Effect of Anesthetic Agents on Uterine Activity & Labor
Sevoflurane, desflurane, isoflurane, and halothane depress uterine activity equally at equipotent doses; all cause dose-dependent uterine relaxation. Low doses (<0.75 MAC) of these agents, however, do not interfere with the effect of oxytocin on the uterus. Higher doses can result in uterine atony and increase blood loss at delivery. Nitrous oxide has minimal, if any, effects.
Opioids minimally decrease the progression of labor; ketamine, in doses of less than 2 mg/kg, appears to have little effect.
The administration of epidural analgesia is usually based upon the patient’s choice, and it is often uti-lized for patients with
maternal or fetal factors that increase the likelihood of prolonged labor or cesarean delivery (Table 40–2). Current evidence indicates that dilute combinations of a localanesthetic (eg, bupivacaine, 0.125% or less) and an opioid (eg, fentanyl, 5 mcg/mL or less) for epidural
or combined spinal–epidural (CSE) analgesia do not prolong labor or increase the likelihood of operative delivery.
When greater concentrations of local anesthetic (eg, bupivacaine, 0.25%) are used for continuous epidural analgesia, the second stage of labor may be prolonged by approximately 15–30 min. Intense regional analgesia/anesthesia can remove the urge to bear down during the second stage (Ferguson reflex), and motor weakness can impair expulsive efforts, often prolonging the second stage of delivery. Use of dilute local anesthetic–opioid mixtures can preserve motor function and allow effective push-ing. Intravenous fluid loading (crystalloid boluses) is often used to prevent or reduce the severity of hypo-tension following an epidural injection. So-called fluid loading does not reduce the incidence of hypotension and has been shown to reduce endog-enous oxytocin secretion from the pituitary and transiently decrease uterine activity. Epinephrine-containing local anesthetic solutions could theoreti-cally prolong the first stage of labor if absorption of epinephrine from the epidural space results in sig-nificant systemic β-adrenergic effects. Prolongation of labor is generally not clinically observed with very dilute (eg, 1:400,000) epinephrine-containing local anesthetics.
Uterine muscle has both α and β receptors. α1-Receptor stimulation causes uterine contraction, whereas β2-receptor stimulation produces relax-ation. Large doses of α-adrenergic agents, such as phenylephrine, in addition to causing uterine arte-rial constriction, can produce tetanic uterine con-tractions. Small doses of phenylephrine (40 mcg) may increase uterine blood flow in normal parturi-ents by raising arterial blood pressure. In contrast, ephedrine has little effect on uterine contractions.
Oxytocin (Pitocin) is usually administered intrave-nously to induce or augment uterine contractions or to maintain uterine tone postpartum. It has a half-life of 3–5 min. Induction doses for labor are 0.5–8 mU/min. Complications include fetal dis-tress due to hyperstimulation, uterine tetany, and, less commonly, maternal water retention (antidiuretic effect). Rapid intravenous infusion can cause transient systemic hypotension due to relaxation of vascular smooth muscle; reflex tachycardia may also be noted.
Uterine atony is the most common cause of severe postpartum hemorrhage. Immediate admin-istration of oxytocin after delivery is a standard measure to prevent this complication. Despite this practice, uterine atony complicates 4–6% of pregnan-cies. The concentration of volatile anesthetics should be reduced to 0.5 MAC in obstetric patients undergo-ing general anesthesia for cesarean delivery to avoid the uterine-relaxing effects of these drugs. Second-line oxytocics are methylergonovine (Methergine) and carboprost tromethamine (Hemabate).
Methylergonovine (Methergine) causes intense and prolonged uterine contractions. It is therefore given only after delivery (postpartum) to treat uterine atony. Moreover, because it also constricts vascular smooth muscle and can cause severe hypertension if given as an intravenous bolus, it is usually admin-istered only as a single 0.2 mg dose intramuscularly or in dilute form as an intravenous infusion over 10 minutes.
Carboprost tromethamine (Hemabate, prostaglan-din F2α) is a synthetic analogue of prostaglandin F2 that stimulates uterine contractions. It is often used to treat refractory postpartum hemorrhage. An ini-tial dose of 0.25 mg intramuscularly may be repeated every 15–90 min to a maximum of 2 mg. Common side effects include nausea, vomiting, broncho-constriction, and diarrhea. It is contraindicated in patients with bronchial asthma. Prostaglandin E1 (Cytotec, rectal suppository) or E 2 (Dinoprostone, vaginal suppository) is sometimes administered and has no bronchoconstricting effect.
Magnesium is used in obstetrics both to stop pre-mature labor (tocolysis) and to prevent eclamptic seizures. It is usually administered as a 4 g intra-venous loading dose (over 20 min) followed by a 2 g/h infusion. Therapeutic serum levels are consid-ered to be 6–8 mg/dL. Serious side effects include hypotension, heart block, muscle weakness, and sedation. Magnesium in these doses and concentra-tions intensifies neuromuscular blockade from non-depolarizing agents.
The β2-adrenergic agonists ritodrine and terbutaline inhibit uterine contractions and are used to treat premature labor.
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