The National Institutes of Health State-of-the-Science statement on cesarean delivery on maternal request emphatically concluded that “maternal request for cesarean delivery should not be motivated by unavailability of effective [labor] pain management.” While most hospitals in the United States now offer labor epidural analgesia, this is not the case in many parts of the world, and studies suggest that the introduction of labor epidural analgesia may be an effective approach to decrease the cesarean delivery rate in these settings.

Adequate maternal analgesia and perineal relaxation are also important for instrumental (forceps, vacuum) vaginal delivery. Neuraxial techniques can optimize anesthetic conditions for these obstetric procedures (see Chapter 24 ).

Singleton breech presentation occurs in 3% to 4% of term pregnancies. The Royal College of Obstetricians and Gynaecologists and the American College of Obstetricians and Gynecologists (ACOG) caution against vaginal breech delivery, given poorer neonatal outcomes compared with planned cesarean delivery. ECV is a procedure by which manual external pressure is applied to the maternal abdomen to change the fetal presentation from breech to cephalic. ECV is usually performed between 36 and 39 weeks’ gestation (see Chapter 34 ).

Metaanalyses of available trial data support the finding that neuraxial, intravenous, or inhalation analgesia/anesthesia increases the success rate of attempted ECV. Moreover, these studies show that the use of neuraxial blockade does not appear to compromise maternal and fetal safety, nor increase the risk for placental abruption, fetal bradycardia or death, or cesarean delivery. ACOG supports the use of neuraxial analgesia, in combination with tocolytic therapy, to increase ECV success.

Evidence of intrapartum fetal compromise (nonreassuring fetal status) should prompt the obstetric team (including obstetric, anesthesia, and nursing providers) to attempt intrauterine fetal resuscitation ( Box 26.3 ). These actions include changing maternal position to relieve aortocaval compression, administering vasopressors and intravenous fluid to treat maternal hypotension, discontinuing exogenous oxytocin administration, and, in cases of uterine tachysystole, administration of a tocolytic agent such as terbutaline or nitroglycerin (see Chapter 8 ).

Box 26.3

Obstetric Management of Nonreassuring Fetal Status

• •

  Optimize maternal position:

  • •

    To avoid or relieve aortocaval compression.

  • •

    To relieve umbilical cord compression.

• •

  Administer supplemental oxygen.

• •

  Maintain maternal circulation:

  • •

    Perform rapid intravenous administration of a nondextrose-containing balanced salt solution.

  • •

    Treat hypotension with either ephedrine or phenylephrine.

• •

  Discontinue oxytocin.

• •

  Consider administration of a tocolytic agent for treatment of uterine tachysystole.

All women admitted for labor and delivery are potential candidates for the emergency administration of anesthesia, and an anesthesia provider ideally should evaluate every woman shortly after admission. Optimally, for high-risk patients, preanesthesia consultation should occur in the late second or early third trimester, even if a vaginal delivery is planned. This practice, which can be accomplished remotely via video communication (i.e., “telemedicine”), offers the opportunity to provide patients with information, solicit further consultations, optimize medical conditions, and discuss plans and preparations for the upcoming delivery. Early communication among the members of the multidisciplinary team is encouraged. In some cases, the urgent nature of the situation limits the time for evaluation before induction of anesthesia and commencement of surgery; nonetheless, essential information must be obtained and risks and benefits of alternative anesthetic management decisions should be considered.

A focused preanesthetic history and physical examination includes (1) a review of maternal health and anesthetic history, relevant obstetric history, allergies, and baseline blood pressure and heart rate measurements; and (2) performance of an airway, heart, and lung examination consistent with the American Society of Anesthesiologists (ASA) guidelines.

Peripartum hemorrhage remains a leading cause of maternal mortality worldwide (see Chapters 37 and 39 ). There is little difference in blood loss between an uncomplicated elective cesarean delivery and an uncomplicated planned vaginal birth; however, a cesarean delivery performed during labor or in the setting of abnormal placentation is associated with greater blood loss. Risk factors for peripartum hemorrhage are listed in Box 26.4 .

Box 26.4

Selected Risk Factors for Peripartum Hemorrhage

• •

  Abnormal placentation

• •

  Advanced maternal age

• •

  Anticoagulation

• •

  Bleeding disorder

• •

  Chorioamnionitis

• •

  Fetal demise

• •

  Fetal malpresentation

• •

  General anesthesia

• •

  Increased parity/grand multiparity

• •

  Instrumental vaginal delivery

• •

  Internal trauma (e.g., curettage, internal version)

• •

  Oxytocin augmentation of labor

• •

  Placental abruption

• •

  Precipitous delivery

• •

  Preeclampsia

• •

  Premature rupture of membranes

• •

  Previous uterine surgery (e.g., cesarean delivery, myomectomy)

• •

  Prolonged labor

• •

  Retained placenta

• •

  Tocolytic therapy

• •

  Trauma

• •

  Uterine distention (e.g., macrosomia, multiple gestation, polyhydramnios)

• •

  Uterine leiomyoma

Preparation for obstetric hemorrhage includes: (1) reviewing the patient’s history for anemia or risk factors for hemorrhage; (2) consulting with the obstetric team regarding the presence of risk factors; (3) reviewing reports of ultrasonographic or magnetic resonance imaging (MRI) of placentation; (4) obtaining a blood sample for a type and screen or cross-match; (5) contacting the blood bank to ensure the availability of blood products; (6) obtaining and checking the necessary equipment (blood filters and warmers, infusion pumps and tubing), compatible fluids and medications, and standard clinical laboratory collection tubes; and (7) consulting with a blood bank pathologist, hematologist, and/or interventional radiologist in selected cases ( Box 26.5 ).

Box 26.5

Suggested Resources for Obstetric Anesthesia

LMA , Laryngeal mask airway.Modified from the American Society of Anesthesiologists, Society for Obstetric Anesthesia and Perinatology. Practice guidelines for obstetric anesthesia: an updated report by the American Society of Anesthesiologists Task Force on Obstetric Anesthesia and the Society for Obstetric Anesthesia and Perinatology. Anesthesiology . 2016;124:270–300.

Monitors

• •

  Electrocardiogram

• •

  Noninvasive blood pressure

• •

  Pulse oximetry

• •

  Capnography

• •

  Oxygen and volatile anesthetic analyzers

• •

  Ventilator (with appropriate pressure and disconnection sensors/alarms)

• •

  Peripheral nerve stimulator

For Hemorrhage

• •

  Large-bore intravenous catheters

• •

  Fluid warmer

• •

  Forced-air body warmer

• •

  Availability of blood bank resources

• •

  Equipment for infusing intravenous fluids and blood products rapidly (e.g., hand-squeezed fluid chambers, hand-inflated pressure bags, automatic infusion devices)

• •

  Availability of interventional radiology service

• •

  Cell salvage equipment

For Routine Airway Management

• •

  Laryngoscope and assorted blades

• •

  Videolaryngoscope

• •

  Oral airways of assorted sizes

• •

  Endotracheal tubes of assorted sizes (6.5 and 7.0 mm) with stylets

• •

  Oxygen source

• •

  Suction source with tubing and catheters

• •

  Self-inflating bag and mask for positive-pressure ventilation

• •

  Medications for blood pressure support, hypnosis, and muscle relaxation

For Difficult Airway Management

• •

  Rigid laryngoscope blades of alternative design and size from those routinely used

• •

  Supraglottic airway devices (e.g., laryngeal mask airway)

• •

  Endotracheal tube guides (e.g., semirigid stylets with or without hollow cores for jet ventilation, light wands, and forceps designed to manipulate the distal portion of the endotracheal tube)

• •

  Retrograde intubation equipment

• •

  At least one device suitable for emergency nonsurgical airway ventilation (e.g., hollow jet ventilation stylet with a transtracheal jet ventilator; supraglottic airway device, such as a Combitube [Sheridan Catheter Corporation, Argyle, NY] or intubating LMA [Fastrach LMA, LMA North America, San Diego, CA])

• •

  Fiberoptic intubation equipment

• •

  Equipment suitable for emergency surgical airway access (e.g., cricothyrotomy)

• •

  Topical anesthetics and vasoconstrictors

Currently, there is a lack of consensus as to which patients require a blood type and screen and which patients require a cross-match. The maternal history (previous transfusion, existence of known red blood cell antibodies) and anticipated hemorrhagic complications, as well as local institutional policies, should guide decision-making. In certain high-risk cases (e.g., suspected placenta accreta), blood products (e.g., 2 to 4 units of packed red blood cells) should be physically present near or in the operating room before making the surgical incision, if possible.

Attention should be given to the availability and proper functioning of equipment and monitors for the provision of anesthesia and the management of potential complications (e.g., failed tracheal intubation, cardiopulmonary arrest). Equipment should be checked on a daily basis and serviced at recommended intervals. The equipment and facilities available in the labor and delivery operating room suite should be comparable to those available in the main operating room.

The ASA standards for basic monitoring apply to the provision of anesthesia for all patients. Within obstetrics, basic monitoring consists of maternal pulse oximetry, electrocardiography (ECG), and noninvasive blood pressure monitoring, ^a

as well as fetal heart rate (FHR) monitoring.

ECG abnormalities are often observed in late pregnancy and are believed to be caused by hyperdynamic circulation, circulating catecholamines, and/or altered estrogen and progesterone concentration ratios (see Chapter 2 ). During cesarean delivery with neuraxial anesthesia, ECG changes, including ST segment depression, have been reported at a high frequency (64%), but are almost always associated with normal (nonischemic) echocardiographic wall motion. The administration of droperidol , ondansetron , oxytocin , and carbetocin may be associated with prolongation of the QTc interval, and ST-segment depression. The significance of these ECG findings as an indicator of cardiac pathology remains unclear, because only a small minority of parturients experience myocardial ischemia as measured by elevated serum cardiac troponin levels or echocardiographic wall motion abnormalities. The placement of five ECG leads improves the sensitivity of detecting ischemic events; combining leads II, V ₄ , and V ₅ resulted in a sensitivity of 96% for detecting ST-segment changes in a nonobstetric population. In a prospective study of 254 healthy women undergoing cesarean delivery with spinal anesthesia, Shen et al. determined the incidence of first- and second-degree atrioventricular block (3.5% for each), severe bradycardia defined as a heart rate < 50 beats/min (6.7%), and multiple premature ventricular contractions (1.2%). The investigators speculated that a relative increase in parasympathetic activity occurred as a result of spinal blockade of cardiac sympathetic activity. Most of the dysrhythmias were transient and resolved spontaneously.

Processed electroencephalogram monitors used to indicate the depth of anesthesia have received only limited evaluation in women undergoing cesarean delivery. Whether routine use of these monitors can reduce the incidence of intraoperative awareness during general anesthesia for cesarean delivery is unclear (see discussion below).

An indwelling urinary catheter is used in almost all women undergoing cesarean delivery. A urinary catheter helps avoid overdistention of the bladder during and after surgery. In cases associated with hypovolemia and/or oliguria, or anticipated significant blood loss, a collection system that allows precise measurement of urine volume is helpful.

The FHR is often assessed by a qualified individual before and after administration of anesthesia. However, data are insufficient to determine the value of FHR monitoring before elective cesarean delivery in patients without risk factors. Our practice is to monitor FHR until the abdominal skin preparation for cesarean delivery has begun.

In some cases of emergency cesarean delivery, a previously placed fetal scalp (or buttock) ECG electrode can be used to monitor the FHR before, during, and after the initiation of anesthesia. Typically, the fetal scalp electrode is removed when the surgical drapes are applied to the abdomen, but in some cases the scalp electrode may be left in place until just before delivery, when the circulating nurse reaches under the drapes to disconnect the electrode. Continuous FHR monitoring is useful in this setting for at least three reasons. First, the FHR abnormality often resolves; in some cases the obstetric provider may then elect to forgo the performance of a cesarean delivery, and in other cases continuous FHR monitoring may facilitate the administration of neuraxial anesthesia (e.g., extension of epidural anesthesia or administration of spinal anesthesia) for cesarean delivery. Second, continuous FHR monitoring may guide management in cases of failed tracheal intubation; if there is no evidence of fetal compromise, both the anesthesia provider and the obstetric provider may have greater confidence to awaken the patient and proceed with an alternative anesthetic technique, or alternatively, if there is evidence of ongoing fetal compromise, the anesthesia provider may decide to provide general anesthesia for cesarean delivery with a facemask or supraglottic airway (see Chapter 29 ). Third, intraoperative FHR monitoring allows the obstetric provider to modify the surgical technique according to the urgency of delivery.

Invasive monitoring (e.g., an intraarterial catheter), noninvasive cardiac output monitoring, or echocardiography may be indicated for individual patients at high risk for cardiopulmonary compromise.

Labor and delivery units may be adjacent to or remote from the main operating rooms. In some facilities, the unit is located on a separate floor but shares a common operating room facility (used for other surgical procedures), whereas in others it is a geographically separate, self-contained unit with its own operating room facilities. Regardless of location, the equipment, facilities, and support personnel available in the labor and delivery operating room should be comparable to those available in the main operating room. In addition, personnel and equipment should be available to care for obstetric patients recovering from major neuraxial or general anesthesia.

Resources for the conduct and support of neuraxial anesthesia and general anesthesia should include those necessary for the basic delivery of anesthesia and airway management as well as those required to manage complications (e.g., failed tracheal intubation). The immediate availability of these resources is particularly important, given the frequency and urgency of anesthesia care. Consideration should be given to having some of the equipment and supplies immediately available in one location or in a cart (e.g., difficult airway cart, massive hemorrhage cart, malignant hyperthermia box) specifically located on the labor and delivery unit. Equipment and supplies should be checked on a frequent and regular basis. Securing special-situation equipment and supplies in a cart with a single-use breakthrough tie helps ensure that the cart is kept in a fully stocked state.

