PAIN MANAGEMENT IN THE CRITICALLY ILL OBSTETRIC PATIENT

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PAIN MANAGEMENT IN THE CRITICALLY ILL OBSTETRIC PATIENT Chandra Jayasinghe, MD, and Norman H. Blass, MD

Safe and successful pain management in pregnant women requires an understanding of the normal physiologic changes of pregnancy. Important maternal cardiorespiratory changes occur during pregnancy, in, for example, blood volume, cardiac output, stroke volume, heart rate, and systemic vascular resistance. Respiratory changes that occur during pregnancy include alterations in lung volumes and increased ventilation. Pain experienced by the mother during labor can produce harmful physiologic responses in mother and fetus. Critical illness affecting the cardiovascular and respiratory systems causes substantial morbidity and mortality. Some hemodynamic changes of labor and delivery are attenuated by effective epidural analgesia. The ideal analgesic agent for the laboring parturient should produce rapid onset of analgesia that lasts throughout labor without any adverse effect on the mother, fetus, or labor. There is no ideal analgesic for pain relief in labor. The physiologic changes of labor and delivery will be reviewed along with the commonly used analgesic techniques, with special emphasis on the critically ill obstetric patient with concomitant cardiac disease. PHYSIOLOGIC CHANGES DURING LABOR AND DELIVERY

Respiratory System

Minute volume increases continuously during pregnancy, changes that are seen within the first few weeks of pregnancy. The minute From the Department of Anesthesiology, The University of Texas Medical Branch, Galveston, Texas

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volume is 40% to 50% higher during pregnancy, resulting in a decline in Paco, to about 30 mm Hg for the remainder of pregnancy. The minute ventilation increases further during labor because of increases in tidal volume and respiratory rate. Pain and fear, the main reasons for maternal hyperventilation during labor, can lead to respiratory alkalosis, increased oxygen consumption, and lactate acc~mulation.~~ Hyperventilation during labor decreases the Paco, to very low values. The resulting hypocapnia leads to hypoventilation between contractions, which contributes to fetal h y p o ~ i aIn . ~ anesthetized ~ pregnant ewes, maternal hypocapnia without signs of stress decreased umbilical blood flow, producing a fall in fetal Hypocapnia also results in a leftward shift of the oxygen dissociation curve, reducing fetal oxygenation further. Parenteral opioids do not completely abolish the hyperventilation due to but lumbar epidural analgesia reduces the maternal hyperventilation59 hypoventilation cycle and its effe~ts.2~. Maternal metabolism and work of breathing are increased during pregnancy, and oxygen uptake is markedly increased both at rest and during exercise (Fig. 1). Oxygen consumption is increased by 40% to 75% during the first and second stages of labor, respectively; the increase is due to the pain associated with uterine contractions. These effects are attenuated by epidural analge~ia.,~ The increase in oxygen consumption 50

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Figure 1. Percent changes of minute ventilation, oxygen uptake, basal metabolism, and the ventilation equivalent for oxygen at monthly intervals throughout pregnancy. (From Prowse CM, Gaensler EA: Maternal physiology: Respiratory and acid-base changes during pregnancy. Anesthesiology 26:381, 1965; with permission.)

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may not affect a healthy parturient but will benefit the parturient who cannot increase oxygen delivery, as in a patient with limited cardiac reserve and respiratory disease. Ackerman et a14described a patient with the acute respiratory distress syndrome (ARDS) and noted a decrease in mixed venous oxygen saturation with each uterine contraction. This decrease in oxygen saturation was corrected with epidural analgesia, suggesting a benefit of effective analgesia on oxygen consumption. During labor, maternal desaturation can occur52and can be harmful for both mother and fetus, particularly in the presence of maternal cardiovascular disease and impaired placental perfusion. Hypoxia during labor can result from hypocapnia with reduced ventilatory drive after hyperventilation, increased oxygen consumption, respiratory depression due to parenteral opioids, breath-holding while the mother is pushing, and from diffusion hypoxia if nitrous oxide is being used. Maternal hypoxemic episodes can lead to a reduction in fetal oxygenation. Healthy women undergoing uncomplicated labor and delivery can tolerate the decrease in oxygen delivery, but those with cardiorespiratory disease may If the fetus is already compromised and placental function is borderline, a small decrease in oxygen delivery across the placenta during labor would be harmful to the fetus. Many potential causes of hypoxia are removed by effective epidural which has been shown to reduce the incidence of maternal hypoxemia during labor when compared with systemic meperidine and with no analgesia. Effective epidural analgesia would also be advantageous for those with 31 and for those partumarginal uteroplacental circulation and function30, rients who are critically ill. Acid-base Balance

If pain relief is inadequate, the mother will develop progressively increasing metabolic acidosis, which will be accompanied by a significant degree of respiratory alkalosis during uterine contractions. If severe pain is allowed to continue, the severity of metabolic acidosis increases. This may not affect the healthy mother, but it can affect some parturients with cardiac disease and those with impaired placental function, with the fetus becoming more distressed and developing arrhythmia^.^^ Failure to relieve labor pain can result in maternal exhaustion and lead to reduction of the efficacy of uterine work. Successful epidural analgesia reduces oxygen consumption and the work performed by the mother and prevents metabolic acidosis during the first and second stages of labor.62Newborns whose mothers have had epidural analgesia have less metabolic acidosis than babies born after parenteral analgesics or no analgesia.6z Adrenergic Response

Maternal pain and stress can reduce uterine blood flow secondary to release of endogenous n~repinephrine.~~ In pregnant ewes, an increase

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in uterine vascular resistance during periods of stress was associated with a decrease in uterine blood flow of 32% to 52y0.~'Studies using radioactive xenon to measure intervillous blood flow confirm that the decrease in catecholamines due to uncomplicated lumbar epidural analgesia improves uterine blood Lumbar epidural analgesia, when administered without any complications to women with severe pregnancy-induced hypertension (PIH), increases uterine blood flow in labor.

Cardiovascular System Changes in the cardiovascular system occur to provide for the needs of the fetus and prepare the mother for the delivery. By term gestation, plasma volume increases by approximately 45% to 50Y0.~~ Red blood cell mass increases by 20% compared with plasma volume and is the reason for the relative anemia of pregnancy. This hemodilution improves placental blood flow and compensates for blood loss at delivery. Increases in intravascular volume seen in pregnancy are poorly tolerated by those with ischemic heart disease, valvular disease, and myocardial disease, and can lead to congestive heart failure or ischemia. During pregnancy, cardiac output increases by 40% to 50% by term (Fig. 2).57Heart rate and stroke volume are increased without a change in mean arterial blood pressure, and systemic vascular resistance and pulmonary vascular resistance decrease. During labor cardiac output increases by 25% in late first stage and by 40% during the second 6s These changes, mainly resulting from an increase in sympathetic nervous system are reduced in women who receive epidural analgesia as compared with those who receive local anesthesia (Figs. 3 and 4).32,6s With each uterine contraction 300 to 500 mL of blood enters the central circulation and causes an increased stroke volume and arterial pressure. Increased venous return results in an increase in cardiac output by 15% to 25%, but this increase is 10% to 15% less in those who receive epidural analgesia.66The greatest increase in cardiac output, 80% above prelabor values, occurs in the immediate postpartum period67and results from loss of aortocaval compression, uterine contractions, and loss of low-resistance placental circulation. Healthy pregnant women tolerate these hemodynamic changes, but some cardiac patients do not. These changes, along with further decreases in systemic vascular resistance, hemorrhage, and administration of oxytocic drugs, lead to rapid decompensation, especially in patients with fixed cardiac output (e.g., mitral stenosis) and in those whose cardiac output depends on an adequate preload (e.g., pulmonary hypertension). The parturient with cardiac disease will greatly benefit from epidural analgesia, which reduces hemodynamic fluctuations during labor. But even if the parturient with cardiac disease has effective epidural analgesia, some cardiovascular instability can occur at delivery.

