This chapter should be cited as follows:
Wong, C, Glob. libr. women's med.,
(ISSN: 1756-2228) 2008; DOI 10.3843/GLOWM.10217
Under review - Update due 2018

Anesthesia in High-Risk Obstetrics

Cynthia A. Wong, MD
Assistant Professor, Northwestern University Medical School; Chief, Section of Obstetric Anesthesiology, Northwestern Memorial Hospital, Chicago, Illinois

INTRODUCTION

Anesthesiologists often contribute to the care of obstetric patients at high risk. The anesthetic care of parturients at high risk in the peripartum period has been discussed elsewhere. This chapter reviews anesthetic issues involved in caring for women at high risk with diseases or conditions unrelated to their pregnancy that complicate their obstetric or their obstetric anesthesia care. Often, these women have special anesthetic considerations. Appropriate anesthetic management can assist in the obstetric management of these women. Antepartum consultation between the obstetrician, anesthesiologist, and specialist managing the pregnant woman's chronic condition will help assure the best outcome possible for both the mother and her child(ren).

NONOBSTETRIC SURGERY DURING PREGNANCY

Maternal physiologic and anatomic changes that accompany pregnancy, as well as consideration of the developing fetus, influence the conduct of anesthesia for nonobstetric surgery during pregnancy. Physiologic changes associated with pregnancy may affect maternal safety during anesthesia. Fetal oxygenation depends on maternal oxygen carrying capacity, maternal cardiac output, and uteroplacental perfusion. Therefore, any interventions that compromise these factors may lead to fetal asphyxia. It is often difficult to determine whether adverse fetal outcomes are the result of maternal disease, the surgical procedure, or the anesthetic.

Changes in the cardiovascular system during pregnancy need to be considered when caring for the pregnant surgical patient. Pregnant women respond differently than nonpregnant patients to hemorrhage. Compression of the great vessels by the gravid uterus after 20 weeks' gestation may decrease maternal cardiac output and uteroplacental blood flow.1 After 20 weeks' gestation the pregnant patient should not undergo operations or be nursed in the supine position. Because maternal blood volume is increased and hematocrit is decreased, pregnant women can tolerate a higher percentage of blood loss before becoming symptomatic. For example, pregnant ewes acutely lost 30% to 35% of estimated blood volume with no change in maternal blood pressure.2 Thus, the degree of hypovolemia may initially be underestimated.

Changes in respiratory anatomy and physiology must also be considered. Evaluation of maternal oxygen carrying capacity must take into account the increased maternal metabolic rate (approximately 50% at term3) and fetal oxygen requirements. Maternal functional residual capacity (FRC) is decreased by 20%.4 General, high-spinal, and high-epidural anesthesia are associated with a further decrease in FRC.5,6 Therefore, oxygen reserve is compromised in the anesthetized pregnant patient. Even short periods of apnea (e.g., during induction of general anesthesia) may result in rapid and severe hypoxemia, leading to both maternal and fetal compromise.7 After upper abdominal and thoracic procedures, FRC continues to decrease to a nadir at 48 hours postoperatively.8 Therefore, consideration should be given to monitoring maternal oxygenation or providing supplemental oxygen during this time. Maternal hyperoxia is not an issue, because even with maximal maternal pO2 levels, fetal pO2 never increases to more than 60 mm Hg.9

Carbon dioxide readily crosses the placenta; therefore, maternal pCO2 levels reflect fetal pCO2 levels. Maternal hypoventilation results in increased fetal pCO2 and fetal respiratory acidosis. Maternal hyperventilation shifts the oxyhemoglobin dissociation curve to the left, thus increasing the affinity of hemoglobin for oxygen and decreasing the transfer of oxygen across the placenta.10 In addition, maternal positive-pressure mechanical hyperventilation can lead to decreased venous return and decreased maternal cardiac output.11

Sensitivity to central nervous system depressants (including inhaled12,13 and intravenous agents14 and local anesthetics15) is increased during pregnancy. Drug volume of distribution may be altered during pregnancy.16 In addition, decreases in maternal protein binding may cause an increase in the free drug concentrations of highly protein-bound drugs.17 Therefore, pregnant patients are at increased risk for an anesthetic overdose.

Both anatomic-induced and hormonally-induced changes in the gastrointestinal system cause pregnant women to be at increased risk for gastroesophageal reflux and pulmonary aspiration.18 This is an issue during periods of maternal obtundation (e.g., general anesthesia, conscious sedation, or central nervous system pathology).

Virtually all anesthetic agents administered to the mother cross the placenta to the fetus. This is of particular concern during the period of organogenesis, although the brain continues to develop well after the first trimester. The teratogenicity of most anesthetic agents has not been well studied in humans, because both birth defects and exposure to anesthetic agents during pregnancy are unusual events. Several retrospectives reviews suggest there is no increased risk for congenital anomalies in the children of women who undergo surgery while pregnant, but there is a risk of abortion, growth restriction, and an increased incidence of very-low and low-birth-weight infants.19,20 A review from Swedish health care registries of more than 2200 women who underwent surgery during the first trimester found a possible increase in neural tube defects in their children.21 A case-controlled study in Atlanta found an increased risk of hydrocephalous if surgery was performed in the first trimester.22 However, the studies did not control for indication for surgery, type of surgery, type of anesthesia, or other exposures. None of the anesthetic agents currently used is a known teratogen in humans. However, fetal hypoxia secondary to either anesthetic or surgical procedures is a known risk to the fetus. Therefore, most anesthesiologists recommend that elective surgical procedures be postponed until after the first trimester. Although fetal exposure to drugs is more limited during spinal compared with general anesthesia, there is no evidence that one type of anesthesia is safer than another.

Laparoscopy During Pregnancy

The number of laparoscopic procedures performed during pregnancy is increasing.23 Studies in pregnant ewes have found that maternal blood pressure and cardiac output generally decrease during carbon dioxide pneumoperitoneum, but that fetal cardiac output is maintained. However, animal studies conflict as to the relationship between maternal end-tidal CO2 and pCO2 (and hence, fetal pCO2) during CO2 pneumoperitoneum. Despite controlled ventilation to maintain end-tidal CO2 at a constant level, two studies found maternal and fetal hypercarbia, that is, a large end-tidal to arterial CO2 gradient,24,25 while one-third found no change in maternal and fetal pCO2.26 A small study in pregnant women undergoing laparoscopic cholecystectomy found no increase in the end-tidal to arterial pCO2 gradient during CO2 insufflation.27 Prolonged exposure of pregnant laboratory animals to carbon dioxide results in congenital anomalies in their offspring.28 Although there is no evidence in humans that laparoscopy is associated with an increased risk for congenital anomalies, the Society of American Gastrointestinal Endoscopic Surgeons' Guideline for Laparoscopic Surgery During Pregnancy states that “maternal end-tidal CO2 and arterial blood gases should be monitored.”29

Trauma

Advanced trauma life support protocols should be used for pregnant trauma patients.30 Women of childbearing age should be evaluated for pregnancy early in trauma management.31 Operative anesthetic considerations are discussed elsewhere in this chapter. In an emergency, O-negative, cytomegalovirus (CMV)-negative red blood cells should be used, and Rh-immunotherapy should be administered if the possibility of uterine injury exists.31 The decision to perform a perimortem cesarean delivery should be made within 5 minutes of maternal to arrest to improve the chances of fetal survival.32

Anesthesia for Fetal Surgery

Fetal surgery may be indicated for selected fetal anomalies and is currently an area of investigation in selected centers. Anesthetic considerations are similar to those for women undergoing nonobstetric surgery during pregnancy. Additional considerations include the need for fetal anesthesia, fetal immobility, and profound uterine relaxation, while maintaining fetal cardiovascular and acid–base status.33,34

The human fetus responds to environmental stimuli. Noxious stimuli result in an autonomic response and an increase in stress hormone levels.35,36 In premature infants undergoing surgery, this stress response is ameliorated by adequate anesthesia.37 Although there is no evidence to support a difference in outcome, it seems intellectually logical and humane to provide fetal anesthesia during fetal surgery.

