Anesthesia for Cesarean Delivery

Anesthetic Complications

Awareness and Recall

Cesarean delivery is considered to be a high-risk procedure for the occurrence of intraoperative awareness, defined as the spontaneous postoperative recall of an event that occurred during general anesthesia.⁶² The following factors contribute to the risk for maternal awareness during cesarean delivery: (1) the avoidance of sedative premedications, (2) the deliberate use of a low concentration of a volatile halogenated agent, (3) the use of muscle relaxants, (4) the reduction in dose of anesthetic agents during hypotension or hemorrhage, (5) the presence of a partial neuraxial blockade in parturients requiring conversion to general anesthesia after failed neuraxial anesthesia, and (6) the (mistaken) assumption that high baseline sympathetic tone is responsible for intraoperative tachycardia in parturients.

Concern about neonatal depression and uterine atony associated with volatile halogenated agents has led to administration of relatively low doses of these agents. Administration of a barbiturate induction agent followed by nitrous oxide 50% in oxygen resulted in maternal awareness in 12% to 26% of cases.³³¹^,³³² Using an isolated forearm technique, King et al.³⁶⁰ assessed 30 women undergoing cesarean delivery with thiopental 250 mg, succinylcholine infusion, and 0.5% halothane in 50% nitrous oxide; the majority of patients signaled pain in the first minute. The incidence of recall with this anesthetic regimen was approximately 1%.³⁶¹ The use of higher concentrations of a volatile halogenated agent has subsequently become a more common practice, leading to an incidence of maternal awareness of approximately 0.26%.⁶² However, the result of increasing the depth of maternal anesthesia is that neonates born to women who receive general anesthesia tend to have lower Apgar and neurobehavioral scores, particularly when the I-D interval exceeds 8 minutes.³⁶²

The optimal doses and concentrations of anesthetic agents to prevent awareness remain unclear, in part because of the difficulty in assessing awareness. Studies have evaluated several tools for assessment of depth of maternal anesthesia, including the electroencephalogram, brainstem auditory evoked potentials, and the bispectral index.⁶²^,²⁷⁶^,³¹¹ The bispectral index is an empirically derived electroencephalographic parameter in which values less than 60 are suggested to predict a low probability of intraoperative recall and awareness.³⁶³ With each of these monitoring devices, the threshold for awareness will need further validation, particularly during pregnancy³⁶⁴; moreover, many of these devices are not suitable for the emergency conditions under which most general anesthetics for cesarean delivery are administered.

Yeo et al.³⁶⁵ evaluated 20 women undergoing cesarean delivery and noted that an end-tidal concentration of 1% sevoflurane (approximately 0.5 MAC) with 50% nitrous oxide resulted in a range of bispectral index values between 52 and 70; no patient experienced intraoperative dreams, recall, or awareness. Using a similar regimen, Yoo et al.²⁷⁶ demonstrated that bispectral index values were lower during general anesthesia in women who were in labor prior to cesarean delivery than in nonlaboring women; the nonlaboring group did not reliably have values less than 60, and the mean value at tracheal intubation was 64 ± 10. Ittichaikulthol et al.³⁶⁶ found that mean bispectral index values in women undergoing cesarean delivery with 3% and 4.5% desflurane in 50% nitrous oxide were 62 ± 8 and 49 ± 12, respectively. Chin et al.²⁷⁵ observed that an 80% probability of maintaining bispectral index values less than 60 required a sevoflurane concentration of at least 1.2% to 1.3%.

Although pregnancy diminishes anesthetic requirements by 25% to 40%,²⁷³ administration of 0.5 MAC of a volatile halogenated agent may not reliably provide adequate depth of anesthesia to consistently prevent maternal awareness. Robins and Lyons⁶² have recommended a larger induction dose of barbiturate (e.g., thiopental 5 to 7 mg/kg instead of 3 to 4 mg/kg), an end-tidal volatile anesthetic concentration greater than 0.8 MAC, the highest concentration of nitrous oxide compatible with appropriate oxygenation, and the administration of an opioid and a benzodiazepine after delivery. Intravenous induction or infusion techniques that may reduce the risk for maternal awareness include the administration of repeat doses of thiopental,³⁶⁵ the use of ketamine,³¹⁰ or a combination of thiopental and ketamine.³¹³ Midazolam 0.075 mg/kg provides 30 to 60 minutes of anterograde amnesia when given to women undergoing elective cesarean delivery under epidural anesthesia.³⁶⁷ Induction of general anesthesia with propofol 2.4 mg/kg compared with thiopental 5 mg/kg has been associated with a significantly greater incidence (50% versus 10%) of rapid low-voltage (8-9 Hz) waves, suggestive of a light plane of anesthesia.²⁹⁵ Infusion of propofol 8 mg/kg/h with 67% nitrous oxide has also been used with satisfactory amnestic effect.³⁶⁸ Propofol exhibits an amnestic effect that is not dependent on the degree of sedation; however, the effect is significantly less than that with midazolam.³⁶⁹

The psychological morbidity associated with awareness should not be underestimated.⁶² Further investigations into the anesthetic regimens and monitoring necessary to prevent awareness and recall in pregnant women undergoing operative procedures are needed. These studies should incorporate the growing data on gender- and pregnancy-related differences in pharmacokinetics and pharmacodynamics of drugs used for anesthesia.³⁷⁰^,³⁷¹

Paradoxically, the issue of recall is not limited to the administration of general anesthesia. In women undergoing cesarean delivery with a neuraxial technique who desire treatment for anxiety, the administration of anxiolytic or hypnotic agents may result in a lack of recall of delivery, which is typically undesirable.

Dyspnea

After the initiation of neuraxial anesthesia, the patient may complain of dyspnea. The most common cause of this complaint is hypotension (causing hypoperfusion of the brainstem); therefore, the complaint of difficulty in breathing should prompt immediate assessment of blood pressure and treatment, if appropriate. Other causes of dyspnea are the blunting of thoracic proprioception, the partial blockade of abdominal and intercostal muscles, and the recumbent position, which increases the pressure of the abdominal contents against the diaphragm. The sensation of dyspnea appears related to the cephalad extent of the sensory blockade and may be mitigated by using a low-dose hyperbaric spinal bupivacaine technique in women undergoing cesarean delivery.³⁷²

Despite these changes, significant respiratory compromise is unlikely, primarily because the neuraxial blockade rarely affects the cervical nerves that control the diaphragm. Lirk et al.³⁷³ evaluated the effects of spinal bupivacaine 10 mg, ropivacaine 20 mg, and levobupivacaine 10 mg, all with fentanyl 15 µg, on women undergoing cesarean delivery. Reductions in the functional vital capacity (3 to 6%) and peak expiratory flow rate (6 to 13%) were observed; however, the findings had no apparent clinical significance, were similar for all local anesthetics, and did not differ for sensory blockade that extended higher, versus no higher, than the T4 dermatome.

If the patient loses the ability to vocalize, demonstrate a strong hand grip, and/or maintain normal oxyhemoglobin saturation (e.g., symptoms suggestive of high spinal anesthesia), a rapid-sequence induction with cricoid pressure and placement of an endotracheal tube should be performed to maintain ventilation and prevent pulmonary soiling with gastrointestinal contents.

Hypotension

Hypotension is a common sequela of neuraxial anesthesia and, if severe and sustained, may lead to impairment of uteroplacental perfusion and result in fetal hypoxia, acidosis, and neonatal depression or injury.³⁷⁴ Severe maternal hypotension can also have adverse maternal outcomes, including altered consciousness, pulmonary aspiration, apnea, and cardiac arrest.

Although not universally accepted, most investigators accept the following definitions for maternal hypotension: (1) a decrease in systolic blood pressure of more than 20% to 30% from baseline measurements or (2) a systolic blood pressure lower than 100 mm Hg.³⁷⁵ Neuraxial anesthetic techniques produce hypotension through blockade of sympathetic nerve fibers, which control vascular smooth muscle tone. Several studies using noninvasive measures of cardiac output have demonstrated that cardiac output commonly increases after spinal anesthesia, even in the presence of a phenylephrine infusion and fluid administration.³⁷⁶^-³⁷⁸ These studies emphasize that spinal anesthesia–induced hypotension is principally related to a marked decrease in systemic vascular resistance, rather than decreased cardiac output. The rate and extent of the sympathetic involvement, and subsequently the severity of hypotension, are determined by the onset and spread of the neuraxial blockade³⁷⁹; hypotension may be less common with epidural anesthesia than with spinal anesthesia because of the slower onset of neuroblockade and the earlier recognition and treatment.³⁸⁰

Risk Factors for Hypotension

A number of studies have attempted to identify pregnant women at increased risk for development of hypotension. Of interest, women with severe preeclampsia³⁸¹ or in established labor appear less likely to experience hypotension during administration of spinal anesthesia for cesarean delivery.

Using a modified orthostatic challenge (i.e., “tilt test”), Kinsella and Norris³⁸² were unable to establish a correlation in the observed change in blood pressure or heart rate with hypotension after spinal anesthesia. Similarly, Frölich and Caton³⁸³ could not establish a correlation between orthostatic blood pressure and heart rate changes and the hypotension that developed after spinal anesthesia; however, the investigators found that patients with a baseline heart rate higher than 90 bpm had a 83% chance (positive predictive value) of experiencing marked hypotension (decrease in blood pressure > 30%), whereas patients with a baseline heart rate lower than 90 bpm had a 75% chance (negative predictive value) of not experiencing marked hypotension.

Dahlgren et al.³⁸⁴ hypothesized that the response of pregnant women to a preoperative supine stress test would predict the occurrence of maternal symptoms, a need for ephedrine, or a decrease in blood pressure below 80 mm Hg during administration of spinal anesthesia for cesarean delivery. The supine stress test was considered positive if it was associated with (1) an increase in maternal heart rate greater than 10 bpm, (2) a decrease in systolic blood pressure of more than 15 mm Hg, or (3) signs and symptoms related to the supine position (e.g., nausea, dizziness). These investigators found that the preoperative stress test had a sensitivity of 69% and a specificity of 92% in identifying those who would have hypotension.