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Figure 3. Percent change in cardiac output measured serially during labor and immediately postpartum, showing influence of anesthesia. Open bar = local; crosshatched bar = caudal. (From Ueland K: Pregnancy and cardiovascular disease. Med Clin N Am 61:17-42, 1977; with permission.)

Effect of Position

The gravid uterus can occlude the inferior vena cava and aorta when the parturient assumes a supine position. This occlusion can cause a decrease in maternal cardiac output,@blood pressure, and uteroplacental perfusion, with resulting fetal bradycardia (Figs. 5 and 6). Aortocaval compression can affect venous return and cardiac output as early as 20 weeks. The lateral decubitus position will correct this hemodynamic disturbance. In an unanesthetized parturient, increased venous tone will maintain cardiac output and uteroplacental perfusion. If aortocaval compression is not avoided during central nervous system blockade, sympathetic blockade will cause a decrease in venous return, in cardiac output, and in uteroplacental perfusion. Therefore, it is essential to avoid aortocaval compression during central nervous system blockade in every parturient; the importance of preventing compression in the parturient with limited cardiac reserve cannot be overemphasized. Pain Pathways

Pain during the first stage of labor is mainly due to uterine contractions and cervical dilatation. Pain sensation during first stage of labor is

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Figure 4. The influence of anesthesia and type of delivery on the maternal cardiovascular system, expressed as percent change from prelabor and preanesthesia values. Ten of 12 patients required therapy to treat profound hypotension after anesthesia unresponsive to uterine displacement. (From Ueland K, Metcalfe J: Circulatory changes in pregnancy. Clin Obstet Gynecol 18:41-50, 1975; with permission.)

transmitted via visceral afferents that accompany sympathetic nerve fibers and enter the spinal cord at the T10, T11, and T12 thoracic and L1 spinal segments. Visceral pain is severe, dull, aching, and poorly localized, and is easier to block than somatic fibers. Opioids are useful in relieving the pain. In late first stage and second stage of labor, pain is due to distension of the pelvic floor, vagina, and perineum, with descent of the fetal presenting part. Pain sensation is transmitted via somatic nerve fibers traveling in the pudendal nerves, which enter the spinal cord at the S2, S3, and S4 spinal segments. Somatic pain is sharp and well localized to the vagina and perineum. Opioids are not effective in pain relief in late stage of labor; conduction blockade with local anesthesia (LA) is necessary for pain relief at this stage. EPIDURAL ANALGESIA

In earlier times, epidural labor pain relief was provided by intermittent bolus injection. With increased knowledge of the complications of

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Figure 5. Effect of posture on maternal hemodynamics. PP = postpartum; solid line = supine; dashed line = side; dotted line = sitting. (From Cotton DB: Pregnancy-induced physiologic alterations. In Clark SL, Cotton DD, Hankins GDV, et al (eds): Critical Care Obstetrics (ed 3). Oxford, Blackwell Science, 1997, p 15; with permission.)

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Figure 6. Serial hemodynarnic studies in a patient who exhibits supine hypotension. After the patient has been lying supine for 6 minutes, a profound fall in arterial blood pressure can be seen. (From Kerr MG: Cardiovascular dynamics in pregnancy and labor. Br Med Bull 24:19, 1968; with permission.)

this method and after the introduction of infusion pumps, interest grew in continuous epidural infusion (CEI) for pain relief in labor. Continuous epidural infusion with LA has many advantages over intermittent bolus injection. It maintains a stable level of analgesia and reduces the need for bolus injections. Hemodynamic disturbances are thus reduced, and fetal and neonatal outcome are improved. The risks of infection and intrathecal and intravascular migration of the epidural catheter are reduced, and safety is increased. A combination of LA and epidural opioids produces good analgesia with rapid onset and longer duration of action and fewer side effects than LA alone.'O Parturients receiving epidural infusions of LA and opioids receive less bupivacaine, with reduced motor block at delivery.68Continuous epidural infusion of bupivacaine is safe and does not cause hernodynamic changes or result in accumulation of LA in the mother or fetus. The most commonly used LA is bupivacaine, at a standard concen-

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tration of 0.25% for bolus injections with an infusion of 0.125%, with fentanyl as the opioid at a rate of 8 to 12 mL/hr. Pain varies among parturients, so the bolus injections and rate of infusion must be varied greatly for adequate pain relief. Recent literature suggests an increased incidence of instrumental delivery rate63related to epidural use in laboring women, but this conclusion is d i ~ p u t e dThe . ~ result of this debate has been a surge of interest in the use of dilute concentrations of LA with opioids. Ultra-low concentrations of bupivacaine with opioids have been used with resulting good pain relief.13 These low concentrations produce minimal or no motor block and let the mother remain able to walk. Sufentanil with bupivacaine provides good analgesia with significantly less motor weakness. The addition of sufentanil to epidural bupivacaine infusions given in labor improves analgesia and also reduces bolus requirement^.'^ Carefully titrated continuous epidural analgesia to a T10 sensory level provides satisfactory analgesia for labor and delivery. Epidural analgesia with appropriate monitoring would be useful for labor analgesia in most critically ill parturients providing there are no contraindications to placement of an epidural catheter. Uterine displacement must be maintained at all times to avoid aortocaval compression. Decreases in blood pressure must be corrected with careful fluid management and vasopressors. The epidural catheter can be used for operative delivery and also for postoperative pain management. INTRATHECAL OPlOlDS

When compared with LA, spinally administered opioids produce selective analgesia. Intrathecal opioids do not produce motor block, sympathectomy, hypotension, or adverse effects on uterine contractility. When given in small doses, they produce no adverse fetal or neonatal effects. Intrathecal morphine (0.5-2.0 mg) has been shown to provide good analgesia in the early first stage of labor, which lasts up to 11 hours.2 It takes 30 to 60 minutes for the parturient to experience significant pain relief with intrathecal morphine: and side effects can last for more than 24 hours, outlasting the duration of labor. Significant side effects of intrathecal morphine are itching, nausea and vomiting, urinary retention, and somnolence. Smaller doses of intrathecal morphine 200250 pg are used, but the incidence of side effects still remains high compared with other, newer opioids.8Intrathecal morphine is unacceptable to some practitioners because of its slow onset of action and the incidence of side effects. A single intrathecal injection of fentanyl, sufentanil, and meperidine provides labor analgesia within a few minutes of administration, lasting 1 to 3 hours (Fig. 7).15,29 To overcome the slow onset of intrathecal morphine, fentanyl25 pg can be added.37This intrathecal drug combination provides rapid pain relief that lasts only for about 2 hours, but the side effects of morphine persist after the analgesic effects have waned.8 There is no ideal agent

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Cervical Dilation (cm) Figure 7. Pain visual analogue scale (VAS) versus cervical dilation.*P< 0.05 for meperidine versus fentanyl and sufentanil. Solid line = fentanyl; dashed line = sufentanil; dotted line = meperidine. (From Honet JE, Arkoosh VA, Norris MC, et al: Comparison among intrathecal fentanyl, meperidine, and sufentanil for labor anlagesia. Anesth Analg 75:734, 1992; with permission.)

