Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

CHAPTER 19 – Pregnancy and Complications of Pregnancy

David Hepner, MD,
Bhavani Shankar Kodali, MD,
Scott Segal, MD



Physiologic Changes of Pregnancy



Nonobstetric Surgery In Pregnancy



General Considerations



Laparoscopic Surgery During Pregnancy



In-Vitro Fertilization



Obstetric Anesthesia for Uncommon Conditions



Morbid Obesity in Pregnant Women



Amniotic Fluid Embolism



Complications of Preeclampsia: Eclampsia, HELLP Syndrome, and Pulmonary Edema



Abnormal Placentation and Massive Hemorrhage



Peripartum Cardiomyopathy



Cardiac Arrest and Cardiopulmonary Resuscitation in Pregnancy



Conditions Complicating Regional Anesthesia



Regional Anesthesia and Anticoagulation



Local Anesthetic Allergy




Pregnancy is neither uncommon nor a disease. One study in a well-defined, continuously screened female population between 18 and 44 years of age found a pregnancy rate of over 10% per year.[1] The routine anesthetic care of pregnant women is certainly not an uncommon situation. Given that 1% to 2% of pregnant women will undergo nonobstetric surgery during their pregnancies, [2] [3] even this clinical scenario would not qualify as “uncommon.” Even unrecognized pregnancy in outpatients occurs in about 1 in 300 women.[4] Why, then, is a chapter on pregnancy included in this book?

The challenge of care of the obstetric patient lies in the physiologic changes of pregnancy and their interaction with anesthetic drugs and techniques. In addition, the urgency of care is often intensified by the presence of a viable fetus. In this chapter we explore some of the more unusual clinical challenges, both in obstetric anesthesia and analgesia, as well as in the anesthetic care of the pregnant patient undergoing nonobstetric procedures.


Administration of safe anesthesia for any pregnant woman necessitates a clear understanding of the physiologic changes that are associated with pregnancy. Thorough reviews of physiologic changes are beyond the scope of this chapter. Nonetheless, it should be emphasized that there are several important physiologic changes that have direct bearing on anesthetic management of obstetric patients ( Table 19-1 ). [5] [6] They are (1) airway changes in pregnancy that could pose intubation difficulties; (2) changes in the metabolic and respiratory system, resulting expeditiously in hypoxemia during apnea; (3) changes in the gastrointestinal system, predisposing the parturient to regurgitation and aspiration; (4) the pressure of the growing uterus on the aorta and inferior vena cava; and (5) mechanical, hormonal, and biochemical factors that can result in increased spread of intrathecal and epidural local anesthetic agents in pregnancy.

TABLE 19-1   -- Physiologic Changes of Pregnancy

Respiratory System

Minute ventilation

↑ 50%

Functional residual capacity

↓ 20%

Oxygen consumption

↑ 20%

Carbon dioxide production

↑ 20%

Apneic desaturation



32 mm Hg


-1 to 0.75 mm Hg

Cardiovascular System

Cardiac output

↑ 50%

Stroke volume

↑ 25%

Heart rate

↑ 25%

Systemic vascular resistance

No change

Blood pressure

No change at term gestation

Gastrointestinal System

Barrier pressure

Gastric emptying time

No change

Renal system:


Plasma creatinine



Minimal alveolar concentration


Free drug availability

Plasma cholinesterase activity

Data from Farraghar R, Bhavani Shankar K: Obstetric anesthesia. In Healy TEJ (ed): Wylie and Churchill Davidson's A Practice of Anesthesia, 7th ed. London, Arnold, 2003, pp 923-940; and Chang B: Physiological changes of pregnancy. In Obstetric Anesthesia: Principles and Practice. Philadelphia, Elsevier, 2004, pp 15-36.



The implications of these physiologic changes on the coexisting disease, or vice versa, must be evaluated in every pregnant woman presenting with a coexisting disease or a complication of pregnancy. A coexisting disease, such as a cardiovascular lesion or a pulmonary condition, can translate physiologic changes into a morbidly pathologic state, thereby contributing to an increasing morbidity and mortality. In addition, pharmacokinetic and pharmacodynamic profiles are altered in pregnancy, and drug administration must be titrated carefully to the desired effect. With the increase in blood volume there is a greater volume of distribution; the low albumin and increased α glycoprotein can also alter the free drug concentrations. Issues of fetal well-being, such as maintenance of uteroplacental blood flow and oxygenation, prevention of fetal asphyxia, avoidance of teratogenic drugs, and prevention of pre-term labor, are essential to consider when taking care of the pregnant patient. Maintenance of uteroplacental blood flow is essential to fetal well-being.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


General Considerations

The anesthetic management of pregnancy patients undergoing nonobstetric procedures has been extensively reviewed in major textbooks of obstetric anesthesiology, as well as several reviews. The principal considerations are maternal safety, fetal physiologic well-being, avoidance of teratogenicity, and prevention of preterm labor ( Table 19-2 ).

TABLE 19-2   -- General Considerations for Nonobstetric Surgery in Pregnancy



Maternal Safety



Respiratory system



Fragility of nasal mucosa



Upper airway edema



↑Risk of difficult intubation



↑Risk of desaturation



Gastrointestinal system



↑Risk aspiration (? Timing in gestation)



Cardiovascular system



Expansion of blood volume (normal filling pressures)



Elevated cardiac output



Physiologic anemia of pregnancy



Fetal Safety



Direct effects of anesthesia



Maternal hypoxia and hypotension➙fetal acidosis



Avoid uteroplacental vasoconstrictors (?alpha agonists, vasopressin, ketamine, high systemic local anesthetic concentrations)



Teratogenicity of drugs



No specific link to any anesthetic drug



Caution with nitrous oxide



Inhalation anesthetics may cause “behavioral teratogenicity” (behavioral abnormalities without structural defects)



Avoidance of preterm labor



Maternal Safety

Maternal safety requires understanding of the altered physiology of pregnancy. The most important changes affecting the anesthetic management of these patients are the respiratory, gastrointestinal, and cardiovascular systems.Although there is considerable controversy regarding the physiology of gastric emptying and gastric acid production in pregnancy, it seems prudent whenever practical to consider pregnant patients beyond the late second trimester to be at a somewhat elevated risk of aspiration. The cardiovascular changes of greatest interest are the expansion of blood volume (but normal central venous pressure [CVP] and pulmonary capillary wedge pressure [PCWP]), elevated cardiac output, physiologic anemia of pregnancy, and aortocaval compression. Respiratory system changes affecting anesthetic management most notably include the increased fragility of the respiratory mucosa, upper airway edema, more difficult mask ventilation, a tenfold increase in the risk of difficult intubation, functional residual capacity and oxygen consumption changes that predispose to desaturation during apnea, and chronic respiratory alkalosis.[6]

In addition, general anesthesia in pregnant patients must take into consideration the altered response to anesthetic drugs. Minimal alveolar concentration (MAC) decreases in pregnancy, well before endorphins increase during labor.[7] Indeed, increased sensitivity to intravenous and inhalation anesthetics occurs during the first trimester. There is increased sensitivity to succinylcholine,[8] and patients receiving magnesium sulfate for preterm labor or preeclampsia are more sensitive to nondepolarizing neuromuscular blocking drugs as well.[9] Decreased protein binding due to lower concentrations of plasma proteins, as well as increased volume of distribution due to increased blood volume and weight (fat) gain, make pharmacokinetics of various drugs complex.[6] The responses to many anesthetic drugs, particularly those employed in some of the unusual situations described in this chapter, are unknown. Caution is therefore in order whenever any agent is used in the pregnant patient.

Fetal Safety

The fetus is potentially at risk by three separate mechanisms: direct effects of anesthetic agents and techniques on fetal cardiorespiratory homeostasis, teratogenic effects of maternally administered drugs, and induction of preterm labor.

Maternal hypoxia and hypotension can adversely affect the fetus. Modest hypoxia is well tolerated by the fetus due to the high concentration of fetal hemoglobin and its affinity for O2. More severe hypoxia is associated with fetal desaturation and asphyxia. Conversely, hyperoxia does not adversely affect the fetus, owing to high placental shunt flow and the inability of high maternal Po2 to increase maternal oxygen content significantly. High maternal concentrations of oxygen may be given whenever indicated for maternal well-being.[10]

Conversely, the fetus poorly tolerates maternal hypotension if it is severe or prolonged.[11] Uteroplacental blood flow is highly dependent on maternal systemic blood pressure, and decreases in the latter lead to fetal asphyxia. During nonobstetric surgery, causes of maternal hypotension may include hypovolemia, deep general anesthesia, high spinal or epidural anesthesia, aortocaval compression, hemorrhage, positive-pressure hyperventilation, and systemic hypotensive drugs. However, good fetal outcomes have been reported after moderate deliberate hypotension during neurosurgery.[12]Uteroplacental blood flow may also be impaired by systemic agents that produce uterine arterial vasoconstriction or significantly increase myometrial tone.[13] Drugs that may cause these effects include large doses of α-adrenergic agonists, vasopressin, ketamine, and high doses of local anesthetics. In contrast to classic animal studies, however, maternal administration of moderate dose phenylephrine has been associated with normal fetal blood gases at delivery.[14]

Teratogenicity of maternally administered drugs has been extensively reviewed elsewhere, and the reader is referred to these sources for more information. To date, no anesthetic agent has been definitively shown to induce congenital abnormalities in the developing fetus. However, there are a number of associations between anesthetics and either anomalies or abortion strong enough to dictate prudence in their use. Importantly, many drugs found to be teratogenic in earlier animal or uncontrolled human epidemiologic studies have proven safe when using more sophisticated methodology. This includes all commonly used opioids, benzodiazepines, barbiturates, and local anesthetics. [15] [16]

Inhalation anesthetics present a more complex picture. In animals, prolonged exposure to more than 50% nitrous oxide (N2O) induces fetal resorption and skeletal or visceral anomalies, depending on the timing of exposure. [17] [18] [19] However, the etiology is complicated and not completely understood. N2O impairs 1-carbon metabolism via its action on vitamin B12.[20] This cannot explain all of its effects, however, because supplementation with folinic acid or methionine (which should bypass many of the effects of inhibition of methionine synthase on DNA synthesis and methylation reactions) only partially reverses effects on the developing fetus. [21] [22] Furthermore, co-administration of isoflurane or halothane blocks many of the effects of N2O, possibly implicating α-adrenergic uterine vasoconstriction in the pathophysiology of the latter agent's effects.[23] Human epidemiologic studies of healthy women exposed to N2O in the workplace have yielded conflicting results, and positive studies have shown only a slight increase in spontaneous abortion that may be explained by confounding variables. [24] [25] Large epidemiologic investigations have confirmed slight increases in early pregnancy loss and low birth weight but have yielded inconclusive or negative results with regard to congenital anomalies. It is impossible to separate the effect of anesthesia from that of the surgical procedure or underlying disease process requiring surgery in human epidemiologic studies.[3]

Recently, a more ominous and insidious effect of inhalation anesthetics has been suggested and termed behavioral teratogenicity. The term refers to behavioral abnormalities occurring in the absence of obvious structural defects. Even relatively brief intrauterine exposure to halogenated anesthetics in rodents has resulted in persistent defects in memory and learning (maze solving). [26] [27] Studies in cell culture and pathologic investigation of neonatal brains of rodents exposed in utero to isoflurane have shown widespread apoptosis and, specifically, defects in hippocampal synaptic function, effects that may explain the behavioral phenomena.[26] These results have yet to be confirmed in humans but would suggest caution in blithely exposing the pregnant woman to these agents.

Finally, preterm labor is associated with surgery in pregnancy. Although halogenated anesthetics inhibit uterine contractions, this effect is short lived and does not protect against preterm labor. Intra-abdominal procedures and those occurring during the third trimester are the most likely to be associated with preterm labor. It is not clear from epidemiologic studies whether the surgery itself, or the underlying condition prompting it, is responsible.[28] There is no evidence that any anesthetic technique either increases or decreases the chance of preterm labor. However, tocolytic therapy with magnesium, cyclooxygenase inhibitors, calcium channel blockers, or β-adrenergic agonists can have important anesthetic implications.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Laparoscopic Surgery During Pregnancy

Occasionally, pregnancy can be complicated by acute intra-abdominal pathology, requiring surgical intervention. Laparoscopic surgery is generally preferred to conventional open procedures, and therefore the anesthesiologist must be familiar with the physiologic implications and anesthetic management of pregnant women requiring laparoscopic procedures. In the past decade, laparoscopic procedures have become increasingly popular compared with open procedures, owing to decreased morbidity and convalescence.[29] Although pregnancy was considered a contraindication to laparoscopic cholecystectomy less than a decade ago,[30] it has become the most commonly performed laparoscopic procedure during pregnancy.[31] Other types of laparoscopic surgeries performed safely during pregnancy include appendectomy, ovarian cystectomy,[32] management of adnexal torsion,[33] diagnostic laparoscopies for abdominal pain,[34] splenectomy,[35] heterotopic pregnancies,[36] and adrenal pheochromocytoma.[37]

General Considerations and Effect of Pneumoperitoneum

When faced with providing anesthesia for the pregnant patient undergoing laparoscopic surgery, the anesthesiologist must not only consider the maternal and fetal issues, and prevention of preterm labor, but also pay special attention to patient positioning during surgery and the physiologic and mechanical effects of the CO2 pneumoperitoneum.

