Glycopyrrolate
Heparin
Insulin
Nondepolarizing neuromuscular blocker
Succinylcholine
This chapter will also discuss many pharmacologic therapies for the pregnant patient. Local anesthetics and opioids are the foundation of most neuraxial techniques used for labor analgesia and cesarean delivery. Pharmacologic induction and maintenance of general anesthesia is another anesthetic option for cesarean sections or non-obstetric surgeries. Tocolytic medications can stop unwanted uterine contractions (e.g., in the management of preterm labor patients). Uterotonic medications can be used to induce labor, augment uterine contractions, or to treat uterine atony. Teratogenic medications will also be reviewed as they may have possible deleterious consequences on the fetus.
Local Anesthetics for Neuraxial Anesthesia
Local Anesthetics
Introduction
Local anesthetics are used in different regional anesthetic techniques. Single-shot spinal injections are fast in onset but limited in duration. An epidural delivers medications using a catheter to administer a continuous titratable infusion or a bolus to the patient. These neuraxial techniques are central to obstetric anesthesia practice, but local anesthetics can also be administered in other ways (e.g., local infiltration, paracervical or pudendal blockade) to provide analgesia.
Drug Class and Mechanism of Action
The main role of local anesthetics in neuraxial anesthesia is to target the nerve root emerging from the spinal cord. (See Chap. 8.)
Indications/Clinical Pearls
During labor and delivery, visceral and somatic stimulation triggers different pain pathways. Primarily using local anesthetic and/or opioid medications, anesthesiologists temporarily block these pathways through epidural and/or spinal techniques.
Three percent 2-chloroprocaine should be considered in emergent cesarean sections for patients with in situ epidurals. The onset is fast because of the high concentration, but 3 % 2-chloroprocaine is relatively safe because of its rapid maternal and fetal metabolism [3].
Spinal doses for cesarean section vary widely between providers (see dosing options below) and are often adjusted based on patient factors and anticipated surgical duration. One starting point is the ED95 of intrathecal bupivacaine combined with commonly used adjuncts fentanyl and morphine. Consider 11.2 mg of hyperbaric bupivacaine with 10 mcg of fentanyl and 200 mcg of morphine or 13 mg of isobaric bupivacaine with 10 mcg of fentanyl and 200 mcg of morphine [4, 5].
Spinal doses for labor analgesia, usually by way of a combined spinal-epidural technique, vary greatly and the optimal doses are an active area of study. In an informal survey of practices, bupivacaine doses range from 0 to 3 mg in this application. An opioid, with or without isobaric bupivacaine, is commonly employed.
The addition of epinephrine (1:200,000) to epidural solutions can help reduce vascular absorption of local anesthetics by inducing vasoconstriction and decreasing vascular uptake. This adjunct can prolong the epidural block. The addition of sodium bicarbonate 8.4 % (e.g., 1–10 ml of lidocaine) to epidural solutions can speed the onset of local anesthetics by decreasing its ionization which makes it conducive for nerve penetration [6]. These adjuncts are commonly added to lidocaine epidural mixtures for cesarean delivery.
Dosing Options
For cesarean patients, there are many neuraxial anesthetic options (see Tables 41.2 and 41.3). The dosing requirement for epidural and spinal local anesthetics is approximately 30 % less in pregnancy due to the following: (a) engorgement of the epidural veins which decreases the CSF and epidural volumes in the vertebral column; (b) elevation in progesterone levels which may cause the neuron to be more sensitive to the local anesthetic; and (c) increases in CSF and epidural space pressures secondary to the progression of labor [8].