The patient should be asked about oral intake, although insufficient evidence exists regarding the relationship between recent ingestion and subsequent aspiration pneumonitis (see Chapter 28 ). Gastric emptying of clear liquids during pregnancy occurs relatively quickly; the residual content of the stomach (as measured by ultrasonographic assessment of the cross-sectional area of the gastric antrum 60 minutes after the ingestion of 300 mL of water) does not appear to be different from baseline fasting levels in either lean or obese nonlaboring pregnant women. Wong et al., using serial gastric ultrasonographic examinations and acetaminophen (paracetamol) absorption, reported that gastric emptying half-time was shorter after ingestion of 300 mL of water (24 [SD 6] minutes) compared with 50 mL of water (33 [8] minutes) in healthy, nonlaboring, nonobese pregnant women. Bouvet et al. reported that the gastric emptying fraction at 90 minutes after a light meal was lower in laboring women receiving epidural analgesia compared with nonpregnant and nonlaboring pregnant women; furthermore, the gastric emptying fraction was lower in laboring women not receiving epidural analgesia compared with laboring women receiving epidural analgesia.

The healthy patient undergoing elective cesarean delivery may drink modest amounts of clear liquids up to 2 hours before induction of anesthesia. Examples of clear liquids are water, fruit juice without pulp, carbonated beverages, clear tea, black coffee, and sport drinks. The volume of liquid ingested is less important than the absence of particulate matter. Patients with additional risk factors for aspiration (e.g., morbid obesity, diabetes, difficult airway) or laboring patients at increased risk for cesarean delivery (e.g., nonreassuring FHR pattern) may have further restrictions of oral intake, determined on a case-by-case basis.

Ingestion of solid foods should be avoided in laboring patients and patients undergoing elective surgery (e.g., scheduled cesarean delivery or postpartum tubal sterilization). A fasting period for solids of 6 to 8 hours, depending on the fat content of the food, has been recommended.

A reduction in gastric content acidity and volume is believed to decrease the risk for damage to the respiratory epithelium should aspiration occur. Oral administration of a nonparticulate antacid (e.g., 0.3 M sodium citrate , pH 8.4) causes the mean gastric pH to increase to greater than 6 for 1 hour; it does not affect gastric volume. Histamine-2 (H ₂ )-receptor antagonists (e.g., ranitidine, famotidine ), proton pump inhibitors (e.g., omeprazole ), and metoclopramide reduce gastric acid secretion and volume but require at least 30 to 40 minutes to exert their effects. A systematic review of interventions used to reduce the risk for aspiration pneumonitis in women undergoing cesarean delivery found that there were significant reductions in the risk for gastric pH < 2.5 with antacids (relative risk [RR], 0.17; 95% CI, 0.09 to 0.32), H ₂ -receptor antagonists (RR, 0.09; 95% CI, 0.05 to 0.18), and proton-pump inhibitors (RR, 0.26; 95% CI, 0.14 to 0.46), compared with no treatment or placebo. The combined use of an antacid and an H ₂ -receptor antagonist was found to be more effective in reducing gastric acidity than administration of placebo or an antacid alone. However, in a randomized evaluation, sodium citrate was associated with a higher incidence and severity of nausea than an H ₂ -receptor antagonist (famotidine), suggesting that a H ₂ -receptor antagonist may be the preferred agent in selected patients. Metoclopramide is a promotility agent that hastens gastric emptying, increases lower esophageal sphincter tone, and decreases nausea and vomiting. Before surgical procedures, the timely administration of a nonparticulate antacid, an H ₂ -receptor antagonist, and metoclopramide should be considered, especially for nonelective procedures.

Prophylactic antibiotic administration results in a 60% decrease in the incidence of endometritis, a 25% to 65% decrease in the incidence of wound infection, and fewer episodes of fever and urinary tract infections for both elective (nonlaboring) and nonelective (laboring) cesarean deliveries. The ACOG has recommended the prophylactic administration of a narrow-spectrum antibiotic, such as a first-generation cephalosporin, within 1 hour of the start of cesarean delivery.

Antibiotics with efficacy against gram-positive, gram-negative, and some anaerobic bacteria are commonly used for prophylaxis for cesarean delivery. Appropriate antibiotics include IV ampicillin 2 g, cefazolin 2 g, or ceftriaxone 1 g. Appropriate antibiotic coverage should last for 3 to 4 hours; therefore, ampicillin may be less appropriate owing to a shorter half-life than the cephalosporins. In parturients with a significant allergy to beta-lactam antibiotics (e.g., history of anaphylaxis, angioedema, respiratory distress, or urticaria), intravenous clindamycin with gentamicin is a reasonable alternative.

Higher doses of antibiotics may be considered in women with a body mass index (BMI) > 30 kg/m ² or an absolute weight > 120 kg because of a greater volume of distribution. After administration of cephazolin 2 g, Pevzner et al. observed that the minimum inhibitory tissue concentration for gram-negative rods was not achieved at the time of skin incision or closure in 20% of obese women and 33% of morbidly obese women.

A randomized controlled trial addressed whether surgical site infection prophylaxis should be broadened to cover species commonly associated with postcesarean infection (e.g., ureaplasma). Women undergoing cesarean delivery after labor or rupture of membranes were randomized to receive standard antibiotics with or without the addition of azithromycin (500 mg). Although the addition of azithromycin decreased the rate of the composite infection endpoint by half (6.1% versus 12.0%), almost three-fourths of the trial participants were obese, raising concern that the standard antibiotics may have been underdosed. The 2018 ACOG guidelines suggest that prophylactic azithromycin administration may be considered for nonelective cesarean delivery.

In the past, prophylactic antibiotics were typically administered after umbilical cord clamping because of concern that fetal antibiotic exposure might mask a nascent infection and/or increase the likelihood of a neonatal sepsis evaluation. However, a metaanalysis demonstrated that preincision antibiotic prophylaxis reduces the incidence of postcesarean endometritis and total maternal infectious morbidity, without evidence of adverse neonatal effects. Thus, current guidelines recommend administration of prophylactic antibiotics, including azithromycin (when indicated), within 60 minutes before the start of the cesarean delivery.

In the early 19th century, Ignác Semmelweis observed that puerperal fever, known as “childbed fever,” was most likely transmitted when the first stage of labor was prolonged and multiple individuals performed vaginal examinations with contaminated hands. Since that time, the practice of hand hygiene has caused a significant reduction in maternal and neonatal infectious morbidity.

The immunologic changes of pregnancy may impair clearance of infections. Epidural abscess and meningitis have been reported as complications of neuraxial procedures in obstetric patients (see Chapter 31 ). As a consequence, obstetric anesthesia providers should always give careful attention to aseptic technique, especially during the performance of a neuraxial procedure. Proper sterile technique for neuraxial procedures includes wearing a facemask, performing hand hygiene, and donning sterile gloves (see Chapter 12 ). Although wearing sterile gowns is common in many countries, there is little available evidence addressing this practice and wearing gowns is controversial and less common in the United States. Attention should also be given to the careful preparation of anesthetic drugs during administration of either general or neuraxial anesthesia. An increasing number of institutions are using premixed solutions of local anesthetic and opioid (prepared under aseptic conditions in a hospital or compounding pharmacy) to limit breaches in aseptic technique during the administration of neuraxial anesthesia.

The establishment of functional intravenous access is of critical importance to the successful outcome of many clinical situations in obstetric anesthesia practice. According to the Hagen-Poiseuille equation, laminar flow of fluid through a cylindrical tube is directly proportional to the pressure gradient of the fluid and the fourth power of the tube’s radius, and inversely proportional to the viscosity of the fluid and the tube’s length. Extrapolation to intravenous catheters indicates that the size of the catheter, more than the size of the vein, dictates the flow rate; the use of a short, large-diameter catheter (e.g., 18-, 16-, or 14-gauge) is associated with the best flow.

In general, a smaller but functional catheter is likely to be more effective than a larger catheter that is unreliable or requires frequent manipulation. In an emergency situation, if only a 20- or 22-gauge intravenous catheter is present, high flow rates for volume resuscitation can be achieved (without evidence of greater red blood cell destruction) by application of a pressure bag and diluting red blood cells with normal saline. Devices are available to change a small-gauge intravenous catheter to a large-gauge intravenous catheter using a Seldinger technique. In situations when large blood loss is anticipated, or administration of multiple blood products is required, the anesthesia provider may choose to insert a central venous catheter.

Although the administration of intravenous fluids may decrease the incidence of neuraxial anesthesia-associated hypotension, initiation of anesthesia should not be delayed to administer a fixed volume of fluid, particularly in the case of an emergency cesarean delivery, in which the life and health of the mother and the infant are best preserved with timely delivery. The type of fluid (crystalloid, colloid) and the volume, rate, and timing of administration are relevant factors in the prevention and treatment of hypotension. In most situations, a balanced salt solution such as lactated Ringer’s solution is acceptable. Blood products are most often administered with normal saline. Crystalloid or colloid solutions that contain calcium or glucose should not be administered with blood products, owing to the risks for clotting (caused by reversal of the citrate anticoagulant) and clumping of red blood cells, respectively.

Traditionally, approximately 1 L of crystalloid solution has been administered intravenously before induction of neuraxial anesthesia (as “preload” or “prehydration”) to prevent or reduce the incidence and severity of hypotension. However, preload, even with large volumes (30 mL/kg), is minimally effective in preventing neuraxial anesthesia-induced hypotension. Although an initial study found that administering crystalloid solution at the time of the intrathecal injection (“coload” or “cohydration”) was more efficacious than preload in preventing hypotension, later studies did not support this finding, likely because the infusion rate was too slow. Colloid preload or coload is more effective than crystalloid for preventing hypotension. Colloid coload is equally efficacious as preload. In healthy patients, we rapidly administer approximately 1 L of crystalloid starting at the time of initiation of neuraxial anesthesia. For patients at high risk for hypotension or its consequences, colloid preload or coload may be considered. Regardless of fluid administration, hypotension is best prevented and treated using vasopressors (see discussion below).

The administration of benzodiazepines, even low doses (e.g., midazolam 0.02 mg/kg), may result in amnesia ; therefore, benzodiazepines are typically avoided during awake cesarean delivery. However, on occasion, particularly in women with severe anxiety or undergoing an emergency cesarean delivery, the use of low doses of intravenous midazolam or an opioid may facilitate performance of a neuraxial technique, awake tracheal intubation, or the induction of general anesthesia. Anxiolytics may also assist in mitigating the feelings of distress during the birthing experience, which may lessen the risk for developing posttraumatic stress disorder. The use of low doses of sedative or anxiolytic agents has minimal to no neonatal effects. In a trial of healthy women randomized to receive intravenous midazolam (0.02 mg/kg) and fentanyl (1 µg/kg ^b

) or saline before administration of spinal anesthesia for cesarean delivery, no differences in neonatal Apgar scores, neurobehavioral scores, or oxygen saturation were observed between the two treatment groups.

After 20 weeks’ gestation, most practitioners position patients with left uterine displacement to minimize aortocaval compression. The supine hypotension syndrome , which is caused by compression of the inferior vena cava and the aorta by the gravid uterus, can manifest as pallor, tachycardia, sweating, nausea, hypotension, and dizziness. Uteroplacental blood flow is compromised by decreased venous return and cardiac output, increased uterine venous pressure, and compression of the aorta or common iliac arteries.

The full lateral position minimizes aortocaval compression but does not allow performance of cesarean delivery. Fifteen degrees of left lateral tilt (left uterine displacement) has been proposed to significantly reduce the adverse hemodynamic consequences of the supine position, although both the aorta and inferior vena cava may remain partially compressed. However, most anesthesia providers overestimate the degree of lateral tilt applied. These elements may explain the results of a 2013 systematic review that concluded that left compared with right lateral tilt was associated with some maternal and fetal benefit, but outcomes were not dramatically different among different positions. Overall, data were insufficient to prove or disprove the benefits of tilting or flexing the operating room table or using wedges or mechanical displacers during positioning for cesarean delivery.

Whether left uterine displacement is necessary in the context of patients receiving a coload of fluid and a prophylactic phenylephrine infusion at the time of induction of spinal anesthesia has been questioned. In healthy, term women undergoing elective cesarean delivery, there was no difference in neonatal acid-base status in women randomized to the supine position versus left uterine displacement, despite mean maternal cardiac output being lower in the supine group. The trial excluded women at increased risk for aortocaval compression (e.g., polyhydramnios, multiple gestation, obesity) or women with impaired placental perfusion (e.g., fetal growth restriction, preeclampsia). Given these limitations, and the apparent absence of adverse maternal or fetal effects with lateral uterine displacement, the routine use of this technique should not be abandoned. Anesthesia providers should recognize that (1) susceptibility to aortocaval compression varies among individuals ; (2) visual estimates of lateral tilt may be in error ; and (3) in symptomatic women, increasing the extent of left uterine displacement may be beneficial. Lateral tilt should be used in all women in mid- to late pregnancy after the administration of neuraxial or general anesthesia, with greater tilt used when feasible if aortocaval compression is suspected as the cause for maternal or fetal compromise.

The use of a slight (10 degrees) head-up position may help reduce the incidence of hypotension after initiation of hyperbaric spinal anesthesia. A 30-degree head-up position significantly increases functional residual capacity compared with the supine position in term parturients, although this effect diminishes with increasing BMI. In morbidly obese patients receiving general anesthesia, a 25-degree head-up position may be particularly useful to improve denitrogenation and glottic view during direct laryngoscopy ; this position can be accomplished with blankets or commercially available devices (see Chapters 29 and 48 ). If blankets are used to create the ramp position, they should be stacked rather than interlaced, to allow for rapid removal and readjustment of the head and neck position, if necessary. The ideal position aligns the external auditory meatus and the sternal notch in a horizontal plane; this position (1) aligns the oral, pharyngeal, and tracheal axes (“sniffing position”) and (2) facilitates insertion of the laryngoscope blade.