Investigators have used other methods, including assessment of heart rate variability³⁸⁵^,³⁸⁶ and noninvasive measurements of systemic vascular resistance (e.g., thoracic impedance³⁸⁷) in an attempt to identify parturients at risk for neuraxial anesthesia–induced hypotension for cesarean delivery. Hanss et al.³⁸⁵^,³⁸⁸ suggested that the low- to high-frequency ratio of heart rate variability could identify pregnant patients at risk for severe spinal anesthesia–induced hypotension and could guide prophylactic treatment with fluid and vasopressors. To date, predicting which parturients will have hypotension after neuraxial anesthesia for cesarean delivery has not proven feasible clinically and will likely require more sophisticated studies that employ a number of different methodologies; the reason may be the myriad of factors that control the autonomic, physiologic, and hormonal changes and hemodynamic responses that occur during pregnancy.

Prevention of Hypotension

A number of strategies can mitigate hypotension after spinal anesthesia for cesarean delivery, including fluid administration, vasopressor administration, lower local anesthetic doses, leg elevation or wrapping, and left uterine displacement.

The use of intravenous fluid to prevent hypotension can be manipulated by (1) timing of administration, either prior to (preload) or coincident with (co-load) the intrathecal injection, and/or (2) type of fluid, either crystalloid or colloid. Rate of fluid administration may also play a role. A crystalloid preload is minimally effective, even when volumes as great as 30 mL/kg are infused.⁹³ By contrast, a colloid preload consistently reduces the incidence and severity of hypotension. Ueyama et al.³⁸⁹ compared the administration of 1500 mL of lactated Ringer's solution and 500 mL and 1000 mL of hydroxyethyl starch solution (HES) 6% prior to spinal anesthesia for cesarean delivery; the incidence of hypotension (systolic blood pressure < 100 mm Hg and < 80% of baseline) was 75%, 58%, and 17%, respectively. Significant increases in intravascular volume and cardiac output, as measured by indocyanine green spectrophotometry, were observed in the HES groups (Figure 26-7). At 30 minutes, 100% of the HES volume, versus 28% of the lactated Ringer's volume, remained within the intravascular space.

FIGURE 26-7 The relationship between the changes (%) in blood volume and cardiac output after volume preload in parturients undergoing spinal anesthesia. Cardiac output (CO) was estimated with indocyanine green pulse spectrophotometry methodology. HES, hydroxyethyl starch solution; LR, lactated Ringer's solution. (Modified from Ueyama H, He Y, Tanigami H, et al. Effects of crystalloid and colloid preload on blood volume in the parturient undergoing spinal anesthesia for elective cesarean section. Anesthesiology 1999; 91:1571-6.)

In one trial,⁹⁴ the rapid administration of a crystalloid co-load (20 mL/kg in 10 minutes, initiated immediately on induction of spinal anesthesia) was more effective than crystalloid preload in preventing hypotension; however, a meta-analysis of randomized trials comparing crystalloid preload to co-load did not find a difference in the incidence of hypotension.⁹⁵ Similarly, no difference in the incidence of hypotension is observed with a colloid preload versus co-load, likely reflecting the intravascular dwell time of colloid.⁹⁵ Additionally, co-load administration of colloid is as effective, and likely more effective, than co-load administration of crystalloid.³⁷⁶

The cost and associated pruritus, mild coagulation abnormalities, and potential for allergic reaction to colloid starch solutions, particularly with first-generation agents, have tempered their widespread use. Possible fetal and neonatal effects related to the type and timing of maternal fluid administration deserve further investigation; for example, the rapid administration of 1500 to 2000 mL of fluid can release atrial natriuretic peptide, which may result in vasodilation and reduced sensitivity to vasoconstrictors.³⁹⁰ Our current practice is to administer a rapid crystalloid co-load (approximately 15 mL/kg) to healthy parturients undergoing elective cesarean delivery with spinal anesthesia. Parturients at high risk for hypotension (e.g., history of supine hypotension syndrome), or at high risk for the adverse consequences of hypotension (e.g., hypertrophic cardiomyopathy), receive a colloid preload (500 mL).

Vasopressor agents, including ephedrine and phenylephrine, can be titrated to maintain maternal blood pressure and have been observed to be more effective than crystalloid solution or placebo in preventing spinal anesthesia–induced hypotension. In a meta-analysis, Lee et al.³⁹¹ concluded that ephedrine was superior to placebo in the prevention of spinal anesthesia–induced hypotension for women undergoing cesarean delivery. Although greater doses of ephedrine provided more effective prophylaxis, hypotension was still observed and reactive hypertension and umbilical artery metabolic acidosis were more common.

Traditionally, ephedrine was used to prevent and treat the hypotension associated with neuraxial anesthesia because of fear that pure alpha-adrenergic agonists would decrease uterine blood flow. However, phenylephrine is equally efficacious to ephedrine for the prevention and treatment of hypotension, and it is less likely to depress umbilical arterial blood pH and base excess.³⁹² Phenylephrine crosses the placenta at a lower rate than ephedrine and undergoes greater fetal metabolism than ephedrine.³⁹³ Presumably, fetal ephedrine contributes to stimulation of fetal metabolism, resulting in lower pH and base excess than phenylephrine.³⁹⁴

There is some controversy as to whether vasopressors should be administered as a continuous infusion or bolus, particularly for the prevention of hypotension. When administered as an infusion, phenylephrine infusion rates of 25 to 100 µg/min are usually used to prevent hypotension.³⁹⁵^,³⁹⁶ However, the number of interventions to maintain systolic blood pressure within 20% of baseline are lower for phenylephrine infusions of 25 and 50 µg/min than for infusions of 75 and 100 µg/min because of the number of interventions required to treat hypertension with the higher doses. Using an up-down sequential allocation study design, the effective phenylephrine bolus dose for preventing hypotension in 95% of patients (ED₉₅) was estimated at 159 µg (95% CI, 122 to 371 µg).³⁹⁷ Reflex decreases in heart rate and reductions in cardiac output may occur with phenylephrine; however, this does not appear to affect umbilical cord blood gas measurements or neonatal Apgar scores in uncompromised infants delivered via elective cesarean delivery.³⁹⁶ The effect on infants that have been subjected to intrauterine compromise remains unclear.

One study demonstrated a salutary effect of a prophylactic infusion of ephedrine combined with phenylephrine compared with infusion of ephedrine alone.³⁹⁸ However, another study comparing infusions of different ephedrine-to-phenylephrine ratios found that as the proportion of ephedrine increased, the incidence of hypotension and nausea/vomiting also increased, whereas umbilical cord blood pH and base excess were decreased.³⁹⁹

The titration of vasopressor infusions often requires frequent infusion rate adjustments, and this mode of administration may be more cumbersome than bolus administration of the same agents. Thus, some clinicians prefer to administer a bolus dose of vasopressor to prevent or treat hypotension. Loughrey et al.⁴⁰⁰ tested various ratios of ephedrine combined with phenylephrine, administered as a bolus, but were unable to identify a combination that reliably prevented hypotension yet avoided hypertension. Methods under investigation include a closed-loop feedback computer-controlled infusion of phenylephrine for maintaining blood pressure during spinal anesthesia.⁴⁰¹

The combination of fluid and vasopressor administration may be the most effective regimen to prevent hypotension. Ngan Kee et al.⁴⁰² reduced the incidence of spinal anesthesia–associated hypotension to almost zero (1.9%) by combining a rapid crystalloid co-load with a prophylactic phenylephrine infusion (beginning at 100 µg/min); the incidence of hypotension was 28% in the women who received phenylephrine without the co-load. No difference in neonatal outcome was observed between groups.

The use of lower doses of spinal local anesthetic is associated with a lower incidence of hypotension, particularly when high and low doses are compared (e.g., hyperbaric bupivacaine 6.5 versus 9.5 mg, or 3.75 versus 9 mg; and plain bupivacaine 5 versus 10 mg combined with fentanyl 25 µg).⁴⁰³ However, the desire to use a low dose of spinal local anesthetic (e.g., bupivacaine ≤ 8 mg) should be tempered by the potential for an increased requirement for intraoperative supplemental analgesia or conversion to general anesthesia.⁴⁰⁴ The optimal local anesthetic dose is likely influenced by a number of factors, including technical factors (e.g., precision of dose, spinal level of injection, concomitant opioid use, positioning of patient during and after the block), and other factors (e.g., genetic sensitivity, patient expectations, differences in operative technique); these factors are often not controlled in studies of local anesthetic dose.⁴⁰³ Anesthesia providers who administer an intermediate or low dose of local anesthetic should consider the use of a catheter-based technique (continuous spinal or CSE anesthesia), given the frequent need (up to 40%) for supplemental administration of additional local anesthetic through the catheter.⁴⁰³

Physical methods to prevent hypotension include the use of lower limb compression bandages or pneumatic compression devices, which have demonstrated some success³⁷⁵ and may assist in preventing thromboembolic complications. Compared with the supine position, left uterine displacement does not consistently reduce the occurrence of maternal hypotension during cesarean delivery,³⁷⁵ most likely reflecting the variable presence and significance of supine hypotension syndrome. However, in some studies, adequate left uterine displacement was associated with higher umbilical arterial blood pH measurements and better neonatal outcomes than the supine position, indicating that maternal blood pressure measured at the level of the brachial artery may not always predict uteroplacental perfusion. It is not known a priori who will experience hypotension; more important, diminished uterine blood flow may occur in the presence or absence of maternal hypotension. Thus, we consider the use of left uterine displacement mandatory during anesthesia for cesarean delivery.