Volatile anesthetic agents would seem to be the ideal agents to anesthetize both the mother and the fetus for fetal surgery. They provide both fetal anesthesia and immobility and uterine relaxation. However, animal studies of the effects of volatile anesthetic agents on uteroplacental blood flow, fetal blood pressure, heart rate, oxygen status, and acid–base status are conflicting.38,39,40 The cardiovascular effects of volatile anesthetic agents are dose-dependent in both the mother and the fetus,38 and maintenance of maternal cardiovascular stability, as well as other factors affecting oxygen delivery to the placenta, are important.

Other fetal anesthetic techniques have been described, including the direct fetal injection (umbilical vein or intramuscular) of fentanyl and pancuronium.33 Volatile anesthetic-induced uterine relaxation can be supplemented with maternal intravenous administration of nitroglycerine, magnesium or β-mimetics, or rectal indomethacin.34 The results of animal studies suggest that controlling maternal postoperative pain decreases myometrial irritability after fetal surgery.41,42 Continuous epidural analgesia with low-concentration bupivacaine and fentanyl is used by several centers performing fetal surgery.33,34

Both the mother and fetus require monitoring during fetal surgery. Standard monitors are used for the mother. Invasive arterial and central venous pressure monitoring, and a Foley catheter, may be indicated if large fluid shifts are anticipated, especially if β-mimetic tocolysis is used, because this increases the risk of maternal pulmonary edema.34 Ultrasonography is used to determine fetal and placental orientation, and to monitor fetal heart rate (FHR) and contractility.33 In the pregnant ewe model, fetal pulse oximetry had a high sensitivity and negative predictive value for monitoring fetal well being in utero.43

Maternal Systemic Disease

MORBID OBESITY

Many of the anatomic and physiologic changes of pregnancy are accentuated by obesity. Chest wall compliance is decreased. Oxygen consumption and carbon dioxide production are increased further. Lung volumes are further decreased in obese parturients.44 Oxygenation worsens in the supine or Trendelenburg position,45 often contributing to the difficulty of positioning these patients for surgical procedures. Cephalad retraction of a large panniculus may contribute to maternal hypotension and fetal compromise.46

Similarly, cardiac output and blood volume are increased in obesity and obese patients are at increased risk for hypertension.47,48 It is not clear whether the gastrointestinal changes associated with pregnancy are exacerbated by obesity, although it seems likely that the obese pregnant patient is at increased risk for pulmonary aspiration.45 Obesity influences the distribution, elimination, and response to anesthetic drugs. There is a higher incidence of difficult airway,47 and this, combined with an increased metabolic rate and decreased FRC, makes airway catastrophes more likely. Several studies have found that obesity increases the risk for anesthesia-related maternal mortality during cesarean section.49,50

Obesity does not affect the severity of labor pain.51 However, it is technically more difficult to establish epidural analgesia in the obese parturient and several attempts at catheter placement may be necessary to obtain effective analgesia.47 Epidural analgesia does not affect the outcome of labor in obese parturients weighing more than 300 pounds.47 However, the risk of cesarean delivery is greater in obese parturients.47,52 Therefore, early labor epidural analgesia is recommended.

Even more so than in nonobese women, neuraxial anesthesia is preferable to general anesthesia for cesarean delivery. Spinal anesthesia can be used successfully in morbidly obese women; however, operative times tend to be prolonged,48 and if the duration of surgery extends beyond the duration of spinal anesthesia, the anesthesiologist will be forced to induce general anesthesia intraoperatively. Obese patients are at increased risk for postoperative pulmonary morbidity.53,54 A vertical skin incision increases the risk of postoperative hypoxemia.55 Finally, in the postoperative period, opioid-induced respiratory depression can have more profound effects in the obese patient who has less oxygen reserve.

ASTHMA

Asthma is becoming more prevalent in the general and pregnant population.56 During labor and delivery, high-dose opioid analgesia may cause respiratory depression and decompensation in a wheezing patient. Neuraxial analgesia prevents pain-induced hyperpnea without respiratory depression and also ameliorates the maternal stress response.57 This may be important for women who have exercise or stress-induced asthma.58 An additional benefit of epidural analgesia is that epidural anesthesia can be rapidly induced for an emergency cesarean delivery, thus avoiding the need for general anesthesia and intubation. Airway instrumentation is the greatest risk factor for bronchospasm in the perioperative period.59 In nonpregnant asthmatic patients, volatile anesthetics are the agents of choice because they produce dose-dependent bronchodilation60 and suppress airway reflexes.61 However, high concentrations of volatile anesthetic agents also relax uterine, as well as bronchial, smooth muscle62 and may increase the risk of postpartum hemorrhage. In the nonasthmatic pregnant patient, extubation of the trachea when the patient is wide-awake minimizes the risk of pulmonary aspiration. However, the presence of an endotracheal tube in an asthmatic patient who is awake may stimulate bronchospasm. Inhaled beta-adrenergic agents administered before anesthesia emergence may decrease this risk. However, the wheezing patient under general anesthesia should probably remain sedated and intubated until bronchospasm is controlled. Similarly, a wheezing patient using accessory muscles of respiration may not tolerate the mid-to-high thoracic motor blockade induced by spinal or epidural anesthesia and may require intubation and general anesthesia to support ventilation.

OBSTRUCTIVE SLEEP APNEA

Sleep apnea is of particular concern to anesthesiologists.63 Sleep apnea can be either obstructive or central. Normal sleep is a state of rousable unconsciousness. Arousal protects apneic patients from further hypoxemia and hypercarbia. Residual anesthetic-induced or analgesic-induced sedation interferes with normal arousal, with potentially life-threatening consequences in patients with sleep apnea. Although not rigorously studied, residual anesthetic agents, sedatives, and analgesics appear to worsen or precipitate obstructive sleep apnea by decreasing pharyngeal tone, depressing reflex ventilatory responses to hypoxia and hypercarbia, and inhibiting arousal responses to hypoxia and hypercarbia. Central respiratory depression may also result.63 Aggravating factors include the site of surgery (e.g., upper abdominal, thoracic, or upper airway procedures), and nursing in the supine position.

Symptoms of sleep apnea include heavy snoring, sudden nighttime awakenings, witnessed apnea by a bed partner, and daytime somnolence and headache. In as much as sleep symptoms are common during pregnancy, the diagnosis of sleep apnea may not be entertained.64 The incidence of obstructive sleep apnea syndrome is likely increased during pregnancy.65 Obese pregnant women are at increased risk for sleep-related disordered breathing.66 Patients with diagnosed sleep apnea, or a history suggestive of sleep apnea, should be considered at high risk for difficult airway management under anesthesia.

Anesthetic and postoperative analgesic techniques that minimize the use of sedatives and opioid analgesics are safer for these patients.63 Usually, this involves neuraxial anesthesia/analgesia or some type of nerve block. The intensity of postoperative monitoring and nursing care depends on the severity of sleep apnea, the anesthetic and surgical procedure, and need for postoperative opioid analgesia. Patients who use continuous positive airway pressure (CPAP) preoperatively should continue the therapy in the immediate postoperative period (starting in the postanesthesia care unit). Oxygen therapy alone is not adequate.

CARDIOVASCULAR DISEASE

The diagnosis and treatment of congenital heart disease has improved markedly over the past several decades, leading to an increase in the number of pregnant women with congenital heart disease. Women may present in pregnancy with corrected, partially corrected, or uncorrected lesions. A referral for an anesthesiology consult prior to delivery is indicated. A multidisciplinary team approach involving the obstetrician, cardiologist, and anesthesiologist may provide the best maternal and fetal outcomes.

Pregnant women with corrected lesions and normal heart function may require no special interventions, except peripartum antibiotic prophylaxis if indicated. Women with lesions resulting in left-to-right intracardiac shunting, for example, small atrial septal, or ventricular septal defects, or a patent ductus, should consider early neuraxial analgesia.67 Early administration of neuraxial analgesia will mitigate the pain-induced increased in systemic vascular resistance (SVR), which might worsen the left-to-right shunt and result in pulmonary hypertension or right heart failure. Infusion of air in both intravenous and epidural catheters should be avoided, as a transient right-to-left shunt could result in a paradoxical air embolus. Epidural analgesia should be induced slowly to avoid an acute decrease in SVR that might cause a right-to-left shunt and maternal hypoxemia. Alternatively, neuraxial analgesia can be induced with intrathecal opioids, which avoids the acute onset of local anesthetic-induced sympathectomy and decrease in SVR. Finally, maternal oxygen saturation should be monitored, because mild hypoxemia can lead to an increase in pulmonary vascular resistance and a right-to-left shunt. Similarly, hypercarbia and acidosis can also worsen pulmonary hypertension and lead to shunt reversal.