Local anesthetic | Concentration (%) | Max dose (mg) | Onset (min) | Duration | Common adjuncts |
|---|---|---|---|---|---|
Bupivacaine (Marcaine) | 0.5 | 175–200 | 15–20 | 2–5 h | Epinephrine Fentanyl Meperidine Morphine Sufentanil Sodium bicarbonate |
Chloroprocaine (Nesacaine) | 3 | 800–1,000 | 5–10 | 30–60 min | |
Lidocaine (Xylocaine) | 2 | 350–500 | 5–15 | 60–120 min | |
Ropivacaine (Naropin) | 1 | 200–250 | 15–20 | 2–4 h |
Local anesthetic | Concentration (%) | Dose (mg) | Onset | Duration (min) | Common adjuncts |
|---|---|---|---|---|---|
Bupivacaine (Marcaine) | 0.5–0.75 | 0.75–15 | Fast | 60–120 | Epinephrine Fentanyl Meperidine Morphine Sufentanil |
Lidocaine (Xylocaine) | 2–5 | 40–100 | Fast | 45–60 | |
Tetracaine (Pontocaine) | 0.2–0.5 | 5–10 | Fast | 75–150 | |
Ropivacaine (Naropin) | 0.05–1 | 15–22.5 | Fast | 75–150 |
Labor epidural practices and pump settings also differ greatly across individual practices. In the United States, the most commonly used epidural solutions rely upon bupivacaine or ropivacaine as these local anesthetics provide a favorable differential blockade between motor and sensory effects. So-called “low-dose” epidurals for labor include bupivacaine concentrations less than or equal to 0.125 %. These concentrations are well studied for their efficacy and safety, and a lipophilic opiate (e.g., fentanyl, sufentanil) is frequently combined for its dose-sparing effect on the amount of local anesthetic needed. Ropivacaine has a higher minimum local analgesic concentration compared to bupivacaine, with a 0.6 potency ratio in parturients [9].
Side Effects
The sympathetic fibers that innervate the heart and vasculature pass through the thoracic and lumbar regions of the spinal cord. The local anesthetic can block these fibers and cause a sympathectomy leading to hypotension if the block ascends high enough. This may be further complicated by supine aortocaval compression. Untreated or prolonged hypotension can cause uteroplacental hypoperfusion and subsequent fetal distress.
Sympathetic blockade also affects gut motility by allowing the parasympathetics to be unopposed. This causes increases in peristalsis, gut contraction, and sphincter relaxation.
The motor nerve fibers are affected by the local anesthetic concentration and can result in temporary muscular weakness and even paralysis. Efforts to communicate these possible effects to the mother should be made as paralysis can be disconcerting to the uninformed, awake patient. Muscle relaxation may impede the ability to ambulate during labor and to push during vaginal deliveries. Urinary retention is common as patients lose both the micturition reflex and the sensation of bladder fullness. Pregnant patients with neuraxial blocks often receive urinary catheters because of these effects and their inability to easily ambulate to bathroom because of motor blockade. A full bladder may hinder delivery efforts [11].
A thoracic blockade can affect the patient’s perception of breathing and use of accessory muscles. A cervical level may cause diaphragmatic paralysis and respiratory distress.
Around the time of delivery, shivering is common and may be multifactorial but neuraxial techniques seem to potentiate a nonthermoregulatory etiology [12].
Neuraxial local anesthetics lower maternal blood pressure which can cause uterine hypoperfusion. This has potentially deleterious effects on oxygen delivery to the fetus [13]. In addition, there is possible fetal “ion trapping” that could subject the fetus to increased concentrations of local anesthetics. Fetal distress increases this risk as local anesthetics ionize and accumulate in the more acidic fetal circulation [14].
The antepartum patient is more susceptible to intravascular injections of local anesthetics due to venous distension of epidural veins. This increases risk of systemic exposure to local anesthetics which can result in serious cardiac and neurological complications. Cardiac toxicity can induce ventricular arrhythmias and cardiac arrest. Bupivacaine, a commonly used anesthetic for labor analgesia, binds to the heart avidly, raising the risk for cardiotoxicity. Serious neurological consequences include altered mental status, respiratory depression, loss of consciousness, and seizures. Spinal doses are unlikely to cause toxicity. However, there is an associated complication known as transient neurological symptoms that manifests as back, buttock, and lower extremity pain. It is most commonly described after 5 % hyperbaric lidocaine [15].