Treatment of Hypotension

The ideal treatment of hypotension would be reliable, titratable, easy to use, and devoid of maternal and fetal side effects. Almost 40 years ago, ephedrine, a mixed alpha- and beta-adrenergic receptor agonist, emerged as the leading choice for the treatment of hypotension on the basis of studies demonstrating its efficacy and apparent superiority (over other agents) in protecting and/or restoring uterine blood flow in gravid ewes and other pregnant animal models.⁴⁰⁵ By contrast, other agents, including metaraminol and phenylephrine, while restoring maternal blood pressure, were associated with a decrease in uterine artery blood flow and fetal pH.⁴⁰⁵

Contemporary animal studies have provided a mechanistic understanding of these effects. During pregnancy vasopressors appear to constrict the femoral artery more than the uterine artery, which increases blood pressure and protects uterine blood flow. This differential pressor effect is greater for ephedrine than metaraminol.⁴⁰⁶ A second mechanism appears to be the up-regulation of nitric oxide synthase (NOS) in the uterine artery during pregnancy.⁴⁰⁷ The presence of NOS potentially makes this artery less sensitive to vasopressors; this effect may be further augmented by ephedrine, a drug observed to independently cause the release of NOS.

In a quantitative systematic review, Lee et al.³⁹² noted that the use of ephedrine for treatment of maternal hypotension during administration of spinal anesthesia for cesarean delivery was associated with lower umbilical cord blood pH measurements than the use of phenylephrine. This surprising clinical result (which differs from results in animal studies) may reflect interspecies differences in vascular smooth muscle physiology, control of blood flow, and drug metabolism. Also, this result may reflect the fetal effects of ephedrine given to the mother. Cooper et al.³⁹⁴ developed a measurement index by subtracting the umbilical vein PCO₂ from the umbilical artery PCO₂ to determine the amount of CO₂ generated by the fetus; the index indicated a higher metabolic production of CO₂ in fetuses whose mothers received ephedrine. Ngan Kee et al.³⁹³ observed that the greater depression of fetal pH and base excess with ephedrine compared with phenylephrine appears related to its ability to cross the placenta to a greater extent, undergo less early metabolism or redistribution in the fetus, and consequently produce greater fetal concentrations of lactate, glucose, and catecholamines.

The NICE guidelines state that phenylephrine and ephedrine are equally effective as vasopressors.⁴⁰⁸ Given the efficacy of phenylephrine in the treatment of hypotension and the better umbilical cord blood acid-base measurements associated with its use in clinical studies, many anesthesia providers now use phenylephrine as a first-line agent for the prevention and treatment of maternal hypotension.⁴⁰⁹ Regardless of the vasopressor agent selected to treat hypotension, therapy should be administered as soon as the blood pressure begins to decrease, rather than after the occurrence of clinically significant hypotension.⁴¹⁰ In addition, vasopressor administration strategies can optimize maternal, and potentially fetal, hemodynamics and well-being by maintaining blood pressure near baseline, instead of lower target goals such as 80% or 90% of baseline measurements.⁴¹¹ Ephedrine is usually administered intravenously in bolus doses of 5 to 10 mg. Phenylephrine may be administered intravenously in bolus doses of 50 to 100 µg or by continuous infusion beginning at 25 to 50 µg/min,³⁹⁵ with titration to maintain maternal arterial blood pressure at or near baseline and avoidance of maternal bradycardia.³⁷⁸ Administration of ephedrine may lead to tachycardia, as well as tachyphylaxis. By contrast, phenylephrine may result in reflex maternal bradycardia, which, if treated with an anticholinergic agent in the absence of hypotension, may result in significant hypertension.

Failure of Neuraxial Blockade

“Failed” neuraxial anesthesia can be defined as neuroblockade insufficient in extent, density, or duration to provide anesthesia for cesarean delivery. Four to 13 percent of epidural anesthetics and 0.5% to 4% of spinal anesthetics fail to provide sufficient anesthesia for the initiation or completion of cesarean delivery.⁴¹²^,⁴¹³ Epidural techniques are more often associated with failure, given that the catheter is often placed during early labor, and over time the catheter may migrate out of the epidural space. Factors that may correlate with failed extension of labor epidural anesthesia for cesarean delivery include a higher number of bolus doses for the provision of labor analgesia (i.e., treatment of breakthrough pain), patient characteristics (e.g., obesity, distance from the skin to the epidural space), and the time elapsed between placement of the epidural catheter and cesarean delivery.⁴¹³

The causes of failure of neuraxial techniques include anatomic, technical, and obstetric factors. Steps to reduce the likelihood of epidural block failure include meticulous attention to technical detail, the administration of a solution that contains both a local anesthetic and an opioid, and a better understanding of the characteristics of epidural versus spinal blockade. Moreover, the patient should be prepared to expect the sensation of deep pressure and movement yet be reassured that reports of discomfort or pain will be addressed promptly. Initiation of surgery should be delayed until adequate thoracic and sacral sensory blockade has been achieved; on rare occasions, in the setting of an urgent procedure for which a developing epidural block is present at T10 but has yet to achieve a T4 level, surgery can commence with the understanding that adjuvant treatments or alternative forms of anesthesia may be required.

Evaluation of intraoperative pain requires (1) determination of the location and extent of discomfort, (2) evaluation of the sensory level of anesthesia, (3) assessment of the current status of the surgery (e.g., incision, delivery, uterine repair, skin closure), and (4) assessment of the presence of confounding factors (e.g., hemorrhage, anxiety). Shoulder pain can originate from irritation of the diaphragm (usually by amniotic fluid or blood) and is mediated by the phrenic nerve (C3 to C5); prolonged abduction and extension of the arms can also cause discomfort. Additional discomfort can occur from visceral stimulation such as uterine manipulation, which often involves the greater splanchnic nerve (T5 to T10). Alternatively, the extent of the block may be adequate but the density of neuroblockade of the large nerve fibers in the lumbosacral plexus may be inadequate. Inadequate anesthesia can result from regression of the block from a cephalad or caudad direction.

Management of breakthrough pain should begin with acknowledgement of the patient's discomfort and a consideration of the fetal (e.g., presence of nonreassuring fetal status), surgical (e.g., ongoing or anticipation of prolonged surgery), and anesthetic (e.g., maternal airway examination, BMI) implications, as well as the anesthesia provider's experience. Emergent or ongoing surgery may require administration of general anesthesia. If no block exists, the surgery has not begun, and time allows, neuraxial anesthesia can be repeated; whether an epidural or spinal technique is attempted depends on the previously mentioned factors. If an inadequate, partial block exists in an elective situation, either the surgery can be postponed (to allow resolution of the partial block) or a second neuraxial technique may be performed with caution.

The disadvantages of replacing a failed neuraxial block with epidural anesthesia include (1) the potential for local anesthetic toxicity (particularly after epidural administration of a large dose of local anesthetic for the initial attempt), (2) the time required to establish an adequate block, and (3) the unpredictable reliability and quality of the resulting block. As a consequence, many practitioners intent on replacing a failed epidural technique suggest the cautious use of a technique with an intrathecal component (i.e., spinal, CSE, or continuous spinal technique).⁴¹⁴

The performance of a spinal technique in the setting of a partial but failed epidural or spinal anesthetic technique is controversial. In this setting, intrathecal administration of a standard intrathecal dose of bupivacaine may result in a high spinal block.⁴¹⁵ Radiographic evidence suggests that the dural sac is compressed by prior epidural drug administration.²⁵⁴ Thus, when performing a spinal anesthetic technique after failed epidural or spinal anesthesia, the anesthesia provider should consider (1) using a different interspace to avoid the anatomic distortions (e.g., from the loss of resistance to saline or previous needle passes) or difficulties; (2) reducing the dose of bupivacaine (with the chosen dose depending on the extent of existing neuroblockade); (3) placing the patient in a semi-sitting (Fowler's) position to limit cephalad spread of the local anesthetic; (4) using a CSE technique with a small intrathecal dose of local anesthetic, and, if necessary, titrating the sensory level with additional drugs administered through the epidural catheter; and (5) intentionally placing an epidural catheter into the intrathecal space for administration of continuous spinal anesthesia. This last strategy may be especially useful in obese patients in whom the technical difficulty of the neuraxial approach may otherwise limit success.

If discomfort is reported after the start of surgery, it is often helpful to ask the surgeons to halt the operation while an assessment is made. If an epidural catheter is in place, an alkalinized local anesthetic with an opioid (e.g., 3% 2-chloroprocaine with fentanyl) should be administered. The density of epidural anesthesia may be improved by “repainting the fence.” An additional dose of local anesthetic (20% to 30% of the initial dose [e.g., 4 to 7 mL]) is administered approximately 20 minutes after the initial dose. This second dose serves to improve the density of neuroblockade without extending the sensory level. Some anesthesia providers routinely administer this supplemental dose, without waiting for a patient's complaint of breakthrough pain.

Intravenous administration of an opioid (fentanyl), inhalation of nitrous oxide (40% to 50% in oxygen), or intravenous anxiolysis (midazolam) may be helpful for the treatment of breakthrough pain. Severe pain may require intravenous ketamine in 5- to 10-mg increments. However, care should be taken, because the administration of multiple agents can result in significant sedation, loss of consciousness, and the presence of psychomimetic and amnestic effects. The obstetrician can infiltrate the wound or instill the peritoneal cavity with local anesthetic; however, at this point, the induction of general anesthesia with tracheal intubation is often necessary.

If the anesthesia provider anticipates that the duration of the surgical procedure will be longer than the predicted duration of epidural or CSE anesthesia, additional local anesthetic (with or without an opioid) should be administered before anticipated regression of neuroblockade (see Table 26-6). The usual dose to maintain neuroblockade is half of the initial dose.