Theoretically, the Trendelenburg (head-down) position may augment venous return and increase cardiac output. The value of this approach in preventing hypotension during neuraxial anesthesia has been questioned. After the initiation of hyperbaric spinal anesthesia, the Trendelenburg position was reported to result in more cephalad spread of anesthesia in one study but not in others. However, this position had no effect on the incidence of hypotension after the administration of hyperbaric spinal anesthesia.

The optimal patient position for initiation of neuraxial anesthesia may depend on clinical circumstances and the preferences and skills of the anesthesia provider (see Chapter 12 ). Whether the use of the lateral or the sitting position is best for routine initiation of neuraxial anesthesia is controversial. Advocates of the lateral position cite reduced vagal reflexes, which can result in dizziness, diaphoresis, pallor, bradycardia, and hypotension, and improved uteroplacental blood flow, compared with the sitting position. The lateral position may also be associated with a small increase in maternal cardiac index, stroke volume index, heart rate, and systolic blood pressure compared with the sitting or supine positions. Further, in a randomized controlled trial, the severity and duration of hypotension were greater in women randomly assigned to receive CSE anesthesia (hyperbaric spinal bupivacaine with fentanyl) in the sitting position than the lateral position, despite no differences in the level of sensory blockade.

Some parturients find the lateral position more comfortable during administration of neuraxial anesthesia, whereas others find the sitting position more comfortable. Moreover, because uterine compression of the vena cava diverts blood into the epidural venous plexus, the use of the lateral position can reduce hydrostatic pressure and engorgement of the epidural venous plexus. Studies suggest that epidural catheter placement in the lateral recumbent head-down position results in lower risk for lumbar epidural venous plexus cannulation than the sitting or the lateral recumbent horizontal position in both obese and nonobese parturients.

MRI and computed tomography studies have shown that the cross-sectional area and the anteroposterior diameter of the dural sac at the level of the L3 to L4, L4 to L5, and L5 to S1 interspaces are significantly influenced by posture. Lumbar cerebrospinal fluid (CSF) pressure is lower and the dural sac cross-sectional area smaller in the recumbent compared with the upright position. Theoretically, the lateral position may be of value during advancement of an epidural needle because it minimizes the prominence of the dural sac. By contrast, a bulging dural sac might be preferable during administration of spinal, dural puncture epidural (DPE), or CSE anesthesia. Bulging of the lumbar dural sac—particularly in the sitting position—may decrease the force required to create a dural puncture with a Tuohy epidural needle, but this possibility is unproven.

The sitting position also has some advantages, including easier landmark recognition in obese parturients and ease of positioning patients in a symmetrical position (the spine is often rotated in the lateral position because the bottom shoulder is fixed). Given that there is no evidence that one position is universally better than the other, patient position for initiating neuraxial anesthesia is largely a matter of practitioner preference. However, anesthesia providers should be facile with the placement of needles for neuraxial techniques in both the sitting and lateral positions because the sitting position should not be used in some situations (e.g., umbilical cord prolapse, footling breech presentation).

The routine administration of supplemental oxygen during elective cesarean delivery with neuraxial anesthesia is controversial. It became a common practice following the 1971 report by Fox and Houle that demonstrated improved oxygenation, better umbilical cord blood acid-base measurements, and less time to sustained respiration in the neonate when mothers undergoing cesarean delivery with neuraxial anesthesia breathed 100% oxygen instead of air for at least 10 minutes. However, this practice has not been supported by subsequent work. A 2021 metaanalysis of randomized trials performed in low-risk women undergoing elective cesarean delivery with singleton, nonanomalous pregnancies, found that the administration of supplemental oxygen compared with room air was associated with higher umbilical arterial (UA) Pa o ₂ , and no significant differences in UA base excess, UA pH < 7.2, Apgar scores, or neonatal intensive care unit (ICU) admissions.

The use of a fractional inspired concentration of oxygen (F io ₂ ) of 0.35 to 0.4, which cannot be obtained by using a nasal cannula or a simple face mask with a flow rate < 6 L/min, does not improve fetal oxygenation during labor or elective cesarean delivery. Although respiratory function can deteriorate in parturients receiving neuraxial anesthesia, maternal or fetal hypoxemia does not normally occur when parturients breathe room air. An F io ₂ of 0.6 in nonlaboring women undergoing elective cesarean delivery with spinal anesthesia was shown to increase umbilical venous (UV) oxygen content by only 12%; an increase in oxygen content was not observed when the uterine incision-to-delivery (U-D) interval exceeded 180 seconds.

Supplemental oxygen may have detrimental effects. High levels of maternal F io ₂ are necessary for significant maternal-fetal oxygen transfer, but also result in the formation of reactive oxygen species and subsequent peroxidation of lipids, alteration of cellular enzymatic functions, and destruction of genetic material. Known to extend ischemia-reperfusion injury, deplete antioxidants, and suppress immune function, free radicals have also been implicated in the pathogenesis of disorders related to prematurity, including neonatal retinopathy, bronchopulmonary dysplasia, necrotizing enterocolitis, and intraventricular hemorrhage.

Nonetheless, the emergency cesarean delivery of the compromised fetus should include maternal oxygen administration of high F io ₂ , particularly in the setting of uterine contractions, which can exacerbate fetal compromise; in these situations, supplemental oxygen may reduce the severity of fetal hypoxia with limited oxygen free-radical effects. Term (but not preterm) fetuses may be able to withstand the adverse effects of these reactive oxygen species through a compensatory increase in antioxidants during labor. Antioxidants, the defense against reactive oxygen species, consist of enzymatic inactivators (superoxide dismutase, catalase, peroxidase) and scavengers (ascorbate, glutathione, transferrin, lactoferrin, ceruloplasmin). The activity of these compensatory mechanisms and their relationship to gestational age and labor suggest that the highest risk for ischemia-reperfusion injury occurs in preterm fetuses before the onset of labor.

The use of high F io ₂ (>0.6) improves oxygen transfer to hypoxic fetuses for a limited period (approximately 10 minutes); beyond this time, continued hyperoxia, especially in the setting of restored perfusion, increases reactive oxygen species, placental vasoconstriction, and fetal acidosis. A lower F io ₂ may be of benefit in some situations. Of interest, when asphyxiated infants are immediately resuscitated at birth with air instead of 100% oxygen, better short-term outcomes have been observed ; this finding may be a result of the shift in the balance between beneficial oxygenation and detrimental free radicals.

All women who are at risk for requiring general anesthesia for emergency cesarean delivery should receive an F io ₂ of 1.0 after transfer to the operating table to simultaneously promote maternal oxygenation and denitrogenation; denitrogenation significantly reduces the risk for maternal hypoxemia during apnea before tracheal intubation.

Although the value of supplemental oxygen use during elective cesarean delivery with neuraxial anesthesia of a noncompromised fetus is questionable, some obstetric anesthesia providers place nasal cannulae or a mask to monitor ventilation using expired carbon dioxide analysis.

Overall, neuraxial (epidural, spinal, CSE) techniques are the preferred method for providing anesthesia for cesarean delivery; specific benefits and risks of each technique dictate the eventual choice. In contemporary practice, neuraxial anesthesia is administered to some patients who would have received general anesthesia in the past. Umbilical cord prolapse, placenta previa, and preeclampsia with severe features are no longer considered absolute indications for general anesthesia. For example, in some cases, a prolapsed umbilical cord can be decompressed, and if fetal status is reassuring, a neuraxial technique can be used. In an analysis of obstetric anesthesia trends in the United States between 1981 and 2012, a progressive increase was noted in the use of neuraxial anesthesia, especially spinal anesthesia, for both elective and emergency cesarean deliveries. Neuraxial anesthesia is now used for more than 95% of elective cesarean deliveries and 80% of emergency cesarean deliveries in the United States, with progress in a similar direction among high- and low-resource countries.

The greater use of neuraxial anesthesia for cesarean delivery has been attributed to several factors, including (1) the growing use of epidural techniques for labor analgesia, (2) an awareness of the possibility that an in situ epidural catheter may decrease the necessity for general anesthesia in an urgent situation, (3) improvement in the quality of neuraxial anesthesia with the addition of an opioid to the local anesthetic, (4) appreciation of the risks of airway complications during general anesthesia in parturients, (5) the desire for limited neonatal drug transfer, and (6) the ability of the mother to remain awake to experience childbirth and to have a support person present in the operating room. Spinal anesthesia is considered an appropriate technique even in the most urgent settings; in a tertiary care institution with an average of 9500 cesarean deliveries annually, neuraxial anesthesia was used in more than 99% of cesarean deliveries over a 6-year period. In the setting of a category 1 (immediate threat to life of woman or fetus) cesarean delivery, Kinsella et al. described a “rapid-sequence spinal” technique, by which skin preparation, spinal drug combinations, and the spinal technique were simplified; the median time from positioning until satisfactory neuroblockade was 8 minutes (interquartile range [IQR], 7 to 8 minutes; range, 6 to 8 minutes).

Maternal mortality following general anesthesia has been a primary motivator for the transition toward greater use of neuraxial anesthesia for cesarean delivery. Hawkins et al. compared the anesthesia-related maternal mortality rate from 1979 to 1984 with that for the period from 1985 to 1990 in the United States. The estimated case-fatality risk ratio for general versus neuraxial anesthesia was as high as 16.7 in the years 1985 to 1990. However, a subsequent analysis by the same group found a nonsignificant risk ratio of 1.7 in the years 1991 to 2002. Possible explanations for this change include better anesthetic monitoring, published standards for anesthetic care, and technological advances in the devices available for airway management and their widespread dissemination (e.g., supraglottic airways, fiberoptic bronchoscopes). It is possible that the relative risk associated with general anesthesia may be overstated because general anesthesia is mainly used when medical reasons or time constraints preclude the use of neuraxial anesthesia.

The type of maternal morbidity differs between neuraxial anesthetic techniques and general anesthesia. A systematic review of randomized and quasirandomized controlled trials comparing major maternal and neonatal outcomes with the use of neuraxial anesthesia and general anesthesia for cesarean delivery found less maternal blood loss and shivering but more nausea in the neuraxial anesthesia group. The intraoperative “perception” of pain was greater in the neuraxial group, but the time elapsed before the first postoperative request for analgesia was longer. Prospective audits of postcesarean delivery outcomes have indicated that in the first postoperative week, patients who received neuraxial anesthesia had less pain, gastrointestinal stasis, coughing, fever, and depression and were able to breastfeed and ambulate more quickly than patients who received general anesthesia.

Neonatal outcomes associated with maternal anesthetic selection require further study. Apgar and neonatal neurobehavioral scores are relatively insensitive measures of neonatal well-being, and umbilical cord blood gas and pH measurements may reflect the reason for the cesarean delivery rather than differences related to the anesthetic technique. In a metaanalysis, lower umbilical cord blood pH measurements were associated with spinal, but not epidural, anesthesia compared with general anesthesia. However, the study included both randomized and nonrandomized trials and both elective and nonelective procedures, and most trials were conducted in an era when ephedrine was used to support maternal blood pressure (see discussion below). In a systematic review of randomized trials in which the indication for cesarean delivery was not urgent, no differences in umbilical cord arterial blood pH measurements were found among general and neuraxial anesthetic techniques ; similar findings were observed when the anesthesia induction-to-delivery interval was prolonged, such as in more complex obstetric surgeries (e.g., placenta accreta spectrum, higher-order cesarean deliveries, and morbid obesity).

Table 26.4 outlines the relative advantages and disadvantages of the various neuraxial anesthetic techniques for cesarean delivery. With all neuraxial techniques, an adequate sensory level of anesthesia is necessary to minimize maternal pain and avoid the urgent need for administration of general anesthesia. Because motor nerve fibers are typically larger and more difficult to block, the complete absence of hip flexion and ankle dorsiflexion most likely indicates that a functional sensory and sympathetic block is also present in a similar (primarily lumbosacral) distribution. However, because afferent nerves innervating abdominal and pelvic organs accompany sympathetic fibers that ascend and descend in the sympathetic trunk (T5 to L1), a sensory block that extends rostrally from the sacral dermatomes to T4 should be the goal for cesarean delivery anesthesia.

The manner in which the level of sensory blockade is assessed has implications for the success of a neuraxial technique. The different methods of assessing the extent of sensory blockade (i.e., sensation to light touch, pinprick, cold) may indicate levels of blockade that differ by several spinal segments. A prospective study of 102 women undergoing cesarean delivery with spinal anesthesia indicated that although sensory blockade to light touch differed from sensory blockade to pinprick or cold sensation by 0 to 11 spinal segments, no constant relationship among these levels could be determined. The investigators concluded that a T6 blockade to touch would likely provide a pain-free cesarean delivery for most women.

Sensory examination should move caudad to cephalad in the midaxillary line on the lower extremities but can be performed in the midclavicular line on the torso. The time at which an adequate block is achieved, as well as the cephalad level of the block and the presence of surgical anesthesia of the lower abdomen, should be documented on the anesthetic record.

Because the undersurface of the diaphragm (C3 to C5) and the vagus nerve may be stimulated by surgical manipulation during cesarean delivery, maternal discomfort (including shoulder pain) and other symptoms (e.g., nausea and vomiting) may occur despite a T4 level of blockade. Neuraxial or systemic opioids help prevent or alleviate these symptoms (see discussion below).