Pregnant women with cyanotic heart lesions (right-to-left shunts) require special care. Neuraxial anesthesia-induced decreases in SVR may acutely worsen the shunt and hypoxia, which in turn worsen pulmonary hypertension. Examples of these lesions include uncorrected tetralogy of Fallot and Eisenmenger's syndrome. The anesthetic management goals in Eisenmenger's syndrome include maintaining SVR, intravascular volume and preload (traditional epidural analgesia does the opposite), prevent pain, hypoxia, hypercarbia and acidosis, which worsen pulmonary vascular resistance, and avoid myocardial depression (with anesthetic agents).67,68,69 Supplemental oxygen, maternal pulse oximetry, and perhaps invasive arterial blood pressure monitoring are indicated. Pulmonary artery catheter monitoring is controversial, and the risks may outweigh the benefits.67,70,71,72 For vaginal delivery, intrathecal opioids can provide analgesia during the first stage of labor without an associated sympathectomy. Second stage analgesia can be provided with a pudendal block or the judicious use of local anesthetics administered into the lumbar epidural space.67 Both general and epidural anesthesia have been used for cesarean delivery.67 The hemodynamic changes that occur in the immediate postpartum period are especially stressful to the patient with Eisenmenger's syndrome.73

The anesthetic considerations in caring for patients with primary pulmonary hypertension mimic those of Eisenmenger's syndrome. Single-shot spinal anesthesia is contraindicated for both these lesions, although slow-onset epidural anesthesia has been used for cesarean deliveries.74

The anesthetic considerations in parturients with asymmetric septal hypertrophy include maintaining intravascular volume and venous return, maintaining SVR, maintaining a slow heart rate and sinus rhythm, and preventing an increase in myocardial contractility.67 Beta-adrenergic receptor blockade should be continued during labor and delivery. Neuraxial analgesia techniques associated with a slow onset of sympathectomy, as discussed, are appropriate for these patients. Phenylephrine, rather than ephedrine or epinephrine, is the preferred vasopressor. Although slow-onset epidural anesthetic has been described for cesarean deliveries, these patients tolerate general anesthesia well.75 Single-shot spinal anesthesia is contraindicated.

Women with valvular heart lesions also require special consideration. In general, stenotic lesions are less well-tolerated than regurgitant lesions. The anesthetic management goals of aortic stenosis include maintaining normal heart rate and sinus rhythm, maintaining SVR, maintaining intravascular volume and venous return, and avoiding drug-induced myocardial depression.67,76 Moderate-to-severe aortic stenosis is an indication for peripartum invasive arterial pressure monitoring. A central venous or pulmonary artery catheter may be used to monitor volume status. Single-shot spinal anesthesia is contraindicated. Neuraxial labor analgesic techniques that avoid an acute decrease in preload, as described, are appropriate. Slow-onset epidural anesthesia has been described for cesarean delivery,76,77 although some anesthesiologists prefer general anesthesia for women with severe aortic stenosis.

The anesthetic goals for patients with mitral stenosis are similar to aortic stenosis. Sinus rhythm should be maintained, if present, and rapid atrial fibrillation should be treated aggressively. A slow heart rate improves ventricular filling and cardiac output, as does the avoidance of hypovolemia. However, hypervolemia may lead to pulmonary edema. Finally, pain, hypoxemia, hypercarbia, and acidosis may increase pulmonary vascular resistance. Again, a neuraxial labor technique that insures the slow onset of sympathectomy is appropriate. Small doses of phenylephrine should be used to treat hypotension. Tachycardia can be treated with esmolol. After delivery, oxytocin, methylergonovine, and 15-methyl prostaglandin F2a may increase pulmonary vascular resistance.67 Finally, the patient with mitral stenosis is most at risk for pulmonary edema in the immediate postpartum period, as peripartum cardiac output is the highest during this time. These patients may benefit from the sympathectomy and analgesia afforded by continuing a continuous infusion of epidural local anesthetics in the immediate postpartum period.67 Intensive care may be required.

Neuraxial analgesia/anesthesia is beneficial to women with aortic insufficiency. It prevents an increase in SVR, which worsens aortic insufficiency. Other hemodynamic goals include maintaining a normal or slightly increased heart rate, maintaining preload, and avoiding drug-induced myocardial depression.67

Similarly, women with mitral regurgitation benefit from the decrease in SVR associated with neuraxial analgesia/anesthesia. Normal sinus rhythm should be maintained, with a normal or slightly increased heart rate. Preload should be maintained, but hypervolemia should be avoided, as should increases in pulmonary vascular resistance. Invasive hemodynamic monitoring may be warranted, as well as continuous ECG monitoring.

Women with mitral value prolapse are good candidates for neuraxial analgesia/anesthesia. Phenylephrine, rather than ephedrine, may be preferable for treating hypotension to avoid precipitating tachydysrhythmia.

Women with prosthetic heart values are often anticoagulated with heparin or low-molecular-weight heparin. Neuraxial analgesia/anesthesia is contraindicated when anticoagulation is maintained during labor and delivery. The American Society of Regional Anesthesia and Pain Medicine has recently published an updated consensus statement regarding neuraxial anesthesia and anti-coagulation (http://www.asra.com/items_of_interest/consensus_statements/index.iphtml). In general, neuraxial analgesia/anesthesia should not be initiated for 24 hours after the last therapeutic dose of low-molecular-weight heparin. Low-molecular-weight heparin should not be administered for at least 2 hours after epidural catheter removal. Regular heparin has a shorter half-life than low-molecular-weight heparin, but chronic use can be associated with thrombocytopenia; therefore, a platelet count should be checked before initiating neuraxial blockade. Aspirin use does not contraindicate neuraxial blockade.

There are several considerations when caring for the pregnant patient with a transplanted heart.67 The immunosuppressive regimen may include corticosteroids, and stress doses of steroids should be administered in the peripartum period. Aortocaval compression and maintenance of intravascular volume is essential, because the heart does not reflexly compensate for hypovolemia. There is up-regulation of cardiac beta-adrenergic receptors, resulting in increased sensitivity of adrenergic agents (e.g., epinephrine in local anesthetic solutions78). Neuraxial blockade should be induced slowly to decrease the risk of hypotension. Additional intravenous fluids and direct acting vasopressors can be used to treat hypotension.79

Regional labor analgesia is beneficial to patients with ischemic heart disease. Effective analgesia decreases maternal circulating catecholamine levels,57,80 thus preventing tachycardia and increases in myocardial work. Patients with peripartum cardiomyopathy, or other myopathies, also benefit from neuraxial blockade.81 This avoids the myocardial depressant effects of systemic anesthetic agents.

SICKLE CELL DISEASE

Epidural labor analgesia may aid in the care of the laboring patient with sickle cell disease in several ways.82 Pain control is of obvious importance in the patient with sickle cell disease. Epidural analgesia to manage pain during a sickle crisis that occurred during labor has been described.83 An additional advantage is that epidural blockade is associated with decreased peripheral venous stasis.84 Euvolemia should be maintained, as well as normothermia.

COAGULATION DISORDERS

Regional anesthesia is contraindicated in the presence of frank coagulopathy. Spinal/epidural hematoma may result in permanent neurologic damage if not diagnosed and decompressed within 6 to 12 hours after onset of symptoms.85 Unfortunately, laboratory tests of coagulation are often neither sensitive nor specific for clinical bleeding. A clinical history of bleeding and physical examination looking for bruising or bleeding from venipuncture sites may be a better indicator of the risk of bleeding. However, pregnant women often have epistaxis and bleeding around the gums without having a coagulopathy.