High Neuraxial Blockade

It is not uncommon for the parturient to report mild dyspnea or reduced ability to cough, especially if the neuraxial blockade has achieved a T2 sensory level. If impaired phonation, unconsciousness, respiratory depression, or significant impairment of ventilation occurs, administration of general anesthesia should be performed. High neuraxial blockade may also result in cardiovascular sequelae, including bradycardia and hypotension. An easy method to diagnose a clinically significant high neuraxial blockade is to ask the patient to make a fist (“squeeze your fingers”). A weak hand grasp indicates high thoracic and cervical motor blockade.

High neuraxial block can be caused by several mechanisms, including an exaggerated spread of spinal or epidural drugs and unintentional intrathecal or subdural administration of an “epidural dose” of local anesthetic. The rapid epidural administration of a large volume of local anesthetic solution in the presence of a large-bore dural puncture (e.g., after a “wet tap”) may also result in high neuroblockade.

Nausea and Vomiting

Nausea and vomiting are regulated by the chemoreceptor trigger zone and the vomiting center, which are located in the area postrema and the medullary lateral reticular formation, respectively. The vomiting center receives impulses from the vagal sensory fibers in the gastrointestinal tract, the semicircular canals and ampullae (labyrinth) of the inner ear, higher cortical centers, the chemoreceptor trigger zone, and intracranial pressure receptors. Impulses from these structures are influenced by dopaminergic, muscarinic, tryptaminergic, histaminic, and opioid receptors, which are subsequently the targets for antiemetic agents. Efferent impulses from the vomiting center are transmitted through the vagus, phrenic, and spinal nerves to the abdominal muscles, which causes the physical act of vomiting.

Preoperative Nausea and Vomiting

Nausea and vomiting may occur separately or in combination and are not uncommon during pregnancy. A number of metabolic, endocrine, and anatomic changes have been implicated in the genesis of gestational nausea and vomiting, including human chorionic gonadotropin, estrogen, progesterone, prostaglandins, and immune system dysregulation.⁴¹⁶ When vomiting is sufficiently severe to produce weight loss, dehydration, acidosis from starvation, alkalosis from loss of hydrochloric acid in vomitus, and hypokalemia, it is referred to as hyperemesis gravidarum (see Chapter 16). This disorder most commonly occurs in early pregnancy, but as many as 10% of pregnant women have nausea and vomiting that persist beyond 22 weeks' gestation.⁴¹⁶ Severe and persistent hyperemesis may result in maternal and fetal morbidity.

The presence of delayed gastric emptying during labor and administration of opioids are risk factors for nausea and vomiting before cesarean delivery.

Intraoperative Nausea and Vomiting

Intraoperative nausea and vomiting associated with cesarean delivery can be variable in incidence and presentation, depending on preexisting symptoms, anesthetic and obstetric techniques, and preventive and therapeutic measures. The incidence of nausea may be as high as 80%, particularly when the anesthesia provider specifically assesses for the presence of intraoperative symptoms; symptoms occur frequently with exteriorization of the uterus.⁷ Anesthetic causes of intraoperative nausea and vomiting include hypotension and increased vagal activity; nonanesthetic causes include surgical stimuli, bleeding, medications (e.g., uterotonic agents, antibiotics), and motion at the end of surgery.⁴¹⁷ Many of these elements occur simultaneously.

Hypotension is among the most common sequelae associated with the administration of neuraxial anesthesia. Centrally, hypotension may lead to cerebral and brainstem hypoperfusion, which results in stimulation of the medullary vomiting center. Peripherally, hypotension may cause gut ischemia with release of emetogenic substances (e.g., serotonin) from the intestine.⁴¹⁸ Strict maintenance of intraoperative blood pressure can reduce the occurrence of emesis; Datta et al.⁴¹⁰ observed that the incidence of intraoperative nausea and vomiting was 66% when the blood pressure decreased more than 30% from baseline, but was less than 10% when blood pressure was maintained at baseline with ephedrine. Similarly, Ngan Kee et al.⁴¹¹ demonstrated progressive increases in intraoperative nausea and vomiting when blood pressure control with an infusion of phenylephrine was less aggressive; the incidence of nausea and vomiting was 4% when blood pressure was maintained at 100% of baseline, 16% when maintained at 90% of baseline, and 40% when maintained at 80% of baseline during spinal anesthesia for cesarean delivery.

Uterotonic agents may also contribute to intraoperative nausea and vomiting. Ergot alkaloids may cause nausea and vomiting by interacting with dopaminergic and serotoninergic receptors. Oxytocin causes nausea and vomiting primarily as a result of the hypotension produced through release of nitric oxide and atrial natriuretic peptide.⁴¹⁹ A 29% incidence of nausea and a 9% incidence of vomiting have been reported with an intravenous bolus of oxytocin 5 units during elective cesarean delivery with neuraxial anesthesia.⁴²⁰ Administration of 15-methyl prostaglandin F_2α causes nausea through the stimulation of smooth muscles of the gastrointestinal tract; a 10% incidence of nausea and vomiting has been observed after administration of 250 µg intramuscularly.⁴¹⁷

Surgical stimuli, including exteriorization of the uterus, intra-abdominal manipulation, and peritoneal traction, can cause visceral pain and subsequent nausea through the stimulation of vagal fibers and activation of the vomiting center; despite high levels of thoracic sensory block obtained for cesarean delivery anesthesia, visceral pain may still occur, particularly after the neuraxial administration of a local anesthetic without opioid.⁴²¹ The administration of neuraxial opioids reduces visceral pain–induced nausea and vomiting. Neuraxial fentanyl both improves the quality of neuraxial anesthesia and decreases intraoperative nausea; the minimal effective doses are 6.25 µg given intrathecally and 50 µg given epidurally, respectively.¹⁸⁰

Postoperative Nausea and Vomiting

Risk factors for postoperative nausea and vomiting have not been specifically studied in obstetric patients; however, studies have identified risk factors in nonobstetric patients receiving general or neuraxial anesthesia (Box 26-10).⁴²²^,⁴²³ Apfel et al.⁴²³ identified the following four highly predictive factors for postoperative nausea and vomiting in nonobstetric patients after general anesthesia, which may have relevance in the pregnant population: (1) female gender, (2) history of motion sickness or postoperative nausea and vomiting, (3) nonsmoking status, and (4) the use of perioperative opioids. The incidence of postoperative nausea and vomiting was 10% if the patient had no risk factors, 21% for one, 39% for two, 61% for three, and 79% for four. A subset of pregnant women may have a lower threshold for nausea and vomiting associated with motion.⁴¹⁶ Changes in position and transfer to and on the stretcher may stimulate afferent neural pathways that trigger emesis. Because the histamine-1 (H₁) and muscarinic cholinergic pathways play primary roles in this response, antihistamine and anticholinergic agents should be considered first-line treatments.⁴²⁴ Postoperative nausea and vomiting may be related to postoperative ileus, which in turn is influenced by the effect of opioids on the gastrointestinal tract, the activation of the sympathetic nervous system, the occurrence of intestinal wall inflammation, and the presence of volume overload or edema.⁴¹⁶

Prophylaxis and Treatment of Nausea and Vomiting

Preventing maternal hypotension may be the best means of preventing nausea and vomiting (see earlier). Several options exist for the pharmacologic prophylaxis of nausea and vomiting, and several different classes of drugs are available (Table 26-7). Although various algorithms have been developed to prevent postoperative nausea and vomiting, primarily targeting the nonpregnant patient population, none has been universally successful.⁴²⁵ However, the prophylactic use of these agents either before or after umbilical cord clamping during cesarean delivery with neuraxial anesthesia has been demonstrated to be highly effective. Balki and Carvalho⁴¹⁷ suggested an algorithm consisting of metoclopramide as a first-line agent, dimenhydrinate as a second-line agent, and ondansetron or granisetron as a third-line agent. Multimodal therapies may eventually prove the most effective.

TABLE 26-7

Agents for Prevention of Nausea and Vomiting in Women Undergoing Cesarean Delivery with Neuraxial Anesthesia *

^* If nausea and vomiting occur despite prophylaxis, the anesthesia provider should consider administration of a drug from a different pharmacologic class. There is no evidence that a second administration of the same drug within 6 hours provides additional benefit.

^† Studies in nonobstetric patients suggest that administration of dexamethasone at induction of anesthesia results in better efficacy, but the optimal timing in obstetric patients is unclear.

^‡ Has not been studied in patients undergoing cesarean delivery with neuraxial anesthesia; however, this drug has proved effective for prophylaxis of postoperative nausea and vomiting in studies of nonobstetric patients after administration of general anesthesia.

IM, intramuscularly; IV, intravenously.

Metoclopramide is the agent most frequently given, owing to its favorable prokinetic effects. Common side effects include dizziness, drowsiness, and fatigue; more rare side effects include extrapyramidal reactions and acute dystonias. In a meta-analysis of 11 studies of 702 patients undergoing cesarean delivery, Mishriky and Habib⁷⁵ found that intravenous metoclopramide 10 mg, administered before neuraxial blockade, resulted in a significant reduction in intraoperative nausea (RR, 0.27; 95% CI, 0.16 to 0.45) and vomiting (RR, 0.14; 95% CI, 0.03 to 0.56) when metoclopramide, rather than placebo, was administrated before neuraxial blockade. This approach was more effective than giving metoclopramide after delivery, an approach that also resulted in a significant reduction in perioperative nausea and vomiting. Early postoperative nausea (RR, 0.47; 95% CI, 0.26 to 0.87) and vomiting (RR, 0.45; 95% CI, 0.21 to 0.93) were also reduced with metoclopramide.