Besides the maternal, fetal, and preterm labor issues, other factors that affect physiologic changes during laparoscopic surgery include pneumoperitoneum and patient positioning. Pneumoperitoneum during laparoscopy can cause cardiovascular and respiratory alterations in nonpregnant patients, and these changes become accentuated in the parturient. Adding pneumoperitoneum to an enlarged uterus further limits diaphragm expansion and is associated with an increase in peak airway pressure, decrease in functional reserve capacity, increased ventilation-perfusion mismatching, increased alveolar-arterial oxygen gradient, decreased thoracic cavity compliance, and increased pleural pressure.[38] Pneumoperitoneum and Trendelenburg positioning moves the carina cephalad, which can convert a low-lying tracheal tube to an endobronchial position. The Trendelenburg position increases intrathoracic pressure and accentuates all the respiratory-related physiologic changes. The combination of pregnancy and CO2 pneumoperitoneum predisposes the parturient to hypercapnia and hypoxemia. Insufflation of CO2 results in CO2 absorption across the peritoneum and into the maternal blood stream. Elimination depends on an increase in minute ventilation; however, mechanical hyperventilation can reduce uteroplacental perfusion, probably owing to decreased venous return.[39] Although end-tidal CO2concentrations (ETCO2) correlate well with PaCO2 in healthy patients, they are a poor guide to PaCO2 in sicker patients. Any increase in maternal PaCO2 or decrease in Pao2 can affect fetal well-being.[38] The cardiovascular changes associated with CO2 insufflation include reduction in cardiac index and venous return, which can be exacerbated by reverse Trendelenburg positioning.[40] The observed increase in intracardiac filling pressures are probably secondary to an increase in intrathoracic pressure. A combination of reverse Trendelenburg position, general anesthesia, and peritoneal insufflation can decrease the cardiac index by as much as 50%.[41] The hemodynamic effects of aortocaval compression by the gravid uterus could further accentuate the hemodynamic effects of pneumoperitoneum and reverse Trendelenburg positioning, resulting in significant hypotension. [38] [42] Steinbrook and Bhavani-Shankar[42] studied the cardiac output changes in four pregnant patients (17 to 24 weeks' gestation) undergoing laparoscopic surgery using thoracic bioimpedance cardiography. Intravenous ephedrine (10 mg) was given if the systolic blood pressure decreased by more than 20% with respect to baseline. The authors noted a 27% decrease in cardiac index after 5 minutes of CO2 insufflation. Cardiac index remained 21% below baseline after 15 minutes of insufflation. The authors' aggressive management of blood pressures during anesthesia (treating any decrease in blood pressure approaching 20% of baseline measurements with intravenous ephedrine so as to minimize decreases in uterine blood flow) may have resulted in the somewhat smaller reduction in cardiac index during CO2 insufflation in their patients (27%), as compared with 30% to 50% in nonpregnant subjects in most studies. Mean arterial pressures and systemic vascular resistance increased in these study subjects during CO2 insufflation, which is similar to that generally observed in nonpregnant subjects laparoscopic surgery.


With the large number of physiologic changes associated with pregnancy, as well as the cardiovascular and pulmonary changes induced by laparoscopic surgery, optimal perioperative monitoring is unclear. The main debate centers on whether perioperative monitoring of arterial blood gases and fetal and uterine activity is necessary in parturients undergoing laparoscopic surgery. The Society of American Gastrointestinal Endoscopic Surgeons (SAGES) published guidelines for laparoscopic surgery during pregnancy that include perioperative monitoring of arterial blood gases, as well as perioperative fetal and uterine monitoring.[43] This belief has been echoed by other authorities. [34] [44] [45] Amos and colleagues[34] reported four fetal deaths in seven pregnant women who underwent laparoscopic cholecystectomy or appendectomy. During the same period, no fetal deaths occurred in patients who underwent pelvic surgeries by laparotomy. Even though no arterial blood gas data were collected, these authors suggested that the fetal demise could have been due to prolonged respiratory acidosis, despite maintaining ETCO2 in the physiologic range (low to mid 30s mm Hg).[34] These concerns stem from previous studies indicating that elevation in maternal PaCO2 could impair fetal CO2 excretion across the placenta and could exacerbate fetal acidosis. Other risk factors, however, were present for fetal loss in this series, including perforated appendix and pancreatitis.

Steinbrook and colleagues[38] reported a case series of 10 pregnant women, gestational age 9 to 30 weeks, undergoing laparoscopic cholecystectomy. These authors did not monitor arterial blood gases or perioperative fetal and uterine activity. The patients underwent general anesthesia with controlled ventilation, and the ETCO2 maintained between 32 and 36 mm Hg. Fetal heart rate and uterine activity were assessed preoperatively and immediately postoperatively. All patients had an uneventful recovery and did not need postoperative tocolysis, and no adverse maternal or fetal outcomes were noted. Seven patients were followed to delivery and had normal infants. The authors concluded that standard monitors recommended by the American Society of Anesthesiologists (ASA) are sufficient for the safety and well-being of the parturient and the fetus. Based on a series of 45 laparoscopic cholecystectomies and 22 laparoscopic appendectomies performed during all three trimesters, Affleck and associates[47]supported the use of noninvasive monitors and maintenance of the ETCO2 within the physiologic range. They also recommended preoperative and postoperative fetal heart rate and uterine activity monitoring and no prophylactic tocolysis. In their series there was no fetal loss, nor were there uterine injuries or spontaneous abortions. There was no significant difference in preterm delivery rate, Apgar scores, or birth weights between the open and laparoscopic surgery groups. As in previous reports, the operative groups (both open and laparoscopic appendectomies and cholecystectomies) had a slightly higher rate of preterm labor compared with the general population. Furthermore, multiple case reports have reported successful outcomes with noninvasive monitoring. [48] [49] Bhavani-Shankar and coworkers[50] prospectively evaluated the PaCO2-ETCO2 difference in eight parturients undergoing laparoscopic cholecystectomy with CO2 pneumoperitoneum. The intra-abdominal pressures were maintained around 15 mm Hg. These women underwent surgery with general anesthesia during the second and third trimester of their pregnancies. After adjusting minute ventilation to maintain the ETCO2at 32 mm Hg, the arterial blood gases (alpha-stat method) were measured at fixed surgical phases: before insufflation, during insufflation, after insufflation, and after completion of surgery. The authors found no significant differences in either mean PaCO2-ETco2 gradient or PaCO2 and pH during the various phases of laparoscopy. During the surgical phase the maximal PaCO2-ETCO2 difference detected was 3.1 mm Hg (range, 1.1 to 3.1 mm Hg). It appears that ETCO2 correlates well with arterial CO2, and adjusting ventilation to maintain ETCO2 also maintains optimal maternal arterial CO2. These results do not support the need for arterial blood gas monitoring during laparoscopy in pregnant patients. Laparoscopic procedures have been performed safely during all trimesters of pregnancy; however, some authors have advocated reserving semi-elective, nonobstetric surgery during pregnancy only during the second trimester. During this period, organogenesis is complete and spontaneous abortions are less common than in the first trimester. Furthermore, procedures during the third trimester have been associated with more preterm labor and potential difficulty in visualization with an enlarged uterus. [31] [33] [51]

Anesthetic Technique

A summary of recommended anesthetic and surgical interventions for laparoscopy during pregnancy is noted in Table 19-3 .[52]

TABLE 19-3   -- Suggested Anesthetic Plan for Laparoscopic Surgery During Pregnancy


Left or right uterine displacement


Oral sodium citrate, 30 mL; metoclopramide, 10 mg intravenously


Rapid-sequence sodium pentothal and succinylcholine

Ventilatory adjustments

Keep end-tidal PCO2 between 32 and 34 mm Hg

Maintenance of anesthesia

Desflurane, fentanyl, oxygen in air, and muscle relaxants (vecuronium)


Gradual change to reverse Trendelenburg

Fetal heart rate monitoring

16 weeks, preoperative and immediate postoperative period

Insufflation technique

Open trocar technique


Terbutaline, 0.25 mg subcutaneous, if needed


Increments of ephedrine

Postoperative period

Left or right uterine displacement, oxygen supplements, fetal heart monitoring

Data from Bhavani-Shankar K: Anesthetic considerations for minimally invasive surgery. In: Current Review of Minimally Invasive Surgery, 2nd ed. Philadelphia, 1998, p 29.




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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

In-Vitro Fertilization

Infertility is defined as 1 year of frequent unprotected sex without achieving a pregnancy and is not an irreversible state. Infertility is becoming more common with the trend for advanced maternal age before conception. [53] [54] The prognosis for infertility caused by major causes and tubal and male factors has improved significantly with the introduction of assisted reproductive technologies (ART).[55]ART involves the handling and manipulation of the oocyte and spermatozoa to achieve a successful pregnancy. In-vitro fertilization (IVF), the most common form of ART, was first introduced in 1978[56]and has increased tremendously over the past two decades, with a recent article from North America reporting over 88,077 ART cycles since its inception. [57] [58] The majority of these cycles (63,639) consisted of IVF, with a delivery rate per retrieval of 29.8%.[58] Overall, there was an increase of 7.5% and 0.4% for cycles and deliveries per retrieval, respectively. However, the high cost and the 70% failure rate have led reproductive endocrinologists to analyze factors that may affect the outcome of IVF, such as stimulation protocol, embryo factor, physician supervising the cycle, and patient selection.[59] [60] As such, close scrutiny of other factors that may affect outcome, including medications and techniques used to provide anesthesia, would be expected.[61]

IVF produces a variable amount of pain that many practitioners consider a significant disadvantage.[62] Abdominal pain levels have been correlated with body mass index, number of follicles, and duration of technique and may vary between patients. Although conscious sedation remains the most widely used method for pain relief, and is used in 95% of centers in the United States, [63] [64] it is rarely effective in preventing ovarian puncture pain. Lack of coverage for IVF by most insurance companies[65] and a concern for a decreased pregnancy rate with anesthetic agents may account for the decreased use of general and regional techniques for IVF.[57] However, recent state laws requiring that insurance companies provide either partial or complete coverage for IVF,[65] and similar embryo implantation and pregnancy rates with the use of local anesthetics and short-acting general anesthetic agents,[57] are likely to increase the use of general and regional anesthesia. Therefore, it is important to understand the implications of anesthetic techniques on IVF as well as the implications of assisted reproductive techniques on regional and general anesthesia (Table 19-4 19-5 [4] [5]).

TABLE 19-4   -- Different Types of Assisted Reproductive Techniques







Average Duration

10-20 min

60-90 min

Two different procedures: embryo retrieval (10-20 min) followed by transfer (30-60 min) 24-48 hr after fertilization

Embryo Transfer

Fertilized oocyte on day 3 or 5

Unfertilized oocyte transferred shortly after retrieval

Fertilized oocyte transferred 24-48 hr after retrieval

Anesthetic Options

Multiple; general or spinal preferred

Mainly general owing to need for laparoscopy

Two different anesthetics: intravenous general or short-acting spinal preferred for embryo retrieval and general anesthetic preferred for laparoscopy for transfer

TUGOR, Transvaginal ultrasound-guided oocyte retrieval; GIFT, gamete intrafallopian transfer; ZIFT, zygote intrafallopian transfer; PROST, spronuclear stage tubal transfer; TET, tubal embryo transfer.




TABLE 19-5   -- Anesthetic Options for Assisted Reproductive Techniques


General Anesthesia

Neuraxial Blockade

Paracervical Block

Conscious Sedation


Fast induction and emergence

Able to avoid intravenous agents if so desired

Fast induction and emergence without the need for anesthesia personal


Conflicting results on the effects of different agents on embryo implantation and pregnancy rates

Longer induction and recovery times

Ovaries are not anesthetized; operator dependent; lidocaine appears in the follicular fluid

Relies on adequate local anesthesia that is difficult to achieve



Anesthetic Implications on IVF

Transvaginal ultrasound guided oocyte retrieval (TUGOR) is a relatively short procedure. On average the procedure lasts 10 to 20 minutes and could be performed under conscious sedation, paracervical block, neuraxial blockade, or general anesthesia. Therefore, short-acting agents are desired to minimize the recovery time of patients undergoing this treatment. Monitored anesthesia care or conscious sedation relies on adequate local anesthesia. However, it is inadequate to anesthetize the ovary. Patient discomfort, motion due to pain, and a deep level of conscious sedation leading to airway obstruction are serious risks. In addition, significant discomfort may leave patients with bad memories and may discourage future attempts at IVF. Therefore, we prefer to use neuraxial techniques or intravenous general anesthesia (IVGA).

Embryo transfer (ET) is a simple procedure that occurs on day 3 or 5 after TUGOR, relies on a fertilized oocyte, and rarely requires any anesthetic involvement. After speculum insertion into the vagina and examination of the cervix, a flexible catheter loaded with embryos and culture medium is advanced past the cervical os and injected into the uterus. Conscious sedation or light IVGA may be necessary in cases of significant discomfort with speculum insertion, or when there is difficulty advancing the flexible catheter past the cervical opening.

