of the diaphragm results from increasing volume of the gravid uterus leading to a decrease in functional residual capacity (FRC), so that it is possible for airway closure to occur at end-expiration. Reduction in oxygen storage capacity from reduced FRC leads to an unusually rapid decline in PaO2 during apnoea. Some compensation for the tendency of the FRC to decrease is achieved by increases in the transverse and craniocaudal diameters of the chest cavity and flaring of the ribs.
Other systems
Liver function is generally well maintained during pregnancy. Plasma protein concentration is decreased but total plasma protein is increased due to increase in blood volume.
Renal plasma flow (RPF) and glomerular filtration rate (GFR) increase progressively, paralleling the increases in blood volume and cardiac output. Due to increases in renal clearances blood urea and creatinine levels are lower than in non-pregnant animals.
Uterine blood flow is directly proportional to perfusion pressure and inversely proportional to uterine vascular resistance, so that it can be compromised from vasoconstriction due to catecholamine release from fright or anxiety.
Pharmacology of drugs administered during pregnancy
The effects of pregnancy on drug disposition, biotransformation and excretion are largely unknown in domestic animals. The minimum alveolar concentration (MAC) of inhalation agents is decreased due to inconclusive mechanisms. The increase in RPF and GFR favours renal excretion of drugs. Any drug administered to the mother is liable to cross the placenta to the fetus(es) and induce effects similar to those observed in the mother.
Placental transfer of drugs is governed by the physiochemical properties of the drug and anatomical features of the placenta. Transfer of drugs can occur by simple diffusion, facilitated diffusion via transport systems, active transport and pinocytosis. Of these, simple diffusion is by far the most important and this will be affected by the surface area and thickness of the placenta. The larger farm animals have thick epitheliochorial placentae with relatively small areas for diffusion due to their cotyledonary or patchy diffuse distribution, whereas dogs and cats have thinner endotheliochorial placentae with larger zonular areas of implantation. Thus, the placental diffusion barrier is greatest in ruminants, pigs and horses and least in dogs and cats. However, the diffusion barrier does not appear to be of great clinical significance in the transfer of drugs from mother to fetus(es) in any species of animal.
More important is the diffusion constant which is unique to each drug and determined by molecular weight, degree of protein binding in maternal blood, lipid solubility and degree of ionization in the plasma. Most drugs used in anaesthesia have large diffusion constants – low molecular weights, high lipid solubility and poor ionization – and diffuse rapidly across the placenta. The exceptions are the neuromuscular blocking drugs, which are highly ionized and of low lipid solubility.
Maternal blood concentrations of drug depend on total dose administered, site or route of administration, rate of distribution and uptake of it by maternal tissues and maternal detoxification and excretion. Thus drugs with rapidly declining plasma concentration after administration of a fixed dose (e.g. thiopental) result in a short exposure of the placenta, and hence fetus(es), to high maternal concentrations. Drugs administered continuously (e.g. inhalation anaesthetics, infused agents during TIVA) are associated with a continuous placental transfer to the fetus(es).
The concentration of drug in the umbilical vein of a fetus is not that to which the fetal target organs such as the heart and brain are exposed, for most of the umbilical blood passes initially through the liver, where the drug may be metabolized or sequestrated. The remainder of the umbilical blood passes through the ductus venosus to the vena cava where it is diluted by drug-free blood from the hind end of the fetus. Thus, the fetal circulation protects vital tissues and organs from exposure to sudden high drug concentrations.
Clinical significance of changes during pregnancy and parturition
Circulatory changes of pregnancy and parturition can put a mother suffering from even normally well compensated heart disease at risk unless care is taken to ensure a minimum cardiac depression from anaesthetic drugs. Ecbolics used early on in labour can have an adverse effect on cardiovascular function. Oxytocin will induce vasodilation and hypotension that will have an adverse effect on both mother and fetus(es) due to decreased tissue and placental perfusion. Venous engorgement of the epidural space decreases the volume of solutions needed to produce block to any given level.
Reduction in FRC means that any respiratory depression caused by drugs is more significant in pregnant than in non-pregnant animals and hypoventilation will lead to hypercapnia and hypoxaemia; the hypoxaemia is particularly undesirable during labour when oxygen consumption is increased. In small animals, induction of anaesthesia with inhalational agents will be more rapid than in non-pregnant animals due to the decrease in FRC and increased alveolar ventilation as well as the decrease in MAC, but in recumbent large animals shunting of pulmonary blood may make the maintenance of inhalation anaesthesia more difficult.
In monogastric animals, there is an increased risk of both vomiting and silent aspiration of gastric contents in parturient animals for the time of last feeding is frequently unknown, and intragastric pressure is increased in the stomach displaced by the gravid uterus. Risk of regurgitation of ruminal contents when general anaesthesia is induced seems to be great in cattle, but perhaps not in sheep and goats which normally have less fluid rumen contents.
Drug actions
Opioids
Opioids rapidly cross the placenta from mother to fetus(es) and can cause marked respiratory and central nervous depression in neonate(s) with sleepiness and reluctance to feed. Some clinicians use a short-acting opioid for premedication in small animals, others wait until the puppies or kittens are delivered before administering an opioid to the dam. An opioid antagonist such as naloxone can be given to the neonate(s). Because the action of naloxone is shorter than that of some opioids, depression may return when naloxone is metabolized and careful observation is indicated to allow this to be detected and treated by the injection of more naloxone.