Abouleish et al.⁴²⁶ found that ondansetron was more effective than placebo for the prevention of intraoperative nausea and vomiting during cesarean delivery with spinal anesthesia. Pan and Moore⁴²⁷ observed that when administered after umbilical cord clamping, ondansetron 4 mg was more effective than metoclopramide 10 mg in preventing nausea (26% versus 51%) but not vomiting (15% versus 18%). In a systematic review, Griffiths et al.⁴²⁸ concluded that the use of a serotonin antagonist (e.g., ondansetron, granisetron) in women undergoing neuraxial anesthesia for cesarean delivery was associated with a reduction in intraoperative nausea (but not vomiting) and postoperative nausea and vomiting, compared with placebo. Furthermore, serotonin antagonists were found to be more effective in reducing postoperative nausea than dopamine antagonists (e.g., metoclopramide, droperidol).⁴²⁸

In an animal toxicology study that was followed by a human clinical trial, Han et al.⁴²⁹ demonstrated no histologic changes in spinal cord tissues after epidural administration of ondansetron in rats. Moreover, in 80 women undergoing elective cesarean delivery with CSE anesthesia, the incidence of postoperative nausea was lower in women randomized to receive an epidural infusion of ondansetron than in women who received an intravenous infusion (8 mg over 48 hours) at both 24 and 48 hours.⁴²⁹ However, future investigations are needed to validate the safety of the neuraxial administration of ondansetron before this route of administration can be recommended.

In a meta-analysis, Allen et al.⁴³⁰ found that a single intravenous dose of dexamethasone 5 to 10 mg (but not 2.5 mg) compared with placebo reduced the incidence of postoperative nausea (23% versus 41%, respectively) and vomiting (20% versus 36%, respectively) in women who received neuraxial morphine for cesarean delivery. In a subgroup analysis, the authors identified a lower incidence of postoperative nausea and vomiting in women who received epidural morphine; however, they were unable to draw definitive conclusions regarding the effect of dexamethasone on postoperative nausea and vomiting in women who received spinal morphine because of the small sample size.

Harnett et al.⁴³¹ observed that the administration of a transdermal scopolamine 1.5-mg patch after umbilical cord clamping was as effective as ondansetron 4 mg in the prevention of nausea and vomiting after cesarean delivery with spinal anesthesia (bupivacaine 12 mg with fentanyl 10 µg and morphine 0.2 mg); compared with placebo, both drugs resulted in a reduction in the incidence of postoperative emesis from approximately 60% to approximately 40%. The use of scopolamine may be limited by side effects, particularly dry mouth and blurry vision. The results of a systematic review suggest that the use of an anticholinergic agent (e.g., scopolamine, glycopyrrolate) in women undergoing neuraxial anesthesia for cesarean delivery results in a significant reduction in intraoperative nausea but not vomiting.⁴²⁸

Alternative therapies may play a role in preventing or treating perioperative nausea and vomiting. Several studies have found a favorable effect of acupressure on the P6 acupoint (on the inner aspect of the wrist). After spinal anesthesia for cesarean delivery, acupressure has been observed to result in a lower incidence of nausea (36% and 15%, respectively) and vomiting (17% and 9%, respectively), when compared with placebo.⁴³² Two systematic reviews of randomized controlled trials involving a total of 649 women undergoing neuraxial anesthesia for cesarean delivery concluded that despite heterogeneity in the data, P6 stimulation (compared with placebo) appears to reduce intraoperative nausea but not intraoperative vomiting or postoperative nausea or vomiting.⁴²⁸^,⁴³³

One study found that the administration of supplemental oxygen (FIO₂ of 0.7) between umbilical cord clamping and the end of cesarean delivery with neuraxial anesthesia was not associated with a lower incidence of nausea and vomiting than the administration of room air.⁴³⁴ This finding is consistent with a meta-analysis⁴³⁵ of randomized controlled trials in the nonobstetric population; there was no difference in the incidence of nausea and vomiting with the use of supplemental oxygen (FIO₂ of 0.8) compared with the use of lower oxygen concentrations (FIO₂ of 0.3 to 0.4).⁴³⁵

A systematic review⁴²⁸ suggests that the administration of subhypnotic doses of propofol (0.5 to 1.5 mg/kg/h) for the reduction of intraoperative and postoperative nausea and vomiting in women undergoing neuraxial anesthesia for cesarean delivery is more effective than placebo; however, there are insufficient data to compare this method with other therapies.⁴²⁸

Perioperative Pain

In contrast to surveys performed in the general surgical patient population, in which patients have revealed a primary concern for postoperative nausea and vomiting, a survey performed in obstetric patients during their expectant parent class indicated that pain during and after cesarean delivery was their greatest concern.⁴³⁶ Inadequate neuraxial anesthesia leading to pain during labor or cesarean delivery was the most frequent “damaging event” in obstetric claims (31%) against the National Health Service in the United Kingdom from 1995 to 2007.⁴³⁷ Although pain during cesarean delivery was generally classified as “mild” or “moderate” (when accompanied by post-traumatic stress disorder), it represented an especially frequent cause of low-severity obstetric claims.⁴³⁷ Pain due to inadequate neuraxial anesthesia is also a common cause of obstetric complaints in the American Society of Anesthesiologists Closed-Claims Project database (see Chapter 33).

A preoperative discussion about pain and discomfort can help allay patient concerns. The anesthesia provider should (1) explain that there may be some deep pressure, pain, or discomfort during cesarean delivery performed with a neuraxial technique; (2) reassure the patient that the anesthesia provider will be present throughout the operation to administer additional analgesics or general anesthesia if necessary; (3) ensure and document adequacy of neuraxial blockade before the start of surgery; (4) communicate with the patient frequently during the procedure, specifically about pain or discomfort; and (5) treat pain when it arises, in agreement with the patient's wishes. During the postoperative visit, the anesthesia provider should address any concerns that may have arisen during or after surgery.

The anesthetic technique for the cesarean delivery may be altered because of postoperative pain management considerations. For example, an epidural catheter–based technique may be optimal for the patient with a significant pain history (e.g., sickle cell vaso-occlusive crises, chronic pain syndromes, drug-seeking behavior) so that the epidural catheter may be used for postoperative pain management.

By directly activating spinal and supraspinal opioid receptors, epidurally and spinally administered opioids blunt nociceptive input and produce analgesia of greater intensity than parenterally or intramuscularly administered doses.²¹⁴ A number of opioids have been used in the epidural and spinal spaces; however, morphine has emerged as the leading agent for postcesarean analgesia, owing to its long duration of action and low cost (see Chapter 28). When morphine is administered intrathecally or epidurally, doses of 0.1 mg and 3.75 mg, respectively, appear to provide optimal analgesia after cesarean delivery.¹⁹²^,²²² Neuraxial morphine has a peak analgesic effect at 60 to 90 minutes but continues to provide effective analgesia for up to 24 hours.²²² Thus, intrathecal morphine is often co-administered with the local anesthetic and lipid-soluble opioid administered for spinal anesthesia, and epidural morphine is administered intraoperatively, after the umbilical cord is clamped, to allow sufficient time for the onset of epidural morphine analgesia before the regression of epidural anesthesia.

The local anesthetic selected for epidural anesthesia may influence postoperative analgesia. The epidural administration of 2-chloroprocaine has been observed to adversely affect the subsequent efficacy of epidural morphine analgesia,⁴³⁸ although this remains a matter of some dispute.⁴³⁹ The mechanism for this potential interaction remains unknown, however, the use of 2-chloroprocaine should be limited to emergency situations in which rapid augmentation of epidural anesthesia is desired (see earlier discussion).

Adverse effects of neuraxial morphine include pruritus, nausea and vomiting, urinary retention, and delayed respiratory depression. Frequent evaluations (hourly for the first 12 hours, and then every 2 hours for another 12 hours) should be conducted.⁴⁴⁰ Postpartum women who are morbidly obese or have preexisting respiratory issues (sleep apnea) are at greater risk for respiratory depression.

Postoperative pain has at least two components, somatic and visceral. A multimodal approach with different agents (e.g., ketamine) and techniques (e.g., infiltration, peritoneal spraying, transversus abdominis plane [TAP] block) provides the most effective postcesarean analgesia (see Chapters 27 and 28). The administration of nonsteroidal anti-inflammatory drugs has been associated with potential adverse effects (platelet dysfunction, uterine atony), and some investigators have expressed concerns related to neonatal exposure through breast milk. However, the American Academy of Pediatrics⁴⁴¹ has stated that ibuprofen and ketorolac are compatible with breast-feeding.

Pruritus

The incidence of pruritus with the administration of opioids can be as high as 30% to 100%, and pruritus is more commonly observed when opioids are administered intrathecally than epidurally. Pruritus may be generalized or localized to regions of the nose, face, and chest and is typically self-limited in duration. The particular combinations and doses of opioid and local anesthetic may influence the incidence and severity of pruritus, and the addition of epinephrine to an opioid–local anesthetic solution has been observed to worsen pruritus.⁴⁴² Pruritus does not represent an allergic reaction to the neuraxial opioid. If flushing, urticaria, rhinitis, bronchoconstriction, or cardiac symptoms also occur, an allergic reaction to another substance should be considered.

The cause of neuraxial opioid–induced pruritus is not known, although multiple theories have been proposed. They include µ-opioid receptor stimulation at the medullary dorsal horn, antagonism of inhibitory transmitters, and activation of an “itch center” in the central nervous system.⁴⁴³ Pharmacologic prophylaxis or treatment of pruritus may include an opioid antagonist, an opioid agonist/antagonist, droperidol, a serotonin antagonist (e.g., ondansetron), and/or a subhypnotic dose of propofol (Table 26-8).⁴⁴³ Intravenous administration of granisetron 3 mg may reduce the severity but not the incidence of intrathecal morphine–induced pruritus when compared with administration of ondansetron 8 mg.⁴⁴⁴ Dexamethasone in doses of 2.5 to 10 mg has not been found to reduce the incidence of pruritus associated with neuraxial morphine in women undergoing cesarean delivery.⁴³⁰ Although opioid antagonists, such as naltrexone and naloxone, and partial agonist/antagonists, such as nalbuphine, are currently the most effective treatments for pruritus, a single dose or continuous intravenous infusion of any of these agents may reverse analgesia. Because the primary mechanisms of opioid-induced pruritus appears unrelated to histamine release, antihistamines seldom represent a viable treatment option, although some benefit may be derived from the accompanying sedative qualities of these agents.