Spinal anesthesia is a simple and reliable technique that allows visual confirmation of correct needle placement (by visualization of CSF) and is technically easier to perform than epidural anesthesia. Spinal anesthesia provides rapid onset of dense neuroblockade that is typically more profound than that provided with epidural anesthesia, resulting in a reduced need for supplemental intravenous analgesics or conversion to general anesthesia. Only a small amount of local anesthetic is needed to establish functional spinal blockade; therefore, spinal anesthesia is associated with negligible maternal risk for local anesthetic systemic toxicity (LAST) and with minimal drug transfer to the fetus. Given these advantages, spinal anesthesia is the most commonly used anesthetic technique for cesarean delivery in the developed world. Spinal anesthesia is also associated with predictable and relatively prompt recovery that enables patients to quickly transition through the postanesthesia care unit (PACU); in some settings, such a recovery may result in a cost savings to the institution.

Spinal anesthesia is usually administered as a single-injection procedure (“single-shot” technique) through a noncutting, pencil-point needle that is 25-gauge or smaller. A number of different needle designs are available (see Chapter 12 ); the size and design of the needle tip affect the incidence and severity of postdural puncture headache (see Chapter 30 ).

The spinal technique should be performed at the L3 to L4 interspace or below (see Chapter 12 ). This space is used to avoid the potential for spinal cord trauma; although the spinal cord ends at L1 in most adults, it extends to the L2 to L3 interspace in a small minority (see Chapter 31 ). Additionally, anesthesia providers often misidentify the location of the needle insertion site on the spinal column, and the needle is frequently introduced at a higher level than intended.

On occasion, a continuous spinal anesthetic technique is used, particularly in the setting of an unintentional dural puncture with an epidural needle followed by the intentional threading of the epidural catheter into the intrathecal space. Planned continuous spinal anesthesia may be desirable in certain settings, when the reliability of a spinal technique and the ability to precisely titrate the initiation and duration of anesthesia are strongly desired (e.g., a morbidly obese patient with a difficult airway). Continuous spinal anesthesia may be administered through purpose-intended spinal catheters or using equipment designed for epidural anesthesia (see Chapter 12 ).

Local Anesthetic Agents

The choice of local anesthetic agent (and adjuvants) used to provide spinal anesthesia depends on the expected duration of the surgery, the postoperative analgesia plan, the preferences of the anesthesia provider, and availability. For cesarean delivery, the local anesthetic agent of choice is typically bupivacaine ( Table 26.5 ). In the United States, spinal bupivacaine is formulated as a 0.75% solution in dextrose 8.25%; in other countries, use of a 0.5% concentration is common.

Table 26.5

Drugs Used for Spinal Anesthesia for Cesarean Delivery

Drug	Dose Range	Duration (min) a
Local Anesthetic Agents
Lidocaine	60–80 mg	45–75
Bupivacaine	7.5–15 mg	60–120
Levobupivacaine	7.5–15 mg	60–120
Ropivacaine	15–25 mg	60–120
Opioids
Fentanyl	10–25 µg	180–240
Sufentanil	2.5–5 µg	180–240
Morphine	100–200 µg (0.1–0.2 mg)	720–1440
Hydromorphone	60–75 µg (0.060–0.075 mg)	720–875
Meperidine b	60–70 mg	60
Adjuvant Drugs
Epinephrine c	100–200 µg (0.1–0.2 mg)

The dose of intrathecal bupivacaine that has been successfully used for cesarean delivery ranges from 4.5 to 15 mg. In general, pregnant patients require smaller doses of spinal local anesthetic than nonpregnant patients. Reasons include (1) a smaller CSF volume in pregnancy, (2) cephalad movement of hyperbaric local anesthetic in the supine pregnant patient, and (3) greater sensitivity of nerve fibers to the local anesthetic during pregnancy. Overall, the mass of local anesthetic, rather than the concentration or volume, is thought to be the most important factor influencing the spread of the resulting blockade ; however, the specific influence of the dose/concentration and baricity on the efficacy of the block is controversial. The required dose may be influenced by other factors, such as coadministration of neuraxial opioids and surgical technique (e.g., exteriorization of the uterus during closure of the uterus is more stimulating than closure in situ ).

A dose-finding study in 48 women undergoing cesarean delivery demonstrated that the ED ₅₀ and ED ₉₅ values (effective dose in 50% and 95% of patients, respectively) for plain bupivacaine with fentanyl 10 µg and morphine 0.2 mg were 7.25 and 13 mg, respectively. However, other studies have shown that lower doses of hyperbaric or plain bupivacaine can be used successfully, particularly when coadministered with an opioid (e.g., 9 mg with fentanyl 20 µg, and 6.6 mg with sufentanil 3.3 µg ). Use of lower doses of local anesthetic has been shown to decrease the incidence of hypotension and nausea. Whether hyperbaric or plain bupivacaine provides better anesthesia remains unclear. Finally, in a comparison of plain bupivacaine 4.5 mg with hyperbaric bupivacaine 12 mg (both with fentanyl 50 µg and morphine 0.2 mg), similar cephalad sensory levels (C8), incidence of hypotension (approximately 75%), side effects, and patient satisfaction scores were found with the two approaches. Five of 27 (19%) patients in the bupivacaine 4.5-mg group and 1 of 25 (4%) patients in the bupivacaine 12-mg group required supplemental analgesia; no conversion to general anesthesia occurred. Altogether, while these data indicate that lower anesthetic doses can be used, whether they should be used is controversial. The anesthesia provider should consider whether adjuvant drugs will be used and whether the risks of giving supplemental analgesia or conversion to general anesthesia that are associated with low doses of bupivacaine outweigh the potential benefits (i.e., less hypotension, faster recovery). However, using lower doses of bupivacaine facilitated by higher doses of opioids is generally not an advisable strategy given the side effects (e.g., pruritis, nausea) associated with higher doses of opioids.

For a single-shot spinal technique, most clinicians use a dose of bupivacaine between 10 and 15 mg, in combination with an opioid. Most studies of hyperbaric bupivacaine (12 to 15 mg) have shown that the patient’s age, height, weight, and BMI do not have an important influence on the resulting neuraxial blockade, although a weak correlation has been shown between vertebral column length and cephalad spread. The use of the larger dose (15 mg) results in a longer duration of surgical anesthesia; however, cervical sensory blockade is achieved more frequently ( Fig. 26.1 ). In patients with extremes of height (<5 feet/152 cm or >6 feet/183 cm), some anesthesia providers alter the dose of local anesthetic. The baricity of the local anesthetic does appear to be associated with an increase in the speed of onset with hyperbaric solutions, and can affect the extent of blockade spread. When the cephalad spread of hyperbaric local anesthetic is desired, the patient can be placed in a slight head-down position; the blockade spread is malleable, particularly with longer duration local anesthetic agents such as bupivacaine.

Maximum cephalad sensory level for analgesia or anesthesia in 52 term parturients after spinal injection of hyperbaric bupivacaine 15 mg with morphine 0.15 mg.

Modified from Norris MC. Patient variables and the subarachnoid spread of hyperbaric bupivacaine in the term patient. Anesthesiology . 1990;72:478–482.

Ropivacaine is approximately 40% less potent than bupivacaine after spinal injection in nonpregnant individuals. In a dose-finding study of 72 patients undergoing elective cesarean delivery with CSE anesthesia randomly assigned to receive plain ropivacaine 10, 15, 20, or 25 mg, the ED ₅₀ and ED ₉₅ were determined to be 16.7 and 26.8 mg, respectively. Subsequently, the same investigators demonstrated that hyperbaric spinal ropivacaine 25 mg produced a more rapid block with faster recovery and less requirement for supplemental epidural anesthesia compared with the same dose of plain ropivacaine in women undergoing cesarean delivery with spinal anesthesia.

Whether ropivacaine has advantages over bupivacaine for spinal anesthesia is questionable. Given the low doses used for spinal anesthesia the risk for LAST is not an important consideration. Studies that have compared ropivacaine and bupivacaine for spinal anesthesia have not always used doses that accounted for differences in potency.

Similarly, it is unclear whether spinal levobupivacaine is as effective as bupivacaine. A randomized trial assigned 90 parturients to receive bupivacaine 8 mg, levobupivacaine 8 mg, or ropivacaine 12 mg (all with sufentanil 2.5 µg); effective anesthesia was achieved in 97%, 80%, and 87% of patients, respectively. The duration of levobupivacaine and ropivacaine sensory and motor blockade was shorter than that with bupivacaine. The US Food and Drug Administration (FDA) has not approved ropivacaine or levobupivacaine for intrathecal administration. Thus, in the United States, bupivacaine remains the most commonly used agent for spinal anesthesia for cesarean delivery.

Hyperbaric spinal lidocaine or mepivacaine (60 to 80 mg) may be used when the obstetric provider can reliably perform cesarean delivery in less than 45 minutes. The use of hyperbaric lidocaine for spinal anesthesia remains controversial because of concerns about transient neurologic symptoms (see Chapter 31 ).

Adjuvant Agents

Adjuvant medications contribute to spinal anesthesia by different mechanisms from those of local anesthetics. For cesarean delivery, adjuvant agents can improve the quality of intraoperative anesthesia, prolong postoperative analgesia, and reduce the dose, and therefore the side effects, of local anesthetics. It is important that the use of novel or untested agents in the neuraxial space should be studied initially in animal models with rigorous assessment of safety and efficacy, and avoided in routine clinical care until fully validated.

Opioids have been shown to improve intraoperative and postoperative comfort for patients undergoing spinal anesthesia for cesarean delivery. Intraoperatively, this effect can be observed through a reduction in local anesthetic drug doses and the need for analgesic supplementation. In a systematic review of intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids, 24% of patients undergoing cesarean delivery with spinal hyperbaric bupivacaine alone required supplemental intraoperative analgesia compared with 4% who also received intrathecal opioids. Opioids augment the quality and prolong the duration of local anesthetic–induced blockade, an effect most likely modulated by A-delta (pinprick) and C (cold) nerve fibers; muscle function (A-alpha nerve fibers) does not appear to be affected. The mechanism for the opioid-induced prolongation of sensory block remains unclear but may include modulation of sensory input at the spinal and supraspinal level as well as an alteration of consciousness of peripheral sensations.

An additional advantage of intrathecal opioid administration is its salutary effect on the incidence of intraoperative nausea and vomiting. During periods of visceral stimulation (i.e., exteriorization of the uterus and fascial stimulation during closure), patients often complain of nausea; the incidence of nausea is decreased by the addition of spinal fentanyl (10–25 µg) to lidocaine or bupivacaine.

Clinicians commonly add both a lipid- and water-soluble opioid to the local anesthetic for spinal anesthesia for cesarean delivery. This practice takes advantage of the fast onset of the lipid-soluble agent and the prolonged duration of the water-soluble agent ( Fig. 26.2 ) (see Chapter 13 ). However, there is some evidence that the administration of a lipid-soluble agent (e.g., fentanyl, sufentanil) with a water-soluble agent (e.g., morphine) may lead to acute spinal opioid tolerance. In a study of 60 patients undergoing cesarean delivery, there was no difference in intravenous patient-controlled analgesia (PCA) morphine consumption within the first 6 hours in patients randomized to receive spinal fentanyl 25 µg or saline added to plain bupivacaine 10 mg. However, between 6 and 23 hours, there was a 63% increase in morphine use in the group that received fentanyl. In another a study of 40 women undergoing cesarean delivery using intrathecal fentanyl (0, 5, 10, or 25 µg) combined with hyperbaric bupivacaine 12 mg and morphine 0.2 mg, higher postoperative pain scores were observed in the patients who received fentanyl, but no differences were observed among groups in postoperative intravenous PCA morphine consumption. Women who did not receive fentanyl had a higher incidence of intraoperative nausea and vomiting, suggesting that fentanyl is an important adjunct for intraoperative anesthesia. In general, we believe the improvement of intraoperative analgesia outweighs the potential for acute opioid tolerance. We therefore recommend the administration of both a lipid- and a water-soluble opioid when spinal anesthesia is administered for cesarean delivery.

Schematic illustration of the pharmacokinetic and pharmacodynamic activities resulting from the neuraxial administration of a lipid-soluble opioid (e.g., fentanyl) and a water-soluble opioid (e.g., morphine) for analgesia. The transition point varies according to the opioid drugs and doses administered. For most commonly used opioids, this transition point occurs in the postoperative period.

The optimal dose of spinal opioids is influenced by the type, dose, and baricity of the accompanying local anesthetic and the presence of other adjuvants. A systematic review and metaanalysis showed that addition of fentanyl (10 to 25 µg) to intrathecal bupivacaine for cesarean delivery reduced the need for supplemental analgesia by 82%, and reduced the incidence of intraoperative nausea/vomiting by 59%. Intrathecal fentanyl increased intraoperative pruritus; the incidence was 8%, although there was insufficient evidence to establish whether this was dose related. In contemporary practice, spinal doses of fentanyl 10 to 25 µg are commonly used for cesarean delivery anesthesia (see Table 26.5 ).

Spinal sufentanil 2.5 to 20 µg has been used with bupivacaine for cesarean delivery. A study of 37 parturients undergoing elective cesarean delivery with sufentanil (0, 10, 15, or 20 µg) added to hyperbaric bupivacaine 10.5 mg found better quality and longer duration of analgesia in all sufentanil groups than in the control group; Apgar scores, umbilical cord blood gas measurements, and Early Neonatal Neurobehavioral Scale scores were similar among groups. No cases of respiratory depression occurred. A randomized study assigned parturients to receive hyperbaric bupivacaine 12.5 mg with sufentanil (0, 2.5, 5, or 7.5 µg). Analgesia lasted longer with sufentanil 5 and 7.5 µg, and pruritus and somnolence were more pronounced with 7.5 µg. Thus, there appears to be little justification for giving a dose of sufentanil > 5 µg in this setting. A Bayesian network metaanalysis of randomized controlled trials of intrathecal opioids during cesarean delivery found only sufentanil and morphine were associated with significant increases in the incidence of respiratory depression.