for intrathecal opioid analgesia, but sufentanil 10 pg appears to relieve pain faster and more effectively and to last longer than fentanyl.6None of the opioids provide analgesia for the duration of labor.8 Side Effects Side effects of intrathecal fentanyl and intrathecal sufentanil appear to be mild and do not require treatment. Intrathecal sufentanil, being more potent and lipid soluble than intrathecal fentanyl, can cause respiratory depression and apnea,2O and the parturient should be monitored carefully for at least 1 hour after injection. Intrathecal sufentanil used alone in labor causes a segmental sensory block and a motor block in 30% of patients.15 Intrathecal fentanyl and intrathecal sufentanil do not appear to have LA properties, but the sensory changes may be due to an effect on the opioid receptors in the spinal The disadvantage of intrathecal opioids is that they reduce the visceral pain of early first stage of labor but are not very effective in reducing somatic pain in late first stage and second stage of labor. When pain becomes somatic as labor progresses, the only intrathecal opioid that is effective in relieving labor pain is meperidine; probably because of its LA properties. Intrathecal administration of meperidine 10 to 20 mg produces pain relief within a few minutes, with a duration of 1 to 3 One of the disadvantages of meperidine is hypotension; thus, meperidine is not often used in labor analgesia. Several investigators have reported a significant incidence of hypo-

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tension with the use of intrathecal opioids in laboring women.15Although meperidine causes sympathectomy and hypotension, intrathecal sufentanil does not cause sympathectomy in laboring women and blood pressure is maintained in male v0lunteers.5~The etiology of the hypotension resulting from intrathecal sufentanil and intrathecal fentanyl is not known, but it is possible for an elevated blood pressure to return to normal once labor pain is relieved. Fetal bradycardia associated with uterine hyperactivity has been reported after administration of intrathecal sufentanil and intrathecal fentan~1.l~ The reason may be changes in catecholamine levels due to regional analgesia. Regional analgesia decreases epinephrine levels but not norepinephrine levels, and this change can lead to substantial increases in uterine contractility, especially during oxytocin augmentation. Parturients who receive intrathecal sufentanil and have uterine hyperactivity do not appear to have a high incidence of emergency cesarean delivery when compared with those who receive systemic medications for labor analge~ia.~ These effects are important in parturients with borderline uteroplacental insufficiency and in those with cardiac disease. Parturients should be carefully monitored for hypotension and fetal heart rate (FHR) abnormality after intrathecal opioid injection. Anesthesiologists who are reluctant to use LA in those parturients with Eisenmenger’s syndrome or pulmonary hypertension find spinal opioids useful.’ Intrathecal injections of small amounts of opioid and LA give good pain relief and long duration of action with reduced side effects.I6This drug combination has a synergistic effecP and can be used in the late stages of labor with very good effect. Bupivacaine 2.5 mg with intrathecal sufentanil or intrathecal fentanyl can be used, but blood pressure and FHR should be monitored. Epinephrine with intrathecal sufentanil has been used to prolong action, but the effect is not long-lasting enough to make it a useful combination. The major limitation of single-dose injection of intrathecal opioids and LA is lack of flexibility. If the parturient experiences increasing pain or if operative delivery is required, another technique of analgesia or anesthesia is required. To prolong the analgesic effect, an epidural catheter can be placed simultaneously in the epidural space to be used for CEI once the analgesic effects of intrathecal opioids have waned. Another option would be to use a 20-gauge epidural catheter in the intrathecal space and provide pain relief with a continuous spinal technique. COMBINED SPINAL-EPIDURAL ANALGESIA

A combined spinal-epidural (CSE) anesthesia technique provides rapid onset of analgesia with drugs administered via a small-gauge pencil-point spinal needle into the intrathecal space. An epidural catheter placed simultaneously provides flexibility of epidural analgesia. Pain relief can be provided later with the epidural catheter when the parturi-

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ent requests further analgesia. Patient satisfaction is greater with this technique, as intrathecal opioids provide instantaneous analgesia.I6The disadvantages of motor block and the slow onset of analgesia of CEI can be overcome by the CSE technique with the use of low doses of bupivacaine and fentanyl in the intrathecal space. The incidence of spinal headache is much less with this technique because of the use of small-gauge pencil-point needles.16 CONTINUOUS SPINAL ANALGESIA

The development of small-bore catheters produced an interest in continuous spinal analgesia techniques for labor. The catheter overcomes some of the drawbacks of single opioid injections. Reports of cauda equina syndrome after widespread use of small-gauge spinal catheters53 led to withdrawal of the catheter from the market in 1992 by the Food and Drug Administration. A 20-gauge epidural catheter allows opioids to be used as intermittent boluses or as a continuous infusion during labor; it allows the use of LA in the second stage of labor; and the block can be extended for operative delivery. The spinal catheter allows analgesia and anesthesia to be achieved with a minimum dose of the drug within a short period of time. The main drawback of spinal catheter is the postdural puncture headache (PDPH) resulting from use of the 17-gauge Tuohy needle. PATIENT-CONTROLLED EPIDURAL ANALGESIA

Pain varies greatly among parturients during labor and even within the same parturient during the course of labor. Some parturients like to participate more actively in all aspects of intrapartum care, including pain relief. The advantages of patient-controlled epidural analgesia (PCEA) are control of pain relief by the parturient to her own needs, high patient titration of the sensory blockade to satisfactory levels with a reduced dose of drugs,4" optimal analgesia with reduced side effects, and reduced physician time. A dose-sparing effect has been observed40compared with CEI, and this effect is greater when fentanyl and epinephrine are added to the bupivacaine solution. Several studies have shown that a background infusion is not required to produce adequate analgesia21 and that fewer supplements are required when compared with CEI,7I further reducing the LA and opioid requirement. The disadvantages of PCEA include errors in programming; the possibility of the patient's receiving a bolus of LA when not under supervision; and the expense of the equipment. This technique is most effective in parturients who understand that they are in control of their own pain relief. Inadequate analgesia and intravascular and subarachnoid migration of the catheter can still occur, and patients should be monitored carefully for these events.

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As with other forms of maintenance analgesia, patients should have a satisfactory bilateral sensory level before PCEA is instituted. Bupivacaine 0.25% alone and 0.0625% to 0.125% bupivacaine with fentanyl or sufentanil have been used successfully. Patient-controlled epidural analgesia can be used in parturients with cardiorespiratory disease, as long as a sensory level is maintained at all times, with careful monitoring.

PATIENT-CONTROLLED INTRAVASCULAR ANALGESIA

An apparatus for patient-controlled intravascular analgesia (PCIA) in labor has been shown to be successful and safe. The goal of PCIA is to produce a relatively stable blood level by allowing the patient to give multiple frequent small bolus doses of narcotic, after an initial loading dose. Patient-controlled intravascular analgesia with meperidine and nalbuphine produces satisfactory analgesia and reduces the consumption of systemically administered opioid. Nalbuphine produces good pain relief in labor when compared with meperidine, and fentanyl appears to be better than meperidine. Fentanyl is more useful than other narcotics in labor due to its rapid onset, short duration, lack of active metabolites, and reduced side effects in both mother and fetus.51Patientcontrolled intravascular analgesia with fentanyl has been used successfully in patients with thrombocytopenia during in whom epidural placement is contraindicated. The disadvantage of PCIA is that as the labor progresses, the changing intensity of pain may not be satisfactorily controlled in some parturients by small doses of opioids. Another disadvantage of PCIA opioid administration compared with PCEA is the use of large doses of opioids, with undesirable effects on mother, fetus, and neonate. But total opioid requirement is much less with PCIA use as compared with systemic administration. Administration of fentanyl results in decreases in beat-to-beat variability of the FHR.33,51 The safety of PCIA with fentanyl in the fetus and neonate has not been demonstrated. Patient-controlled intravascular analgesia requires a loading dose of opioid to establish analgesia, and there is no agreement on the drug dose for the laboring parturient. Patient-controlled intravascular analgesia can be used as an alternative to epidural analgesia in labor, especially in situations where epidural analgesia is contraindicated, as in patients with coagulopathy, increased intracranial pressure, or sepsis. The technique can be used successfully by nurses in situations where the parturient is unable to use the PCIA pump. This technique can also be useful in painful conditions during pregnancy, such as in sickle cell crisis. Patient-controlled intravascular analgesia is also very useful in postoperative pain relief. Inhalation analgesia, transcutaneous electrical nerve stimulation (TENS), and alternative regional anesthetic techniques are not described in this review.73