There are no data to support a specific platelet count cut-off, above which neuraxial analgesia/anesthesia is safe. Epidural or spinal hematoma is a rare complication of neuraxial anesthesia in pregnant women85 and is seen most often in patients with a known coagulopathy.86 Almost all anesthesiologists will initiate neuraxial anesthesia if the platelet count is more than 100,000/mm3. A platelet count of 50,000/mm3 is the absolute lower limit acceptable to most anesthesiologists.87 These same parameters apply for removing an epidural catheter as epidural hematomas can occur after catheter removal in a coagulopathic patient.85

Patients with hypercoagulable states, for example, protein C, S, or antithrombin III deficiency, or Leiden factor V, may be receiving either prophylactic or therapeutic doses of heparin. Prophylactic regular heparin (5000 units subcutaneous) is not a contraindication to neuraxial blockade, but 12 hours should elapse after the last dose of prophylactic enoxaparin, and 24 hours after dalteparin. The Consensus Statement from the American Society of Regional Anesthesia and Pain Medicine is discussed.

The decision to proceed with neuraxial analgesia in patients with borderline coagulation status, or unknown coagulation status, should involve an assessment of risk versus benefit. Labor epidural analgesia is an elective procedure for most women. The risk of epidural hematoma is greater when large-bore epidural needles and catheters are used compared with a small-gauge single-shot spinal needle.88 Women with continuous epidural analgesia may have sensory blockade for many hours and therefore may not perceive the symptoms of a developing spinal/epidural hematoma (progressive back and leg pain, urinary retention, and lower extremity weakness). In contrast, the benefit may outweigh the risk for women who are at high risk for cesarean delivery and difficult intubation, for example, women with preeclampsia, because the risk of difficult intubation is probably greater than the risk of spinal/epidural hematoma. Use of continuous epidural infusion of dilute solutions of local anesthetic, combined with opioid, minimize motor blockade during continuous epidural labor analgesia, and may be safer because there is less risk of masking the symptoms of hematoma. If the decision is made to proceed with neuraxial analgesia/anesthesia, regular lower extremity neurologic checks should be performed during and after neuraxial blockade.

MUSCULOSKELETAL DISORDERS

Epidural analgesia/anesthesia is more likely to be incomplete or fail in patients with chronic back pain and previous back surgery.89,90,91 Onset of epidural analgesia can be delayed in patients with back pain or disc disease.89 Epidurography demonstrated that contrast material injected into the epidural space did not reach the nerve root in 33% of patients with disc herniation and did not move beyond the affected interspace in 5% of patients.92 In one study, epidural anesthesia was successful in 91% of patients with previous limited back surgery, compared with 98.7% in patients with no history of back surgery.90 Lumbar epidural labor analgesia is usually initiated in the lower lumbar interspaces. Afferent stimuli during the first stage of labor originate from the L1 through T10 dermatomes, whereas stimuli from the late first stage and second stage of labor also originate from sacral dermatomes. Therefore, anesthetic injected into the epidural space above the site of lumbar spinal surgery may diffuse upwards, but sacral analgesia may be incomplete. Conversely, anesthetic injected below the level of surgery may provide satisfactory sacral analgesia, but first stage analgesia may be incomplete. A two-catheter technique has been described.93 Spinal analgesia/anesthesia is likely to be more successful than epidural analgesia/anesthesia. It is helpful to refer these patients for anesthesia evaluation before delivery, or at least to ask the patient to obtain a copy of her surgical report. The back skin scar is often more extensive than the actual surgery.

Patients with scoliosis should also be referred for evaluation before delivery. Review of spine radiographs and operative reports help determine the level of fusion and identify interspaces that are less distorted. These patients may be candidates for neuraxial analgesia/anesthesia. However, it is technically more difficult to identify the epidural space, multiple attempts may be necessary, and the incidence of unintentional dural puncture is higher, as is the incidence of failed or incomplete block.94,95 Continuous caudal analgesia has been used successfully for patients with spine instrumentation.96

Malignant hyperthermia is a hypermetabolic disease of skeletal muscle that is triggered in genetically susceptible people by exposure to volatile anesthetic agents or succinylcholine. It is life-threatening if a crisis is not recognized and treated appropriately. A history of malignant hyperthermia susceptibility in the parturient or her family should prompt an antenatal interview with an anesthesiologist. Additionally, the anesthesia team should be notified when the patient is admitted for labor and delivery, because the anesthesia machine and drugs need to be specially prepared. Epidural analgesia for labor will decrease the likelihood that a patient with malignant hyperthermia susceptibility will require general anesthesia for emergency cesarean delivery. Although it is possible to administer safe general anesthesia to the malignant hyperthermia-susceptible patient, it is more cumbersome in the emergency situation, because the drugs commonly used to induce general anesthesia for emergency cesarean delivery are also triggers of malignant hyperthermia.

INFECTIOUS DISEASE

Neuraxial analgesia/anesthesia is contraindicated in the presence of systemic infection (risk of hematogenous spread if the procedure is performed during bacteremia or viremia) or local infection at the site of skin puncture. Reports of spinal/epidural abscess or meningitis in obstetric patients are rare.97 Symptoms of spinal/epidural abscess may take days or months to develop.98,99 Fever and backache are followed by radicular symptoms (sensory deficits and motor and sphincter weakness over a span of hours to weeks98). Leukocytosis is usually present. Similarly, the onset of meningitis can also vary from days to weeks.97

Human immunodeficiency viral (HIV) particles can be isolated from cerebrospinal fluid (CSF) at the time of initial infection.100 Therefore, neuraxial analgesia/anesthesia does not risk introduction of the virus into the central nervous system, because this has already occurred. In a group of 18 HIV-positive patients who received neuraxial anesthesia, there was no evidence of accelerated disease progression or increased infectious or neurologic complications after delivery.101 Similarly, in a group of 45 HIV-infected women who were receiving antiviral therapy, and who underwent elective cesarean delivery under spinal anesthesia, there were no intraoperative or postoperative complications compared with a cohort of uninfected women.102

Some HIV patients may use protease inhibitors. This class of drugs is metabolized in the liver by the cytochrome P-450 system, specifically by the CYP3A isoenzyme.104 However, clinical experience suggests they can be used, but careful titration and monitoring is necessary.105

Patients with symptomatic herpes simplex virus type 2 (HSV-2) often present for cesarean delivery. Primary HSV-2 infection is associated with transient viremia, but recurrent infections are not.106 Retrospective studies have found no sequelae after neuraxial anesthesia in patients with symptomatic HSV-2.107,108,109,110 However, very few patients in these studies had primary infections. There is a general consensus among anesthesiologists that neuraxial anesthesia is safe for parturients with secondary HSV-2 infections. There are not enough data to support the safety of neuraxial anesthesia in parturients with primary infections. Therefore, the theoretical risk of introducing virus into the central nervous system must be weighed against the risks of general anesthesia.111

SUBSTANCE ABUSE

Many drugs, both legal and illegal, have the potential to adversely impact the anesthetic care of a patient.

COCAINE

There are increased risks to both general and neuraxial anesthesia in cocaine-abusing parturients. General anesthesia is associated with a higher risk of severe hypertension and dysrhythmias.112 In an animal model, acute cocaine intoxication and general anesthesia also resulted in myocardial ischemia.113 Long-term cocaine use is associated with a increased sensitivity to inhalation anesthetic agents, whereas acute toxicity may increase the requirement for anesthetic agents.114

There are several considerations when choosing neuraxial analgesia/anesthesia. Controversy exists as to whether cocaine abuse is associated with thrombocytopenia.112,115 After neuraxial blockade, the degree of hypotension is more profound.112,115 Because ephedrine is both an indirect- and direct-acting vasopressor, it is less effective in treating hypotension in the cocaine-positive parturient.112 Finally, cocaine-abusing parturients often report pain despite apparent adequate regional anesthesia.114

AMPHETAMINES

Acute and/or long-term amphetamine abuse complicates the administration of both general and neuraxial anesthesia. As with cocaine, general anesthesia is associated with hypertension and dysrhythmias.116 Acute ingestion increases anesthetic requirements, while long-term use decreases anesthetic requirements.117 Neuraxial anesthesia may be associated with severe hypotension and unpredictable response to vasopressors. There are two reported cases of cardiac arrest after general118 and regional119 anesthesia for cesarean delivery.