Summary
Local anesthetics are frequently used for labor and delivery to reduce the patient’s pain and, in higher doses, they can be used for surgical anesthesia.
Opioids
Introduction
Opioids can provide analgesia for labor and delivery by several routes. Anesthesiologists frequently utilize opioids, usually with local anesthetics, in neuraxial techniques. Neuraxial opioids target the nerve roots and dorsal horn. In the usual neuraxial doses, the systemic uptake will not produce sufficient plasma concentrations to provide significant analgesia.
Indications/Clinical Pearls
Neuraxial opioids can improve block density and the duration of postoperative analgesia. The addition causes synergistic analgesia and has a dose-sparing effect on the amount of local anesthetics needed. Parenteral and enteral opioids are frequently offered as an alternative to neuraxial labor analgesia and for postdelivery pain relief.
Parenteral meperidine is commonly used around the world to treat early labor pain. An intramuscular dose (e.g., 100 mg) will provide pain relief for several hours [16].
Nalbuphine is a mixed agonist and partial antagonist of opiate receptors. It offers analgesia in early labor (e.g., 10 mg/70 kg IM, IV, or SC) and relief of opioid-induced pruritus (e.g., 2.5–5 mg IV) [17].
Dosing Options
For neuraxial opioid administration, drugs are chosen based on the pharmacologic properties best suited for their specific role, most notably lipid solubility.
Lipophilic agents will penetrate neuronal membranes and the dural sac quickly. Fentanyl and sufentanil are highly lipophilic with fast onset times (5–10 min) but relatively short durations (2–4 h). They are frequently used when the need for analgesia is immediate and/or brief. As an adjunct to local anesthetics, intrathecal dosing for fentanyl is 10–25 ug [18] and sufentanil is 2.5–7.5 ug [19]. The epidural dose for fentanyl is 50–100 ug and sufentanil 10–20 ug [1].
Conversely, agents like morphine and hydromorphone are less lipid soluble and therefore their onset and duration times are prolonged as they remain in the CSF/epidural space longer. Morphine has an onset time of 30–60 min and has an analgesic effect lasting up to 24 h, making it popular for postoperative pain relief. For this application, the morphine dose for spinals is 0.1–0.2 mg and the dose for epidurals is 3–4 ug [1]. A morphine sulfate extended-release liposome injection is also available and extends the duration of epidural analgesia beyond 24 h [20].
Drug Interactions
Neuraxial opioid doses are unlikely to precipitate adverse drug interactions.
Side Effects
Opioids cause pruritus especially when given neuraxially. Other maternal effects include decreased bowel motility, increased nausea and vomiting, sedation, urinary retention, and respiratory depression [21].
Summary
Opioids have a wide range of uses in obstetrics and play a significant role in neuraxial techniques.
General Anesthetics and the OB Patient
Introduction
In the United States, rates of cesarean delivery are on the rise but few are performed under general anesthesia. Pregnant women may also present for non-obstetric surgeries requiring general anesthesia.
Indications/Clinical Pearls
General anesthesia during pregnancy is typically reserved for patients with contraindications to regional anesthesia, for situations where the benefit of quickly establishing surgical anesthesia outweighs the risks or for surgeries necessitating general anesthesia. Pregnant women have greater associated morbidity, largely related to the increased risk for aspiration and difficult airway. Therefore, the anesthetics should be carefully chosen.
Nitrous oxide has analgesic properties which have been exploited for labor analgesia. In some countries, a 50/50 mixture of oxygen and nitrous oxide is self-administered by laboring women [25].
General anesthesia may be employed in situations where uterine relaxation is desired, such as uterine inversion.
Pregnant patients undergoing cesarean section have a greater risk for intraoperative awareness [26]. Postdelivery treatment with an amnestic agent like a benzodiazepine can help minimize recall until other maintenance anesthetics can be delivered in sufficient amounts.
Dosing Options
For rapid induction of general anesthesia, there are several options including etomidate (0.2–0.3 mg/kg), ketamine (1–2 mg/kg), increasingly popular propofol (2 mg/kg), and now rarely used thiopental (3–4 mg/kg) [1].