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NEW DRUGS

Stimulation of a2adrenoreceptors by epinephrine and clonidine in the spinal cord produces analgesia. Therefore, epidurally administered epinephrine and clonidine have the potential to produce segmental analgesia, Clonidine produces hemodynamic disturbances and sedation, and this drug is still being tested experimentally with human volunteers. Neostigmine, a cholinesterase inhibitor, potentiates the analgesic effect of acetylcholine in the spinal cord dorsal horn in response to painful stimulus. Intrathecal neostigmine has been used in labor but provides little labor analgesia when used alone.43These drugs are being investigated for pain management and are best avoided in critically ill patients. POSTOPERATIVE PAIN RELIEF

Effective analgesia after cesarean section must maintain the patient’s ability to walk and avoid significant sedation, to allow the mother to interact with the newborn. Intramuscular analgesics have traditionally been used, but these cause undue sedation and do not provide adequate analgesia. Patient-controlled intravascular analgesia allows patients to titrate the opioids as necessary, achieving good analgesia and main25 taining steady plasma levels as compared to intramuscular The technique does not provide complete analgesia, but parturients seem to tolerate mild, nondistressing pain. Mild respiratory depression can occur with intramuscular and PCIA opioids; severe respiratory depression has been reported with PCIA, as a result of human error.19 Morphine is the drug most commonly used with PCIA, but there is no consensus as to the best drug. As a cesarean section is commonly performed under epidural anesthesia, the continuation of epidural anesthesia as an alternative method of postoperative pain relief has been advocated. Epidural opioid administration provides good postoperative analgesia with less sedation as compared to intramuscular and PCIA drugs.” Epidural morphine can cause bothersome side effects such as itching, nausea and vomiting, 25 Delayed respiratory urinary retention, and respiratory depres~ion.’~, depression remains the most feared complication of epidural morphine. Fortunately, the incidence of respiratory depression in this patient population is low (0.4y0):~but close monitoring is still required. Patients receiving epidural morphine require some other form of analgesic within the first 24 hours.I9Repeated morphine boluses or continuous infusions of opioid through the epidural catheter are associated with side effects. Patient-controlled epidural analgesia has the advantage of flexibility and convenience. It gives good analgesia, rapid recovery, and a shorter hospital stay compared with conventional analgesia. A dose-sparing effect has been The efficacy of PCEA is not improved by the addition of LA (0.03% or more), and the sensory loss in the lower

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extremities results in an inability to walk in a significant proportion of patient^.'^, 46 A background infusion is not required in patients receiving PCEA. Morphine has a slow onset of action and high incidence of side effects and may not be the ideal agent for PCEA use. Hydromorphone does not appear to be better, has side effects such as pruritus and nausea and vomiting, and has a short duration of action compared with morphine. The incidence of side effects such as vomiting and dizziness appears to be greater with sufentanil than with fe11tany1.l~ Fentanyl has a rapid onset of action. Some suggest that the analgesic effect of epidural fentanyl is due to systemic effect rather than a direct spinal action," but this suggestion has been disputed.I7Patient-controlled epidural analgesia with meperidine appears to be effective and is preferred by some.45 Intrathecal morphine has been used for postoperative analgesia with good r e s ~ l t s Large .~ doses are associated with side effects that include pruritus, nausea and vomiting, and respiratory depression. Intrathecal morphine in a dose of 100 pg appears to produce effective analgesia.4l COAGULOPATHY AND CENTRAL NERVOUS BLOCKADE Some critically ill parturients develop coagulopathy or may be on anticoagulants such as heparin. It is important to examine the complications of central neural blockade in the presence of coagulopathy and anticoagulants. Spinal hematomas are rare complications of spinal or epidural anesthesia. Acute spinal cord compression from a hematoma in the epidural, subdural, or subarachnoid space can rapidly produce permanent paraplegia. In most reports, spinal hematoma after epidural placement has been associated with coagulopathy. Complete or partial neurologic recovery is possible if decompression laminectomy is undertaken within 6 hours of the onset of symptoms. The benefits of epidural analgesia in the parturient and fetus with PIH are significant. These benefits must be weighed against the remote risk of epidural hematoma, which can cause considerable morbidity. Therefore, clinical judgment is the most important factor in assessing the risk of spinal hematoma in an individual patient. Thrombocytopenia Thrombocytopenia occurs during pregnancy with an incidence of 1.2%of pregnant women having a platelet count below 100,000/mm3.A platelet count of 100,000/mm3is often judged as the safe lower limit for central nervous system blockade, but this conclusion is not supported by some reports.6yIt is an arbitrary limit, and the safe lower limit for platelet count before central nervous system blockade is unknown.

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Uncomplicated epidural placement has been accomplished in parturients who were subsequently found to have very low platelet counts. In the absence of any other contraindications, some authors consider the lower limit of the platelet count to be 75,000 to 80,000/mm3.38, 69 Orlikowski et a P used thromboelastography (TEG) and platelet count to determine the platelet count at which TEG variables become abnormal in parturients with PIH. They demonstrated that a platelet count of 54,000/ mm3 was associated with adequate TEG-derived clot formation (95% confidence for counts of 40,000-75,000/mm3) and concluded that a platelet count of 75,000/mm3 is the safe lower limit for conduction blockade in parturients with PIH.

Disseminated lntravascular Coagulation

Disseminated intravascular coagulation (DIC) is the result of abnormal activation of the coagulation cascade, leading to formation of thrombi, depletion of coagulation factors, activation of the fibrinolytic system, and hemorrhage. The disorders associated with DIC can be due to release of procoagulant-like material into the circulation or due to diffuse or localized endothelial damage. Obstetrical accidents are common events that lead to DIC and are well recognized during pregnancy. They include severe PIH, placental abruption, amniotic fluid embolism, sepsis, and intrauterine fetal death. Disseminated intravascular coagulation may be chronic and subclinical in intrauterine fetal death. Removal of the triggering event will stop the DIC process. Delivery of the fetus is the treatment except in cases of amniotic fluid embolism, of unknown etiology. Regional anesthesia is absolutely contraindicated in parturients with frank coagulopathy. Pain relief for labor can be provided with PCIA in these parturients. If coagulopathy occurs after placement of the epidural catheter, the parturient should be observed during labor and in the postpartum period for signs and symptoms of spinal cord compression. Continuous epidural infusion should be provided with low concentrations of LA with opioid to reduce the motor weakness of lower limbs, and neurologic examination should be done frequently. In parturients who develop coagulopathy after placement of the epidural catheter, the catheter should be removed as soon as possible, as catheter migration can occur, causing further bleeding.61Others recommend removing the catheter once the coagulation is normal.