OPIOIDS

Long-term opioid use affects the administration of analgesia/anesthesia in several ways. The parturient's baseline opioid use should be calculated and administered to prevent maternal and neonatal withdrawal. Treatment of labor pain, or postoperative pain, will require additional doses of opioid. Neuraxial analgesic/anesthetic techniques may be advantageous for the opioid addict because analgesia can be provided with local anesthetics (without opioids). As with cocaine abuse, apparently adequate regional anesthesia may not provide acceptable pain relief in some opioid users.120 Finally, intravenous drug users have an increased risk of spontaneous epidural abscess.121

CANNABIS

Cannabis may enhance the sedative–hypnotic effects of other central nervous system depressants.122 It impairs lung function in a manner similar to tobacco. Acute cannabis intoxication has been associated with uvular edema and airway obstruction after general anesthesia.123

ENDOCRINE DISEASE

There are few studies of the anesthetic management of diabetic parturients. In nonpregnant diabetic patients with autonomic neuropathy, general anesthesia is associated with higher vasopressor use.124 Gastroparesis, another manifestation of autonomic dysfunction, may increase the risk of pulmonary aspiration.

Labor and delivery represents one of the few situations in which an anesthetic might have to be administered to a patient who is not euthyroid. Patients should be made euthyroid if at all possible before a surgical procedure or if there is a risk of perioperative thyroid storm. No prospective randomized studies have compared the safety of anesthetic techniques in hyperthyroid patients.125 Potential anesthetic considerations include the hyperdynamic cardiovascular system and possibility of cardiomyopathy, airway obstruction from an enlarged thyroid gland, respiratory muscle weakness, and electrolyte abnormalities.125 The hyperthyroid patient who requires emergency surgery should receive propylthiouracil, sodium iodide, glucocorticoids, and propranolol.125,126

Clinical manifestations of hypothyroidism that may potentially affect anesthetic management include myocardial dysfunction, coronary artery disease, defects in respiratory drive, obstructive sleep apnea, paresthesias, hyponatremia, decreased glucocorticoid reserves, anemia and abnormal coagulation factors, and platelet dysfunction.125 Again, no studies have addressed whether one type of anesthetic management is superior to another in these patients. The coagulation system should be assessed before initiation of neuraxial analgesia/anesthesia.

Pregnant women with pheochromocytoma may require tumor resection early in pregnancy or cesarean delivery followed by tumor resection.127 General, neuraxial, and combined anesthetic techniques have been used successfully for tumor resection,128,129,130 but no randomized study has been performed.

NEUROLOGIC AND NEUROMUSCULAR DISORDERS

There are several anesthetic considerations for women with epilepsy. Many anticonvulsants induce hepatic liver enzymes and affect the metabolism of other drugs, including drugs commonly used in the administration of anesthesia.131 In addition, these women may be at risk for deficiency in their vitamin K-dependent clotting factors.133

There is controversy as to the appropriate anesthetic/analgesic for the laboring patient with multiple sclerosis. There is theoretic concern that exposing demyelinated areas of the spinal cord to local anesthetic agents could result in worsening of the disease. Two small retrospective reports identified a small percentage of patients with multiple sclerosis who had a relapse after spinal anesthesia.134,135 However, this can also occur after general anesthesia. In a retrospective series of 32 parturients with multiple sclerosis who received neuraxial analgesia/anesthesia, the incidence of relapse was not greater than in a cohort of women who received local infiltration analgesia.136 The pregnant woman with multiple sclerosis should be counseled that there is a increase in exacerbations within the first several months after delivery137 and that it is not known whether neuraxial anesthesia influences the risk of a relapse.

Myasthenic gravis may be worsened by a number of drugs, including drugs commonly used in the provision of anesthesia. Patients with myasthenia gravis are extremely sensitive to nondepolarizing muscle relaxants.138 Their response to succinylcholine is unpredictable.139 Neuraxial analgesia/anesthesia is the anesthetic technique of choice in these patients because it avoids the potential respiratory depressant effects of systemic opioids and makes the need for general anesthesia less likely. Patients with myasthenia gravis are at increased risk for requiring postoperative mechanical ventilation.138

Women with spinal cord injuries above the level of T7 to T5 are at risk for autonomic hyperreflexia during labor and delivery. Neuraxial anesthesia with local anesthetic agents will prevent labor-induced autonomic hyperreflexia. Epidural fentanyl without local anesthetic did not prevent autonomic hyperreflexia during labor.140 An additional anesthetic concern in patients with spinal cord injury is the use of succinylcholine. Succinylcholine used within 1 year of the injury can precipitate life-threatening hyperkalemia.141

LIVER DISEASE

The anesthetic management of parturients with liver disease, who have no hepatic synthetic or metabolic impairment, is unchanged from the routine. However, parturients with acute viral hepatitis, advanced cirrhosis, portal hypertension, or other diseases that are associated with liver dysfunction often have multiorgan disease as a result of their liver dysfunction. Liver parenchymal disease may result in deficiencies of clotting factors synthesized in the liver. Cholestasis can lead to malabsorption of vitamin K and deficiencies in the vitamin K-dependent clotting factors.142 Therefore, coagulation status should be assessed before the initiation of neuraxial analgesia/anesthesia.

Cardiovascular changes associated with liver disease include increased cardiac output and low systemic vascular resistance. Blood volume is increased and there may be a cardiomyopathy. Invasive monitoring may be indicated. Portopulmonary shunts and impaired hypoxic pulmonary vasoconstriction contribute to hypoxia. Orogastric or nasogastric tubes are relatively contraindicated in the presence of esophageal varices. Other organ systems affected include the brain (hepatic encephalopathy), multiple metabolic derangements, and renal dysfunction.

Ascites may impair venous return, elevate the diaphragm, leading to a more profound decrease in functional residual capacity, and increase intraabdominal pressure, thus increasing the risk of gastroesophageal reflux and pulmonary aspiration. It may also lead to engorged epidural veins, thus complicating epidural anesthesia.

Drug distribution and clearance are altered in liver disease. For example, the volume of distribution of lidocaine is doubled and the half-life increases three-fold in patients with cirrhosis.143

Volatile anesthetic agents all reduce hepatic blood flow.144 It is unclear whether this contributes to postoperative liver dysfunction, or worsening of liver dysfunction. Neuraxial anesthesia also reduces hepatic blood flow.145,146

RENAL DISEASE

The parturient with mild-to-moderate renal insufficiency and well-controlled hypertension and euvolemia requires minimal special consideration.148 Patients with chronic uremia have delayed gastric emptying and increased gastric acidity, which may increase the risk of pulmonary aspiration.147 Serum potassium should be checked before the administration of succinylcholine, because succinylcholine is associated with a .5- to .7-milliequivalent increase in potassium concentration.149 Intravenous fluids that do not contain potassium should be used.

Patients who have undergone a renal transplantation, without other systemic disease, do not require special anesthetic considerations. Patients with urolithiasis may benefit from epidural analgesia, as this provides analgesia with less fetal exposure to drugs and may facilitate passage of the calculus through decreased ureteral spasm.150

SUMMARY

There are a number of anesthetic issues that should be considered when providing anesthetic care to the parturient with chronic disease. In addition, appropriate labor analgesia and surgical anesthesia may help mitigate some of the adverse affects of labor and delivery on chronic disease. A multidisciplinary team approach involving the obstetrician, anesthesiologist, disease specialist, and other health care providers is likely to provide the best outcome. Antepartum consultation allows all members of the team, and the patient, to understand the issues involved and plan for a safe labor and delivery.