Gamete intrafallopian transfer (GIFT) is an alternative to IVF-ET that was more common prior to the recent improvement in embryo culture techniques and successful pregnancies with IVF-ET. After hormone stimulation and TUGOR, unfertilized oocytes are mixed with sperm and transferred shortly after retrieval into the fallopian tube. Laparoscopy performed under general anesthesia is preferred so as to have direct visualization of the flexible catheter and fallopian tubes. Although spinal anesthesia is rarely used for laparoscopic procedures because of concerns of shoulder discomfort and difficulty breathing with CO2, there is a report highlighting the safety of spinal anesthesia for laparoscopic oocyte retrieval.[66] There is another technique performed with a minilaparoscopic approach, allowing for a reduction in intraperitoneal pressure and CO2, and obviating the need for general anesthesia.[67] Pregnancy rates are similar between IVF-ET and GIFT, and therefore IVF-ET, being less invasive, is more commonly performed. GIFT allows for the oocyte fertilization in vivo and may be acceptable for couples with religious beliefs that preclude IVF. Other transfer options include zygote intrafallopian transfer (ZIFT), pronuclear stage tubal transfer (PROST), and tubal embryo transfer (TET). Although fertilization is confirmed before embryo transfer, all of these techniques require TUGOR to aspirate the follicular fluid and laparoscopically guided transfer into the fallopian tube 24 to 48 hours after fertilization. Similar pregnancy rates, and the need for two different procedures and anesthetics, have led to a marked decline in the performance of these techniques.

Earlier reports of IVF, when the procedure length was significantly longer, reported the use of general endotracheal anesthesia with a combination of inhalation agents, with or without N2O. General endotracheal anesthesia is now rarely used, except in cases of laparoscopic oocyte retrieval or when dictated by the patient's condition. Concern about the use of N2O for these procedures originated from earlier reports suggesting that it had a teratogenic effect and caused fetal death in rats when used during organogenesis.[68] In addition, lower DNA and RNA content and morphologic abnormalities have been demonstrated in the embryos of pregnant rats when exposed to N2O during organogenesis. [69] [70] This potential teratogenicity has been attributed, in part, to the inactivation of methionine synthase. Short exposures to clinical concentrations of N2O, isoflurane, and halothane had no deleterious effect on IVF and early embryonic growth up to the morula stage in the mouse.[71] Despite the deleterious effect of N2O in some rat studies, no significant differences between rates of fertilization or pregnancy were demonstrated in humans undergoing laparoscopic oocyte retrieval and isoflurane/N2O or isoflurane/air general anesthesia.[72] Inhaled agents have not been demonstrated to possess a teratogenic or embryo effect.[73] Furthermore, halothane has been demonstrated to protect against N2O-induced teratogenicity and spontaneous abortions in rats.[23] In addition, greater pregnancy rates have been demonstrated in women undergoing laparoscopic pronuclear stage transfer (PROST) under isoflurane/N2O when compared with propofol/N2O anesthesia.[74]

Propofol is an ideal induction and maintenance agent owing to its short-acting half-life and antiemetic properties. There were some reservations regarding the use of this agent, because early reports demonstrated that propofol diffuses into follicular fluid, with greater levels observed with higher doses of propofol. [75] [76] Even though follicular fluid concentrations have been demonstrated to be higher in the last follicle when compared with the first follicle, no differences were found in the ratio of mature to immature follicles, or in fertilization, cleavage, or embryo cell number.[76] In addition, a report on the use of propofol for intravenous general anesthesia for TUGOR of donor oocytes demonstrated a lack of negative effect on the oocyte, as evaluated by cumulative embryo scores and rates of implantation and pregnancy.[77] Reports on the use of propofol (propofol, N2O) for the transfer of fertilized embryos demonstrated fewer pregnancies when compared with an isoflurane, N2O-based anesthesia.[74]However, higher maternal serum concentrations were needed in this study to provide anesthesia for laparoscopic pronuclear stage transfer when compared with the use of propofol for IVF-ET procedures.[78] Another study on mouse oocytes demonstrated that high levels of propofol in the follicular fluid may affect pregnancy rates.[79] The use of thiopental and thiamylal for laparoscopic egg retrieval has also been associated with accumulation in follicular fluid,[80] and a comparison of thiopental and propofol when used for laparoscopic GIFT demonstrated similar pregnancy rates.[81] A case-controlled study comparing propofol IVGA to paracervical block did not demonstrate any difference between the fertilization rates, embryo cleavage characteristics, or pregnancy rates between the two groups.[82]Neither group received premedication, both groups received 0.5 mg alfentanil at the time of anesthesia induction, and the propofol group received a full induction dose (2 mg/kg), followed by a continuous infusion without any additional anesthetic.[82] The results of this study are compelling, as an IVGA was compared to a local anesthetic group without premedication. In addition, there are no studies demonstrating a teratogenic effect of propofol. Overall, the data support the notion that although propofol, when used for intravenous general anesthesia for brief IVF procedures, may appear in follicular fluid, it does not have an adverse effect on pregnancy rates.

Fentanyl, alfentanil, and midazolam, when used as premedications prior to TUGOR, reach very low intrafollicular levels and have no effect on rates of implantation or pregnancy. [83] [84] The absolute concentration of intrafollicular levels is extremely low when compared with plasma levels. [84] [85] Alfentanil had the lowest follicular fluid to plasma ratio (1:40) when compared with midazolam (1:20) and fentanyl (1:10).[84] Remifentanil is a relatively new analgesic agent with pharmacokinetic properties, including a fast onset and a very short recovery, suitable for IVF procedures. A comparison of propofol/fentanyl anesthesia to a midazolam/remifentanil technique demonstrated a decreased need for manual ventilation and a faster recovery of function in the latter group. More patients in the former group experienced intraoperative awareness and did not enjoy the anesthetic, but there were no differences in the time to discharge.[86] Other studies have compared a propofol-based anesthetic with a sedative combination of ketamine and midazolam without demonstrating a difference in the recovery profile, embryo transfers, or pregnancy rates.[87] Of note, there are sparse data on the safety of ketamine or remifentanil on ART.

Nonsteroidal anti-inflammatory agents (NSAIDs), such as intravenous ketorolac, would be ideal for the acute visceral pain during and after TUGOR. However, there is reluctance to use them because prostaglandins (PGE2, PGF2a, PGI2) in the embryo and endometrium are involved in processes that are important for implantation. [88] [89] Prostaglandin H synthase, also known as cyclooxygenase, is an essential enzyme in prostaglandin synthesis, is primarily localized in the endometrial epithelium, and is important for embryo implantation.[90] Despite these concerns, there are no animal or human data that demonstrate any changes produced by cyclooxygenase inhibitors on the embryo or on implantation rates. Furthermore, implantation does not occur until 3 to 5 days after egg retrieval. Some centers in the United Kingdom routinely use NSAIDs without any known effects on endometrial lining or implantation rates.[91] We prefer to use NSAIDs for egg donors or for patients with pain refractory to significant doses of opioids until further data are available. Future studies should help to clarify some of these concerns.

Nausea and vomiting are the most common complications of general anesthesia but is reduced with the use of propofol, low doses of opioids, and the avoidance of inhaled anesthetic agents. We prefer to avoid metoclopramide in patients undergoing IVF, as the risk of affecting embryo implantation and a successful pregnancy is greater than its benefit in patients that are not at a significantly high risk for acid aspiration syndrome. Metoclopramide, a dopamine receptor antagonist, causes elevated prolactin levels that may be associated with inhibition of pulsatile gonadotropic releasing hormone secretion, a hypoestrogenic state, and ovulatory dysfunction.[92] Although not helpful for gastric motility, ondansetron use for the treatment or prevention of nausea and vomiting is not contraindicated during IVF. Serotonergic agents, unlike 5-HT3 receptor antagonists such as ondansetron, may also cause an elevation of prolactin levels. We prefer to use a neuraxial technique for patients at increased risk for postoperative nausea and vomiting or acid aspiration syndrome.

During TUGOR, a transvaginal approach is utilized to puncture the ovary and aspirate the follicular fluid. Both sympathetic and parasympathetic nerves supply the ovaries. Although most of the sympathetic nerves are derived from the ovarian plexus that accompanies the ovarian vessels, a minority are derived from the plexus that surrounds the ovarian branch of the uterine artery.[93] Acute visceral pain is often diffuse in distribution, vague in location of origin, and referred to remote areas of the body.[94] Paracervical block (PCB) has been utilized with and without conscious sedation for TUGOR to improve pain relief. [63] [95] [96] It has been postulated that PCB anesthetizes the vaginal mucosa, uterosacral ligaments, and peritoneal membrane over the pouch of Douglas.[95] Although the ovaries are not anesthetized, their pain sensitivity is the lowest when compared with the rest of the internal female genital organs.[94] PCB with 150 mg of lidocaine reduced abdominal pain by one half when compared with placebo.[95] The Visual Analogue Pain Score (VAPS 0-100 mm linear visual analogue scale) decreased from 43.7 to 21.2 mm when evaluated 4 hours after TUGOR.[95] Another study demonstrated no difference in VAPS when 50 mg of lidocaine was compared with 100 and 150 mg for PCB.[96] Assessing VAPS immediately after the procedure demonstrated median abdominal pain levels of 30 to 32 mm. Although small concentrations of lidocaine appear in the follicular fluid and have been shown to have adverse effects in mouse oocyte fertilization and embryo development, [95] [97]they do not affect embryo implantation or pregnancy rates.[98] PCB alone is not sufficient to provide complete analgesia, owing to its 10% to 15% failure rate and lack of interference with afferent sensory fibers originating from the ovarian plexus. This finding is reflected in the 2.5 times higher vaginal and abdominal pain levels with PCB alone when compared with PCB with the addition of conscious sedation.[63]

Neuraxial techniques have also been utilized for TUGOR and are more likely to anesthetize the ovary, vaginal mucosa, and peritoneal membrane. A thoracic dermatomal level of T10 or higher is needed to anesthetize the ovaries. Spinal anesthesia is more likely to be beneficial owing to its increased reliability and fast onset. It requires minimal to no conscious sedation for its performance and can be tailored to minimize high sensory levels and motor blockade. The optimal spinal anesthetic should allow adequate surgical anesthesia with minimal side effects, a fast onset, a short recovery time, and a similar rate of successful pregnancies when compared with other anesthetic techniques. Earlier reports described the use of 60 mg of 5% lidocaine for spinal anesthesia,[99] but long recovery times and the finding of transient neurologic symptoms caused some concerns. In an effort to decrease recovery times and keep patients comfortable, Martin and colleagues[100] decreased the dose to 45 mg of lidocaine and evaluated the benefit of adding 10 μg of fentanyl to the spinal anesthetic. A comparison of these studies [99] [100] demonstrated decreased times to ambulate, void, and discharge in the lower dose lidocaine group. The addition of fentanyl to the lidocaine resulted in improved analgesia during the procedure and, postoperatively, a decreased opioid consumption and no change in side effects or in the ability to ambulate, void, or be discharged. The addition of increased amounts of fentanyl to the spinal technique, and surgical improvements leading to a shorter duration in egg retrievals, led to a further decrease in the dose of lidocaine to 30 mg. Although we have had a good success with the use of subarachnoid 30 mg of lidocaine combined with fentanyl of 25 μg, controversy due to lidocaine and transient neurologic symptoms led to the evaluation of bupivacaine as an alternative. However, a comparison of 30 mg of lidocaine with equipotent doses of bupivacaine (3.75 mg) demonstrated a longer time to micturition and recovery with bupivacaine.[101] Of note, patients undergoing IVF procedures demonstrate decreased serum albumin and α1-acid glycoprotein levels during supraphysiologic estrogen states at the time of oocyte retrieval. This may lead to an increased free fraction of highly protein bound drugs such as bupivacaine.[102] However, this may only be significant when using larger doses of bupivacaine during epidural anesthesia, which is rarely used during IVF. At our institution, spinal anesthesia even with low doses of local anesthetic and opioid is associated with longer times to voiding and discharge when compared with intravenous general anesthesia. This finding and short surgical time led us to use IVGA as our standard anesthetic for TUGOR. Spinal anesthesia with 30 mg of lidocaine and 25 μg of fentanyl is used at the patient's request in patients with significant gastroesophageal reflux disease and/or morbid obesity, in cases where the patient has eaten and the oocytes must be retrieved before spontaneous ovulation occurs, or when indicated because of severe side effects to IVGA, such as postoperative nausea and vomiting.

Male factor is the most common form of infertility.[103] New variations of IVF include direct sperm harvesting and a single sperm injection into the cytoplasm of the oocyte (intracytoplasmic sperm injection [ICSI]). ICSI has markedly increased pregnancy rates in patients with male factor infertility due to low sperm counts and is often combined with direct sperm aspiration from the epididymis or testicular biopsy. Earlier reports described a more invasive microepididymal sperm aspiration (MESA) with an open surgical aspiration of the scrotum.[104] Recent work has pioneered less invasive techniques such as percutaneous epididymal sperm aspiration (PESA) and testicular sperm aspiration (TESA).[104] These two techniques have been reported to be done under local anesthesia of the superior and inferior spermatic nerves and the genital branch of the genitofemoral nerve without any premedication.[104] We prefer to use spinal anesthesia or IVGA for these procedures to minimize patient discomfort and movement.

IVF Implications on Anesthesia

IVF consists of different stages, including suppression therapy, stimulation therapy, trigger or ovulation therapy, egg retrieval, fertilization, postovulation therapy with progesterone, and embryo transfer. Therapy with leuprolide acetate (Lupron), a gonadotropin-releasing hormone agonist, causes suppression of gonadotropins (follicle-stimulating hormone [FSH] and luteinizing hormone [LH]) and results in a lack of production of estrogen and progesterone. Stimulation therapy is conducted with FSH- and LH-containing human menopausal gonadotropin and causes ovarian follicle growth. Human chorionic gonadotropin (hCG) causes ovulation to occur within 36 hours, and TUGOR is performed at this time. Supplemental progesterone is given after embryo transfer.