Anticoagulation Therapy

Warfarin is not used during pregnancy because of the risk of teratogenicity in early pregnancy and the risk of central nervous system abnormalities in the second and third trimesters. Heparin is the anticoag-

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ulant of choice during pregnancy; because of its large molecular size, it does not cross the placenta. In a retrospective study the incidence of spinal hematoma appeared to be high in patients who received heparin as an anticoagulant after lumbar puncture.58There are many case reports of epidural hematomas associated with epidural placement and subsequent administration of heparin, and caution must be exercised. Heparin, if used for anticoagulation during pregnancy, is discontinued briefly during delivery to minimize hemorrhage. The decision to withhold epidural analgesia because of heparin must be weighed against maternal and fetal morbidity, which epidural analgesia can prevent. The coagulation profile will return to normal within 6 hours of discontinuing heparin. Epidural analgesia can be safely administered once the coagulation profile is normal. If immediate reversal of heparin is necessary, protamine sulfate 50 mg can be administered intravenously, and additional doses can be given, depending on the activated partial thromboplastin time. Once heparin is reversed, an epidural catheter can be placed safely. The epidural catheter should be removed after delivery, before heparin anticoagulation is resumed. Low-dose Heparin Spinal hematoma after central nervous system blockade has not been reported in association with low-dose subcutaneous heparin prophyla xi^.^^ A recent FDA safety alert warns of an association between spinal and epidural catheter placement and hematoma with low molecular weight heparin (enoxaparin sodium), which results in permanent neurologic abnormality in some patients. Aspirin Low-dose aspirin (30-300 mg daily) inhibits platelet cyclooxygenase, and larger doses (1.5-2.0 g daily) inhibit prostacyclin production in vascular endothelium. The effects of aspirin last for 7 to 10 days, the platelet lifetime, as compared to a duration of 1 to 3 days for other nonsteroidal anti-inflammatory drugs nonsteroidal anti-inflammatory drugs (NSAIDS).~~ The risk of spinal hematoma in patients receiving aspirin or other NSAIDs is very low. Excess aspirin ingestion has caused spontaneous spinal hematoma. The incidence of epidural hematoma is increased in those taking aspirin and heparin.58 PAIN RELIEF FOR NONOBSTETRIC PROBLEMS Pregnancy is associated with physiologic changes that can affect the pharmacokinetics of drugs. These effects are caused by alteration in the

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activity of drug metabolizing enzyme systems, excretion, secretion and transport process, changes in body composition, and alteration of protein binding. Most of the medications that are used during pregnancy reach the fetus to some degree, with the exception of highly charged polar compounds such as heparin. Exposure to certain drugs during the most critical period of organogenesis, during days 31 to 71 after the last menstrual period, can result in malformations. The long-term effect of drug exposure in utero may not become apparent for many years, and drug use should be reduced or postponed during pregnancy. When possible, drug therapy should be avoided, or the minimum dose should be used, and parturients should be educated about nonpharmacologic techniques of pain relief during pregnancy. Mild analgesics such as acetaminophen, aspirin, and NSAIDs are useful in treating mild to moderate pain. Acetaminophen has no teratogenic effects or effects on prostaglandin synthesis or platelet function and is useful as a mild analgesic during pregnancy. Aspirin, by its effect on prostaglandin synthesis, might cause prolonged gestation and labor. Even though it is not a teratogen, when given in large doses aspirin can affect neonatal platelet function. The use of NSAIDs during pregnancy is controversial. In addition to their effects on platelet function and possible prolonged gestation and labor, NSAIDs can cause constriction of fetal ductus arteriosus and reversible oligohydramnios. Short-term use of ibuprofen and naproxen appears to be safe during the first two trimesters. The effects of ketorolac may be similar to those of other NSAIDs, but its effects on pregnant women have not been studied. Severe pain may require opioid treatment and require hospital admission if parenteral therapy is used. Short-term opioid treatment does not appear to cause harmful effects to the fetus and reduces its addiction potential in the mother. Preterm labor is a concern after surgery, so opioids with active metabolites (e.g., meperidine) that can accumulate in the fetus and cause long-lasting neonatal depression are best avoided if delivery is imminent. Postoperative pain in pregnant women having nonobstetric surgery can be treated in the same way as described for pain after cesarean section. Epidural or intrathecal opioids can be useful in the postoperative period and for other severe painful conditions. These methods reduce the maternal plasma concentration and placental transfer of opioids. The potential benefits of neuraxial opioids in the critically ill pregnant patient are the reduced side effects and associated morbidity, as compared with conventional analgesic techniques. Postoperative pain that does not require parenteral opioids can be treated with acetaminophen with or without hydrocodone. Moderately severe pain may require oxycodone with or without acetaminophen. More severe pain can be treated with oral morphine or hydromorphone. Pregnant patients with chronic pain present a different therapeutic dilemma by the nature of the chronicity of the disease and the potential for psychologic involvement. The most common drug therapies include

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nonopiate analgesics, antidepressants, anticonvulsants, neuroleptics, and sympatholytics.

Pain Relief in Sickle Cell Disease

Management of pain during vasoocclusive crisis is mainly supportive and symptomatic. Understanding the factors that precipitate sickle cell crisis and its pathophysiology is essential in management of these patients. Rehydration, correction of acidosis, oxygen, treatment of infection, pain management, and transfusion to reduce sickle cell hemoglobin are of utmost importance. In patients whose pain can be managed with mild analgesics, acetaminophen is preferable to acetylsalicylic acid, because large amounts of salicylic acid can cause acidosis in the parturient. Severe pain can be managed with parenteral opioids. Patient-controlled analgesia morphine is a better alternative for patients who can control their own pain relief. As soon as the painful symptoms begin to abate, nonopioids must be used. Care must be exercised in using opioids long term as drug misuse or addiction is possible. Epidural analgesia has been used safely in parturients during a painful crisis. Sympathectomy and vasodilatation caused by local anesthetics probably improve local blood flow and decrease sludging through the affected area.

CARDIAC DISEASE AND PREGNANCY

Acquired heart disease such as rheumatic heart disease is uncommon in young women but with advances in medical care those with congenital heart disease survive to reproductive age. Problems in the pregnant woman with cardiac disease are due to normal physiologic changes that occur during pregnancy. Pregnant cardiac patients with symptoms of right or left ventricular failure and asymptomatic patients need effective analgesia and invasive hemodynamic monitoring during labor and delivery. Management of the patient is based on the information derived from these monitors, and the risk of pulmonary artery catheter placement is worth the risk in these sick patients. Labor pain and sympathetic stimulation add a great stress on the cardiovascular system of the critically ill cardiac parturient. Effective analgesia with central nervous system blockade will reduce these changes. Pushing during second stage of labor will cause hemodynamic changes that should be avoided, and outlet forceps delivery with good analgesia will minimize some of these effects. Still, some cardiovascular instability will occur at delivery.