REFERENCES

1

Clark SL, Cotton DB, Pivarnik JM et al: Position change and central hemodynamic profile during normal third-trimester pregnancy and post partum. Am J Obstet Gynecol 164:883, 1991

 

2

Greiss FC Jr: Uterine vascular response to hemorrhage during pregnancy, with observations on therapy. Obstet Gynecol 27:549, 1966

 

3

Spätling L, Fallenstein F, Huch A et al: The variability of cardiopulmonary adaptation to pregnancy at rest and during exercise. Br J Obstet Gynaecol 99:(S8):1, 1992

 

4

Alaily AB, Carrol KB: Pulmonary ventilation in pregnancy. Br J Obstet Gynaecol 85:518, 1978

 

5

Askrog VF, Smith TC, Eckenhoff JE: Changes in pulmonary ventilation during spinal anesthesia. Surg Gynecol Obstet 119:563, 1964

 

6

Farber NE, Pagel PS, Warltier DC: Pulmonary pharmacology. In: Miller RD (ed): Anesthesia. pp 125-146, 5th ed. Philadelphia, Churchill Livingston, 2000

 

7

Archer GW Jr, Marx GF: Arterial oxygen tension during apnoea in parturient women. Br J Anaesth 46:358, 1974

 

8

Alexander JI, Spence AA, Parikh RK et al: The role of airway closure in postoperative hypoxaemia. Br J Anaesth 45:34, 1973

 

9

Khazin AF, Hon EH, Hehre FW: Effects of maternal hyperoxia on the fetus. I. Oxygen tension Am J Obstet Gynecol 109:628, 1971

 

10

Motoyama EK, Rivard G, Acheson F et al: The effect of changes in maternal pH and P-CO2 on the P-O2 of fetal lambs. Anesthesiology 28:891, 1967

 

11

Levinson G, Shnider SM, deLorimier AA et al: Effects of maternal hyperventilation on uterine blood flow and fetal oxygenation and acid-base status. Anesthesiology 40:340, 1974

 

12

Palahnuik RJ, Shnider SM, Eger II EI: Pregnancy decreases the requirement for inhaled anesthetic agents. Anesthesiology 41:82, 1974

 

13

Gin T, Chan MT: Decreased minimum alveolar concentration of isoflurane in pregnant humans. Anesthesiology 81:829, 1994

 

14

Gin T, Mainland P, Chan MTV et al: Decreased thiopental requirements in early pregnancy. Anesthesiology 86:73, 1997

 

15

Butterworth JF IV, Walker FO, Lysak SZ: Pregnancy increases median nerve susceptibility of lidocaine. Anesthesiology 72:962, 1990

 

16

Morgan DJ, Blackman GL, Paull JD et al: Pharmacokinetics and plasma binding of thiopental. II. Studies at cesarean section Anesthesiology 54:474, 1981

 

17

Wood M, Wood AJJ: Changes in plasma drug binding and alpha1-acid glycoprotein in mother and newborn infant. Clin Pharmacol Ther 29:522, 1981

 

18

Hawkins JL, Koonin LM, Palmer SK et al: Anesthesia-related deaths during obstetric delivery in the United States, 1979–1990. Anesthesiology 86:277, 1997

 

19

Mazze RI, Kallen B: Appendectomy during pregnancy: A Swedish registry study of 778 cases. Obstet Gynecol 77:835, 1991

 

20

Mazze RI, Kallen B: Reproductive outcome after anesthesia and operation during pregnancy: a registry study of 5405 cases. Am J Obstet Gynecol 161:1178, 1989

 

21

Kallen B, Mazze RI: Neural tube defects and first trimester operations. Teratology 41:717, 1990

 

22

Sylvester GC, Khoury MJ, Lu X et al: First-trimester anesthesia exposure and the risk of central nervous system defects: A population-based case-control study. Am J Public Health 84:1757, 1994

 

23

Affleck DG, Handrahan DL, Egger MJ et al: The laparoscopic management of appendicitis and cholelithiasis during pregnancy. Am J Surg 178:523, 1999

 

24

Hunter JG, Swanstrom L, Thornburg K: Carbon dioxide pneumoperitoneum induces fetal acidosis in a pregnant ewe model. Surg Endosc 9:272, 1995

 

25

Cruz AM, Southerland LC, Duke T et al: Intraabdominal carbon dioxide insufflation in the pregnant ewe. Uterine blood flow, intraamniotic pressure, and cardiopulmonary effects Anesthesiology 85:1395, 1996

 

26

Barnard JM, Chaffin D, Droste S et al: Fetal response to carbon dioxide pneumoperitoneum in the pregnant ewe. Obstet Gynecol 85:669, 1995

 

27

Bhavani-Shankar K, Steinbrook RA, Brooks DC et al: Arterial to end-tidal carbon dioxide pressure difference during laparoscopic surgery in pregnancy. Anesthesiology 93:370, 2000

 

28

Haring O: Cardiac malformations in rats induced by exposure of the mother to carbon dioxide during pregnancy. Circ Res 8:1218, 1960

 

29

Anonymous: Guidelines for laparoscopic surgery during pregnancy. Society of American Gastrointestinal Endoscopic Surgeons (SAGES) Surg Endosc 12:189, 1998

 

30

American College of Surgeons: Advance Trauma Life Support. Chicago, American College of Surgeons, 1998

 

31

Prentice-Bjerkeseth R: Perioperative anesthetic management of trauma in pregnancy. Anesthesiol Clin North Am 17:277, 1999

 

32

Katz VL, Dotters DJ, Droegemueller W: Perimortem cesarean delivery. Obstet Gynecol 68:571, 1986

 

33

Cauldwell CB: Anesthesia for fetal surgery. Anesthesiol Clin North Am 20:211, 2002

 

34

Gaiser RR, Kurth CD: Anesthetic considerations for fetal surgery. Semin Perinatol 23:507, 1999

 

35

Rose JC, Macdonald AA, Heymann MA et al: Developmental aspects of the pituitary-adrenal axis response to hemorrhagic stress in lamb fetuses in utero. J Clin Invest 61:42, 1978

 

36

Giannakoulopoulos X, Sepulveda W, Kourtis P et al: Fetal plasma cortisol and beta-endorphin response to intrauterine needling. Lancet 344:77, 1994

 

37

Anand KJ, Sippell WG, Aynsley-Green A: Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: Effects on the stress response. Lancet 1:62, 1987

 

38

Palahniuk RJ, Shnider SM: Maternal and fetal cardiovascular and acid-base changes during halothane and isoflurane anesthesia in the pregnant ewe. Anesthesiology 41:462, 1974

 

39

Biehl DR, Tweed WA, Cote J et al: Effect of halothane on cardiac output and regional flow in the fetal lamb in utero. Anesth Analg 62:489, 1983

 

40

Biehl DR, Yarnell R, Wade JG et al: The uptake of isoflurane by the foetal lamb in utero Effect on regional blood flow. Can Anaesth Soc J 30:581, 1983

 

41

Fauza DO, Berde CB, Fishman SJ: Prolonged local myometrial blockade prevents preterm labor after fetal surgery in a leporine model. J Pediatr Surg 34:540, 1999

 

42

Tame JD, Abrams LM, Ding XY et al: Level of postoperative analgesia is a critical factor in regulation of myometrial contractility after laparotomy in the pregnant baboon: Implications for human fetal surgery. Am J Obstet Gynecol 180:1196, 1999

 

43

Luks FI, Johnson BD, Papadakis K et al: Predictive value of monitoring parameters in fetal surgery. J Pediatr Surg 33:1297, 1998

 

44

Eng M, Butler J, Bonica JJ: Respiratory function in pregnant obese women. Am J Obstet Gynecol 123:241, 1975

 

45

Dewan DD: Obesity. In: Chestnut DH (ed): Obstetric Anesthesia, Principles and Practice. pp 986-999, 2nd ed. St. Louis, Mosby, 1999

 

46

Hodgkinson R, Husain FJ: Caesarean section associated with gross obesity. Br J Anaesth 52:919, 1980

 

47

Hood DD, Dewan DM: Anesthesia and obstetric outcome in morbidly obese parturients. Anesthesiology 79:1210, 1993

 

48

Johnson SR, Kolberg BH, Varner MW et al: Maternal obesity and pregnancy. Surg Gynecol Obstet 164:431, 1987

 

49

Endler GC, Mariona FG, Solol RJ et al: Anesthesia-related mortality in Michigan 1972–1984. Am J Obstet Gynecol 159:187, 1988

 

50

May WJ, Greiss FC: Maternal mortality in North Carolina: A four year experience. Am J Obstet Gynecol 161:555, 1989

 

51

Ranta P, Jouppila P, Spalding M et al: The effect of maternal obesity on labour and labour pain. Anaesthesia 50:322, 1995

 

52

Young TK, Woodmansee B: Factors that are associated with cesarean delivery in a large private practice: The importance of prepregnancy body mass index and weight gain. Am J Obstet Gynecol 187:312, 2002

 

53

Mircea N, Constantinescu C, Jianu E et al: Risk of pulmonary complications in surgical patients. Resuscitation 10:33, 1982

 

54

Vaughan RW, Engelhardt RC, Wise L: Postoperative hypoxemia in obese patients. Ann Surg 180:877, 1974

 

55

Vaughan RW, Wise L: Choice of abdominal operative incision in the obese patient: A study using blood gas measurements. Ann Surg 181:829, 1975

 