Stimulation therapy with gonadotropins such as human menopausal gonadotropin or FSH preparations may lead to very high estrogen levels and ovarian hyperstimulation.[105] High estrogen levels place patients at risk for thromboembolic phenomena. In its more severe form, ovarian hyperstimulation syndrome (OHSS) may lead to increased vascular permeability with leaky capillaries and findings such as weight gain, intravascular volume depletion, ascites, pleural effusions, electrolyte changes, and renal dysfunction. These patients usually experience a state of fibrinolysis with higher fibrinogen, plasmin/α2-antiplasmin, thrombin/antithrombin complexes, and D-dimer levels when compared with women with lower estrogen levels. [106] [107] [108] In addition, tissue factor increases markedly with high estrogen levels and is a powerful trigger of the extrinsic pathway of the coagulation cascade. [108] [109] Treatment is usually supportive, with intravascular volume expansion, analgesics, bed rest, and thrombosis prophylaxis. More invasive methods, such as paracentesis and thoracentesis, are more helpful for relief of symptoms such as abdominal pain and shortness of breath. Conscious sedation is often required for these procedures and should take into account the increased sensitivity to medications due to intravascular volume contraction. Caution should be approached if regional anesthetic techniques are a consideration for these patients because of the potential for anticoagulation.

The retrieval of oocytes from the follicles is not considered an elective procedure, as failure to retrieve them may lead to spontaneous ovulation and a wasted cycle. In addition, failure to empty the follicles may lead to ovarian hyperstimulation syndrome with all of its known complications. Our preference is to perform TUGOR under spinal anesthesia with minimal sedation under these circumstances. Aspiration prophylaxis is recommended with sodium citrate and metoclopramide, despite the concerns for increased prolactin levels with metoclopramide.

In summary, assisted reproductive techniques have increased tremendously over the past two decades. Although the rate of success continues to increase, there are still a significant number of cycles that do not result in a live birth. Therefore, it is expected that close scrutiny will be paid to variables that may affect oocyte retrieval or embryo transfer. It is essential to understand the impact of different anesthetic techniques and medications on IVF and to read carefully any data that links these factors with implantation or pregnancy rates. Not only may there be an impact of the anesthetic on ART but also one of ART on the anesthetic.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Morbid Obesity in Pregnant Women

A weight greater than 300 pounds in a gravida at term is considered to be morbidly obese.[110] Pregnancy in obese patients may have four important implications.[111] First, some of the physiologic changes associated with pregnancy (e.g., increases in blood volume, cardiac output, reduction in functional residual capacity) may further exacerbate deleterious effects produced by pathophysiologic alterations of obesity. Second, there is susceptibility for obese patients to acquire pregnancy-related diseases and complications (e.g., preeclampsia, gestational diabetes). Third, there is an association between increased incidence of obstetric and perinatal complications and morbid obesity. Finally, a combination of these three factors may lead to the fourth implication: an unfavorable outcome of pregnancy.

Obese women should be strongly encouraged to lose weight before conceiving. This will decrease obstetric and perinatal morbidity and mortality. Careful systemic evaluation should be performed at the first opportunity during pregnancy in morbidly obese women to determine the systemic pathophysiologic alterations of obesity. This includes the degree of respiratory impairment resulting in hypoxia, with consequences such as pulmonary hypertension, right ventricular hypertrophy, and right ventricular impairment. The left ventricle undergoes eccentric hypertrophy as a result of increased cardiac output, hypertension, and blood volume. The end result is a biventricular hypertrophy. A bedside method of knowing the degree of hypoxemia is to determine the decreases in oxygen saturation on assuming the supine position from an erect posture. If hypoxia occurs in assuming the supine position, further evaluation should be performed to determine the right ventricular functional changes.[111] Pregnancy in morbidly obese women can exaggerate sleep apnea, resulting in pulmonary hypertension during pregnancy.[112]

Increased body mass index, increased prepregnancy weight, and excessive maternal weight gain increase the risk of cesarean section.[113] Abnormal presentations, fetal macrosomia, and prolonged labor are predisposing factors associated with increased incidence of cesarean delivery among obese women. There is evidence that obese patients are at increased risk for abnormal labor. [114] [115] The incidence of cesarean delivery for failure to progress was much higher in the morbidly obese group than in the control group, although the difference was not statistically significant.

There is high incidence of umbilical arterial pH less than 7.10 among obese women, regardless of whether they had a trial of labor or elective cesarean delivery.[116] There is significantly higher incidences of neonates with an Apgar score of less than 5 at 1 minute, Apgar score less than 7 at 5 minutes, birth weight greater than 4500 g, birth weight less than 2500 g, intrauterine growth retardation, and neonatal intensive care unit admissions among infants born to obese parturients, as compared with those in nonobese parturients.[117] There seems to be an association between gravid obesity and congenital anomalies in infants born to gravid obese parturients. Waller and associates found that these infants are at a greater risk for developing neural tube defects and other congenital malformations.[118]

Anesthetic Management

It is strongly recommended that the patient should be seen by an anesthesiologist at around 28 weeks' gestation to determine the effect of pregnancy on various systems ( Box 19-1 ). A multidisciplinary approach should be instituted, depending on the systemic findings. Careful evaluation of airway should be performed, and the anesthetic plan should be formulated well in advance and communicated to the patient, as well as the obstetrician. Regional anesthesia is most appropriate for labor and delivery. An early institutionalization of epidural anesthesia is recommended, which will provide ample time to negate difficulties encountered during epidural placements. Continuous spinal anesthesia is a reasonable alternative. These two techniques provide satisfactory analgesia and anesthesia as needed for cesarean delivery, urgent or otherwise. If general anesthesia is contemplated, a second pair of hands is a boon, and necessary airway backup equipment should be at hand. Difficult intubation should be anticipated, and a contingency backup plan should be set in motion as needed. Great care must be exercised in appropriately positioning morbidly obese pregnant women for cesarean delivery. Hypoxia may occur in the supine position, which may require elevation of the back rest of the operating table. Retraction of the pannus to facilitate surgery can result in exaggerated supine hypotensive syndrome of pregnancy that may occasionally result in cardiac arrest. A multidisciplinary approach is the key to a successful outcome of pregnancy in morbidly obese women.

BOX 19-1 

Anesthetic Considerations in Morbidly Obese Pregnant Women



Perform a preanesthetic evaluation during pregnancy.



Assess airway.



Evaluate associated cardiorespiratory abnormalities of obesity.



Perform early epidural placement to ensure a good working catheter.



Consider continuous spinal technique if epidural anesthesia is unsuccessful and airway is anticipated to be difficult.



Place several folded bed sheets in a stepwise fashion from the back to the occiput, to attain a good intubating position.



Know that a large pannus may cause hemodynamic instability after induction of regional anesthesia.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Amniotic Fluid Embolism

Amniotic fluid embolism is one of the most intriguing complications of pregnancy. Its diagnosis is difficult and uncertain at times, its pathophysiology is debatable, itstreatment is difficult and often inadequate and nonspecific, and morbidity and mortality are high. Amniotic fluid or amniotic debris enters the maternal circulation more often than perceived. However, only a few develop full-blown amniotic fluid embolism and what initiates the chain of events remains unclear.

The mortality of amniotic fluid embolism continues to be high for patients who are symptomatic. It varies anywhere from 61% to 86%. [119] [120] The classic description of amniotic fluid embolism is profound and unexpected shock, followed by cardiovascular collapse and, in most cases, death.[121] The syndrome was thought most likely to occur in multiparous women who had an unusually strong or rapid labor or who had just followed such a labor.[122] The use of uterine stimulants, meconium staining of the amniotic fluid, or the presence of a large or dead fetus was also believed to increase the risk. However, it has been revealed that there are a number of exceptions to this classic description. There are several case reports of amniotic fluid emboli occurring during cesarean deliveries and therapeutic abortions, as well as occasional cases in the late postpartum period or very rarely in nonlaboring patients. [123] [124] [125] [126] Other cases have been associated with abdominal trauma, ruptured uterus, or intrapartum amnioinfusion. [127] [128]

It has been postulated that amniotic fluid may be trapped in the uterine veins during contraction of the uterus at delivery, which is then released into the circulation later, during normal postpartum uterine involution.[129] This explains why some cases of amniotic fluid embolism occur in the late postpartum period. Another reason for delayed presentation would be that the initial onset was either transient or subclinical and went unrecognized. This, in turn, could account for the delayed or atypical presentation reported in the literature.

Clinical Presentation

Cardiorespiratory collapse was almost invariably present in most of the cases, as seen in the Morgan series.[119] However, the presenting symptom in 51% of patients was respiratory distress. In the remainder, the first indication of a problem was hypotension in 27%, a coagulopathy in 12%, and seizures in 10%. Clark and coworkers, on the other hand, found that, of those women presenting before delivery, 30% had seizures or seizure-like activity, whereas 27% complained of dyspnea.[120] Fetal bradycardia (17%) and hypotension (13%) were the next most common presenting features. Of the 13 patients who developed symptoms after the delivery of the infant, 7 (54%) presented with an isolated coagulopathy manifested by postpartum hemorrhage. Several additional case reports have suggested that the presentation of amniotic fluid embolus can be quite variable with regard to timing, presenting symptoms, and subsequent course.[128] Therefore, there is a need to consider the differential diagnosis carefully while at the same time maintaining a high index of suspicion for this disorder ( Box 19-2 ).

BOX 19-2 

Considerations in Amniotic Fluid Embolus



Cardiorespiratory collapse may be the first sign of amniotic fluid embolism.



Occasionally, hypotension, seizures, dyspnea, and isolated coagulopathy may be the presenting feature.



Coagulopathy is an invariable accompaniment of amniotic fluid.



Presence of squamous cells and other fetal debris (mucin, vernix, lunago) coated with leukocytes in the maternal circulation is the hallmark of amniotic fluid embolism.



Initial pulmonary hypertension, hypoxia, left ventricular failure, and coagulopathy are the primary events in amniotic fluid embolism.



Management is basically symptomatic and directed toward the maintenance of oxygenation, circulatory support, and correction of coagulopathy.


Intact fetal membranes isolate amniotic fluid from the maternal circulation. After delivery, uterine vessels on the raw surface of the endometrium become exposed to amniotic fluid. Normally, uterine contractions are very effective in collapsing these veins. Therefore, in addition to ruptured membranes, for amniotic fluid embolism to occur there must be a pressure gradient favoring the entry of amniotic fluid from the uterus into the maternal circulation.[119] Although the placental implantation site is one potential portal of entry, particularly with partial separation of the placenta, this is otherwise unlikely if the uterus remains well contracted. On the other hand, small tears in the lower uterine segment and endocervix are common during labor and delivery and are now thought to be the most likely entry points.[119] [123] In support of this concept, Bastein and associates reported a case of amniotic fluid embolus where postmortem examination revealed marked plugging of both cervical vasculature and the lungs by various amniotic fluid elements.[130]

There is a misconception in the literature that amniotic fluid routinely enters the maternal circulation at delivery. This misconception arose from the belief that the presence of squamous cells in the pulmonary vasculature was a marker signaling the entry of amniotic fluid into the maternal circulation. Studies have now shown that squamous cells can appear in the pulmonary blood of heterogenous populations of both pregnant and nonpregnant patients who have undergone pulmonary artery catheterization. [131] [132] The presence of these cells is thought to have resulted from contamination by either exogenous sources during specimen preparation or byepithelial cells derived from the entry site of the pulmonary artery catheter.[131] Because it is difficult to differentiate adult from fetal epithelial cells, the isolated finding of squamous cells in the pulmonary circulation of pregnant patients without amniotic fluid embolus is most likely a contaminant and not indicative of maternal exposure to amniotic fluid. Furthermore, it was determined that although squamous cells may be present in both groups (clinical evidence with and without amniotic fluid embolus), only the former had evidence of other fetal debris such as mucin, vernix, and lunago. In these patients, squamous cells and other granular debris were frequently coated with leukocytes, suggesting a maternal reaction to foreign material. Where other occasional unidentifiable debris was detected, the authors stated that the material present in the patients who did not have an amniotic fluid embolism was “clearly different” from that seen in the sample.[132] Additional cause for the confusion regarding whether amniotic fluid routinely enters the maternal circulation centers on the importance of trophoblastic embolization to the maternal lung. Trophoblastic cells are normally free floating in the intervillous space and therefore have direct access to the maternal circulation.[119] Hence, their presence in the maternal peripheral or central vascular circulation is neither surprising nor indicative of an amniotic fluid embolus. Further evidence that amniotic fluid does not normally enter the maternal circulation can be found from autopsies of parturients who died of various complications of pregnancy. Roche and Norris compared lung specimens obtained from 20 toxemic patients with an equal number who had clinical evidence of amniotic fluid embolus. Utilizing a specific stain for acid mucopolysaccharide, they were able to confirm the presence of mucin in the lung secretions from all of the amniotic fluid embolism patients. None of the sections from the toxemic patients stained positive.[133]

In summary, the presence of squamous or trophoblastic cells in the maternal pulmonary vasculature must not be equated with the entry of amniotic fluid into the maternal circulation. There is no evidence to suggest or support that amniotic fluid embolus is a common physiologic event.


Once the amniotic fluid enters the maternal circulation, a number of physiologic changes occur that contribute to the syndrome that we observe. The pathophysiology is multifactorial, and the clinical presentation will depend on the predominant physiologic aberration.