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Pulmonary Hypertension

Whatever the cause, pulmonary hypertension carries a very poor prognosis during pregnancy. Maternal mortality is 30% to 50% during labor and in the peripartum period. Many authors suggest that women with pulmonary hypertension avoid pregnancy and advise therapeutic abortion in early pregnancy. Hemodynamic changes include mean pulmonary pressure in excess of 25 mm Hg, right ventricular hypertrophy, and eventually, heart failure with a low fixed cardiac output. In patients with Eisenmenger’s syndrome the decrease in systemic vascular resistance during pregnancy leads to increased right to left shunting, decreased pulmonary perfusion, and further hypoxia, increasing pulmonary vascular resistance, which further decreases pulmonary blood flow. Decreased systemic vascular resistance from any cause leads to further decreased pulmonary perfusion and hypoxia and can result in sudden death. Hypercarbia, hypoxia, acidosis, stress, and pain can increase pulmonary vascular resistance; these should be avoided during delivery. During labor and delivery it is essential to avoid hypotension from central nervous system blockade, hemorrhage, and aortocaval compression. Hernodynamic monitoring is essential during labor and delivery and for several days after delivery. During labor, the electrocardiogram, oxygen saturation, direct arterial pressure, and central venous pressure should be monitored. Monitoring of pulmonary pressures is controversial. Because right ventricular function is affected in the presence of pulmonary hypertension, central venous pressure measurement is more useful than pulmonary capillary wedge pressure (PCWP). Serial blood gas measurement and oxygen saturation will monitor the degree of shunt in those with Eisenmenger’s syndrome. Therefore, a decision to place a pulmonary artery catheter must be made on an individual basis, and benefits must outweigh the risks. Pushing during delivery should be avoided as it increases intrathoracic pressure and cardiac output, and elective forceps delivery should be carried out in all pregnant cardiac patients. Increasing pulmonary vascular resistance complicates the postpartum period, and it precedes right ventricular failure. The cause of increased pulmonary vascular resistance is not known. The postpartum period is also complicated by deep vein thrombosis and pulmonary embolism, for which heparin is used as prophylaxis. The use of anticoagulants is controversial in these parturients because of bleeding in the postpartum period. Pain, anxiety, and the stress of labor can cause marked increases in pulmonary vascular resistance. It is important to provide good analgesia for labor and delivery to attenuate the cardiovascular and respiratory effects associated with painful uterine contractions. Systemic analgesics are not very effective in relieving labor pain, and large doses can cause maternal respiratory depression with hypercapnia and acidosis and a further increase in pulmonary vascular resistance. Epidural analgesia was previously avoided in these patients and pain relief was provided by parenteral opioids, pudendal block, or paracervical block, but these

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do not effectively relieve pain. Intrathecal opioids can be used in early stages of labor,' and pain relief in the second stage of labor can be provided by another technique such as pudendal block. Combined spinal-epidural analgesia can be used; the epidural catheter can be bolused with small increments of LA, while careful monitoring to avoid aortocaVal compression will prevent the complications of central nervous system blockade. Continuous epidural infusion with bupivacaine and fentanyl has been used safely and effectively and without adverse effects in parturients with severe pulmonary hypertension in labor.55Invasive hemodynamic monitoring is useful during central nervous system blockade. Epidural analgesia can be used for elective forceps delivery. These patients should be observed in the intensive care unit for several days postpartum. Adequate analgesia is essential in the postoperative period. Epidural or intrathecal opioids are useful and allow early ambulation. If spinal opioids cannot be used, PCIA should be available for pain management. After forceps delivery, pain relief can be provided with a single dose of epidural morphine. Mitral Stenosis

Mitral stenosis in pregnancy is an acquired condition commonly due to rheumatic heart disease. The main hernodynamic disturbance is obstruction of left ventricular diastolic filling, resulting in fixed cardiac output. Decreased emptying of the left atrium results in increased left atrial and pulmonary artery pressures, resulting in dyspnea, hemoptysis, and pulmonary edema. Progressive pulmonary hypertension leads to right ventricular hypertrophy and right ventricular failure. Cardiac output in patients with mitral stenosis depends on two factors, diastolic filling time and left ventricular preload.'* Tachycardia of any cause can limit diastolic filling and increase left atrial and pulmonary arterial pressures and pulmonary edema in these patients. Therefore, tachycardia due to pain and anxiety should be treated promptly with beta-blockers and good pain relief technique. Patients with mitral stenosis depend on normal to high left atrial pressures to maintain left ventricular filling and cardiac output. Any change in preload will lead to decompensation. The risk of maternal death is high during labor and immediately after delivery. The sudden increase in blood volume due to autotransfusion and loss of aortocaval compression can result in severe pulmonary edema (Fig. 8). Hypovolemia, however, should be avoided as it results in a decrease in cardiac output. Invasive monitoring should be continued in the postpartum period. Lumbar epidural analgesia is accepted as the best available pain relief technique in the pregnant patient with mitral stenosis. Epidural analgesia has been used successfully in patients with mitral stenosis.'2,26 Intrathecal administration of opioid, CSE technique, and epidural analgesia can be used as in parturients with pulmonary hypertension. Carefully titrated epidural block without any decrease in cardiac output is

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Time Figure 8. lntrapartum alterations in pulmonary capillary wedge pressure (PCWP) in eight patients with mitral stenosis. A, First-stage labor; 6,second-stage labor, 15 to 30 minutes before delivery; C,5 to 15 minutes postpartum; D, 4 to 6 hours postpartum; E, 18 to 24 hours postpartum. (From Clark SL, Phelan JP, Greenspoon J, et al: Labor and delivery in the presence of mitral stenosis: Central hemodynamic observations. Am J Obstet Gynecol 152:984, 1985; with permission.)

essential, and continuous left uterine displacement and careful fluid management should avoid hypotension. Any decrease in blood pressure with decrease in PCWP should be treated with fluid and phenylephrine, as ephedrine can cause tachycardia. Phenylephrine is accepted as a safe drug in pregnant women. Epidural analgesia results in a decrease in systemic vascular resistance (SVR) and is beneficial in patients with congestive heart failure. Epidural analgesia improves cardiac performance by decreasing the PCWP and SVR, and by increasing cardiac Postoperative pain relief is similar to that described for patients with pulmonary hypertension. Aortic Stenosis The major problem associated with aortic stenosis is a limited ability to compensate for the cardiovascular demands of pregnancy. Patients with severe disease will be symptomatic with angina, myocardial infarction, dyspnea, syncope, or sudden death. The maintenance of cardiac output is essential; any factor that diminishes preload will cause an increase in the valvular gradient and a decrease in cardiac output. It is important to maintain sinus rhythm and avoid either tachycardia or a very slow heart rate in these patients. Invasive monitoring is useful in patients with severe stenosis. Hypovolemia is a greater threat in these

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patients than pulmonary edema, and central venous pressure or PCWP should be maintained at a high to normal level to prevent any unexpected hypovolemia from hemorrhage in the postpartum period. Analgesic techniques that are used in a parturient with mitral stenosis can be used in those with severe aortic stenosis with invasive monitoring. Intrathecal opioids, CSE technique, and CEI can be used for pain relief during labor and delivery. Carefully titrated continuous epidural analgesia, avoiding hypotension due to sympathectomy and aortocaval compression, is essential. Postoperative management is similar to that described for patients with pulmonary hypertension. Myocardial Infarction

Myocardial infarction is uncommon in pregnant women. The incidence of myocardial infarction is less than 1:10,000, according to Ginz.22 The prognosis after infarction is significantly worse in late pregnancy, with an overall mortality rate of 40% to 50% in the third trimester.22 According to a review by Hankins et al,24 delivery within 2 weeks of infarction is associated with a high maternal mortality and reinfarction during labor. These observations prompted the recommendation to delay delivery for 2 weeks after myocardial infarction. The hemodynamic changes that occur in labor and delivery and the puerperium contribute to the high mortality rate of women who have acute myocardial infarction in the peripartum period. Efforts must be taken to minimize myocardial oxygen consumption in the anteparturn and intraparturn periods. Pain relief with central nervous system blockade is useful in these patients to decrease the hemodynamic changes due to pain. Combined spinal-epidural and intrathecal opioids are useful in early stages of labor but epidural local anesthetic will be necessary in the late stage of labor. Carefully titrated epidural block with local anesthetic with invasive monitoring is essential. Every effort must be taken to reduce the decrease in blood pressure; aortocaval compression must be avoided at all times. Fluid bolus can be used before the onset of central nervous system blockade to minimize the decrease in blood pressure. A pulmonary artery catheter is useful in these women, and fluid can be infused to maintain the left ventricular filling pressure. Epidural blockade must be maintained more densely than with normal healthy women as maternal expulsive efforts should be avoided during labor. A dilute solution of phenylephrine is preferable to ephedrine in treating the decrease in blood pressure. Continuous spinal blockade can be used, but the incidence of PDPH is high in these women. Peripartum Cardiomyopathy