Spinal morphine , hydromorphone , and diamorphine are primarily used for providing prolonged (12 to 24 hours) postcesarean analgesia (see Chapter 27 ). Spinal morphine has a latency of 30 to 60 minutes for onset of analgesia, and it produces significant analgesia with acceptable side-effect profiles when given in doses ranging from 0.05 to 0.25 mg. In a dose-response study of morphine added to hyperbaric bupivacaine 12.75 mg, morphine 0.1 mg provided analgesia comparable to that provided by doses as high as 0.5 mg. The incidence of pruritus, but not nausea and vomiting, appeared to be dose related. In patients randomized to receive morphine 0.05, 0.10, or 0.15 mg combined with hyperbaric bupivacaine 12 mg and fentanyl 15 µg, and intravenous ketorolac, no difference in measures of analgesia were found among the three groups; pruritus was more common at doses of 0.10 and 0.15 than 0.05 mg. Hydromorphone , while used less commonly than morphine, also appears to provide effective postcesarean analgesia, with an intrathecal potency ratio of 2:1 compared with morphine.

Intrathecal diamorphine is used in the United Kingdom for postoperative analgesia. It is metabolized to the two active compounds 6-acetyl morphine and morphine. Diamorphine is more lipophilic than morphine, enabling a rapid onset (6 to 9 minutes, similar to fentanyl) but a potentially shorter duration of action. In a study of intrathecal diamorphine 0.4 mg combined with bupivacaine 12.5 mg, the intraoperative supplementation rate was less than 5%; however, the incidence of nausea and vomiting was 56% and the incidence of pruritus was 80%.

Neuraxial administration of water-soluble opioids such as morphine may be associated with delayed respiratory depression (6 to 18 hours after administration; see Chapter 27 ). Postoperative monitoring protocols should include observation for respiratory depression, which although infrequent, can lead to mortality, particularly in high-risk patients (e.g., those with sleep apnea or obesity). The respiratory depressant effects of many opioids, including morphine and diamorphine, outlast the antagonism provided by naloxone (approximately 90 minutes). The Society for Obstetric Anesthesia and Perinatology consensus statement for monitoring for respiratory depression associated with neuraxial morphine for cesarean delivery promotes perioperative risk assessment and stratification to determine and adjust the intensity, frequency, and duration of respiratory monitoring.

Spinal local anesthetics are often prepared in dextrose to make the injectate hyperbaric. For example, commercially available hyperbaric bupivacaine contains 8.25% dextrose (82.5 mg/mL). The amount of dextrose required to make a meaningful clinical difference in a spinal technique with local anesthetic agents has not been well characterized. Baricity is defined as the ratio of the density of the local anesthetic solution to the density of CSF measured at the same temperature. The density of CSF is lower in women than in men, particularly during pregnancy and the immediate postpartum period ; even so, CSF density is significantly greater than that of local anesthetics and opioids in the absence of dextrose.

The intrathecal administration of an alpha-adrenergic receptor agonist (e.g., epinephrine [adrenaline], clonidine) increases the density of sensory and motor blockade and may prolong the duration of blockade as well as contribute to postcesarean analgesia. A randomized trial involving 63 women undergoing elective cesarean delivery showed that intrathecal epinephrine 0.1 to 0.2 mg, when combined with hyperbaric bupivacaine, improved the quality of intraoperative analgesia and prolonged both sensory and motor blockade by approximately 15% compared with bupivacaine alone. However, another study found that the addition of epinephrine 0.3 mg to hyperbaric bupivacaine 12.5 mg for elective cesarean delivery increased the incidence of nausea.

Spinal clonidine , in doses of 30 to 150 µg, improves intraoperative analgesia, decreases shivering, and reduces peri-incisional hyperalgesia in women undergoing cesarean delivery; however, it has been associated with hypotension and sedation. This agent is not used commonly in the United States, although it may be considered in specific circumstances (e.g., when patients are expected to be tolerant to the effects of neuraxial opioid analgesia). The FDA has issued a “black box” warning against its use in obstetric patients because of concern for hypotension. A metaanalysis showed that intrathecal dexmedetomidine, an alpha-2 adrenergic receptor agonist similar to clonidine, prolonged the postcesarean pain-free period and reduced the occurrence of postoperative shivering, but not nausea and vomiting, bradycardia, or hypotension; importantly, there were no significant differences in UA oxygen or carbon dioxide, cord blood pH, or Apgar scores. Safety data are lacking and dexmedetomidine has not been approved by the FDA for neuraxial administration.

In women undergoing cesarean delivery, spinal neostigmine in doses up to 100 µg reduced postoperative pain with no effect on FHR or Apgar scores. However, its clinical use is limited by a high incidence of nausea and vomiting refractory to treatment with antiemetic agents.

At many institutions, the spinal agents and doses are standardized so that consistent results are obtained during the provision of spinal anesthesia for cesarean delivery. Such standardization enables the anesthesia, obstetric, and nursing staff to anticipate predictable onset and recovery characteristics and respond to physiologic responses that are outside the norm. Standardization of drugs and doses may also result in fewer errors. At the authors’ institutions, spinal anesthesia for cesarean delivery is provided with 0.75% hyperbaric bupivacaine 12 mg, fentanyl 10 µg, and morphine 0.1 mg. Intrathecal opioids are drawn in a tuberculin or insulin syringe to ensure measurement accuracy. A common practice elsewhere is the administration of 0.75% hyperbaric bupivacaine 12 mg, fentanyl 15 µg, and morphine 0.15 mg.

The use of epidural anesthesia for nonelective cesarean delivery has increased, primarily because of the greater use of epidural analgesia during labor. However, the use of epidural anesthesia is less common for elective cesarean delivery when an epidural catheter is not already in situ , in part because the resulting block is less reliable than that with spinal anesthesia.

Epidural local anesthetic and opioid doses are generally 5 to 10 times greater than doses given intrathecally; this difference results from the requirement for penetration of nerve roots as they traverse the epidural space, the greater capacity of the epidural space, and the presence of the epidural venous plexus, which becomes progressively more engorged during pregnancy. Greater systemic absorption of anesthetic agents occurs with epidural anesthesia than with spinal anesthesia, and the risk for LAST is a real possibility during epidural anesthesia, but not spinal anesthesia.

A possible advantage of epidural anesthesia is a slower onset of sympathetic blockade; this may allow compensatory mechanisms to attenuate the severity of hypotension. This approach has utility in the care of patients with severe cardiac disease for whom even transient hypotension may be poorly tolerated. A catheter-based technique also allows titration of the level, density, and duration of anesthesia, and continuous postcesarean analgesia.

Local Anesthetic Agents

The most common local anesthetic used in the United States for the initiation and maintenance of epidural anesthesia for cesarean delivery is 2% lidocaine with epinephrine ( Table 26.6 ). The epidural administration of lidocaine in concentrations less than 2%, or without the addition of epinephrine, which augments the analgesia through alpha-adrenergic receptor blockade, may result in anesthesia that is inadequate for surgery.

Table 26.6

Drugs Used for Epidural Anesthesia for Cesarean Delivery

Drug	Dose Range a	Duration (min) b
Local Anesthetics
Lidocaine 2% with epinephrine 5 µg/mL	300–500 mg	75–100
2-Chloroprocaine 3%	450–750 mg	40–50
Bupivacaine 0.5%	75–125 mg	120–180
Ropivacaine 0.5%	75–125 mg	120–180
Opioids
Fentanyl	50–100 µg	120–240
Sufentanil	10–20 µg	120–240
Morphine	3–4 mg	720–1440
Hydromorphone	0.6–1.5 mg	780–1090
Meperidine	50–75 mg	240–720

The epidural administration of a 3% solution of 2-chloroprocaine has the most rapid onset and the shortest duration of action of available local anesthetics. These characteristics make it an excellent choice for emergency cesarean delivery (see discussion below) because the dose is administered rapidly, and even if unintentional intravenous administration of drug were to occur, the maternal and fetal sequelae are likely to be less severe than the similar administration of an amide local anesthetic agent. Administration of 2-chloroprocaine has historically been associated with neurologic sequelae, possibly associated with the antioxidant sodium bisulfite, and paralumbar muscle spasms and pain, believed to be a result of calcium chelation by the preservative ethylenediaminetetraacetic acid. Current preparations of 2-chloroprocaine do not contain an antioxidant or a preservative (see Chapter 13 ). Epidural administration of 2-chloroprocaine may be associated with a rapid onset of hypotension and an apparent reduction in the clinical efficacy of subsequently administered epidural opioids (see Chapter 13 ). The pharmacokinetic characteristics of the drug likely play a role. The analgesic effect of epidural morphine administered 30 minutes before 2-chloroprocaine does not appear to be mitigated; however, such timing in the setting of emergency cesarean delivery is not possible. These considerations limit the use of 2-chloroprocaine to those situations in which the rapid onset of anesthesia is paramount. Epidural administration of 3% 2-chloroprocaine 20 mL was demonstrated to be noninferior for rapidly converting labor analgesia to anesthesia to the T7 level for cesarean delivery compared with the combination of 2% lidocaine 20 mL, epinephrine 150 µg, 8.4% bicarbonate 2 mL, and fentanyl 100 µg. This avoids the disadvantage of needing to mix multiple drugs, which is likely helpful in an emergency situation; moreover, an even faster blockade onset is achieved when 3% 2-chloroprocaine 20 mL is administered in the epidural space mixed with 8.4% bicarbonate 2 mL.

Surgical anesthesia can be produced with epidural administration of 0.5% bupivacaine ; however, the slow onset of neuroblockade and the risk for cardiovascular sequelae (i.e., LAST) from unintentional intravascular injection (or systemic absorption) have limited the contemporary use of this agent in the United States. The risk for cardiovascular sequelae resulted in a earlier proscription against the epidural administration of 0.75% bupivacaine in obstetric patients by the FDA. The single-isomer, levorotatory local anesthetics 0.5% and 0.75% ropivacaine and 0.5% levobupivacaine may be preferable to racemic bupivacaine because of their better safety profiles and earlier recovery, although a significant portion of the improved safety profile is caused by the lower potency of these agents (0.5% bupivacaine is more potent than 0.5% levobupivacaine and 0.5% ropivacaine). A randomized controlled trial of 60 patients compared 30 mL of epidural 0.5% levobupivacaine with racemic 0.5% bupivacaine in women undergoing elective cesarean delivery; no differences in the block onset or resolution, signal-averaged ECG results, complications, or maternal and fetal plasma pharmacokinetic profiles between the treatment groups were found. Another study involving 62 patients undergoing cesarean delivery with epidural anesthesia reported no difference in onset, spread, or duration of sensory block in women who received 25 mL of 0.5% levobupivacaine or 0.5% racemic bupivacaine, although levobupivacaine produced lower limb motor blockade of longer duration and less intensity. Finally, a study of 60 patients demonstrated that the onset, duration, and regression of sensory blockade with 0.5% ropivacaine was similar to that provided by 0.5% bupivacaine, although a faster onset and longer duration of motor blockade was observed with bupivacaine. The free concentrations of ropivacaine were approximately twice those of bupivacaine in both maternal and neonatal blood at delivery; however, these measurements were less than the concentrations shown to be toxic in animals.

Adjuvant Agents

As with spinal anesthesia, adjuvant medications are used for their intrinsic analgesic properties and to reduce the dose and side effects of local anesthetic agents. The use of epidural adjuvants can improve the quality of intraoperative anesthesia and result in less motor blockade as well as enhance postoperative analgesia (see Chapter 27 ).

Although some anesthesia providers administer an epidural opioid with the initial therapeutic dose of local anesthetic, others delay opioid administration until confirmation of an appropriate local anesthetic agent-induced blockade (so a less-than-optimal blockade is not obscured), or until clamping of the umbilical cord (to prevent transfer of opioid to the fetus). The onset of analgesia is dictated by complex pharmacokinetics; however, the lipid-soluble opioids (e.g., fentanyl , sufentanil ) have more rapid onset and more rapid clearance than the water-soluble opioids (e.g., morphine ).

The administration of epidural fentanyl (50 to 100 µg) results in activity at both spinal and supraspinal sites of action, improves the intraoperative quality of anesthesia during cesarean delivery, and does not appear to adversely affect the neonate. The optimal dose of epidural fentanyl has not been determined for patients undergoing cesarean delivery; however, in an experimental pain study in nonpregnant patients, there was an analgesic effect at the segmental level of injection for epidural fentanyl 100 µg, but not 50 µg.

Epidural sufentanil (10 to 20 µg) added to 0.5% bupivacaine with epinephrine 5 µg/mL provides significantly better intraoperative anesthesia and longer postoperative analgesia than bupivacaine and epinephrine alone, with minimal maternal side effects and no adverse neonatal effects. Epidural sufentanil is approximately five times more potent than epidural fentanyl, but when equipotent doses are administered, no differences between the agents in onset, quality, or duration of analgesia have been observed.

Epidural administration of the hydrophilic opioid morphine provides prolonged postcesarean analgesia. A dose-response study of epidural morphine (1.25, 2.5, 3.75, and 5 mg) found 3.75 mg to be an optimal dose, above which postcesarean analgesia (as measured by PCA morphine demands) was no better. Extended-release epidural morphine 10 mg provides better postoperative analgesia than epidural morphine 4 mg, with no differences in nausea, pruritus, or sedation scores.