Hemodynamic Changes

Animal models have suggested that severe pulmonary hypertension was the major pathophysiologic change.[134] This was believed to be either due to critical obstruction of the pulmonary vessels by embolic material or to pulmonary vasospasm secondary to the response of the pulmonary vasculature to fetal debris, resulting in acute asphyxiation, cor pulmonale, and, in turn, sudden death or severe neurologic injury. [123] [134] However, human hemodynamic data do not support sustained periods of pulmonary hypertension. [135] [136] In fact, left ventricular failure seems to be the pathognomonic feature in humans.[128] Clark reviewed the available hemodynamic data from the published cases of amniotic fluid embolus in humans and found only mild to moderate elevations in pulmonary artery pressures, whereas all patients had evidence of severe left ventricular dysfunction. Calculation of pulmonary vascular resistance further revealed that, with one exception, all were either normal or in a range that was reflective of isolated left ventricular failure.[134] In an attempt to reconcile clinical and animal experimental findings, Clark proposed a biphasic model to explain the hemodynamic abnormalities that occur with amniotic fluid embolus.[134] He suggested that acute pulmonary hypertension and vasospasm might be the initial hemodynamic response. The resulting right-sided heart failure and accompanying hypoxia could account for the cases of sudden death or severe neurologic impairment. Those patients who survive the initial phase of pulmonary hypertension, which is transient, proceed to the next stage of left ventricular failure. Several mechanisms contribute to the later phase of left ventricular failure. They include hypoxia, leftward shift of interventricular septum secondary to right-sided heart failure (resulting in an decrease in cardiac output, leading to impaired coronary artery perfusion), and the direct myocardial depressant effect of amniotic fluid itself. Endothelin, which is in amniotic fluid in abundance, has been cited as the cause of left ventricular failure.[137] Several authors have suggested that other humoral factors, including proteolytic enzymes, histamine, serotonin, prostaglandins, and leukotrienes, may contribute to the hemodynamic changes and consumptive coagulopathy associated with amniotic fluid embolism.[128] Because of the clinical resemblance of presentation of amniotic fluid embolus with sepsis and anaphylaxis, Clark suggested that the syndrome of amniotic fluid embolism is due to anaphylactoid reaction to amniotic fluid and named the syndrome “anaphylactoid syndrome of pregnancy.” [120] Antigenic potential can vary in individuals and therefore can lead to different grades of the syndrome. For example, women carrying a male fetus are more likely to be affected.[120]Similarly, fluid containing thick meconium may be more toxic than clear amniotic fluid.[120] Human data have shown that, although most patients dying of amniotic fluid emboli have had clear amniotic fluid, there is a shorter time from the initial presentation to cardiac arrest and an increased risk of neurologic damage or death in the presence of meconium or a dead fetus.[120] Further indirect evidence for an immunologic basis is the occurrence of fatal amniotic fluid emboli during first-trimester abortions. This suggests that under the right circumstances, maternal exposure to even small amounts of amniotic fluid can initiate the syndrome.[120] Confirming the theory of “anaphylactoid reaction” to amniotic fluid needs further research using tryptase markers.


The association of a consumptive coagulopathy is common with amniotic fluid emboli. In Morgan's review, 12% of patients presented with a bleeding diathesis, with subsequent development of a bleeding diathesis in an additional 37%.[119] More recent reviews, however, found an even higher incidence. Clark reported that 83% of the cases in the national registry had either clinical or laboratory evidence of a consumptive coagulopathy. The remaining 17% died before the clotting status could be assessed by either clinical or laboratory techniques. Similarly, in 15 cases of fatal amniotic fluid emboli associated with induced abortion, two patients presented with coagulopathy and an additional 75% of initial survivors went on to develop disseminated intravascular coagulation (DIC).[138] It now appears that amniotic fluid embolus is almost always associated with some form of DIC, with or without clinically significant bleeding. Isolated DIC causing maternal hemorrhage may be the first indication of the problem in a small number of patients. [139] [140] The current laboratory evidence also supports the opinion that amniotic fluid embolus is invariably associated with coagulation changes. Harnett and associates studied the effect of varying concentrations of amniotic fluid (10 to 60 μL added to 330 μL of whole blood) on thromboelastography variables and found amniotic fluid to be procoagulant even with a 10-μL study sample.[141]

The etiology of the coagulopathy remains somewhat obscure. Investigations that have attempted to clarify the mechanism have yielded inconclusive and sometimes contradictory results. Although amniotic fluid contains activated coagulation factors II, VII, and X, their concentrations are well below those found in maternal serum at term.[142] On the other hand, amniotic fluid has been shown to have a direct factor X activating property and thromboplastin-like effect. Both of them increase with gestational age. The thromboplastin-like effect is likely due to substantial quantities of tissue factor in amniotic fluid. Potential sources include sloughed fetal skin and epithelial cells derived from the fetal respiratory, gastrointestinal, and genitourinary tract mucosa. Tissue factor activates the extrinsic pathway by binding with factor VII. This complex, in turn, triggers clotting by activating factor X. Lockwood and colleagues speculated that once clotting was triggered in the pulmonary vasculature, local thrombin generation could then cause vasoconstriction and microvascular thrombosis, as well as secretion of vascular endothelin.[142] This vasoactive peptide can depress both myometrial and myocardial contractility and may primarily or secondarily contribute to the hemodynamic changes and uterine atony that are generally associated with this syndrome.


There are no diagnostic criteria to confirm the presence of amniotic fluid embolus. The differential diagnosis includes air or thrombotic pulmonary emboli, septic shock, acute myocardial infarction, cardiomyopathy, anaphylaxis, aspiration, placental abruption, eclampsia, uterine rupture, transfusion reaction, and local anesthetic toxicity.[128] In the presence of central venous access, blood from the pulmonary vasculature should be collected using the method described by Masson.[122] He suggested that to minimize the possibility of maternal or exogenous contamination, a more representative sample of the pulmonary microvasculature can be obtained if blood is drawn from the distal lumen of a wedged pulmonary artery catheter. After discarding the first 10 mL of blood, an additional 10 mL is drawn, heparinized, and analyzed utilizing Papanicolaou's method.[143] The presence of components of amniotic fluid, including squamous cells and mucous strands, reinforces the diagnosis. Although pulmonary vasculature preparations may occasionally be contaminated by maternal squames, when squamous cells are found in large numbers in such a sample it is clinically significant and strongly supportive of the diagnosis of amniotic fluid embolus.[143] This is particularly true if the squamous cells are coated with neutrophils, or if other fetal debris, such as mucin or hair, accompanies them. Lee and coworkers suggested that a more reliable method of confirming the diagnosis might center on the identification of other amniotic fluid elements in the maternal pulmonary vasculature, as opposed to squamous cells.[132] [144]

Recent progress in the diagnosis of amniotic fluid embolus has centered on the attempt to develop simple, noninvasive, sensitive tests utilizing peripheral maternal blood. Kobayashi and coworkers studied maternal serum sialyl Tn antigen levels in four women with clinical amniotic fluid emboli and compared them to both pregnant and nonpregnant controls.[145] Sialyl is a mucin-type glycoprotein that originates in fetal and adult intestinal and respiratory tracts. It is present in both meconium and in clear amniotic fluid. Using a sensitive antimucin antibody, TKH-2, the authors found no difference in the serum levels of pregnant patients throughout gestation or in the early postpartum period, when compared with healthy nonpregnant controls. However, the antigen levels were elevated in the amniotic fluid embolus group.[145] Nonetheless, this test appears promising, although it needs further evaluation. Kanayama and colleagues also studied a second marker of diagnosis that involves the measurement of plasma concentrations of zinc coproporphyrin, a characteristic meconium component, and found they were higher in patients with amniotic fluid embolus.[146]


The management of amniotic fluid embolus is basically symptomatic and directed toward the maintenance of oxygenation, circulatory support, and correction of coagulopathy. Depending on the circumstances, full cardiopulmonary resuscitation protocol may be required. If the fetus is sufficiently mature and is undelivered at the time of cardiac arrest, cesarean delivery should be instituted as soon as possible.

Treatment of hemodynamic instability includes optimization of preload with rapid volume infusion. Direct-acting vasopressors may be required in restoring aortic perfusion pressure in the initial stages. Once this is attained, other inotropes such as dopamine and dobutamine can be added to improve myocardial function. When clinically feasible, pulmonary artery catheterization can be instituted to help guide therapy. Diuretics may be required to mobilize pulmonary edema fluid. Treatment of the coagulopathy associated with amniotic fluid embolus involves the administration of blood component therapy. Amniotic fluid embolus is associated frequently with massive hemorrhage, requiring replacement with packed red cells. O-negative or group-specific blood can be used if crossmatched blood is unavailable. Plasma and platelets are given to replace the clotting factors. Ongoing therapy is generally guided by the clinical condition of the patient and laboratory evidence of coagulopathy. Although cryoprecipitate is not first-line therapy for treating coagulopathy, it may be useful in circumstances in which fibrinogen is low and volume overload is a concern. It has also been reported to be useful in a patient with severe acute respiratory distress syndrome secondary to amniotic fluid embolus.[147] After administration of cryoprecipitate, the patient's cardiopulmonary and hematologic status improved dramatically, leading the authors to suggest that it may be useful in cases in which conventional medical therapy appears unsuccessful in maintaining blood pressure, oxygenation, and hemostasis. Their recommendation was based on similar treatment protocols for severely ill patients with multiple trauma, burns, and postoperative sepsis. In these clinical settings, it is believed that there is impairment in the clearance of circulating microaggregates and immune complexes by the reticuloendothelial system, leading to the development of cardiopulmonary insufficiency and DIC. Cryoprecipitate is rich in opsonic α2 surface-binding glycoprotein, also known as fibronectin, which facilitates the reticuloendothelial system in the filtration of antigenic and toxic particulate matter. Depleted levels of this glycoprotein have been reported in severely ill patients, with marked improvement in the clinical status after repletion of fibronectin levels.[147]

Isolated reports of other modalities of treatment for amniotic fluid emboli exist in the literature. One patient, a serine proteinase inhibitor, FOY, was utilized in the treatment of an associated DIC.[148] Nitric oxide and aerosolized prostacyclin have been used to treat refractory hypoxemia. [149] [150] Clark has suggested the use of high-dose corticosteroids and epinephrine as useful therapeutic adjuvants in the light of the similarities of amniotic fluid embolism to anaphylaxis.[120]

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Complications of Preeclampsia: Eclampsia, HELLP Syndrome, and Pulmonary Edema

Preeclampsia is not uncommon and complicates 6% to 8% of all pregnancies. In this section we consider three conditions that need special mention, because they are not as common as preeclampsia. However, they may coexist with preeclampsia and contribute to significant morbidity and mortality in pregnant women.

Eclampsia is a life-threatening emergency that occurs suddenly, most commonly in the third trimester near term. Approximately 60% of convulsions/coma precede delivery. Most postpartum cases occur during the first 24 hours, but seizures attributed to eclampsia have been reported as late as 22 days after delivery. Approximately 50% of all patients have evidence of severe preeclampsia. In the remaining, the classic triad of preeclampsia (hypertension, proteinuria, and edema) may be absent or mildly abnormal.[151] There is a wide variation in the incidence of eclampsia in the literature (1 in 100 to 1 in 3448 pregnancies).[151] Eclampsia remains a significant complication of pregnancy in the United States. In a study of 399 consecutive women with eclampsia, the mortality rate was 1% and antepartum onset carried the greatest risk, especially before 32 weeks' gestation. Postpartum eclampsia was, however, more likely to be associated with neurologic deficits.[152] Eclampsia remains a common condition and a leading cause of maternal and perinatal mortality in developing countries.[153] Major maternal complications can follow, including placental abruption, HELLP syndrome, DIC, neurologic deficits, pulmonary aspiration, pulmonary edema, cardiopulmonary arrest, and acute renal failure.[152]

Headache, visual disturbances, and epigastric or right upper quadrant pain are consistent with severe preeclampsia and may forewarn of impending eclampsia. Seizures have an abrupt onset, typically beginning as facial twitching and followed by a tonic phase that persists for 15 to 20 seconds. This progresses to a generalized clonic phase characterized by apnea, which lasts approximately 1 minute. Breathing resumes with a long stertorous inspiration, and the patient enters a postictal state, with a variable period of coma. Pulmonary aspiration of gastric contents may complicate a seizure. The number of seizures varies from 1 or 2 to as many as 100 in severe, untreated cases. The causes of eclampsia are poorly understood. It is generally believed that cerebral vasospasm and ischemia result in eclampsia. However, cerebral edema, hemorrhage, and hypertensive encephalopathy have also been implicated in its pathogenesis. [154] [155]

Until proven otherwise, the occurrence of seizures during pregnancy should be considered eclampsia. Conditions simulating eclampsia should be considered (e.g., encephalitis, epilepsy, meningitis, cerebral tumor, and cerebrovascular accident) only after ruling out eclampsia ( Box 19-3 ).[156] Computed tomography (CT) may be normal, or it may show evidence of cerebral edema, infarction, or hemorrhage. The last complication occurs more frequently in elderly gravidas with preexisting hypertension and may frequently result in death or permanent disability.[156] Other neurologic abnormalities include temporary blindness, retinal detachment, postpartum psychosis, and other transient neurologic deficits.[151] Electroencephalography is also abnormal, showing focal or diffuse slowing, as well as focal or generalized epileptiform activity.[155]

BOX 19-3 

Considerations in Eclampsia



Eclampsia can occur during prepartum, intrapartum, and postpartum periods.