Peripartum cardiomyopathy, with an incidence of approximately 1 in 3000 to 4000,70 occurs during the last month of the pregnancy or more

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frequently in the puerperium. Three elements are necessary to make a diagnosis: (1)occurrence during the peripartum period, (2) no previous history of heart disease, and (3) no specific etiology found.Is Patients with peripartum cardiomyopathy exhibit signs and symptoms of left ventricular failure, with occasional evidence of pulmonary and systemic embolization. Maternal mortality rates range from 25% to 50%.*8f28 Some studies suggest that patients with peripartum cardiomyopathy can have recurrence of the disease during subsequent pregnancies18;others have not noted this risk. The long-term prognosis appears to depend on the degree of cardiomegaly persisting beyond delivery. Patients can deliver vaginally with appropriate monitoring facilities. Early diagnosis in the antepartum period allows time for appropriate obstetric and anesthetic plans for these critically ill patients. Management is mostly supportive. If a decision is made to deliver vaginally, invasive monitoring is useful. Heparin that is being given for prophylaxis for thromboembolism should be discontinued before induction of labor. Intrathecal opioids can be used in the early stages of labor but opioids do not provide good pain relief in the second stage of labor. Combined spinal-epidural analgesia can be used, with intrathecal opioids being used in the early stage of labor. Higher concentrations of epidural local anesthetic are useful so the patient will be very comfortable in labor. Tachycardia and other hemodynamic changes should be avoided, and afterload reduction would be an advantage in the patient with low cardiac CONCLUSION

There are different ways of relieving pain in critically ill parturients during labor and delivery. The combination of small doses of intrathecal and epidural LA with opioids produces good analgesia, with minimal effects on the mother and fetus and the progress of labor. Attenuation of hemodynamic disturbances of labor and delivery by effective analgesia is a great advantage in the parturient who is critically ill. No analgesic agent will last for the duration of labor. New drugs that produce spinal analgesia through other mechanisms are being tested, and the search for the ideal labor analgesic continues. References 1. Abboud TK, Raya J, Noueihed R, et al: Intrathecal morphine for relief of labor pain in a parturient with severe pulmonary hypertension. Anesthesiology 59:477, 1983 2. Abboud TK, Shnider SM, Dailey PA, et al: Intrathecal administration of hyperbaric morphine for the relief of pain in labour. Br J Anaesth 56:1351, 1984 3. Abouleish E, Rawal N, Rashad MN: The addition of 0.2 mg subarachnoid morphine to hyperbaric bupivacaine for cesarean delivery: A prospective study of 856 cases. Reg Anesth 16:137, 1991 4. Ackerman WE, Molnar JM, Juneja M M Beneficial effect of epidural anesthesia on

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oxygen consumption in a parturient with adult respiratory distress syndrome. South Med J 86:361, 1993 5. Albright GA, Forster RM: Does combined spinal-epidural analgesia with subarachnoid sufentanil increase the incidence of emergency cesarean delivery? Reg Anesth 22:400, 1997 6. Arkoosh VA, Sharkey SJ, Norris MC, et al: Subarachnoid labor analgesia. Fentanyl and morphine versus sufentanil and morphine. Reg Anesth 19:243, 1994 7. Boreen S, Leighton BL, Kent H, et al: Intrathecal meperidine for labor analgesia preliminary communication. International Journal of Obstetric Anesthesia 1:149, 1992

8. Caldwell LE, Rosen MA, Shnider SM: Subarachnoid morphine and fentanyl for labor analgesia. Efficacy and adverse effects. Reg Anesth 19:2, 1994 9. Chestnut DH: Epidural analgesia and the incidence of cesarean section: time for another close look. Anesthesiology 87472, 1997 10. Chestnut DH, Owen CL, Bates JN, et al: Continuous infusion epidural analgesia during labor: A randomized, double-blind comparison of 0.0625% bupivacaine/0.0002% fentanyl versus 0.125% bupivacaine. Anesthesiology 68:754, 1988 11. Chrubasik S, Chrubasik J: Selection of the optimum opioid for extradural administration in the treatment of postoperative pain. Br J Anaesth 74121, 1995 12. Clark SL, Phelan JP, Greenspoon J, et al: Labor and delivery in the presence of mitral stenosis: Central hemodynamic observations. Am J Obstet Gynecol 152:984, 1985 13. Cohen S, Amar D, Pantuck CB, et al: Epidural analgesia for labour and delivery: Fentanyl or sufentanil? Can J Anaesth 43:341, 1996 14. Cohen S, Amar D, Pantuck CB, et al: Adverse effects of epidural 0.03% bupivacaine during analgesia after cesarean section. Anesth Analg 75:753, 1992 15. Cohen SE, Cherry CM, Holbrook RHJ, et al: Intrathecal sufentanil for labor analgesiasensory changes, side effects, and fetal heart rate. Anesth Analg 771155, 1993 16. Collis RE, Baxandall ML, Srikantharajah ID, et al: Combined spinal epidural (CSE) analgesia: Technique, management, and outcome of 300 mothers. Int J Obstet Anesth 3:75, 1994 17. Cooper DW, Ryall DM, Desira W R Extradural fentanyl for postoperative analgesia: Predominant spinal or systemic action? Br J Anaesth 74184, 1995 18. Demakis JG, Rahimtoola SH, Sutton GC, et al: Natural course of peripartum cardiomyopathy. Circulation M1053, 1971 19. Eisenach JC, Grice SC, Dewan DM: Patient-controlled analgesia following cesarean

section: A comparison with epidural and intramuscular narcotics. Anesthesiology 6 8 4 4 , 1988 20. Ferouz F, Norris MC, Leighton BL: Risk of respiratory arrest after intrathecal sufentanil. Anesth Analg 85:1088, 1997

21. Gambling DR, McMorland GH, Yu P, et al: Comparison of patient-controlled epidural analgesia and conventional intermittent "top-up" injections during labor. Anesth Analg 70:256, 1990 22. Ginz B: Myocardial infarction in pregnancy. Journal of Obstetrics and Gynaecology of the British Commonwealth 77610, 1970 23. Hagerdal M, Morgan CW, Sumner AE, et al: Minute ventilation and oxygen consumption during labor with epidural analgesia. Anesthesiology 59:425, 1983 24. Hankins GD, Wendel GDJ, Leveno KJ, et al: Myocardial infarction during pregnancy: A review. Obstet Gynecol 65:139, 1985 25. Harrison DM, Sinatra R, Morgese L, et al: Epidural narcotic and patient-controlled analgesia for post-cesarean section pain relief. Anesthesiology 68:454, 1988 26. Hemmings GT, Whalley DG, OConnor PJ, et al: Invasive monitoring and anaesthetic management of a parturient with mitral stenosis. Can J Anaesth 34:182, 1987 27. Hollmen AI, Jouppila R, Jouppila P, et al: Effect of extradural analgesia using bupiva-

caine and 2-chloroprocaine on intervillous blood flow during normal labour. Br J Anaesth 542337, 1982 28. Homans DC: Peripartum cardiomyopathy. N Engl J Med 312:1432, 1985 29. Honet JE, Arkoosh VA, Norris MC, et al: Comparison among intrathecal fentanyl, meperidine, and sufentanil for labor analgesia. Anesth Analg 75:734, 1992 30. Huch R Maternal hyperventilation and the fetus. J Perinat Med 143, 1986

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31. Jouppila P, Jouppila R, Hollmen A, et al: Lumbar epidural analgesia to improve intervillous blood flow during labor in severe preeclampsia. Obstet Gynecol 59:158, 1982 32. Jouppila R, Puolakka J, Kauppila A, et al: Maternal and umbilical cord plasma nor33. 34. 35. 36. 37.