Epidural hydromorphone is sometimes used as an alternative to morphine. Doses of 0.6 to 1.5 mg are commonly used. Studies suggest a similar analgesia effect and side-effect profile compared with epidural morphine analgesia, although the duration of analgesia may be slightly shorter.

Epidural diamorphine (2.5 to 3 mg) is commonly used in the United Kingdom for providing prolonged postcesarean analgesia. Optimal dose-finding studies of epidural diamorphine have not been performed; however, the duration and quality of analgesia from epidural diamorphine 3 mg appears to be similar to that provided by spinal diamorphine 0.3 mg, with significantly less pruritus.

Epidural clonidine (75 to 200 µg) combined with morphine or fentanyl reduces the requirement for postcesarean morphine analgesia. The effect of coadministering clonidine and fentanyl appears to be additive rather than synergistic in producing postcesarean analgesia. Common side effects include hypotension and sedation. Currently, epidural clonidine has only one specific neuraxial indication in the United States (intractable cancer pain), and the package insert has a “black box” warning from the FDA stating that “epidural clonidine is not recommended for obstetrical, postpartum and perioperative pain management.”

Epidural neostigmine produces a modest amount of postcesarean analgesia when given after umbilical cord clamping. A dose-finding study investigated the administration of 75, 150, or 300 µg of epidural neostigmine in women undergoing elective cesarean delivery. An increase in intraoperative shivering and sedation was observed in the 300-µg group only; a dose-independent reduction in postoperative pain and sedation was observed in all groups.

Epinephrine may be added to the local anesthetic agent to minimize systemic absorption and peak blood level of the local anesthetic, increase the density of sensory and motor blockade, and prolong the duration of anesthesia. The pharmacokinetic effects of epinephrine coadministered with an opioid vary with the opioid and the sampling site. In the lumbar epidural space, epinephrine lengthened the mean residence time of morphine but shortened that of fentanyl and sufentanil.

The epidural administration of epidural epinephrine in preeclamptic women has been considered controversial because of the potential risks of exacerbating hypertension and decreasing uteroplacental blood flow when large doses of local anesthetic are given for cesarean delivery. However, many practitioners consider the risk/benefit ratio for the addition of epinephrine to lidocaine to be favorable in preeclamptic women (see Chapter 35 ).

When combined with local anesthetic for epidural anesthesia, the usual epinephrine concentration is 2.5 or 5 µg/mL (i.e., 1:400,000 or 1:200,000). The addition of epinephrine to a solution of plain local anesthetic just before administration results in a solution that has a higher pH than commercially prepared epinephrine-containing products, which use (low-pH) antioxidants to preserve the efficacy of the epinephrine (see Chapter 13 ). Thus, use of freshly prepared solutions hastens the onset of anesthesia.

The addition of sodium bicarbonate results in a solution with more local anesthetic molecules in a nonionized state, which hastens the onset and augments the quality of the local anesthetic blockade, particularly if sodium bicarbonate is added to a low-pH solution (see discussion below).

The CSE technique incorporates the rapid and predictable onset of spinal blockade with the ability to augment or prolong anesthesia by injection of additional drug through the epidural catheter (see Chapter 12 ). Compared with a conventional epidural anesthesia for cesarean delivery, further advantages of the CSE technique include: (1) faster onset and lower pain scores at delivery, (2) use of the epidural needle as an introducer for a longer spinal needle when attempts with a traditional introducer and spinal needle have failed, and (3) use of a spinal needle (and return of CSF through the needle) to “confirm” the correct positioning of the epidural needle in the epidural space.

Conventional spinal doses (e.g., 12 mg) of hyperbaric bupivacaine are most often used to provide CSE anesthesia for cesarean delivery; however, a satisfactory block has been reported with plain bupivacaine drug doses as low as 4.5 mg. Although the use of lower doses of local anesthetic is enabled by the presence of the epidural catheter (because additional agents can be administered if discomfort occurs), the block achieved with the CSE technique may be inherently different from the block achieved with a single-shot spinal technique with the same dose(s) of medication. One study, in which men undergoing surgery were positioned in the right lateral position for initiation of neuraxial anesthesia, demonstrated that the ED ₅₀ values for intrathecal hyperbaric bupivacaine (to achieve a T6 sensory level of anesthesia for 60 minutes) for the CSE and spinal techniques were 9.2 and 11.4 mg, respectively. The investigators speculated that the use of the loss-of-resistance to air (during introduction of the epidural needle) resulted in a reduction in lumbar CSF volume and a subsequently higher sensory blockade. Similarly, in another study that initiated neuraxial analgesia with intrathecal bupivacaine 10 mg in parturients undergoing elective cesarean delivery, median sensory levels were C6 and T3 with the CSE and spinal techniques, respectively. The CSE technique was performed with loss-of-resistance to air (2 mL); however, after administration of the spinal medications, the epidural catheter was not inserted. The investigators speculated that the loss of negative pressure in the epidural space created by the introduction of the epidural needle was responsible for the observed differences. However, when investigators from the same institution performed the same anesthetic techniques for cesarean delivery in laboring women, no differences in the block characteristics were observed. The reasons for these differences are unclear.

The sequential CSE technique uses a lower dose of spinal bupivacaine (7.5 to 10 mg) followed by incremental injection of local anesthetic through the epidural catheter to achieve a T4 level of anesthesia. The advantage of this approach is a lower incidence of hypotension. In a study comparing sequential CSE anesthesia using 1.5 mL of 0.5% of hyperbaric bupivacaine (followed by extension with fractionated doses of 0.5% bupivacaine administered through the epidural catheter as needed) versus single-shot spinal anesthesia using 2.5 mL of 0.5% of hyperbaric bupivacaine, there was more gradual onset of hypotension and a lower initial sensory level with the CSE technique (T7) compared with the single-shot spinal technique (T4). The sequential CSE technique may be of particular advantage in high-risk parturients (e.g., significant cardiac disease) in whom avoidance of severe hypotension is vitally important.

Another CSE technique is the extradural volume extension (EVE) technique. Intrathecal administration of a small dose of local anesthetic is followed by the administration of saline through the epidural catheter. Studies have observed a higher cephalad spread of one to four dermatomal segments associated with the use of this technique, presumably because of thecal compression. However, the effect of EVE may depend on the initial dose and baricity of local anesthetic, the time interval between spinal and epidural injection, the volume of epidural saline, and the outcomes measured, as several studies have failed to find a difference in sensory blockade using this technique.

Potential drawbacks of CSE techniques include an untested epidural catheter (although the rates of successful function of epidural catheters placed as part of a CSE technique is very high) and hypotension, which can be generally treated easily with vasopressors. Administering the CSE technique in the sitting position may result in greater severity and duration of hypotension than the left lateral decubitus position. The hypotension may be related to the delay in moving the patient from the sitting to the supine (with leftward tilt) position.

The DPE and CSE techniques use similar methods for insertion, by which a spinal needle is placed through the shaft of a positioned epidural needle to obtain CSF (see Chapter 12 ). Although the DPE technique then introduces all medications via the epidural catheter, a portion of the epidural medications is subsequently translocated via the conduit from the epidural to the subarachnoid space. Rao et al. reported that for elective cesarean delivery, the DPE technique was associated with a faster onset of anesthesia and less intraoperative pain compared with epidural anesthesia, and a slower onset of anesthesia with less hypotension and less phenylephrine requirement compared with CSE anesthesia. Sharawi et al. randomized women having scheduled cesarean delivery to first have a T10 sensory block established using DPE or standard epidural anesthesia, and then epidural extension to T6 using 3% chloroprocaine. They found that the time to achieve surgical anesthesia was faster in the DPE group (422 versus 655 seconds; P <.001), with a more favorable quality of anesthesia blockade.

The extension of epidural labor analgesia to surgical anesthesia sufficient for cesarean delivery can be accomplished with several local anesthetic agents. The selection of agent often depends on the urgency of the case. Extension of epidural analgesia can be initiated as preparations are being made to move the patient from the labor room to the operating room. Whether an in situ epidural catheter should be used for an extension attempt depends on several factors, including the quality of the existing labor analgesia. If obtaining satisfactory epidural labor analgesia has been problematic (e.g., one-sided or “patchy” analgesia), removing the catheter and administering spinal or CSE anesthesia may be a better method to attain rapid and effective anesthesia. A systematic review and metaanalysis found that the risk for failed conversion of labor epidural analgesia to anesthesia is increased by the following factors: (1) a higher number of boluses administered during labor, (2) greater urgency for cesarean delivery, and (3) care being provided by a nonobstetric anesthesiologist.

Specific local anesthetic and adjuvant solutions may influence whether the quality and level of epidural anesthesia is adequate for cesarean delivery. A metaanalysis of 11 randomized controlled trials examining the type of local anesthetic used to “top-up” epidural labor analgesia for emergency cesarean delivery compared 0.5% bupivacaine or 0.5% levobupivacaine, lidocaine with epinephrine (with and without fentanyl), and 0.75% ropivacaine. The pooled analysis suggested that lidocaine with epinephrine resulted in the fastest onset of sensory block; the addition of fentanyl further hastened block onset, but not quality as measured by the need for intraoperative supplementation. Compared with 0.5% bupivacaine or 0.5% levobupivacaine, 0.75% ropivacaine was associated with a lower need for intraoperative supplementation. The epidural administration of 2% lidocaine with freshly added epinephrine 5 µg/mL was compared with 3% 2-chloroprocaine in a randomized trial involving 40 women undergoing elective cesarean delivery. There was no significant difference in the onset of anesthesia between the two groups, although the study was likely underpowered; the median onset was 8 minutes (range, 4 to 13 minutes) in the 2-chloroprocaine group and 5 minutes (range, 2 to 22 minutes) in the lidocaine group. However, given the time taken to prepare the lidocaine with epinephrine solution, the investigators concluded that use of a preprepared solution, such as 2-chloroprocaine, may be preferred.

Alkalinization of the local anesthetic solution not only increases the speed of onset but also improves the quality and prolongs the duration of neuroblockade. Alkalinization shifts more of the local anesthetic molecules to the nonionized, lipid-soluble form, which allows the local anesthetic to pass more easily through the lipophilic neuronal membrane. Although this phenomenon can be demonstrated for all local anesthetics, alkalinization is most often performed with local anesthetic agents of short and medium duration (e.g., 2-chloroprocaine, lidocaine). Typically, 1 mL of 8.4% sodium bicarbonate (1 mEq/mL) is added to each 10 mL of lidocaine or 2-chloroprocaine. Longer-acting agents (e.g., bupivacaine, ropivacaine, levobupivacaine) easily precipitate with the addition of sodium bicarbonate; this occurs even with the addition of 0.2 mEq of bicarbonate to 20 mL of 0.5% bupivacaine. Alkalinization exerts the greatest effect when it is freshly mixed with the local anesthetic solution; however, the mixture is relatively stable. The addition of sodium bicarbonate to local anesthetics has been demonstrated to result in a clinically significant reduction in the time until an adequate anesthetic level is obtained ( Fig. 26.3 ). In a randomized trial, 40 women with functioning epidural labor analgesia received a 3-mL epidural test dose of 2% lidocaine with epinephrine, followed by 12 mL of premixed 2% lidocaine with epinephrine 5 µg/mL (1 : 200,000) and fentanyl 75 µg with 1.2 mL of 8.4% sodium bicarbonate or saline. The mean times to attain a T6 anesthesia level with and without bicarbonate were 5.2 and 9.7 minutes, respectively.

Extension of a T10 level of analgesia to a T4 level of anesthesia typically requires a volume of 15 to 20 mL of local anesthetic with one or more adjuvants. At our institutions, the extension of epidural labor analgesia begins with assessment of the quality of analgesia. For emergency cesarean delivery, we initiate the extension of epidural anesthesia in the labor room by giving 10 mL of alkalinized 2% lidocaine (with epinephrine) or 3% 2-chloroprocaine. The sensory blockade is assessed after transfer of the patient to the operating room; if the blockade is bilateral and moving in a cephalad direction, an additional 5 to 10 mL is administered to bring the sensory level to T4. The use of this fractionated dosing schedule offers several advantages, including (1) greater hemodynamic stability during patient transfer; (2) assessment of the evolving sensory level before administration of the full dose of local anesthetic; (3) minimization of dural sac compression (by a large-volume epidural injection), which enables a less difficult and safer conversion to spinal anesthesia if extension of epidural anesthesia is not successful (see discussion below); and (4) early sensory blockade at the incision site, so that surgery can be initiated in emergency cases before establishment of a full T4 sensory level.

The extension of epidural analgesia to anesthesia in the labor room is controversial. Some anesthesia providers delay epidural administration of additional local anesthetic until the patient has arrived in the operating room. However, this practice may increase the risk for failed epidural anesthesia, necessitating the induction of general anesthesia with its attendant risks (see discussion below).

Although neuraxial anesthesia is usually preferred for cesarean delivery, in some situations general anesthesia is considered more appropriate (see Table 26.2 ). In addition, general anesthesia offers an advantage in cases in which uterine relaxation would be beneficial (e.g., cesarean delivery as part of an ex utero intrapartum treatment [EXIT] procedure; see Chapter 7 ).

The basic elements for preparation and care of the obstetric patient undergoing cesarean delivery apply to the patient undergoing general anesthesia ( Box 26.6 ; see Table 26.1 ). The preanesthetic evaluation should focus on assessment of physical characteristics (e.g., airway) and comorbidities. The consent process should feature the risks associated with airway management, aspiration, and awareness. The importance of a careful airway evaluation cannot be overemphasized (see Chapter 29 ); pregnancy-induced changes in the upper airway may be exacerbated during labor. Acoustic reflectometry showed that soft tissue mucosal edema in both the oral (incisor teeth to oropharyngeal junction) and pharyngeal (oropharyngeal junction to the glottis) tissue increases during labor and results in worsening of the airway classification compared with the prelabor evaluation. Failed tracheal intubation, failed ventilation and oxygenation, and pulmonary aspiration of gastric contents are important potential causes of anesthesia-related maternal death (see Chapters 29 and 39 ). If the airway evaluation suggests the possibility of a difficult intubation, consideration should be given to the placement of a neuraxial catheter during early labor, even if it is not used to provide labor analgesia.