α2-Agonists; ketamine
All α2-adrenoceptor agonists rapidly cross the placenta and can cause respiratory and cardiovascular depression in both mother and babies, although the magnitude differs between species and can be counteracted by antagonists. Unless used in small dosage, xylazine causes significant newborn depression when administered to cows and small ruminants. Xylazine–ketamine combinations are not recommended for caesarean section (CS) in dogs due to excessive newborn depression. Xylazine–ketamine appears to be a satisfactory combination for induction of anaesthesia in mares and sows with satisfactory activity in foals and piglets after vaginal delivery or CS. Information about the fetal depressant effects of medetomidine or dexmedetomidine in small animals is confusing. Some clinicians avoid using this agent while others have used it to their satisfaction as premedication in dogs prior to mask induction with an inhalant. Atipamezole is the reversal agent for medetomidine and, if injected into the newborn, may be sufficiently absorbed to reverse the sedative effects caused by placental transmission.
Intravenous anaesthetics; neuromuscular blockers
Low doses of thiopental, methohexital, propofol and alfaxalone produce varying degrees of respiratory and central nervous depression in neonates. Thiopental has been used in low dose for induction of anaesthesia prior to maintenance with an inhalation agent for CS in humans and other species of animals. Newborns exhibit a degree of depression after maternal administration of thiopental and clinical studies have shown that newborns are more vigorous when IV agents other than thiopental are used for induction of anaesthesia (Copland, 1977; Elovsson et al., 1996; Luna et al., 2004). A study comparing thiopental and alphaxalone/alphadalone for induction of anaesthesia prior to maintenance with halothane for CS in ewes confirmed that a low dose of the steroid anaesthetic was associated with less neonatal depression than thiopental (Copland, 1977). Measurements of cardiovascular parameters in late-term pregnant ewes were used to compare anaesthesia induced and maintained with isoflurane 1.3% with anaesthesia induced with propofol, 2.5 mg/kg, IV followed by an infusion of 0.3 mg/kg/min, tracheal intubation and ventilation with oxygen (Gaynor et al., 1998). Maternal mean heart rate (HR), MAP, and cardiac output were higher during propofol than isoflurane anaesthesia (depths of anaesthesia may not have been equivalent) but uterine arterial and umbilical venous flows were not different between the agents. In a study using higher dose rates, anaesthesia induced with propofol, 6 mg/kg, IV and maintained with an infusion of 0.4 mg/kg/min in pregnant ewes induced significant maternal and fetal respiratory acidosis and a significant decrease in maternal MAP at 5–15 minutes (Andaluz et al., 2005). The pharmacokinetic parameters of an injection of propofol, 6 mg/kg, IV with or without a continuous infusion have been determined in instrumented pregnant ewes (Andaluz et al., 2003). Although propofol rapidly crossed the placenta, fetal blood concentrations were low compared with maternal concentrations. In dogs, administration of one small supplemental bolus of propofol before puppy removal has been advocated as causing minimal fetal depression but maintenance of anaesthesia with an infusion of propofol has yet to be evaluated regarding the degree of puppy depression. Neuromuscular blocking agents may cross the placenta in small amounts but are seldom needed in obstetrical anaesthesia.
Inhalation anaesthetics
Inhalation anaesthetics readily cross the placental barrier with rapid equilibration between the mother and fetus(es). The degree of depression they cause in the neonate is directly proportional to the depth of anaesthesia induced in the mother. While light (1 MAC) anaesthesia with isoflurane induced no significant effect on uterine blood flow or fetal metabolic status, it has been found that deep (2 MAC) anaesthesia induces significant decreases in uterine blood flow and fetal metabolic acidosis within 15 minutes of start of administration (Palahniuk & Shnider, 1974a). At 2 MAC isoflurane or sevoflurane, maternal and fetal MAP and fetal HR were significantly decreased from awake and 1 MAC values (Okutomi et al., 2009). Values were not different between isoflurane and sevoflurane. There is a reduction in requirement for anaesthetic drugs and a decrease in MAC of inhalation agents at term pregnancy. When measured in ewes, MAC is 21–40% lower in gravid as compared with non-pregnant animals (Palahniuk et al., 1974; Okutomi et al., 2009). Use of the less soluble agents isoflurane, sevoflurane and desflurane will lead to more rapid recovery of the newly delivered animals than when more soluble agents such as halothane are employed. Nitrous oxide will often enable concentration of more potent soluble anaesthetic agent to be reduced and its use does not add to depression of the newborn, however, oxygen must be administered for a few minutes after delivery to prevent diffusion hypoxia.
Fetal haemoglobin can carry more O2 for a given PO2 due to the low concentration of 2,3-diphosphoglycerate (2,3-DPG) in fetal red cells. This ensures a higher level of haemoglobin saturation at the normally low PO2 of umbilical venous blood. Administration of O2 to the mother results in a significant increase in fetal oxygenation and maternal inspired O2 concentrations of over 50% during general anaesthesia are associated with delivery of more vigorous newborn.
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