56

James AW: Asthma. Obstet Gynecol Clin North Am 28:305, 2001

 

57

Abboud TK, Artal R, Henriksen EH et al: Effect of spinal anesthesia on maternal circulating catecholamines. Am J Obstet Gynecol 142:252, 1982

 

58

Lindeman KS: Respiratory disease. In: Chestnut DH (ed): Obstetric Anesthesia Principles and Practice. pp 1011-1026, St. Louis, Mosby, 1999

 

59

Shnider SM, Papper EM: Anesthesia for the asthmatic patient. Anesthesiology 22:886, 1961

 

60

Vettermann J, Beck KC, Lindahl SG et al: Actions of enflurane, isoflurane, vecuronium, atracurium, and pancuronium on pulmonary resistance in dogs. Anesthesiology 69:688, 1988

 

61

Warner DO, Vettermann J, Brichant JF et al: Direct and neurally mediated effects of halothane on pulmonary resistance in vivo. Anesthesiology 72:1057, 1990

 

62

Laszlo A, Buljubasic N, Zsolnai B et al: Interactive effects of volatile anesthetics, verapamil, and ryanodine on contractility and calcium homeostasis of isolated pregnant rat myometrium. Am J Obstet Gynecol 167:804, 1992

 

63

Loadsman JA, Hillman DR: Anaesthesia and sleep apnoea. Br J Anaesth 86:254, 2001

 

64

Lefcourt LA, Rodis JF: Obstructive sleep apnea in pregnancy. Obstet Gynecol Survey 51:503, 1996

 

65

Edwards N, Middleton PG, Blyton DM et al: Sleep disordered breathing and pregnancy. Thorax 57:555, 2002

 

66

Maasilta P, Bachour A, Teramo K et al: Sleep-related disordered breathing during pregnancy in obese women. Chest 120:1448, 2001

 

67

Camann WR, Thornhill ML: Cardiovascular disease. In: Chestnut DH (ed): Obstetric Anesthesia Principles and Practice. pp 776-808, 2nd ed. St. Louis, Mosby, 1999

 

68

Pollack KL, Chestnut DH, Wenstrom KD: Anesthetic management of a parturient with Eisenmenger's syndrome. Anesth Analg 70:212, 1990

 

69

Spinnato JA, Kraynack BJ, Cooper MW: Eisenmenger's syndrome in pregnancy: epidural anesthesia for elective cesarean section. N Engl J Med 304:1215, 1981

 

70

Devitt JH, Noble WH, Byrick RJ: A Swan-Ganz catheter related complication in a patient with Eisenmenger's syndrome. Anesthesiology 57:335, 1982

 

71

Robinson S: Pulmonary artery catheters in Eisenmenger's syndrome: Many risks, few benefits. Anesthesiology 58:588, 1983

 

72

Schwalbe SS, Deshmukh SM, Marx GF: Use of pulmonary artery catheterization in parturients with Eisenmenger's syndrome. Anesth Analg 71:442, 1990

 

73

Heytens L, Alexander JP: Maternal and neonatal death associated with Eisenmenger's syndrome. Acta Anaesthesiol Belg 37:45, 1986

 

74

Khan MJ, Bhatt SB, Krye JJ: Anesthetic considerations for parturients with primary pulmonary hypertension: Review of the literature and clinical presentation. Int J Obstet Anesth 5:36, 1996

 

75

Haering JM, Comunale ME, Parker RA et al: Cardiac risk of noncardiac surgery in patients with asymmetric septal hypertrophy. Anesthesiology 85:254, 1996

 

76

Easterling TR, Chadwick HS, Otto CM et al: Aortic stenosis in pregnancy. Obstet Gynecol 72:113, 1988

 

77

Colclough G: Epidural anesthesia for cesarean delivery in a parturient with aortic stenosis [letter]. Reg Anesth 15:273, 1990

 

78

Camann WR, Goldman GA, Johnson MD et al: Cesarean delivery in a patient with a transplanted heart. Anesthesiology 71:618, 1989

 

79

Camann WR, Jarcho JA, Mintz KJ et al: Uncomplicated vaginal delivery 14 months after cardiac transplantation. Am Heart J 121:939, 1991

 

80

Shnider SM, Abboud T, Artal R et al: Maternal catecholamines decrease during labor after lumbar epidural analgesia. Am J Obstet Gynecol 147:13, 1983

 

81

George LM, Gatt SP, Lowe S: Peripartum cardiomyopathy: four case histories and a commentary on anaesthetic management. Anaesth Intensive Care 25:292, 1997

 

82

Sharma SK, Lechner RB: Hematologic and coagulation disorders. In: Chestnut DH (ed): Obstetric Anesthesia Principles and Practice. pp 842-859, 2nd ed. St. Louis, Mosby, 1999

 

83

Finer P, Blair J, Rowe P: Epidural analgesia in the management of labor pain and sickle cell crisis–a case report. Anesthesiology 68:799, 1988

 

84

Poikolainen E, Hendolin H: Effects of lumbar epidural analgesia and general anaesthesia on flow velocity in the femoral vein and postoperative deep vein thrombosis. Acta Chir Scand 149:361, 1983

 

85

Vandermeulen EP, Van Aken H, Vermylen J: Anticoagulants and spinal-epidural anesthesia. Anesth Analg 79:1165, 1994

 

86

Stafford-Smith M: Impaired haemostasis and regional anaesthesia. Can J Anaesth 43:R129, 1996

 

87

Beilin Y, Bodian CA, Haddad EM et al: Practice patterns of anesthesiologists regarding situations in obstetric anesthesia where clinical management is controversial. Anesth Analg 83:735, 1996

 

88

Horlocker TT, Wedel DJ, Schroeder DR et al: Preoperative antiplatelet therapy does not increase the risk of spinal hematoma associated with regional anesthesia. Anesth Analg 80:303, 1995

 

89

Benzon HT, Braunschweig R, Molloy RE: Delayed onset of epidural anesthesia in patients with back pain. Anesth Analg 60:874, 1981

 

90

Sharrock NE, Urquhart B, Mineo R: Extradural anaesthesia in patients with previous lumbar spine surgery. Br J Anaesth 65:237, 1990

 

91

Calleja MA: Extradural analgesia and previous spinal surgery. A radiological appraisal Anaesthesia 46:946, 1991

 

92

Luyendijk W, van Voorthuisen AE: Contrast examination of the spinal epidural space. Acta Radiol Diagn (Stockh) 5:1051, 1966

 

93

Schachner SM, Abram SE: Use of two epidural catheters to provide analgesia of unblocked segments in a patient with lumbar disc disease. Anesthesiology 56:150, 1982

 

94

Daley MD, Rolbin SH, Hew EM et al: Epidural anesthesia for obstetrics after spinal surgery. Reg Anesth 15:280, 1990

 

95

Crosby ET, Halpern SH: Obstetric epidural anaesthesia in patients with Harrington instrumentation. Can J Anaesth 36:693, 1989

 

96

Sudunagunta S, Eckersall SJ, Gowrie-Mohan S: Continuous caudal analgesia in labour for a patient with Harrington rods. Int J Obstet Anesth 7:128, 1998

 

97

Goodman E: Intraamniotic infection. In: Norris MC (ed): Obstetric Anesthesia. pp 549-561, 2nd ed. Philadelphia, Lippincott Williams & Wilkins, 1999

 

98

Tang HJ, Lin HJ, Liu YC et al: Spinal epidural abscess--experience with 46 patients and evaluation of prognostic factors. J Infect 45:76, 2002

 

99

Mackenzie AR, Laing RB, Smith CC et al: Spinal epidural abscess: The importance of early diagnosis and treatment. J Neurol Neurosurg Psychiatry 65:209, 1998

 

100

Denning DW, Anderson J, Rudge P et al: Acute myelopathy associated with primary infection with human immunodeficiency virus. Br Med J 294:143, 1987

 

101

Hughes SC, Dailey PA, Landers D et al: Parturients infected with human immunodeficiency virus and regional anesthesia. Clinical and immunologic response Anesthesiology 82:32, 1995

 

102

Avidan MS, Groves P, Blott M et al: Low complication rate associated with cesarean section under spinal anesthesia for HIV-1-infected women on antiretroviral therapy. Anesthesiology 97:320, 2002

 