Headache, visual disturbances, and epigastric or right upper quadrant pain may forewarn of impending eclampsia.



Seizures have an abrupt onset beginning as facial twitching followed by a tonic phase and clonic phase.



CT may be normal, or it may show evidence of cerebral edema, infarction, or hemorrhage.



Management involves maintenance of airway, oxygenation, and ventilation.



Thiopentone sodium, midazolam, and succinyl choline may be required to facilitate oxygenation and ventilation.



Magnesium sulfate is the preferred drug for the definitive treatment of seizures.



Eclamptic patients should undergo expeditious delivery.



Regional anesthesia to facilitate labor and delivery can be considered in patients who are seizure free, conscious, and rational in behavior with no evidence of increased intracranial pressure and absence of coagulopathy.

Management of Eclampsia

Supplemental oxygen should be delivered immediately during seizure. A soft nasopharyngeal airway may facilitate oxygenation during seizure. Ventilation may be assisted once seizures end. Simultaneously, precautions should be observed to minimize chances of gastric aspiration. Midazolam in incremental doses up to 20 mg may be necessary, either to suppress seizures or facilitate further treatment in a combative patient. Occasionally, thiopentone sodium and succinylcholine may be required to facilitate oxygenation and ventilation. Immediate monitoring should include pulse oximetry, electrocardiogram, and blood pressure recordings. Left uterine displacement should be maintained throughout the resuscitative effort and until delivery of the infant.

Magnesium sulfate is the preferred drug for the definitive treatment of seizures. After an immediate loading dose of 4 to 6 g infused intravenously over 20 to 30 minutes, a maintenance dose of 1 to 2 g/hr is initiated, assuming that the patient has adequate urine output. Hourly monitoring of urine output, regular evaluation of deep tendon reflexes, and observation of respiratory rate should be implemented to guard against magnesium toxicity.

Unless otherwise contraindicated, eclamptic patients should undergo expeditious delivery. The frequent indications of cesarean delivery include fetal distress, placental abruption, prematurity with an unfavorable cervix, persistent seizures, and persistent postictal agitation.

Regional anesthesia to facilitate labor and delivery can be considered in patients who are seizure free, conscious, and rational in behavior with no evidence of increased intracranial pressure and absence of coagulopathy. Moodley and associates found no difference in maternal and neonatal outcomes when comparing epidural anesthesia with general anesthesia for cesarean delivery in conscious women with eclampsia.[157] Unconscious or obtunded patients, or those with evidence of increased intracranial pressure, should have general anesthesia in line with neurosurgical anesthesia recommendations. Hyperventilation can be initiated soon after the delivery of the infant to minimize the effect of low PaCO2 on the uterine arteries. The patient can be extubated at the conclusion of surgery if awake and conscious. On the other hand, if general anesthesia was undertaken in a women who was not conscious to begin with, consideration can be given to leaving the patients intubated and transferring them to intensive care for blood pressure control and controlled weaning from assisted ventilation while assessing neurologic recovery. Prolonged unconsciousness should prompt further evaluation with CT. Magnesium should be continued until the blood pressure normalizes and central nervous system hyperexcitability disappears.

HELLP Syndrome

The HELLP syndrome is believed to be a clinical state that may represent an advanced form of preeclampsia ( Box 19-4 ). Hemolysis, Elevated Liver enzymes, and Low Platelets characterize this condition. Based on the platelet count,the HELLP syndrome is divided into three classes. Class I patients have a platelet count of less than 50,000/mm3, class 2 is defined by a platelet count between 50,000 and 100,000/mm3, and class 3 is defined by a platelet count over 100,000/mm3.[158] The etiology of HELLP remains elusive. Its clinical and pathologic manifestations result from an unknown insult that leads to intravascular platelet activation and microvascular endothelial damage. Hemolysis, which is defined as the presence of microangiopathic hemolytic anemia, is the highlight of the disorder. Sibai, after reviewing published reports, noted a lack of consensus regarding the diagnostic features of HELLP syndrome.[159] He suggested the following diagnostic criteria: (1) hemolysis, defined by an abnormal peripheral blood smear and an increased bilirubin level (1.2 mg/dL or greater); (2) elevated liver enzymes, defined as an increased aspartate aminotransferase of at least 70 U/L and a lactate dehydrogenase level greater than 600 U/L; and (3) a low platelet count (<100,000/mm3). A diagnosis of the HELLP syndrome is made only if all three criteria are present. A diagnosis of partial HELLP syndrome is made if only one or two of the three criteria are present, and a diagnosis of severe preeclampsia is made if none is present.[160] Patients with full HELLP syndrome are likely to have a higher incidence of stroke, cardiac arrest, DIC, placental abruption, need for blood transfusion, pleural effusion, acute renal failure, and wound infections.[160] Most cases of HELLP syndrome occur preterm, but 20% may present post partum. Patients who develop HELLP postpartum have a higher incidence of pulmonary edema and renal failure.[161]

BOX 19-4 

Considerations in HELLP Syndrome



Hemolysis, Elevated Liver enzymes, and Low Platelets characterize this condition.



Classification of HELLP is based on platelet number: class I (< 50,000/mm3), class II 50,000-100,000/mm3), and class III (>100,000/mm3).



Etiology of HELLP still remains elusive.



Delivery represents the only definitive treatment of HELLP syndrome and should be undertaken immediately, with few exceptions.



Dexamethasone increases the platelet number significantly.

A number of studies have demonstrated better maternal outcome with administration of 10 mg of dexamethasone intravenously at 12-hour intervals until disease remission is noted.[162] Dexamethasone therapy is continued until the following occurs: blood pressure is 150/100 mm Hg or less, urine output is at least 30 mL/hr for 2 consecutive hours without a fluid bolus or the use of diuretics, platelet count is greater than 50,000/mm3, the lactate dehydrogenase level begins to decline, and the patient appears clinically stable. When these occur, dexamethasone is decreased to 5-mg doses administered intravenously 12 hours apart.[162]

Compensated DIC may be present in all patients with the HELLP syndrome.[163] In addition, patients with this syndrome may experience right upper quadrant pain and neck pain, shoulder pain, or relapsing hypotension due to subcapsular hematoma and intraparenchymal hemorrhage. Because abnormal liver function tests do not accurately reflect the presence of liver hematoma and hemorrhage, this subset of patients, particularly if associated with thrombocytopenia, should undergo CT examination of the liver.[164] An abnormal hepatic imaging finding was noted in 77% of patients with a platelet count of 20,000/mm3 or less.[164]

Delivery represents the only definitive treatment of the HELLP syndrome and should be undertaken immediately, with few exceptions. Conservative treatment that includes bed rest, antithrombotic agents, and plasma volume expansion is typically unsuccessful and often results in early maternal or fetal deterioration. In the presence of prematurity, corticosteroids may be administered to accelerate lung maturity, followed by delivery 48 hours later. Administration of high doses of corticosteroids may increase platelet numbers to allow placement of a regional anesthetic, especially if a latency of 24 hours is achieved before delivery.[165]

Pulmonary Edema in Preeclampsia

Three percent of women with severe preeclampsia develop pulmonary edema ( Box 19-5 ).[166] Pulmonary edema occurs as a result of low colloid oncotic pressure, increased intravascular hydrostatic pressure, and/or increased pulmonary capillary permeability.[167] Many cases develop 2 to 3 days post partum, and hence there is need to keep patients with preeclampsia under careful surveillance inthe immediate postpartum period. The resolution of pulmonary edema requires management of the underlying cause (e.g., overhydration, sepsis, cardiac failure). Echocardiography may be required to exclude cardiogenic causes of pulmonary edema. [168] [169] The initial treatment includes administration of supplemental oxygen, fluid restriction, and administration of a diuretic. In a subset of patients, if no resolution of pulmonary edema is in sight, pulmonary artery catheter placement may facilitate further management. This includes vasodilator therapy to reduce preload or afterload and administration of dopamine or dobutamine in women with evidence of left ventricular failure. Colloid administration may prove beneficial if the colloid oncotic pressure-pulmonary capillary wedge pressure gradient is lowered. In rare instances, tracheal intubation and ventilation may be required if respiratory failure complicates refractory pulmonary edema.[170] Adult respiratory distress syndrome can complicate severe preeclampsia, especially if an increase in pulmonary capillary permeability exists.[171]

BOX 19-5 

Pulmonary Edema in Preeclampsia



Three percent of women with severe preeclampsia develop pulmonary edema.



Pulmonary edema occurs as a result of low colloid oncotic pressure, increased intravascular hydrostatic pressure, and/or increased pulmonary capillary permeability.



It is likely to occur 2 to 3 days postpartum.



Treatment involves management of the underlying cause (overhydration, sepsis, cardiac failure).



Treatment includes administration of supplemental oxygen, fluid restriction, and administration of diuretic.



Occasionally, pulmonary artery catheter placement may facilitate further management (vasodilators, inotropes).



Rarely, tracheal intubation and ventilation may be required if respiratory failure complicates refractory pulmonary edema.

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Copyright © 2005 Saunders, An Imprint of Elsevier

Abnormal Placentation and Massive Hemorrhage

Despite the overall decrease in maternal mortality during the past decade, peripartum hemorrhage is still a major cause of maternal morbidity and mortality, accounting for around 10% of maternal deaths.[172] Hemorrhage is one of the leading causes of maternal death in the United States and is the leading cause of maternal death in developing countries. There are many conditions that predispose to hemorrhage, and abnormal placentation is one of the major causes, perhaps the one increasing at the fastest rate. An understanding of the risk factors, identification, and obstetric management of abnormal placentation may prove to be lifesaving for the mother and fetus, because unexpected hemorrhage often occurs with little or no warning and may be massive and life threatening. Therefore, proper preparation to manage it may be lifesaving ( Table 19-6 ).

TABLE 19-6   -- Anesthetic Considerations for Patients with Abnormal Placentation


General Anesthesia

Regional Anesthesia

Invasive Monitors

Could be inserted after induction when patient unaware

Need for sedation to minimize discomfort

Blood Loss

Controlled hypotension may help minimize blood loss

Sympathectomy likely to decrease blood loss


Patient is more comfortable in the setting of blood transfusions and decreased blood pressure

Sedation likely will be needed and there should be a low threshold for general anesthesia



Sedation, mental status, and volume resuscitation may compromise airway



Unlike other places in the body where hemostasis depends on vasospasm and blood clotting, hemostasis at the placental site depends on myometrial contraction and retraction. At term, approximately 600 mL/min of blood flows through the placental site.[173] As the placenta separates, the blood from the implantation site may escape into the vagina immediately (Duncan mechanism) or it may be concealed behind the placenta and membranes (Schultze mechanism) until the placenta is delivered.

Placenta Accreta

Adherent pieces of placenta prevent effective contraction of the myometrium and may cause bleeding. Placenta accreta describes any placental implantation in which there is abnormally firm adherence to the myometrium of the uterine wall. It is the result of deficient decidual development resulting in implantation of the placenta into the myometrium without intervening decidua basalis. While in placenta accreta the placental villi are attached to the myometrium, in placenta increta the placental villi invade the myometrium, as opposed to placenta percreta, where the placental villi penetrate through the myometrium. The abnormal adherence may involve all or a few of the cotyledons (total vs. partial placenta accreta). The predominant histopathologic feature is the absence of decidua with direct attachment or invasion of the cotyledon into the myometrium. Decidua deficiency is also partly responsible for placenta previa and may account for the high incidence of their coexistence.[174] Other causes of placenta accreta include prior uterine surgery, infection, or trauma, because they could adversely affect the endometrium. Uterine trauma may occur as a result of dilatation and curettage, endometritis, leiomyoma, Asherman's syndrome, or prior pregnancies. The overall incidence of placenta accreta in the obstetric population is 1:2500 but is markedly elevated in those with a history of placenta previa (1:26), a previous cesarean section (1:10), or both.[175] The greater the number of previous cesarean sections, the greater the risk for placenta accreta.

The incidence of placenta accreta ranges from 0.26% in an unscarred uterus to 25% in the presence of placenta previa and three prior cesarean sections, and it has overtaken uterine atony as the most common reason for a postpartum hysterectomy. A high index of suspicion should be raised in the parturient with placenta previa and/or a prior cesarean section, especially with an anterior placenta, because the diagnosis of placenta accreta may be difficult by ultrasound. Modern ultrasonographic techniques and magnetic resonance imaging are providing a more reliable diagnosis of adherent placenta.

The diagnosis should also be suspected during attempts at manual removal of the placenta without success or with continued bleeding. Typical attempts at removal do not usually succeed, because a cleavage plane between the maternal placental surface and the uterine wall cannot be formed, and continued traction on the umbilical cord may lead to uterine inversion and life-threatening hemorrhage. Successful control of the bleeding may be challenging, because the bleeding is unlikely to respond to uterotonic agents or uterine massage because the uterus is unable to contract with retained placental tissue.