Box 26.6

Steps for Initiating General Anesthesia for Cesarean Delivery ^a

• 1.

  Discuss the operative plan with the multidisciplinary team.

• 2.

  Perform preanesthetic assessment, and obtain informed consent.

• 3.

  Prepare necessary medications and equipment.

• 4.

  Place patient supine with left uterine displacement.

• 5.

  Secure 18-gauge or larger intravenous access. Send blood specimen for baseline laboratory measurements; consider type and screen (or cross-match) if risk factors for peripartum hemorrhage are present.

• 6.

  Give metoclopramide 10 mg and/or ranitidine 50 mg intravenously more than 30 min before induction, if possible.

• 7.

  Give a nonparticulate antacid orally less than 30 min before induction. ^b

• 8.

  Administer antibiotic prophylaxis (with 60 min before incision). ^c

  ⁴⁴

• 9.

  Initiate monitoring.

• 10.

  Perform a team “time-out” to verify patient identity, position, and operative site; procedure to be performed; and availability of special equipment, if needed.

• 11.

  Provide 100% oxygen with a tight-fitting face mask for 3 min or longer, when possible, for denitrogenation/preoxygenation. Otherwise, instruct the patient to take four to eight vital-capacity breaths immediately before induction of anesthesia.

• 12.

  After the abdomen has been prepared and operative drapes are in place, verify that the surgeon and assistant are ready to begin surgery.

• 13.

  Initiate rapid-sequence induction:

  • a.

    Apply cricoid pressure 10 N while awake; increase to 30 N after loss of consciousness.

  • b.

    Give thiopental 4–6 mg/kg or propofol 2–2.8 mg/kg and succinylcholine 1–1.5 mg/kg intravenously; wait 30–40 s. ^d

• 14.

  Perform tracheal intubation. Confirm correct placement of endotracheal tube.

• 15.

  Provide maintenance of anesthesia:

  • a.

    Use isoflurane, sevoflurane, or desflurane (approximately 1 MAC) in 100% oxygen or oxygen/nitrous oxide (up to 50%).

  • b.

    Treat hypotension (e.g., phenylephrine, ephedrine).

  • c.

    If additional muscle relaxant (e.g., rocuronium, vecuronium) is necessary, titrate dose according to response to peripheral nerve stimulator.

• 16.

  Observe delivery of infant.

• 17.

  Administer a bolus and/or a continuous infusion of oxytocin; consider other uterotonic agents (e.g., methylergonovine, 15-methyl prostaglandin F _2α ) if uterine tone is inadequate. Monitor blood loss and respond as necessary.

• 18.

  Adjust maintenance technique after delivery of the infant:

  • a.

    Administer a reduced concentration of a volatile halogenated agent (0.5–0.75 MAC).

  • b.

    Supplement anesthesia with nitrous oxide and an intravenous opioid.

  • c.

    Give attention to risk for awareness and recall. Consider administration of a benzodiazepine (e.g., midazolam).

• 19.

  Perform tracheal extubation when neuromuscular blockade is fully reversed and the patient is awake and responds to commands.

• 20.

  Evaluate postoperative issues (e.g., pain, nausea).

Preparation

All pregnant patients requiring surgical anesthesia should be considered at risk for pulmonary aspiration of gastric contents (see Chapter 28 ). Attempts should be made to minimize both the risk for maternal aspiration and the risk for pulmonary injury if aspiration occurs. Fasting policies should be shared with all members of the obstetric care team. The authors administer metoclopramide 10 mg and ranitidine 50 mg IV 30 to 60 minutes before induction of general anesthesia, when possible, to diminish gastric volume and gastric acid secretion, respectively. A clear, nonparticulate antacid (sodium citrate 30 mL) should also be administered within 30 minutes of surgery to neutralize gastric acid ; the antacid may be particularly important in emergency situations when metoclopramide and ranitidine have not had the necessary time to exert their pharmacologic effects.

Although less common in the era of videolaryngoscopy, in situations where highly difficult or impossible mask ventilation or intubation is anticipated (e.g., neck mass), awake tracheal intubation may be considered (see Chapter 29 ). Preparations include administering an antisialagogue (e.g., glycopyrrolate ), judicious sedation (e.g., midazolam ), and topical airway anesthesia (e.g., aerosolized lidocaine or benzocaine ). Glossopharyngeal and laryngeal nerve blocks may also be considered, although these should be avoided in patients at excess risk for bleeding (e.g., hemolysis, elevated liver enzymes, and low platelet count [HELLP] syndrome).

The patient should be placed supine with left uterine displacement. The head, neck, and shoulders should be optimally positioned for airway management (i.e., the sniffing position). Routine monitoring should be established, including ECG, pulse oximetry, blood pressure, and capnography. Preoxygenation (denitrogenation) with 100% oxygen should be performed to delay the onset of hypoxemia during apnea; this hypoxemia occurs more rapidly because of the pregnancy-induced decrease in functional residual capacity and increase in oxygen consumption. In a computer simulation of the respiratory and cardiovascular systems during pregnancy, the presence of labor, high BMI, and sepsis further accelerated oxyhemoglobin desaturation during apnea; by contrast, multiple gestation and hemorrhage appeared to have minimal effect. Ideally, preoxygenation is accomplished by 3 minutes of tidal-volume breathing with a tight-fitting face mask. Although four maximal deep breaths of 100% oxygen over 30 seconds can achieve a similar Pa o ₂ , the same protection against rapid oxyhemoglobin desaturation is not afforded, owing to differences in tissue and venous compartment oxygen reserves. The method of eight deep breaths over 1 minute appears to provide better protection from oxyhemoglobin desaturation during apnea than the method of four deep breaths over 30 seconds. Recently, the use of high-flow nasal oxygen (HFNO) has been used as a method to provide efficient, prolonged oxygenation (longer apneic time with oxygen saturation > 90%) prior to intubation in women undergoing general anesthesia for cesarean delivery. The effect of HFNO on gastric distention and regurgitation needs further exploration, particularly in pregnant women.

In contrast to most surgical procedures, the patient’s abdomen is prepared and draped before induction of general anesthesia to minimize fetal exposure to general anesthesia. After the surgical drapes have been applied and the operating personnel are ready at the tableside, the surgeon should be instructed to delay the incision until the anesthesia provider confirms correct placement of the endotracheal tube and gives verbal instructions to proceed with surgery.

Induction

A rapid-sequence induction is initiated with denitrogenation/preoxygenation followed by administration of an induction agent, paralysis, and cricoid pressure. Traditionally, mask ventilation is not performed, because when it is applied with inspiratory pressure > 20 cm H ₂ O without the application of cricoid pressure with pressures, insufflation of the stomach can occur (see Chapter 29 ). However, some guidelines have recommended modification of the rapid-sequence induction to include gentle, low-pressure (<20 cm H ₂ O) mask ventilation to confirm that ventilation is possible and to maximize oxygen reserve while awaiting induction and paralysis. Whether rapid-sequence induction with or without modification should be employed, particularly in an appropriately fasted, nonlaboring patient having elective cesarean delivery, has been questioned. Further, the value of cricoid pressure has been challenged owing to (1) physiologic evidence demonstrating that cricoid pressure reduces lower esophageal sphincter pressure, (2) anatomic investigations showing an inability to completely occlude the esophagus, (3) a lack of clinical outcome data that confirm that cricoid pressure reduces the incidence of aspiration, and (4) the frequent misapplication of the technique itself. The technique for cricoid pressure begins with an assistant applying 10 newtons (N) of force, 1 N being the force required to accelerate a mass of 1 kg by 1 m/s ² (as a practical guide to the amount of force to apply, 10 N is approximately equivalent to the downward gravitational force exerted by a weight of 1 kg). Following loss of consciousness, the amount of force is increased to 30 N. Application of the full amount of force while the patient is still awake can provoke active retching and regurgitation. In some cases, cricoid pressure may be briefly released to enable a successful intubation; not infrequently the benefit of release outweighs the risk for regurgitation. Cricoid pressure should then be reapplied until the correct endotracheal tube position is confirmed.

Historically, thiopental (thiopentone) (4 to 6 mg/kg) was the most frequently used induction agent for cesarean delivery. Because of recent lack of availability, it is now rarely used in the United States, although it is still used in other countries. Propofol (2 to 2.8 mg/kg) is now commonly used. In the presence of hemodynamic instability, ketamine (1 to 1.5 mg/kg) or etomidate (0.3 mg/kg) should be substituted for propofol. Paralysis is achieved by succinylcholine (suxamethonium) (1 to 1.5 mg/kg) in 30 to 40 seconds. Administration of a defasciculating dose of a nondepolarizing muscle relaxant is not recommended because it may delay the onset of neuromuscular blockade with succinylcholine. Pregnancy appears to be associated with less severe succinylcholine-induced fasciculations and muscle pain.

Rocuronium (1 mg/kg) may provide intubating conditions similar to those provided with succinylcholine (1 mg/kg) and is a suitable alternative when succinylcholine should be avoided (e.g., malignant hyperthermia susceptibility, myotonic dystrophy, spastic paraparesis). Some data suggest its use in cesarean delivery may be associated with a lower frequency of myalgia compared with succinylcholine. The use of a priming preinduction dose of a nondepolarizing muscle relaxant is not recommended during pregnancy because it may result in complete paralysis and increase the risk for aspiration. Enhanced activity of nondepolarizing agents may also be observed in patients receiving magnesium sulfate (e.g., for seizure prophylaxis in women with preeclampsia or for fetal neuroprotection).

Sugammadex , a modified gamma-cyclodextrin, has been demonstrated to be effective in providing rapid recovery (a train-of-four ratio > 0.9) without recurarization from moderate and profound rocuronium-induced neuromuscular blockade in parturients undergoing cesarean delivery.

A small-diameter cuffed endotracheal tube (i.e., 6.5 or 7.0 mm) should be used during pregnancy; the use of a videolaryngoscopy device (e.g., C-MAC, Glidescope), a flexible stylet within the endotracheal tube, and a bougie on standby allows a “first and best” attempt at tracheal intubation. Tissue trauma and airway edema may occur with repeated attempts at intubation. Correct endotracheal tube placement should be confirmed by checking for a normal capnographic tracing. Auscultation should be performed to rule out inadvertent endobronchial intubation. The anesthesia provider should also observe ongoing evidence of adequate maternal oxyhemoglobin saturation as well as bilateral thoracic movement and breath sounds. If there is doubt, fiberoptic bronchoscopy can confirm the correct placement of the endotracheal tube in the trachea. If incorrect endotracheal tube placement is promptly recognized, extubation (with continued cricoid pressure) will often allow another attempt without the need for additional muscle relaxant. Anticipation of a difficult tracheal intubation, or a failed intubation attempt, should invoke the difficult airway algorithm and a call for assistance (see Chapter 29 ). Options include (1) allowing the patient to awaken, (2) using alternative techniques to place an endotracheal tube, and (3) using alternative airway devices. Emergency airway equipment (including equipment for surgical airway access) should be immediately available in all obstetric operating rooms.

Some authors have suggested that a supraglottic airway device (e.g., laryngeal mask airway [ LMA ]) can be used routinely for general anesthesia for cesarean delivery. One series reported clinically effective airway management with a classic LMA that was placed successfully on the first attempt in 98% of 1067 healthy parturients undergoing elective cesarean delivery with general anesthesia. Cricoid pressure was maintained throughout the cesarean delivery and no adverse sequelae occurred. Another study utilized an LMA with a higher seal pressure than a classic LMA and a built-in gastric draining tube, and reported successful placement in 98% of 3000 healthy parturients undergoing elective cesarean delivery. Cricoid pressure was not maintained after confirmation of successful airway placement; there was one case of regurgitation without aspiration. In both of these studies, patients were excluded if they had symptoms of gastropharyngeal reflux, known/predicted difficult airway, and a prepregnancy BMI > 30 kg/m ² . As supraglottic airway devices do not prevent pulmonary soiling with gastric contents as efficiently as an endotracheal tube, and high morbidity rate is associated with aspiration, the authors do not routinely use these devices for cesarean delivery. However, any device that can facilitate ventilation should be used as a lifesaving device in situations of failed intubation. A number of variations to the classic LMA have been developed that may facilitate airway management in specific situations (see Chapter 29 ).

Maintenance

The goals for anesthetic maintenance include (1) adequate maternal and fetal oxygenation, with maintenance of normocapnia for pregnancy; (2) appropriate depth of anesthesia to promote maternal comfort and a quiescent surgical field and to prevent awareness and recall; (3) minimal effects on uterine tone after delivery; and (4) minimal adverse effects on the neonate. These goals can be accomplished using low concentration inhalational anesthesia or, less commonly, total intravenous anesthesia.

In the absence of fetal compromise, an F io ₂ of 0.3 appears to provide sufficient oxygenation while minimizing the production of oxygen free radicals (see discussion above). Although the use of a higher F io ₂ can increase maternal arterial (MA) and UV blood oxygen content, this action has not been observed to result in differences in 1- or 5-minute Apgar or neurobehavioral scores. As a consequence, in the absence of fetal compromise, inspired oxygen concentrations should be guided by pulse oximetry rather than provision of an arbitrarily set level of F io ₂ .