TABLE 26-8

Agents for Prevention or Treatment of Pruritus in Women Undergoing Cesarean Delivery

Drug Class	Drug and Dose	Comments
Opioid antagonists	Naloxone infusion 1-2 µg/kg/h IV Naltrexone 6-9 mg PO	May reverse analgesia
Opioid agonist/antagonist	Nalbuphine 2.5-5 mg IV
Sedative/hypnotic agent	Propofol 10-20 mg IV	Subhypnotic dose with conflicting evidence regarding efficacy in treating pruritus
Serotonin antagonist	Ondansetron 0.1 mg/kg IV	Conflicting evidence regarding efficacy in treating pruritus
Butyrophenone	Droperidol 1.25 mg IV	Package insert contains an FDA “black box” warning regarding prolongation of corrected QT interval on electrocardiogram

IV, intravenously; PO, orally.

Hypothermia and Shivering

Perioperative hypothermia and shivering are commonly observed in women undergoing cesarean delivery, with a reported incidence of 66% and 85%, respectively.⁴⁴⁵^,⁴⁴⁶ Hypothermia has been associated with a number of adverse outcomes in nonpregnant surgical patients, including wound infection, coagulopathy, increased blood and transfusion requirements, increased oxygen consumption, decreased metabolism, and prolonged recovery.⁴⁴⁷ In a systematic evaluation of randomized trials of normothermic and mildly hypothermic (34° C to 36° C) nonpregnant surgical patients, Rajagopalan et al.⁴⁴⁸ observed that even hypothermia less than 1° C below normal body temperature was associated with a 16% increase in blood loss (95% CI, 4% to 26%) and a 22% increase in risk for transfusion (95% CI, 3% to 37%).

Normally, core body temperature is tightly regulated within a narrow range of 36° C to 37° C. During pregnancy, despite an increase in maternal basal metabolic rate and energy released by the developing fetal and uteroplacental unit, maternal core temperature decreases, reaching a nadir at 12 weeks postpartum (36.4° C).⁴⁴⁹ Major causes of hypothermia during cesarean delivery are most likely related to core-to-periphery heat redistribution due to diminished vasoconstriction and shivering, particularly after neuraxial blockade, and impairment of centrally mediated thermoregulatory control.⁴⁴⁷

The onset and severity of hypothermia and shivering are associated with the patient's baseline thermal status, the perioperative environment, and the anesthetic technique and agents selected. Saito et al.⁴⁵⁰ observed that spinal anesthesia reduced the initial core temperature of patients undergoing cesarean delivery more rapidly than epidural anesthesia, but the overall incidence of shivering was similar. However, the severity of shivering was significantly less in the spinal group, possibly through the induction of a lower shivering threshold or the inhibition of thermoregulatory control as a function of the number of blocked dermatomes.⁴⁵¹

The effect of neuraxial opioids on thermoregulation and shivering in patients undergoing cesarean delivery is not fully understood. Intravenously administered meperidine 12.5 to 25 mg is one of the most effective antishivering drugs known and is unique among opioids in producing this effect at doses not typically associated with respiratory depression. The mechanism of this effect does not appear to be related to κ-opioid receptor activity or inhibition of cholinergic receptors; instead, central α_2B-adrenergic receptor stimulation may be involved.⁴⁵² The α₂-adrenergic receptor agonists clonidine (150 µg) and dexmedetomidine are effective antishivering agents that can lower the shivering threshold,⁴⁵² although both agents may have limited use during pregnancy because of the potential to cause sedation, bradycardia, and hypotension. Other modalities have been used to prevent and treat hypothermia and shivering. Preoperative patient warming using forced air has been shown to reduce the incidence of perioperative and postoperative core hypothermia and shivering in patients undergoing cesarean delivery with epidural anesthesia.⁴⁵³ In contrast, a subsequent study found that perioperative forced-air warming did not prevent maternal hypothermia after cesarean delivery with spinal anesthesia.⁴⁴⁵ Lower limb wrapping has also been observed to have no effect on the incidence of hypothermia or shivering.⁴⁵⁴

Obstetric Complications

Postpartum Hemorrhage

A leading cause of maternal and fetal morbidity and mortality worldwide, mild to moderate obstetric hemorrhage can be masked by pregnancy-related physiologic changes. Underestimation of blood loss and inadequacy of resuscitation remain common problems (see Chapter 38).

Failure of the uterus to contract (uterine atony) after delivery accounts for most cases of postpartum hemorrhage and remains a leading cause of postpartum hysterectomy and blood transfusion. Each minute, 600 to 700 mL of blood flows through the placental intervillous spaces; thus, obstetric hemorrhage can rapidly result in maternal shock. Uterine atony occurs more commonly after cesarean delivery than after vaginal delivery, perhaps as a reflection of the condition(s) that prompted the cesarean delivery or possibly because surgery disrupts the normal postpartum response to uterotonic hormones and pharmacologic agents. Risk factors for uterine atony include (1) high parity, (2) an overdistended uterus (multiple gestation, macrosomia, polyhydramnios), (3) prolonged labor (augmented by oxytocin), (4) chorioamnionitis, (5) abnormalities in placentation (placenta accreta, increta, or percreta), (6) retained placental tissue, and (7) poor perfusion of the uterine myometrium (e.g., with hypotension).

Initial efforts to control uterine atony include uterine massage and exogenous oxytocin administration. Postpartum oxytocin is administered in a wide range of doses, methods, and timing patterns (e.g., before or after delivery of the placenta),⁴⁵⁵ although small doses of oxytocin are sufficient to produce adequate uterine contraction after cesarean delivery in most women.⁴⁵⁵ The effective bolus dose necessary for adequate uterine tone in 90% (ED₉₀) of nonlaboring women undergoing cesarean delivery oxytocin is 0.35 unit⁴⁵⁶; in laboring women who have received approximately 10 hours of oxytocin augmentation, the ED₉₀ is 2.99 units.⁴⁵⁷ George et al.⁴⁵⁸ estimated the ED₉₀ of an oxytocin infusion to be 0.29 unit/min (95% CI, 0.15 to 0.43).

Women receiving oxytocin augmentation for labor have greater blood loss despite higher oxytocin doses; this appears to originate from signal attenuation and desensitization of the oxytocin receptors in a time- and concentration-dependent manner.⁴⁵⁹^-⁴⁶² Continued high-dose oxytocin exposure in the postpartum period can lead to acute receptor desensitization and render the myometrium less responsive to additional oxytocin but not to other uterotonic agents.⁴⁶² Pregnancy causes a 180-fold increase in the concentration of oxytocin receptors with a significant proportion of this increase occurring just before the onset of labor⁴⁶³; this change in receptor number may have relevance to parturients who are delivering preterm infants.

Tsen and Balki⁴⁵⁵ have suggested a “rule of 3's” (oxytocin 3 units, 3-minute evaluation intervals, 3 total doses, and oxytocin 3 units/h for maintenance) protocol for the administration of oxytocin after delivery. The oxytocin 3 units is given as a slow bolus or as an infusion (30 units oxytocin in 500 mL of normal saline [50 mL]), at a rate no faster than over a period of 15 seconds. Uterine tone is reassessed again at 3 and 6 minutes; if inadequate, an additional dose of oxytocin 3 units is given. If uterine atony persists after three total doses of oxytocin, other uterotonic agents should be employed (see later discussion). The specific timing of the initial dose of oxytocin varies by individual practitioner; insufficient data are available to determine whether oxytocin administration immediately on emergence of the infant's shoulder or body or after placental delivery makes a difference in overall blood loss during cesarean delivery. After the establishment of adequate uterine tone, an infusion of 3 units/h for up to 5 hours is recommended.⁴⁵⁵

The administration of oxytocin as a rapid intravenous bolus causes hypotension and may result in cardiovascular collapse⁴⁶⁴^,⁴⁶⁵; patients with preeclampsia may have an unpredictable hemodynamic response to oxytocin administration (i.e., decrease in cardiac output).⁴⁶⁶ Oxytocin has a direct relaxing effect on the vascular smooth muscle, which leads to decreased systemic vascular resistance, hypotension, and tachycardia.⁴⁶⁷ Tachycardia also may result from a direct effect on specific oxytocic receptors in the myocardium and subsequently result in alterations in atrioventricular conduction and myocardial repolarization.⁴⁶⁷ Chest pain and signs suggestive of myocardial ischemia and anaphylaxis may occur. Owing to the structural similarity of oxytocin to vasopressin, water intoxication may occur and, when severe, can lead to hyponatremia, confusion, convulsions, and coma.

If oxytocin proves ineffective, the ergot alkaloid derivative methylergonovine (0.2 mg) may be given intramuscularly to enhance uterine tone; onset time is within 10 minutes and the effect persists for 3 to 6 hours. Intravenous administration (in small divided doses) should be performed only with great caution, because intense vasoconstriction may lead to acute hypertension, seizures, cerebrovascular accident, retinal detachment, and myocardial arrest⁴⁶⁸; this possibility is of special concern in patients with preeclampsia or cardiac disease. Methylergonovine also has additive hemodynamic effects when given with sympathomimetic agents, such as ephedrine and phenylephrine. Nausea and vomiting are common side effects, which most likely reflect a direct central nervous system effect. The co-administration of oxytocin and ergometrine has been demonstrated to improve uterine contractions (as measured by the requirement for additional uterotonic agents) compared with the administration of oxytocin alone; however, the estimated blood loss was not different between groups, and nausea and vomiting were more prevalent with the oxytocin-ergometrine combination.⁴⁶⁹

Uterine sensitivity to prostaglandins increases with advancing gestation. 15-Methyl prostaglandin F_2α causes a dose-dependent increase in the force and the frequency of uterine contractions. The initial recommended dose is 250 µg given intramuscularly; this dose can be repeated if necessary at 15- to 90-minute intervals up to a maximum of eight doses.⁴⁷⁰ Whether 15-methylprostaglandin F_2α is more effective than oxytocin is controversial⁴⁷¹; however, it clearly has a role in the treatment of refractory uterine atony.⁴⁷² In approximately 20% of women, the following side effects occur (listed in descending order of frequency): diarrhea, hypertension, vomiting, fever, flushing, and tachycardia.⁴⁷² Bronchospasm, pulmonary vasoconstriction, and oxyhemoglobin desaturation may also occur.