Once the level of suspicion is high, exploratory laparotomy should be performed in cases of a vaginal delivery. In both vaginal and cesarean deliveries, prompt hysterectomy is the treatment of choice, because 85% of patients will require a hysterectomy. In those cases in which the diagnosis is made and attempts at removal of the placenta are stopped, the maternal mortality is low (3%), with an average blood loss of approximately 3500 mL. There are several case reports of ligation of hypogastric, uterine, and ovarian arteries. However, all of these techniques have a highly variable success rate, and massive blood loss with potential maternal morbidity and mortality is four times higher if conservative management is employed. Selective transcatheter embolization of the pelvic arteries is an alternative to more invasive procedures and has shown promise as a technique that has the potential to preserve the uterus and fertility.[176] It could be performed prophylactically in cases in which massive hemorrhage is suspected in order to decrease the blood flow to the uterus even when the plan is to perform a hysterectomy. It consists of the preoperative placement of balloon catheters in the internal iliac arteries and is performed in the interventional radiology suite. The balloons are inflated at the time that hemorrhage is expected and should be deflated once hemostasis is achieved, to maximize blood flow to the lower extremities. It could also be utilized as a treatment for unexpected massive hemorrhage in a patient who desires to preserve fertility. When properly utilized, it appears to be safe and effective, is minimally invasive, and has often been beneficial in avoiding hysterectomy.[176] Of note, a low threshold should be utilized in performing a hysterectomy once massive hemorrhage develops.

Massive blood loss is common with placenta accreta. Even though antepartum recognition and elective hysterectomy are likely to decrease blood loss and morbidity, significant hemorrhage may occur as a result of the increased vascularity of the gravid uterus. Two large-bore intravenous lines should be started, crossmatched blood should be available, and consideration should be given to invasive monitoring, including arterial and central venous lines. A regional technique is permissible in a patient requiring gravid hysterectomy, as long as no significant hemorrhage has occurred and adequate volume resuscitation is maintained.[177] The most challenging cases happen with the retention of an adherent placenta after delivery of a neonate in a patient without risk factors for placenta accreta, because sudden massive blood loss can happen with multiple attempts at manual removal of the placenta. The anesthetic technique in this situation is very different, owing to major hemodynamic changes that may be present in the parturient. It is highly recommended to assess the ability of the anesthesiologist to both manage the airway and volume resuscitate the patient simultaneously. We perform epidural anesthesia in parturients at high risk or with known placenta accreta, but we ensure that there is a low likelihood of a difficult airway, that we have adequate intravenous access, and that there is a low threshold to convert to general anesthesia. If hypovolemia is suspected, strong consideration should be given to induce general anesthesia to have earlier control of the airway.[178] Other reasons for conversion to general anesthesia include generalized patient discomfort due to prolonged surgery, difficult operating conditions, and earlier control of the airway before swelling results with massive fluid resuscitation. We have previously reported peripartum airway changes during cesarean hysterectomy and fluid resuscitation that gradually resolved over the following 2 days.[179]

Uterine Rupture

Cesarean delivery is the most common operation performed in the United States, with the most common reason being elective repeat cesarean sections. The increased risks of bleeding, infection, thromboembolism, and cost with cesarean section led to a push to encourage vaginal birth after a cesarean section (VBAC) during the past two decades. This was successful, in part, with an increase in the rate of VBAC from 6.6% in 1985 to 30.3% in 1996. However, this rate has declined over the past 5 years, in part owing to publications demonstrating that major complications such as uterine rupture, hysterectomy, injury to uterine arteries, bladder, and ureter, and neonatal mortality were higher in women attempting VBAC when compared with elective repeat cesarean sections. [180] [181] It is well known that uterine rupture may occur at the site of a prior uterine scar, usually a previous cesarean section scar, and that a classic cesarean section scar goes through uterine muscle and is more likely to dehisce than a low transverse cesarean section scar. It was always believed that the risk of uterine rupture in patients attempting VBAC was under 1%. However, recent publications have demonstrated that this rate may be as high as 1.5% with a low transverse incision and higher with other types of incisions. VBAC is allowed only in cases of a low transverse scar. The American College of Obstetricians and Gynecologists (ACOG) has issued a practice bulletin for VBAC recommending that physicians caring for parturients attempting VBAC should be immediately available to provide emergency care.[182] Not only are these parturients at an increased risk for uterine rupture, but its results may be life threatening. The relative risk of uterine rupture is 3-fold to 5-fold with spontaneous labor and labor induced without prostaglandins but an astonishingly 15-fold when there is induction of labor with prostaglandins when compared with elective repeat cesarean section. The incidence of infant death was increased 10-fold in the presence of uterine rupture.[181] This finding led ACOG to issue a committee opinion discouraging the use of prostaglandins for cervical ripening or for the induction of labor in women attempting VBAC.[183]

Risk factors for rupture of the uterus include a tumultuous labor, prolonged labor, infection, previous uterine manipulations (dilation and curettage or evacuation), midforceps delivery, breech version, and extraction and uterine trauma. Signs and symptoms of uterine rupture include sudden abdominal pain, shock, vaginal bleeding, fetal distress, change of uterine contour, and loss of a uterine contraction pattern. Some obstetric authorities used to discourage epidural analgesia for VBAC because of the concern of masking the abdominal pain. However, only a very high and dense epidural anesthetic such as the one used for a cesarean section would blunt the pain of uterine rupture. Regional anesthesia can be safely employed, and although it does not have an effect on the success rate of a vaginal delivery, it is more likely to encourage parturients to attempt a VBAC. It is best to use dilute solutions of local anesthetic with opioids because a sudden incidence of abdominal pain in an otherwise comfortable patient in labor (VBAC) with a labor epidural should raise the suspicion for uterine rupture. Also, abdominal pain is one of the least reliable signs of uterine rupture, because pain may be minimal, particularly when a previous cesarean section scar dehisces. The best diagnostic signs for uterine rupture are changes in contraction pattern, changes in configuration of the abdomen, and fetal distress. Continuous fetal heart rate monitoring is paramount for its early diagnosis. Rapid recognition and management are necessary to prevent maternal and fetal death. Except in partial rupture of a previous low transverse uterine scar, which can be repaired under a spinal or epidural anesthetic, emergency hysterectomy is usually needed. This is likely to require rapid anesthesia induction, even in the presence of shock, to allow control of the hemorrhage. It is important to mention that spontaneous uterine rupture of an unscarred uterus, although much less common (1 in 15,000) than rupture of a previous uterine scar, is more serious and catastrophic. It results in a high maternal (≥50%) and fetal mortality (up to 80%) with massive blood loss, often exceeding 15 units in severe cases.

Management of Massive Hemorrhage

Adequate surgical hemostasis and careful fluid and blood replacement are essential to achieve good hemodynamic control. Increases in maternal blood volume and coagulation proteins compensate for the average blood loss, and parturients are often able to tolerate 1000 to 1500 mL of blood loss without major hemodynamic changes.[184] However, obstetric hemorrhage can occur rapidly, especially when difficulties in placental separation arise, as 600 to 700 mL of blood flows through the placental intervillous spaces each minute. DIC may occur with little or no warning, in part owing to the mixing of fetal and maternal blood and other cellular products and intensify blood loss.[185] Physiologic changes of pregnancy may allow signs of significant hemorrhage to be concealed until sudden hypotension and tachycardia occur. Urine output, heart rate, and blood pressure assessments are useful in estimating the volume status. Aggressive volume replacement is essential to maintain tissue perfusion and oxygenation. Early consideration should be given to colloids and blood products, along with a request for assistance, a second large-bore intravenous line, and rapid infusion equipment for transfusion. A type and crossmatch for at least 2 to 4 units of packed red blood cells should be considered when the potential for significant blood loss is likely, such as in cases of placenta accreta. Uncrossmatched, type O, Rh-negative blood is rarely necessary if sufficient precautions are taken to order blood products in advance, except in cases where massive hemorrhage is unexpected and happens within a short time period. Other blood products may be necessary but are frequently utilized unnecessarily. The ASA task force on blood component therapy recommends the transfusion of packed red blood cells, platelets, and fibrinogen only after the careful assessment of volume status, surgical conditions, and laboratory monitoring. Transfusion of blood components is rarely necessary unless the hemoglobin is less than 6 g/dL, the platelet count is less than 50/mm3 or there is evidence of platelet dysfunction and microvascular bleeding, or the fibrinogen concentration is less than 80 to 100 mg/dL in the presence of microvascular bleeding.[186]

There are some modalities for blood conservation that are especially helpful in parturients that are at high risk for hemorrhage, refuse blood products, and are scheduled for a planned procedure. These include autologous donation (parturient's own blood) prior to the scheduled procedure, acute normovolemic hemodilution immediately before the procedure (parturient's own blood is removed and replaced with an equal proportion of crystalloid or colloid), and intraoperative cell salvage. Although there is the potential for re-infusion of blood containing amniotic fluid, intraoperative cell salvage has been safely utilized with leukocyte depletion filtration to remove amniotic fluid. [187] [188] These techniques are still in evolution, especially in parturients, and future studies will be needed to validate their utility and safety. [189] [190] However, they should always be considered in patients who refuse blood products.

In summary, retention of an adherent placenta and a ruptured uterus could present with little or no warning and should be in the differential diagnosis of postpartum hemorrhage. Massive blood loss is common, and the anesthesiologist should be prepared to provide massive volume resuscitation. Regional anesthesia can be safely and effectively utilized, but some situations warrant general endotracheal anesthesia. Therefore, identification of risk factors, antepartum recognition of the condition and early planning with multidisciplinary teamwork is quite important.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Peripartum Cardiomyopathy

Peripartum cardiomyopathy occurs rarely, with an exact incidence that remains unknown. In part because the definition of the disorder is a matter of some dispute, and perhaps due to reporting bias in different areas of the United States and countries of the world, rates from 1:100 to 1:15,000 live births have been reported.[191] The generally accepted incidence in the United States is 1:3000 to 1:4000.[192] The disease is characterized by onset of cardiac failure occurring late in gestation or, most commonly, in the first few months postpartum. The diagnosis is one of exclusion, because there are no pathognomonic signs or definitive diagnostic tests. Criteria used for establishing the diagnosis were recently formulated by a National Institutes of Health consensus panel and are listed in Table 19-7 .[192]

TABLE 19-7   -- Diagnosis of Peripartum Cardiomyopathy

All of the following must be present:



Cardiac failure occurring in the last month of pregnancy, or within 5 months post partum



Absence of an identifiable cause for the cardiac failure



Absence of heart disease before the last month of pregnancy



Echocardiographic evidence of left ventricular systolic dysfunction (LVEF < 45%, fractional shortening < 30%, or end-diastolic dimension > 2.7 cm/m2)

Data from Pearson GD, Veille JC, Rahimtoola S, et al: Peripartum cardiomyopathy: National Heart, Lung, and Blood Institute and Office of Rare Diseases (National Institutes of Health) workshop recommendations and review. JAMA 2000;283:1183-1188.




The differential diagnosis includes many other causes of the clinical signs of peripartum cardiomyopathy, such as severe hypertension, diastolic dysfunction, pulmonary or amniotic fluid embolism, exacerbation of valvular heart disease, infection, and toxic/metabolic disorders. A wide variety of “risk factors” have been suggested for the condition, but because it is so rare, few are widely accepted or strongly associated. These include maternal age older than 30 years, black race, multiparity, multiple gestation, family history, long-term tocolysis, preeclampsia, cocaine abuse, malnutrition, and infections.[191] In Africa, some populations demonstrate a much higher incidence of peripartum cardiomyopathy (1%), apparently associated with peripartum and postpartum consumption of large salt loads and high ambient temperature.[193]

The clinical presentation is similar to other forms of dilated cardiomyopathy. Patients may complain of dyspnea, orthopnea, cough or hemoptysis, generalized fatigue, and chest or abdominal pain. Physical findings include peripheral edema, crackles on pulmonary auscultation, jugular venous distention, a third heart sound, and a mitral regurgitation murmur.[194] Electrocardiography and chest films will show typical signs of cardiomyopathy, including tachycardia, atrial ectopy, cardiomegaly, and pulmonary edema. As noted earlier, echocardiography shows signs of left ventricular systolic dysfunction.