Maternal ventilation should maintain normocapnia, which at term gestation is a Pa co ₂ of 30 to 32 mm Hg (4.0 to 4.3 kPa). Excessive ventilation can cause uteroplacental vasoconstriction and a leftward shift of the oxyhemoglobin dissociation curve, which may result in compromised fetal oxygenation. On the other hand, hypercapnia can lead to maternal tachycardia and is also undesirable.

Initially, high fresh-gas flows should be used to ensure an adequate end-tidal concentration of the volatile halogenated agent. No specific volatile halogenated agent has been demonstrated to be superior. The anesthetic requirement for volatile halogenated agents is diminished 25% to 40% during pregnancy. A bispectral index (BIS) < 60 typically requires greater than 0.75 minimum alveolar concentration (MAC) of a volatile halogenated agent combined with 50% nitrous oxide and has been suggested to prevent intraoperative awareness and recall in parturients undergoing general anesthesia ; however, this target BIS value requires further study in pregnant women. Several studies suggest the need for a lower volatile agent requirement to maintain a target BIS value in women with prior labor compared with women without prior labor ; these results could not be explained by differences in plasma concentrations of progesterone, prolactin, or cortisol.

In clinical practice, approximately 1.0 MAC of a volatile halogenated agent is typically administered between tracheal intubation and delivery. Volatile halogenated agents cause dose-dependent depression of uterine contractility, which may lead to greater blood loss after delivery. Therefore, the concentration of the volatile agent is reduced to 0.5 to 0.75 MAC after delivery. Nitrous oxide 50% in oxygen is often added to reduce the required concentration of the volatile agent, thereby mitigating adverse effects on uterine tone; intravenous propofol or ketamine can also be administered to maintain an appropriate depth of anesthesia. The administration of a benzodiazepine (e.g., midazolam ) after delivery may reduce the risk for maternal awareness.

Intravenous opioids are often withheld until after delivery to minimize the potential for neonatal respiratory depression; however, there may be circumstances in which maternal hemodynamic stability or blunting of responses to airway manipulation and surgical stimulation favor the administration of opioids during the induction of general anesthesia. Rapidly acting lipid soluble opioids (e.g., remifentanil and alfentanil ) are ideal for mitigating the responses to laryngoscopy and intubation. Intraoperatively, the prolonged activity of hydrophilic agents (e.g., morphine, hydromorphone) can be useful to minimize volatile agent use and for the provision of intraoperative and postoperative analgesia (see Chapter 27 ).

Because of pregnancy-induced stretching of the abdominal wall, additional neuromuscular blockade may not be necessary in the parturient who has an adequate depth of anesthesia (with administration of both a volatile agent and an opioid). A small dose of a short-acting nondepolarizing agent (or an infusion of succinylcholine) may be administered, with maternal response monitored with a peripheral nerve stimulator, if additional muscle relaxation is indicated.

General anesthetic agents can redistribute from the neonatal fat to the central circulation and lead to secondary depression of neonatal ventilatory effort; thus, the presence of a pediatrician (or another neonatal provider) is advisable until a normal ventilatory pattern is observed. Although differences in maternal and umbilical artery acid-base status have been observed in women who underwent elective general anesthesia compared with epidural anesthesia for cesarean delivery, similar neonatal outcomes were demonstrated. Similarly, epidemiologic data suggest that brief exposure to general anesthetic agents at the time of cesarean delivery is not associated with an increased risk for abnormal neonatal neurodevelopment and later learning difficulties.

Emergence and Tracheal Extubation

When the patient awakens, tracheal extubation should be performed with the patient in a semirecumbent position. The patient should demonstrate purposeful response to verbal commands and return of protective airway reflexes before tracheal extubation. In a review of anesthesia-related maternal deaths between 1985 and 2003 in the state of Michigan, deaths associated with hypoventilation or airway obstruction did not occur at induction and tracheal intubation but rather during emergence, extubation, or recovery from anesthesia. Risk factors associated with mortality were obesity and African-American race, which may have delayed the visual recognition of cyanosis; medical management and medication issues were also identified. The ASA Practice Guidelines for Postanesthetic Care suggest that pulse oximetry is associated with early detection of hypoxemia; the guidelines recommend periodic assessment of airway patency, respiratory rate, and oxygen saturation during emergence and recovery. If repeated airway manipulation, massive hemorrhage, or emergency hysterectomy has occurred, delayed extubation and/or transfer to an ICU should be considered.

Pharmacology

Thiopental

Historically, the barbiturates (e.g., thiopental , methohexital , thiamylal ) have been the induction agents most commonly used for cesarean delivery. Extensive published data have confirmed the safety and efficacy of thiopental for induction of anesthesia in patients undergoing cesarean delivery at various gestational ages. Thiopental 4 to 6 mg/kg provides a rapid and reliable induction of anesthesia. As a negative inotrope and vasodilator, thiopental can cause decreased cardiac output and blood pressure, which may result in significant hypotension in hypovolemic patients. Some investigators have attempted to minimize this effect by using a lower dose of thiopental in combination with ketamine or propofol, with varying success.

Thiopental rapidly crosses the placenta. In 11 healthy subjects who underwent induction of general anesthesia with thiopental, the mean umbilical venous-to-maternal venous (UV/MV) ratio was 1.08 with an induction-to-delivery (I-D) interval that ranged from 8 to 22 minutes. Fetal-to-maternal concentration ratios after a single thiopental dose exposure in other studies in term infants exhibited a range of 0.43 to 0.96. The equilibration of thiopental occurs relatively rapidly in the fetus; however, fetal brain concentrations rarely exceed the threshold required for neonatal depression. With a maternal induction dose of 4 mg/kg, umbilical vein concentrations of thiopental are well below the arterial plasma concentrations necessary to produce anesthesia in adults. However, with large induction doses (8 mg/kg), thiopental can produce significant neonatal depression.

Several theories have been proposed to explain the clinical occurrence of an unconscious mother but an awake neonate: (1) preferential uptake of thiopental by the fetal liver, which is the first organ perfused by blood coming from the umbilical vein ; (2) the higher relative water content of the fetal brain ; (3) rapid redistribution of the drug into the maternal tissues, which causes a rapid reduction in the maternal-to-fetal concentration gradient; (4) nonhomogeneity of blood flow in the intervillous space; and (5) progressive dilution by admixture with the various components of the fetal circulation. Because of this rapid equilibration of thiopental and the low fetal brain concentration of thiopental, there is no advantage in delaying delivery until thiopental concentrations decline. There is no evidence that thiopental causes adverse fetal effects when the incision-to-delivery interval is prolonged.

Propofol

Propofol is an induction agent with a rapid onset, rapid recovery, and favorable side-effect profile, which includes a low incidence of nausea and vomiting. Induction with propofol can result in pain on injection and a reduction in maternal blood pressure and cardiac output. The pharmacokinetics of propofol are similar in pregnant and nonpregnant women, except for a more rapid clearance observed during pregnancy, which may partially reflect drug removal through blood loss and the delivery of the infant and placenta.

When given as an intravenous bolus, by continuous infusion, or both, propofol rapidly crosses the placenta and results in an UV/MV ratio of approximately 0.7. In an in vitro human placenta study, propofol produced vasodilation of fetal placental blood vessels and decreased the effect of various vasoconstrictors, most likely through the inhibition of calcium influx through the smooth muscle sarcolemma; lipid emulsion, the propofol carrier solution, was not responsible for these effects. One randomized trial of women undergoing cesarean delivery with general anesthesia reported lower Apgar and neurobehavioral scores in neonates delivered of mothers who received propofol compared with thiopental ; however, this finding was not replicated in a more recent randomized trial. Other studies have found no effect of propofol on neurobehavioral scores or the time to sustained spontaneous respiration with an induction bolus dose of propofol 2.5 mg/kg or with infusion doses < 6 mg/kg/h. However, higher doses of propofol (9 mg/kg/h) have been correlated with a low Neurologic and Adaptive Capacity Score (NACS).

Compared with thiopental, propofol results in a greater incidence of maternal hypotension, which may more effectively attenuate the response to laryngoscopy and tracheal intubation at the risk for reduced uteroplacental blood flow. Care must be given to closely monitor maternal blood pressure following induction with propofol and, if needed, supporting the blood pressure with vasopressors. Maternal heart rate needs to also be carefully monitored; one report noted a transient but severe episode of maternal bradycardia after administration of propofol followed by succinylcholine for rapid-sequence induction. This effect has also been demonstrated in pregnant ewes; one animal experienced severe bradycardia that led to a sinus arrest.

In a study of nonpregnant women, the interaction of propofol and ketamine was found to be additive at hypnotic and anesthetic endpoints; the cardiostimulant effects of ketamine appear to offset the cardiodepressant effects of propofol.

Ketamine

The sympathomimetic properties of ketamine make it an ideal induction agent in the setting of an urgent cesarean delivery in a patient with hypotension or an acute exacerbation of asthma. Ketamine is an analgesic, hypnotic, and amnestic agent associated with minimal respiratory depression; it is often used to supplement a neuraxial technique that may not be providing optimal anesthesia. Ketamine’s effect is likely related to antagonism of the N -methyl- d -aspartate (NMDA) receptor.

An induction dose of ketamine 1 mg/kg is associated with an increase in blood pressure and heart rate immediately after induction, and a further increase is observed after laryngoscopy and tracheal intubation. Such an increase can be desirable in the bleeding hypotensive patient but should be avoided in the parturient with hypertension (e.g., preeclampsia) or heart disease in which tachycardia or hypertension may not be well tolerated. In experimental animal models, ketamine was sometimes associated with direct myocardial depression and decreased cardiac output ; care must therefore be exercised when using this medication to induce patients with severe shock or impaired cardiac function.

Studies in pregnant ewes suggest that the use of ketamine is not associated with a reduction in uterine blood flow. Ketamine is associated with dose-dependent increases in uterine tone, but a single induction dose does not increase uterine tone at term gestation. Using an induction dose of ketamine 0.7 mg/kg in gravid ewes, a 39% increase in resting uterine tone with no effect on uterine blood flow was observed.

Ketamine rapidly crosses the placenta. No neonatal depression is observed with doses < 1 mg/kg. At higher doses, low Apgar scores, neonatal respiratory depression, and need for resuscitation have been reported. Apgar scores and umbilical cord blood gas and pH measurements at delivery with ketamine are similar to those with thiopental. A formulation of the S(+) stereoisomer of ketamine is available for clinical use in some countries outside the United States. In chronically instrumented pregnant sheep, Strumper et al. found that the effects of S(+) ketamine were similar to those of the racemic mixture in terms of maternal and fetal hemodynamics and uterine perfusion; however, S(+) ketamine was associated with a smaller increase in maternal and fetal P co ₂ than that seen with racemic ketamine in spontaneously breathing animals.

The emergence delirium and hallucinations experienced with ketamine, particularly in the unpremedicated patient, have limited the adoption of this drug as a routine induction agent for cesarean delivery. If ketamine is used, a benzodiazepine may be administered to decrease the incidence of these psychomimetic effects. Maternal awareness may still occur after an induction dose of ketamine 1 to 1.5 mg/kg, but the incidence is lower than with thiopental 4 mg/kg or a mixture of ketamine 0.5 mg/kg and thiopental 2 mg/kg. The incidence of maternal awareness can also be diminished with the coadministration of a benzodiazepine.

When used to maintain general anesthesia with 50% nitrous oxide in oxygen for cesarean delivery, a continuous infusion of ketamine (70 µg/kg/min) was followed by a higher incidence of factual recall and postoperative pain than seen with a volatile anesthetic technique, suggesting this approach is not preferred for the maintenance of anesthesia. Whether ketamine, given as a bolus or infusion initiated after infant delivery, can provide postcesarean analgesia and pain modulation remains controversial (see discussion below). One study found that patients who received ketamine 1 mg/kg for induction had lower postoperative morphine consumption than patients who received thiopental 4 mg/kg (anesthesia was maintained with nitrous oxide and isoflurane).

Etomidate

Etomidate is an induction agent that produces rapid onset of anesthesia with minimal effects on cardiorespiratory function. This property makes it ideal for parturients who are hemodynamically unstable or who would not tolerate hemodynamic aberrations (e.g., patients with severe cardiac disease). With an induction dose of 0.2 to 0.3 mg/kg, etomidate undergoes rapid hydrolysis, thereby allowing rapid recovery. Intravenous administration of etomidate may cause pain and involuntary muscle movements in unpremedicated patients; etomidate is also associated with nausea and vomiting, potential activation of seizures in patients with an epileptogenic foci, and an impaired glucocorticoid response to stress.

Etomidate crosses the placenta rapidly; however, large variations in the UV/MV ratio (0.04 to 0.5) have been reported. An induction dose of etomidate 0.3 mg/kg was associated with better neonatal acid-base measurements and overall clinical condition than with thiopental 3.5 mg/kg. A transient (<6 hours) reduction in neonatal cortisol production was observed when an induction dose of etomidate was used for cesarean delivery ; however, the clinical relevance of this finding is unclear.

Midazolam

Midazolam is a short-acting, water-soluble benzodiazepine that has few adverse hemodynamic effects and provides hypnosis and amnesia. It is commonly used as a premedicant before anesthesia but also can be used as an induction agent for cesarean delivery, although there are few indications for this purpose (e.g., when there are relative or absolute contraindications to the use of other agents). Data suggest that compared with thiopental, midazolam (at a dose of 0.2 mg/kg) for induction of anesthesia results in a higher incidence of low Apgar scores and longer time to neonatal spontaneous respiration, as well as lower neurobehavioral scores, body temperature, general body tone, and arm recoil. However, these differences are short lived and do not persist beyond 4 hours after delivery.

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