Rectal or sublingual administration of prostaglandin E₁ (misoprostol) is a uterotonic agent with a rapid onset of action. A systematic review of prophylactic misoprostol (given orally or sublingually in doses ranging from 400 to 800 µg) administered for the active management of the third stage of labor concluded that it is more effective than placebo in preventing severe postpartum hemorrhage but less effective than conventional injectable uterotonic agents.⁴⁷³ Several large studies have assessed misoprostol's role in the treatment of postpartum hemorrhage. An editorial concluded that the drug was no more effective than oxytocin and was associated with more side effects.⁴⁷⁴ These side effects include hyperthermia and severe shivering. There may be a prophylactic role for this drug in low-resource settings where oxytocin is not available.

Preparation for Blood Loss

When risk factors for hemorrhage are identified, several preparatory steps can be considered. Iron supplementation and use of recombinant human erythropoietin are effective therapies for producing red blood cells, particularly in patients with preexisting anemia, renal failure, and/or reasons for preoperative donation of autologous blood.⁴⁷⁵ Antepartum erythropoietin administration may be of value in pregnant women at high risk for hemorrhage; however, additional investigation is needed to determine the optimal dosing, goals of therapy, and side-effect profiles. Hypertension, a problem associated with the use of erythropoietin in patients with renal failure, is a relevant concern during pregnancy. Although normal pregnancy is associated with a twofold to fourfold increase in maternal erythropoietin levels, isolated studies of the effect of erythropoietin on placental vessels suggest that dose-dependent vasoconstriction occurs.⁴⁷⁶ Observation of high erythropoietin levels in hypertensive and preeclamptic parturients has fueled speculation that erythropoietin participates in the humoral mechanisms responsible for preeclampsia and fetal growth restriction (also known as intrauterine growth restriction).⁴⁷⁷ A hyperglycosylated analogue of recombinant human erythropoietin (darbepoetin) has a threefold longer terminal half-life and results in a more rapid and greater erythropoietic response than recombinant human erythropoietin. This novel protein may be useful in the setting of anticipated or actual obstetric hemorrhage if concerns about its adverse effects are alleviated.⁴⁷⁵

The efficacy of preoperative autologous blood donation is limited by the maximum life span of stored blood; collection can start no sooner than 6 weeks before a planned delivery, with an average unit collection interval of 3 to 7 days. This method may be of some use in a woman with maternal antibodies to red blood cell antigens. The technique seems safe but has limited applicability and efficacy in obstetric patients (see Chapter 38).

Acute normovolemic hemodilution has the advantage of reducing the risk for administrative errors and bacterial contamination and allowing the infusion of whole blood replete with functional coagulation factors and platelets. This technique may reduce the need for transfusion in selected patients, and it may be acceptable to Jehovah's Witness patients at increased risk for blood loss during cesarean delivery.

The use of intraoperative red blood cell salvage in obstetric patients is gaining greater acceptance.⁴⁷⁸ In the past, obstetric anesthesia providers have expressed concern that intraoperative cell salvage might precipitate amniotic fluid embolism. Allam et al.⁴⁷⁸ noted that “existing cell salvage systems differ in their ability to clear contaminants and all require the addition of a leucocyte depletion filter.” The cell salvage process does not remove all fetal red blood cells and hemoglobin, and maternal isoimmunization may occur.⁴⁷⁹ Intraoperative cell salvage may be used to prevent morbidity and mortality in parturients who refuse homologous blood or in cases of intractable hemorrhage that may overwhelm blood bank supplies (see Chapter 38).³⁴

Response to Blood Loss

Underestimation of blood loss and inadequate resuscitation are common problems in the management of obstetric hemorrhage. Rapid volume replacement is more important in maintaining tissue perfusion and oxygenation than the type of administered fluid. Colloids and blood products should be considered early, along with a request for assistance, establishment of a second large-bore intravenous catheter, and use of pressurized transfusion equipment. Many institutions require performance of a blood type and screen for parturients at high risk for hemorrhage undergoing a trial of labor for a planned vaginal delivery and in all parturients undergoing cesarean delivery. The immediate availability of two to four units of crossmatched packed red blood cells should be considered when the potential for significant blood loss appears imminent, such as in women suspected placenta accreta. In situations in which the need for emergency blood transfusion precedes the availability of crossmatched blood, type-specific (or type O, Rh-negative blood) should be administered. All institutions should consider the development of a massive transfusion protocol.⁴⁸⁰ Continued blood loss and hemodynamic instability despite transfusion of packed red blood cells is often an indication for placement of an arterial line and invasive central venous pressure monitoring; however, restoration of circulating volume takes precedence. Urine output, heart rate, blood pressure, and transthoracic or transesophageal echocardiography (TTE or TEE)⁴⁸¹ assessments can assist in the rapid evaluation of the adequacy of volume resuscitation.

Fortunately, most pregnant women are healthy and tolerate modest blood loss well. Also, concerns about uteroplacental perfusion and fetal oxygenation are no longer present after delivery of the infant. The ASA Task Force on Blood Component Therapy⁴⁸² has concluded that transfusion of packed red blood cells is rarely indicated when the hemoglobin concentration is greater than 10 g/dL and is almost always indicated when the hemoglobin concentration is less than 6 g/dL. Transfusion of platelets is rarely indicated unless the platelet count is less than 100,000/mm³ (unless platelet dysfunction and microvascular bleeding are present), and replacement of fibrinogen is rarely indicated unless the fibrinogen concentration is less than 150 mg/dL in the presence of microvascular bleeding. However, decreases in fibrinogen concentrations at levels higher than this threshold may serve as an early predictor of the severity of obstetric hemorrhage.⁴⁸³

The prophylactic placement of intravascular balloon occlusion catheters can facilitate the timely control of obstetric bleeding in some parturients at high risk for hemorrhage.⁴⁸⁴ Harnett et al.⁵⁰ have recommended the placement of an epidural catheter prior to an intravascular balloon catheter for the following reasons: (1) once the balloon catheter is placed, flexion of the hips (during positioning for a neuraxial anesthetic technique) is discouraged, because it may result in balloon dislodgement or occlusion and subsequent thrombosis; (2) epidural anesthesia seems preferable to the use of local anesthesia with sedation for balloon catheter placement; (3) during balloon catheter placement, small amounts of heparin are sometimes used, and it seems preferable to have the epidural catheter in place prior to anticoagulation; and (4) should untoward events (e.g., fetal compromise, vessel rupture) occur during the procedure, the epidural catheter allows for rapid extension of anesthesia for cesarean delivery. With prior planning, operative procedures, including cesarean delivery, can be performed successfully under neuraxial anesthesia in the interventional radiology suite.⁵⁰

When uterine bleeding occurs postpartum, the use of uterine tamponade balloon catheters has been demonstrated to tamponade and potentially treat intrauterine sources of bleeding and allow time to correct coagulopathy.⁴⁸⁵ A number of balloon catheters have been used by practitioners for uterine tamponade (e.g., Sengstaken-Blakemore esophageal balloon, Foley urinary catheters). Commercial balloon catheters designed specifically for uterine tamponade are now available. Some of the catheter designs allow for uterine cavity drainage, with variable success in function and ability to identify ongoing, significant bleeding.⁴⁸⁵ The balloons are often left in place for 24 to 48 hours, along with a vaginal pack and continued antibiotic administration. Distention of the uterus causes discomfort, and pain relief should be provided, either with systemic agents or epidural analgesia if a catheter is in situ. We typically provide continuous epidural analgesia, or patient-controlled epidural analgesia, with a dilute solution of local anesthetic and a lipid-soluble opioid, similar to that used for labor analgesia. The epidural catheter, regardless if used for analgesia, is typically kept in place until the uterine balloon is deflated to allow for rapid transition to surgical anesthesia if necessary.

The treatment of postpartum hemorrhage with human recombinant factor VIIa (rFVIIa), a vitamin K–dependent protein licensed for the treatment of bleeding episodes in patients who have hemophilia A or B with inhibitors to factor VIII or factor IX, remains controversial (see Chapter 38). Off-label administration of rFVIIa has resulted in cessation or reduction of severe bleeding refractory to standard hematologic or hemostatic support in a variety of animal and human trials and case reports or series.⁴⁸⁶ Administration of rFVIIa promotes clotting primarily through the extrinsic (tissue factor) pathway with some activation of the intrinsic pathway and should be combined with best practice use of blood products (i.e., blood product component therapy). Administered as an intravenous dose of 60 to 100 µg/kg, rFVIIa has been observed to have a clinical effect within 10 minutes in some cases. The half-life of the drug is 2 to 6 hours, and side effects consist primarily of hypertension, hypotension, bradycardia, renal dysfunction, and thromboembolism.⁴⁸⁶ Observational trials in the setting of traumatic injury are being performed, but to date there have been no large randomized studies of rFVIIa in obstetric patients.