Succinylcholine (1–1.5 mg/kg) can quickly provide adequate intubating conditions. Its speed relative to other paralytics makes it an optimal choice for intubation of obstetric patients given risks of aspiration, the challenges of airway management, and the urgency of delivering the fetus under these circumstances [27]. Serum cholinesterase levels decrease during pregnancy; however, obstetric patients do not experience a significant clinical effect on neuromuscular blockade [28].
Inhalational agents are primarily used for maintenance anesthesia. The parturient requires lower alveolar concentrations to achieve surgical anesthesia. Nitrous oxide is often given to minimize the requirements of halogenated inhalational agents such as sevoflurane and desflurane. Consider delivering sevoflurane or desflurane in doses of 0.5 MAC or less (see side effects below) [1].
Side Effects
Induction agents can enter fetal circulation with adverse effects for the neonate. Maternal hypotension after thiopental and propofol can potentially decrease uteroplacental blood flow.
Nitrous oxide has minimal cardiovascular and uterine effects.
Halogenated agents can increase the risk of uteroplacental insufficiency through vasodilatory and cardiac depressive effects. These gases also attenuate uterine tone in a dose-dependent fashion, increasing the concern for uterine atony and hemorrhage. In addition, their small molecular size and lipophilicity allows them to cross the placenta and possibly cause the same depressive and sedative effects on the neonate [1, 29].
Summary
General anesthesia involves the use of induction, paralytic, and inhalational agents and deserves special pharmacologic considerations when employed in the obstetric population.
Aspiration Prevention
The traditional beliefs that pregnancy leads to increased gastric acid production, decreased gastric pH, decreased gastric emptying, and increased gastroesophageal reflex have been challenged and controversial over the years. The belief that rapid sequence intubation (RSI) is necessary in all pregnant patients undergoing general anesthesia after their first trimester of pregnancy has also been challenged. As always, the anesthetic goal with any pregnant woman is to avoid general anesthesia. General anesthesia is inevitable in some instances though, and therefore, precautions should be taken to avoid possible aspiration including proper ASA guidelines for preoperative fasting, RSI, and medications to help decrease gastric acidity and improve gastric motility.
The medications used to achieve the above results are H2 antagonists, non-particulate antacids such as sodium citrate, and metoclopramide. There is no evidence to support the link between these medications used to increase gastric pH and gastric motility and a decreased risk of pulmonary aspiration of gastric secretions [30]. ASA practice guidelines state, “the literature suggests that H2 receptor antagonists are effective in decreasing gastric acidity in obstetric patients and supports the efficacy of metoclopramide in reducing peripartum nausea and vomiting.” They also agree that non-particulate antacid before operative procedures reduces maternal complications. H2 antagonist medications should be given 60–90 min before induction of general anesthesia, as this is the time taken for them to have their maximum effect on the patient. Non-particulate antacids should be taken 20 min prior to procedure. Particulate antacids must be avoided as their aspiration can lead to serious respiratory complications.
Non-opioid Analgesics
Opioid medications used to treat pain are an important tool in the postoperative care of our patients. The multimodal approach to treating pain has been emphasized in the literature for many years. Using non-opioid analgesics such as ketorolac and acetaminophen has been proven to decrease opioid consumption and overall patient satisfaction with regard to pain control.
Acetaminophen is available in intravenous form. Dosing of the medication is 1 g IV for those > 50 kg or 15 mg/kg for those <50 kg. The medication should be dosed every 6 h with a maximum intake of 4 g daily to avoid adverse side effects. It should be avoided in those with severe hepatic impairment. The IV form of the medication helps to avoid first-pass metabolism, which aids in its increased safety profile. The mechanism of acetaminophen is unknown, but it is thought to act by inhibiting synthesis of prostaglandins in the CNS and by blocking pain impulse generation in the periphery. The added benefits of no gastric irritation, platelet inhibition, respiratory depression, and overall decreased opioid intake in individuals make it an ideal drug for the obstetric population [31].
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