38. 39.

40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55.

adrenaline concentrations during labour with and without segmental extradural analgesia, and during caesarean section. Br J Anaesth,56:251, 1984 Kleirnan SJ, Wiesel S, Tessler MJ: Patient-controlled analgesia (PCA) using fentanyl in a parturient with a platelet function abnormality. Can J Anaesth 38:489, 1991 Lederman RP, Lederman E, Work BAJ, et al: The relationship of maternal anxiety, plasma catecholamines, and plasma cortisol to progress in labor. Am J Obstet Gynecol 132:495, 1978 Lee W, Rokey R, Miller J, et al: Maternal hemodynamic effects of uterine contractions by M-mode and pulsed-Doppler echocardiography. Am J Obstet Gynecol 161:974,1989 Leicht CH, Hughes SC, Dailey PA, et al: Epidural morphine sulfate for analgesia after cesarean section: A prospective report of 1000 patients. Anesthesiology 65:A366, 1986 Leighton BL, DeSimone CA, Norris MC, et al: Intrathecal narcotics for labor revisited: the combination of fentanyl and morphine intrathecally provides rapid onset of profound, prolonged analgesia. Anesth Analg 69:122, 1989 Letsky EA: Hemostasis and epidural anesthesia. International Journal of Obstetric Anesthesia 1:51, 1991 Lynch C, Rizor RF: Anesthetic management and monitoring of a parturient with mitral and aortic valvular disease. Anesth Analg 61:788, 1982 Lysak SZ, Eisenach JC, Dobson C E Patient-controlled epidural analgesia during labor: A comparison of three solutions with a continuous infusion control. Anesthesiology 7244,1990 Milner AR, Bogod DG, Harwood RJ: Intrathecal administration of morphine for elective Caesarean section. A comparison between 0.1 mg and 0.2 mg. Anaesthesia 51:871, 1996 Motoyama EK, Rivard G, Acheson F, et al: Adverse effect of maternal hyperventilation on the foetus. Lancet 1:286, 1966 Nelson K, Foss M, Hood DD, Eisenach JG: Phase I evaluation of intrathecal neostigmine for labor analgesia. In Society for Obstetric Anesthesia and Perinatology 29th Annual Meeting, Bermuda, April 14, 1997, p. 93 Orlikowski CE, Rocke DA, Murray WB, et al: Thrombelastography changes in preeclampsia and eclampsia. Br J Anaesth 77157, 1996 Paech MJ, Moore JS, Evans SF Meperidine for patient-controlled analgesia after cesarean section. Intravenous versus epidural administration. Anesthesiology 80:1268, 1994 Parker RK, Sawaki Y, White PF: Epidural patient-controlled analgesia: Influence of bupivacaine and hydromorphone basal infusion on pain control after cesarean delivery. Anesth Analg 75:740, 1992 Parker RK, White PF: Epidural patient-controlled analgesia: An alternative to intravenous patient-controlled analgesia for pain relief after cesarean delivery. Anesth Analg 75:245, 1992 Penning JP, Yaksh T L Interaction of intrathecal morphine with bupivacaine and lidocaine in the rat. Anesthesiology 771186, 1992 Porter KB, OBrien WF, Kiefert V, et al: Evaluation of oxygen desaturation events in singleton pregnancies. J Perinatol 12:103, 1992 Rao TL, El-Etr AA: Anticoagulation following placement of epidural and subarachnoid catheters: An evaluation of neurologic sequelae. Anesthesiology 55:618, 1981 Rayburn WF, Smith CV, Parriott JE, et al: Randomized comparison of meperidine and fentanyl during labor. Obstet Gynecol 74:604, 1989 Reed PN, Colquhoun AD, Hanning C D Maternal oxygenation during normal labour. Br J Anaesth 62:316, 1989 Rigler ML, Drasner K, Krejcie TC, et al: Cauda equina syndrome after continuous spinal anesthesia. Anesth Analg 72:275, 1991 Riley ET, Walker D, Hamilton CL, et al: Intrathecal sufentanil for labor analgesia does not cause asympathectomy. Anesthesiology 87874, 1997 Robinson DE, Leicht CH: Epidural analgesia with low-dose bupivacaine and fentanyl

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for labor and delivery in a parturient with severe pulmonary hypertension. Anesthesiology 68:285, 1988 56. Robson SC, Dunlop W, Boys RJ, et al: Cardiac output during labour. Br Med J (Clin Res Ed) 2953169, 1987 57. Robson SC, Hunter S, Boys RJ, et al: Serial study of factors influencing changes in cardiac output during human pregnancy. Am J Physiol 256:H1060, 1989 58. Ruff RL, Dougherty JHJ: Complications of lumbar puncture followed by anticoagulation. Stroke 12:879, 1981 59. Sangoul F, Fox GS, Houle GL: Effect of regional analgesia on maternal oxygen consumption during the first stage of labor. Am J Obstet Gynecol 121:1080, 1975 60. Shnider SM, Wright RG, Levinson G, et al: Uterine blood flow and plasma norepinephrine changes during maternal stress in the pregnant ewe. Anesthesiology 50524, 1979 61. Sprung J, Cheng EY, Pate1 S When to remove an epidural catheter in a parturient with disseminated intravascular coagulation. Reg Anesth 17351, 1992 62. Thalme B, Belfrage P, Raabe N: Lumbar epidural analgesia in labour. I. Acid-base balance and clinical condition of mother, fetus and newborn child. Acta Obstet Gynecol Scand 53:27, 1974 63. Thorp JA, Hu DH, Albin RM, et al: The effect of intrapartum epidural analgesia on nulliparous labor: A randomized, controlled, prospective trial. Am J Obstet Gynecol 1692351, 1993 64. Ueland K. Maternal cardiovascular dynamics. VII. Intrapartum blood volume changes. Am J Obstet Gynecol 126:671, 1976 65. Ueland K, Hansen JM: Maternal cardiovascular dynamics. 111. Labor and delivery under local and caudal analgesia. Am J Obstet Gynecol 10323, 1969a 66. Ueland K, Hansen JM: Maternal cardiovascular dynamics. 11. Posture and uterine contractions. Am J Obstet Gynecol 103:1, 196913 67. Ueland K, Novy MJ, Peterson EN, et al: Maternal cardiovascular dynamics. IV. The influence of gestational age on the maternal cardiovascular response to posture and exercise. Am J Obstet Gynecol 104:856, 1969a 68. Van Steenberge A, Debroux HC, Noorduin H: Extradural bupivacaine with sufentanil for vaginal delivery. A double-blind trial. Br J Anaesth 59:1518, 1987 69. Vandermeulen EP, Van Aken H, Vermylen J: Anticoagulants and spinal-epidural anesthesia. Anesth Analg 79:1165, 1994 70. Veille JC: Peripartum cardiomyopathies: A review. Am J Obstet Gynecol 148:805, 1984 71. Viscomi C, Eisenach JC: Patient-controlled epidural analgesia during labor. Obstet Gynecol 77348,1991 72. Wahab SA, Askalani AH, Amar RA, et al: Effect of some recent analgesics on labor pain and maternal and fetal blood gases and pH. International Journal of Gynaecology and Obstetrics 26:75, 1988 73. Wakefield M L Systemic analgesia: Opioids, ketamine, and inhalational agents. In Chestnut DH (ed): Obstetric Anesthesia: Principles and Practice. St. Louis, Mosby-Year Book, Inc., 1994, pp 340-352

Address reprint requests to Chandra Jayasinghe, MD Department of Anesthesiology The University of Texas Medical Branch 301 University Boulevard Galveston, TX 77555-0591