Obstetric Hysterectomy

The incidence of cesarean hysterectomy and emergency postpartum hysterectomy ranges from 0.03% to 0.33% in different hospital settings and countries.⁴⁸⁷ Over a 14-year period in the United States, the rate of peripartum hysterectomy per 100,000 deliveries increased from 71.6 (1994 to 1995) to 82.6 (2006 to 2007); this increased rate was associated with an increased rate of abnormal placentation (e.g., placenta previa, placenta accreta) from 32.9 to 40.5 and an increased rate of uterine atony from 11.2 to 25.9 per 100,000 deliveries.⁴⁸⁸ Increasing rates of cesarean delivery, failed trial of labor, infection, intrauterine fetal death, and disseminated intravascular coagulation are other factors associated with cesarean hysterectomy. Improvements in ultrasonography, color flow Doppler ultrasonography, and magnetic resonance imaging have allowed earlier identification of some women with placenta accreta; however, limitations in diagnostic sensitivity and specificity exist.⁴⁸⁹

Cesarean hysterectomy is considered a high-risk procedure owing to the vascularity and size of the uterus and the distorted anatomic relationships. Bladder and ureteral injuries are common. Prior to performance of hysterectomy, various conservative medical and surgical treatment modalities may be attempted (see Chapter 38). The ligation or embolization of major and collateral uterine vessels with the assistance of an interventional radiologist is becoming more common, particularly in tertiary care settings.⁴⁸⁴

The amount of blood loss depends in part on whether the hysterectomy is elective or an emergency. In a prospective review of all obstetric hysterectomies performed at five university hospitals (1984 to 1987), Chestnut et al.⁴⁹⁰ found an average blood loss of 1319 mL and 2526 mL in 25 elective and 21 emergency cases, respectively, with an average replacement of 1.6 units and 6.6 units of blood, respectively. In a more recent study, Briery et al.⁴⁹¹ performed a multicenter retrospective review of operative and postoperative outcomes in 30 elective and 35 emergency cesarean hysterectomies; the mean (± SD) blood loss for elective and emergency cases was 1963 ± 1180 mL and 2597 ± 1369 mL, with 33% and 66% of the patients requiring blood transfusion, respectively.

The anesthesia provider should consult with the obstetric team to discuss risk factors and the planned course of management. Preparations for the management of potentially massive blood loss should be made, which may include the placement of an epidural catheter and prophylactic intravascular balloon catheters (see earlier discussion). An elective cesarean hysterectomy, or a cesarean delivery in which the patient is at high risk for emergency hysterectomy, is not a contraindication to a neuraxial anesthetic technique, although a catheter-based technique is recommended. Moreover, the occurrence of an emergency cesarean hysterectomy does not necessitate immediate conversion to general anesthesia. Consideration should be given to (1) maternal history (e.g., number of prior abdominal operative procedures, which may lead to more scarring and adhesions); (2) the presence of risk factors (e.g., extent of placentation abnormality, coagulation status); (3) the potential difficulty of conversion to general anesthesia if required (e.g., presence of difficult airway, level of assistance available); (4) the desires and experience of the obstetric team; and (5) the desires of the patient. Chestnut et al.⁴⁹⁰ observed in their review that none of the 12 patients who received continuous epidural anesthesia for cesarean delivery (8 patients from the elective group and 4 from the emergency group) required intraoperative induction of general anesthesia for hysterectomy. In addition, there was no evidence that epidural anesthesia significantly affected blood loss, crystalloid replacement, or requirement for transfusion.

Given the morbidity and mortality associated with a peripartum hysterectomy, particularly if it is accompanied by significant blood loss, postoperative observation of the patient in a critical care setting should be considered. Wright et al.⁴⁹² used the Nationwide Inpatient Sample database to compare women who underwent a peripartum hysterectomy (n = 4,967) with women who had a nonobstetric hysterectomy (n = 578,179) from 1998 to 2007; women in the peripartum hysterectomy group were nine and five times more likely to have bladder and ureteral injuries, respectively, and they had greater rates of reoperation, postoperative hemorrhage, wound complications, and venous thromboembolism. Perioperative cardiovascular, pulmonary, gastrointestinal, renal, and infectious morbidities were also higher for women who had peripartum hysterectomy (P < .001 for all). In addition, women undergoing peripartum hysterectomy had a higher rate of blood transfusion (46% versus 4%), a longer hospital stay, and a higher rate of perioperative mortality.⁴⁹²

Thromboembolic Events

Thromboembolic events constitute a major reason for peripartum maternal mortality, and risks for the development of pregnancy-associated thrombosis include an operative delivery, physiologic changes of pregnancy, and medical history and comorbidities (e.g. obesity, hemoglobinopathies, hypertension, and smoking).⁴⁹³ The risk for venous thromboembolism appears highest in the first postpartum week.⁴⁹³ A number of prophylactic interventions have been evaluated; however, the trials have been small and unable to provide robust results.⁴⁹⁴ Recommended thromboprophylaxis measures include hydration, early mobilization, pneumatic compression devices, and, in high-risk patients, pharmacologic prophylaxis (see Chapter 39).

Key Points

• Cesarean delivery is the most common major surgical procedure performed in many developed countries. The rate of cesarean delivery is increasing worldwide.

• Some cesarean deliveries might be avoided through the provision of satisfactory neuraxial analgesia for labor (including a trial of labor after cesarean delivery), instrumental vaginal delivery, and external cephalic version.

• Gastric emptying is unchanged during pregnancy. The parturient without complications may drink modest amounts of clear liquids up to 2 hours before induction of anesthesia for elective cesarean delivery. The fasting period for solids should be 6 to 8 hours. Slower digestion is observed for foods with high fat content.

• An H₂-receptor antagonist or a proton-pump inhibitor may be given intravenously to increase gastric fluid pH, and intravenous metoclopramide may be given to both accelerate gastric emptying and increase lower esophageal sphincter tone. If possible, these agents should be administered more than 30 minutes before induction of anesthesia. Oral sodium citrate, which also increases gastric fluid pH, should be administered less than 30 minutes before induction.

• Antibiotic prophylaxis, administered within 60 minutes before abdominal incision, decreases the risk for maternal infectious complications after cesarean delivery.

• Although the use of intravenous fluids may reduce the frequency of maternal hypotension, initiation of neuraxial anesthesia should not be delayed to administer a fixed volume of fluid.

• The value of supplemental maternal oxygen during neuraxial anesthesia for the elective cesarean delivery of a noncompromised fetus is questionable.

• Left uterine displacement is essential during cesarean delivery, regardless of the anesthetic technique.

• The estimated case-fatality risk ratio for general versus neuraxial anesthesia has been as high as 16.7 in the years 1985 to 1990; however, in the latest analysis, covering the years 1991 to 2002, a nonsignificant risk ratio of 1.7 has been observed.

• Umbilical cord prolapse (without fetal bradycardia), placenta previa, and severe preeclampsia (in a patient with an acceptable platelet count) are not absolute indications for general anesthesia.

• Among women receiving general anesthesia for cesarean delivery, maternal deaths associated with hypoventilation or airway obstruction are occurring with greater frequency during emergence, tracheal extubation, or recovery, rather than during induction and tracheal intubation; attention to airway and ventilation management should focus on both of these critical time periods.

• The combined spinal-epidural technique offers the benefits of both spinal and epidural anesthesia while minimizing the disadvantages of either technique alone. Advantages include the fast onset of dense anesthesia with a small dose of local anesthetic and the ability to provide prolonged anesthesia and continuous postoperative analgesia.

• Alkalinization of the local anesthetic solution not only increases the speed of onset but also improves the quality and prolongs the duration of neuroblockade. Administration of 3% 2-chloroprocaine with 8.4% sodium bicarbonate (10 mL of 2-chloroprocaine mixed with 1 mL [1 mEq] of bicarbonate) produces the fastest onset of epidural anesthesia.

• The application of cricoid pressure to prevent passive regurgitation during induction of general anesthesia is controversial. If used, pressure should be initiated with a force of 10 newtons (N) on the cricoid cartilage and increased to 30 N once the patient loses consciousness.

• When choosing the concentration of a volatile halogenated agent to maintain general anesthesia, the anesthesia provider must consider the uterine relaxation caused by these agents as well as the reduced MAC (minimum alveolar concentration) of pregnancy and the potential for maternal awareness.

• Either phenylephrine or ephedrine may be used for the prevention and treatment of maternal hypotension during neuraxial or general anesthesia for cesarean delivery. Phenylephrine appears to exert less metabolic effect on the fetus and results in higher umbilical arterial blood pH at delivery compared with ephedrine.

• Underestimation of blood loss and inadequate intravascular volume resuscitation during peripartum hemorrhage are common occurrences that contribute to maternal morbidity and mortality.

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^* Outside the operating room, and before the onset of labor, maternal blood pressure is ideally measured (using an appropriately sized cuff with a bladder length that is 80% and a width that is at least 46% of the arm circumference) after a rest period of 10 minutes or more, with the pregnant woman sitting or lying on her left side with her arm at the level of the right atrium. The onset (phase 1) and disappearance (phase 5) of Korotkoff sounds correspond to systolic and diastolic pressures, respectively.⁵²

^* The Institute of Safe Medicine Practices (ISMP) has recommended that health care providers never use µg as an abbreviation for micrograms, but rather they should use mcg (http://www.ismp.org/tools/errorproneabbreviations.pdf, Accessed February 2013). The use of the symbol µg is frequently misinterpreted and involved in harmful medication errors. The abbreviation may be mistaken for mg (milligrams), which would result in a 1000-fold overdose. The symbol µg should never be used when communicating medical information, including pharmacy and prescriber computer order entry screens, computer-generated labels, labels for drug storage bins, and medication administration records. However, most scholarly publications have continued to use the abbreviation µg. The editors have chosen to retain the use of the abbreviation µg throughout this text. However, the editors recommend the use of the abbreviation mcg in clinical practice.