103

Barry M, Gibbons S, Back D et al: Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations Clin Pharmacokinet 32:194, 1997

 

104

Raffanti S, Haas DW: Antimicrobial agents: Antiretroviral agents. In: Hardman JG, Limbird LE, (eds): Goodman & Gilman's The Pharmacologic Basis of Therapeutics. pp 1349-1380, 10th ed. New York, McGraw-Hill, 2001

 

105

Wlody DJ: Human immunodeficiency virus. In: Chestnut DH (ed): Obstetric Anesthesia Principles & Practice. pp 860-874, St. Louis, Mosby, 1999

 

106

Orey L, Adams HG, Brown ZA et al: Genital herpes simplex virus infections: clinical manifestations, course, and complications. Ann Intern Med 98:958, 1983

 

107

Bader AM, Camann WR, Datta S: Anesthesia for cesarean delivery in patients with herpes simplex virus type-2 infections. Reg Anesth 15:261, 1990

 

108

Crosby ET, Halpern SH, Rolbin SH: Epidural anaesthesia for caesarean section in patients with active recurrent genital herpes simplex infections: a retrospective review. Can J Anaesth 36:701, 1989

 

109

Ramanathan S, Sheth R, Turndorf H: Anesthesia for cesarean section in patients with genital herpes infections: A retrospective study. Anesthesiology 64:807, 1986

 

110

Ravindran RS, Gupta CD, Stoops CA: Epidural analgesia in the presence of herpes simplex virus (type 2) infection. Anesth Analg 61:714, 1982

 

111

Segal S, Carp H, Chestnut D: Fever and infection. In: Chestnut DH (ed): Obstetric Anesthesia Principles and Practice. pp 711-724, 2nd ed. St. Louis, Mosby, 1999

 

112

Birnbach DJ: Interactions in anesthesia: anesthetic management of the drug abusing parturient. Acta Anaesthesiol Belg 52:351, 2001

 

113

Boylan JF, Cheng DC, Sandler AN et al: Cocaine toxicity and isoflurane anesthesia: Hemodynamic, myocardial metabolic, and regional blood flow effects in swine. J Cardiothorac Vasc Anesth 10:772, 1996

 

114

Birnbach DJ: Substance abuse. In: Chestnut DH (ed): Obstetric Anesthesia Principles and Practice. pp 1027-1040, 2nd ed. St. Louis, Mosby, 1999

 

115

Kain ZN, Mayes LC, Ferris CA et al: Cocaine-abusing parturients undergoing cesarean section. A cohort study Anesthesiology 85:1028, 1996

 

116

Stibolt O, Wachowiak-Andersen G: Altered response to intravenous thiopental and succinylcholine in acute amphetamine abuse. Acta Anaesthesiol Scand 46:609, 2002

 

117

Johnston RR, Way WL, Miller RD: Alteration of anesthetic requirement by amphetamine. Anesthesiology 36:357, 1972

 

118

Smith DS, Gutsche BB: Amphetamine abuse and obstetrical anesthesia. Anesth Analg 59:710, 1980

 

119

Samuels SI, Maze A, Albright A: Cardiac arrest during cesarean section in a chronic amphetamine abuser. Anesth Analg 58:528, 1979

 

120

Scheutz F: Drugs addicts and local anesthesia: Effectivety and general side effects. Scand J Dental Res 90:99, 1982

 

121

Koppel BS, Tuchman AJ, Mangiardi JR et al: Epidural spinal infection in intravenous drug abusers. Arch Neurol 45:1331, 1988

 

122

Ashton CH: Adverse effects of cannabis and cannabinoids. Br J Anaesth 83:637, 1999

 

123

Mallat A, Roberson J, Brock-Utne JG: Preoperative marijuana inhalation--an airway concern. Can J Anaesth 43:691, 1996

 

124

Burgos LG, Ebert TJ, Asiddao C et al: Increased intraoperative cardiovascular morbidity in diabetics with autonomic neuropathy. Anesthesiology 70:591, 1989

 

125

Wissler RN: Endocrine disorders. In: Chestnut DH (ed): Obstetric Anesthesia Principles and Practice. pp 809-841, 2nd ed. St. Louis, Mosby, 1999

 

126

Halpern SH: Anaesthesia for caesarean section in patients with uncontrolled hyperthyroidism. Can J Anaesth 36:454, 1989

 

127

Brunt LM: Phaeochromocytoma in pregnancy. Br J Surg 88:481, 2001

 

128

Prys-Roberts C: Phaeochromocytoma--recent progress in its management. Br J Anaesth 85:44, 2000

 

129

O'Riordan JA: Pheochromocytomas and anesthesia. Int Anesthesiol Clin 35:99, 1997

 

130

Hull CJ: Phaeochromocytoma. Diagnosis, preoperative preparation and anaesthetic management Br J Anaesth 58:1453, 1986

 

131

Hernandez-Palazon J, Tortosa JA, Martinez-Lage JF et al: Rocuronium-induced neuromuscular blockade is affected by chronic phenytoin therapy. J Neurosurg Anesthesiol 13:79, 2001

 

132

Pennell PB: Pregnancy in the woman with epilepsy: Maternal and fetal outcomes. Semin Neurol 22:299, 2002

 

133

Modica PA, Tempelhoff R, White PF: Pro- and anti-convulsant effects of anesthetics (part I). Anesth Analg 70:303, 1990

 

134

Stenuit J, Marchand P: Sequelae of spinal anesthesia. Acta Neurol Psychiatr Belg 68:626, 1968

 

135

Crawford JS, James FM, Nolte H et al: Regional analgesia for patients with chronic neurologic disease and similar conditions [letter]. Anaesthesia 36:821, 1981

 

136

Bader AM, Hunt CO, Datta S et al: Anesthesia for the obstetric patient with multiple sclerosis. J Clin Anesth 1:21, 1988

 

137

Whitaker JN: Effects of pregnancy and delivery on the disease activity in multiple sclerosis [editorial]. N Engl J Med 339:339, 1998

 

138

Rolbin SH, Levinson G, Shnider SM et al: Anesthetic considerations for myasthenia gravis and pregnancy. Anesth Analg 57:441, 1978

 

139

Foldes FF, McNall PG: Myasthenia gravis: A guide for anesthesiologists. Anesthesiology 23:837, 1962

 

140

Abouleish EI, Hanley ES, Palmer SM: Can epidural fentanyl control autonomic hyperreflexia in a quadraplegic parturient? Anesth Analg 68:523, 1989

 

141

Stone WA, Beach TP, Hamelberg W: Succinylcholine--danger in the spinal-cord-injured patient. Anesthesiology 32:168, 1970

 

142

Reid RW: Liver disease. In: Chestnut DH (ed): Obstetric Anesthesia, Principles and Practice. pp 921-931, 2nd ed. St. Louis, Mosby, 1999

 

143

Thomson PD, Melmon KL, Richardson JA et al: Lidocaine pharmacokinetics in advanced heart failure, liver disease, and renal failure in humans. Ann Intern Med 78:499, 1973

 

144

Frink EJ Jr., Morgan SE, Coetzee A et al: The effects of sevoflurane, halothane, enflurane, and isoflurane on hepatic blood flow and oxygenation in chronically instrumented greyhound dogs. Anesthesiology 76:85, 1992

 

145

Kennedy WF Jr., Everett GB, Cobb LA et al: Simultaneous systemic and hepatic hemodynamic measurements during high spinal anesthesia in normal man. Anesth Analg 49:1016, 1970

 

146

Kennedy WF Jr., Everett GB, Cobb LA et al: Simultaneous systemic and hepatic hemodynamic measurements during high peridural anesthesia in normal man. Anesth Analg 50:1069, 1971

 

147

Reid RW: Renal disease. In: Chestnut DH (ed): Obstetric Anesthesia, Principles and Practice. pp 1000-1010, 2nd ed. St. Louis, Mosby, 1999

 

148

Tighe KE, Smith ID, Bogod DG: Caesarean section in chronic renal failure. Eur J Anaesthesiol 12:185, 1995

 

149

Miller RD, Way WL, Hamilton WK et al: Succinylcholine-induced hyperkalemia in patients with renal failure? Anesthesiology 36:138, 1972

 

150

Romagnoli A: Continuous epidural block in the treatment of impacted ureteric stones [letter]. Can Med Assoc J 109:968, 1973