The pathophysiology of peripartum cardiomyopathy remains unknown. One prevailing theory suggests that myocarditis of viral or autoimmune origin is responsible for the ventricular failure. Some series have found a high incidence (nearly 80%) of myocarditis on endomyocardial biopsy,[195] but others found an incidence of less than 10%, similar to age- and sex-matched controls with idiopathic cardiomyopathies.[196] Still others have found the incidence of myocarditis to be greater in peripartum cardiomyopathy than in idiopathic dilated cardiomyopathy (29% vs. 9%).[197] The wide discrepancy in myocarditis may be due to differences in timing of biopsy and criteria for diagnosis.[191] Other hypothesized pathophysiologic mechanisms include abnormal cytokines (e.g., tumor necrosis factor α [TNF-α], interleukin-6, Fas/APO-1), abnormalities of relaxin, selenium deficiency, and genetic factors.[191]

Treatment of peripartum cardiomyopathy is largely supportive and aimed at establishing normal hemodynamics, avoiding further deterioration of cardiac function, and avoiding complications of heart failure, such as thromboembolism. In the minority of cases appearing antepartum, consideration must be given to possible adverse effects on the fetus. Sodium and water restriction and diuresis are initial steps. Digoxin has been shown to improve symptoms and is safe in pregnant patients. β-blockade, especially with vasodilating antagonists (e.g., carvedilol), improves hemodynamics and reduces mortality in idiopathic dilated cardiomyopathy, though efficacy in peripartum cardiomyopathy has not been conclusively demonstrated. [192] [198] Recently, Sliwa and associates suggested that the addition of pentoxifylline (which decreases TNF-α) to conventional therapy with diuretics and β blockers significantly improved outcome in patients with peripartum cardiomyopathy.[199] Angiotensin-converting enzyme (ACE) inhibitors are recommended in other dilated cardiomyopathies but cause renal toxicity in the fetus or breastfed newborn. Hydralazine is the vasodilator of choice.[192] Anticoagulation is generally recommended if the left ventricular ejection fraction (LVEF) is markedly decreased. Heparin, low-molecular-weight heparin, and warfarin have been used; warfarin is generally reserved for postpartum patients owing to teratogenic effects in early pregnancy. However, its use in late pregnancy, when peripartum cardiomyopathy occurs, has not been demonstrated to be harmful. All types of anticoagulants may be safely used in postpartum women, including those who are breastfeeding, because none is secreted in breast milk.[192] Other therapies of possible efficacy include maneuvers designed to ameliorate myocarditis, including immunosuppressive drugs such as prednisone and azathioprine[200] or intravenous immunoglobulins.[201] Cardiac transplantation has been described, including the use of left ventricular assist devices (LVAD) as bridges to transplant.[202] Successful pregnancy after transplantation has been reported.[203]

Prognosis is poor unless rapid normalization of LVEF occurs (<6 months). Mortality ranges from 25% to 50%, although more recent series indicate better outcomes than in historical series. [192] [204]Survivors whose ventricular function has returned to normal have reduced contractile reserve and experience further deterioration with subsequent pregnancies.[205]

Anesthetic management of an undelivered parturient with initial or recurrent peripartum cardiomyopathy has been described. Most case reports have utilized continuous spinal or combined spinal-epidural analgesia. [206] [207] [208] [209] [210] Invasive monitoring with an arterial catheter and a central venous or pulmonary artery catheter has generally been recommended as well. [206] [207] [208] [209] [210] [211] Active anticoagulation may contraindicate regional anesthesia. One case report described general anesthesia with target concentration-controlled propofol and remifentanil for emergency cesarean section in a patient with peripartum cardiomyopathy in active labor.[212] Peripartum cardiomyopathy has also first appeared during anesthetic management for cesarean delivery, requiring intraoperative resuscitation.[213] [214] The hemodynamic picture should guide the management of patients who have recovered from a previous episode, although the limited cardiac reserve in these patients should be kept in mind.[211]

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Cardiac Arrest and Cardiopulmonary Resuscitation in Pregnancy

Cardiac arrest occurs infrequently in pregnancy, at an estimated rate of 1:30,000 late pregnancies.[215] Unfortunately, maternal survival is rare. Causes of cardiac arrest in pregnancy include hemorrhage, embolism (air, amniotic fluid), complications of preeclampsia, peripartum cardiomyopathy, preexisting cardiac disease (e.g., coronary syndromes, valvular disease, congenital defects, dysrthythmias), intracranial hemorrhage, trauma, anaphylaxis, sepsis, local anesthetic toxicity, failed airway management, and hemodynamic effects of spinal and epidural anesthesia. Whereas the most common etiology overall is hemorrhage, the most common conditions producing arrest in late pregnancy are embolism and hypertension.[216] As is the case in any resuscitation situation, the fundamental goals are establishment of an effective airway and circulation (basic cardiopulmonary resuscitation [CPR]), followed by electrical and pharmacologic steps to restore spontaneous circulation. The care of the pregnant patient in cardiac arrest must also include consideration of the physiologic changes of pregnancy (see earlier) and the welfare of the fetus, if of viable gestational age ( Table 19-8 ).

TABLE 19-8   -- Cardiopulmonary Resuscitation in Pregnancy

Basic Life Support



No change in technique of chest compressions



Noninvasive ventilation complicated by anatomic and physiologic changes of pregnancy



Early intubation recommended



Left uterine displacement essential (folded clothing, linens, rescuer's knees, Cardiff wedge)

Advanced Cardiac Life Support



No change in ACLS protocols



No change in defibrillation techniques or voltages



Caution when using paddle electrodes to avoid shocking rescuers on enlarged breasts



Obstetric anesthesiologist is logical “code leader”



Consider open-chest massage or cardiopulmonary bypass for reversible conditions not responding to conventional ACLS

Delivery of infant



Delivery within 5 minutes enhances intact neonatal survival



Delivery may improve success of maternal resuscitation



Incision at 4 minutes of ACLS, delivery at 5 minutes



Basic Life Support

A fundamental principle in resuscitation of the arrested pregnant patient is that the best way to care for both mother and infant is to restore circulation to the mother.[217] Thus, pregnant basic life support (CPR) is essentially nonpregnant basic life support. Mouth-to-mouth, pocket mask, or bag/mask ventilation should be established immediately, followed as soon as possible by endotracheal intubation and ventilation. Noninvasive ventilation is made more difficult and potentially dangerous by the higher oxygen consumption, reduced compliance of the chest, pressure on the diaphragm by the enlarged uterus, enlarged breasts, obesity, and potential for regurgitation of gastric contents all associated with pregnancy.[215] Successful use of the laryngeal mask airway in the setting of failed airway in an obstetric emergency has been described.[218] Chest compressions should begin promptly, followed by advanced cardiac life support (ACLS) techniques, as the clinical situation dictates.

A vital aspect of CPR in pregnancy is the maintenance of uterine displacement to facilitate venous return to the heart. Any convenient soft object (e.g., a blanket, towel, pillow, or clothing) may be used as a wedge, placed under the patient's right flank. Chest compressions have been found to be effective in tilted patients up to 30 degrees.[215] However, CPR is more effective when the patient is on a hard surface. For this reason, some have suggested a purpose-built device known as the Cardiff wedge that tilts the patient on a rigid wooden structure with a lip on the dependent edge to keep her from sliding off.[219] To date, this device is not commercially available. A “human wedge” has also been described in which the patient is tilted over the knees of a kneeling person on the right side of the patient.[220] A chair inverted to rest on the seat and top of the back may also provide a firm, tilted support for the arrested pregnant patient.[217]

Advanced Cardiac Life Support

The American Heart Association (AHA) recommends that no changes from standard ACLS protocols be implemented when caring for pregnant patients. The reader is referred to standard texts to review such protocols.[221] A few special considerations are notable. First, there has been theoretical concern regarding the appropriate method for direct-current cardioversion. The enlarged breasts in pregnant patients may make access to the apex of the heart difficult, particularly when the patient is severely wedged. Furthermore, the anatomic and physiologic changes of pregnancy may, in theory, alter the electrical properties of the chest. However, measurements taken in pregnant women have demonstrated normal impedance.[222] However, others have cautioned that care should be taken to ensure that the left breast does not contact the hand of the person administering the shock.[215] There is no known risk to the fetus of direct-current defibrillation or cardioversion. The AHA recommends standard timing and energies for such maneuvers.[221] Similar recommendations have been made for pharmacologic interventions, including large doses of α-adrenergic agonists (epinephrine) to support the maternal circulation, even though these may theoretically decrease uteroplacental blood flow.[221]

A logistical question concerns who should serve as the “code leader” for resuscitative efforts in pregnant patients. Although the availability of various personnel and local customs may dictate otherwise, we believe that a senior anesthesiologist is the most appropriate clinician to fill this role. Anesthesiologists are skilled in airway management, intravenous access techniques, and the pharmacologic interventions of ACLS. Other personnel often present at cardiac arrest situations, including internists and surgeons, may not appreciate the physiologic changes of pregnancy and their impact on resuscitation of the mother to as great an extent as an obstetric anesthesiologist. Finally, the obstetrician should attend to the fetal status and make preparations for possible emergency cesarean delivery.

Delivery of the Infant

Significant controversy surrounds the decision on whether and when to perform an emergency cesarean section during cardiac arrest in pregnant patients. There are two reasons to consider such a drastic intervention. First, there is substantial evidence from retrospective reviews that fetal outcome is markedly improved with cesarean delivery when maternal resuscitative efforts are not rapidly successful. In a review of 61 perimortem cesarean sections performed in the 20th century through the mid 1980s, Katz and coworkers[223] reported 100% of the 42 infants delivered within 5 minutes of maternal arrest survived with no neurologic sequelae. As the interval from arrest to delivery lengthened, the chance of survival decreased and the incidence of severe neurologic damage increased among survivors. When the interval exceeded 15 minutes, intact survival was rare. Although no large series has appeared in the ensuing two decades, most authors continue to advocate early delivery of the viable infant when initial maternal resuscitation is unsuccessful. [224] [225] [226] [227] [228] [229] Katz and colleagues[223] and subsequent authors, including the AHA,[217] have recommended that preparations for operation begin immediately, incision occur at 4 minutes of arrest, and delivery be accomplished by 5 minutes.

A second reason to consider emergency cesarean delivery during CPR is to improve the maternal condition. [217] [225] [227] [229] This may be the case even when the fetus is pre-viable, because the mechanism of improvement may be both relief of aortocaval compression and removal of the low-resistance uteroplacental circulation.[217] The AHA recommends cesarean delivery even for very premature infants if the maternal condition does not appear immediately reversible, so that some chance of fetal survival is preserved and maternal resuscitation is facilitated.[217]

Additional Interventions

Cardiopulmonary arrest during pregnancy is considered one of the possible indications for attempting open chest cardiac massage, although the AHA does not specifically endorse its use.[217] In cases in which anatomic factors limit the success of closed-chest CPR or the etiology of the arrest indicates it (e.g., pulmonary embolus, penetrating chest or abdominal trauma), thoracotomy and open cardiac massage may be considered. Retrospective data suggest invasive CPR is most likely to be successful when initiated relatively early in the resuscitation sequence.

Finally, cardiopulmonary bypass has been successfully employed in selected clinical situations involving pregnant patients in cardiac arrest. This includes hypothermia due to massive transfusion,[230]bupivacaine cardiotoxicity,[231] and pulmonary embolism.[226]

Postresuscitation Considerations

Restoration of spontaneous circulation may be accompanied by other problems, depending on the etiology of the arrest. Liver rupture has been reported after CPR in pregnant patients.[232] Hemostasis during cesarean section in the setting of cardiac arrest may initially be straightforward, owing to shunting of blood away from the uterus, but subsequently cause further hemodynamic compromise after resuscitation.[216] Management of brain-dead mothers with spontaneous circulation and undelivered infants has also been reported.[233]

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Regional Anesthesia and Anticoagulation

Pregnancy is a prothrombotic state with an increase in most coagulation factors (except factors XI and XIII) and a decrease in clot inhibitors such as protein S. The hypercoagulable state of pregnancy is also characterized by increased platelet hemostatic capacity, despite a decreased platelet count. Fibrinogen increases by as much as 50%.[93] Prothrombin and the thrombin-antithrombin complex are also elevated in normal pregnancies, whereas fibrinolysis is diminished. This is demonstrated by elevated levels of plasminogen activator inhibitor 1 and 2.[234] In addition, the increase in estrogen that accompanies pregnancy is a well-known prothrombotic cause.[235] The tendency toward exaggerated coagulation is further worsened by anatomic factors, such as the decrease of the blood flow in the lowerextremities by the gravid uterus, a condition worsened in the supine position, the increased maternal vascular volume, and by a decreased ability to exercise, leading to venous congestion of the lower extremities and an impediment to venous return. Maternal conditions such as preterm labor and placenta previa, in addition to a decreased exercise capacity due to normal physiologic changes, may lead to prolonged periods of bed rest and further predispose the patient to lower extremity venous thrombosis.

Hypercoagulable states are very common in the general population, with some reports demonstrating that 5% of whites are heterozygous for factor V Leiden, a point mutation of factor V that renders it resistant to activated protein C. Other less common but more severe hypercoagulable states include factor V Leiden homozygosity, and deficiencies of protein S, protein C, and antithrombin III.[236] Many of the low-risk thrombophilias, such as being heterozygous for factor V Leiden, are silent until pregnancy, when they may become manifest as a result of the imbalance between the prothrombotic and antithrombotic forces. Initial manifestations of prothrombotic conditions during pregnancy may include the first presentation of deep venous thrombosis, repeated missed abortions, and recurrent late fetal losses. [237] [238] [239] Prophylactic anticoagulation may be indicated in some cases to prevent venous or placental thrombosis, because improved placental blood flow is likely to lead to better pregnancy outcomes.

Common anticoagulation options include warfarin, unfractionated heparin, and low-molecular-weight heparin ( Table 19-9 ). It is our belief that knowledge of the pharmacokinetics and pharmacodynamics of these agents is essential for the practitioner involved in the care of parturients, because this will lead to a better understanding of the implications on the obstetric and anesthetic management. Currently accepted guidelines for the use of regional anesthesia and anticoagulation [240] [241] are better used to complement rather than to replace the understanding of the pharmacology of commonly utilized anticoagulants during the puerperium.

TABLE 19-9   -- Comparison of Unfractionated Heparin and Low-Molecular-Weight Heparin


Unfractionated Heparin

Low-Molecular-Weight Heparin

Molecular Weight

3,000-30,000 daltons

1,000 to 10,000 daltons

Placental Passage



Anti–Factor Xa/Factor IIa Ratio


Greater than 2:1


Around 30%

Close to 100%


1-2 hr

3-6 hr

Measurement of Activity

Activated plasma thromboplastin time

Anti–factor Xa activity


Saturable cellular mechanism; dose dependent


Protamine Response

Neutralizes activity

Partial reversal due to reduced binding



Warfarin, a competitive inhibitor of vitamin K, is rarely used during pregnancy, because it readily crosses the placenta, is a first-trimester teratogen, and may cause fetal intracranial hemorrhage during the third trimester of pregnancy. [242] [243] [244] It is most important to avoid warfarin during weeks 6 to 12, the period of organogenesis, and the last 2 weeks of pregnancy to diminish the risk of warfarin embryopathy and of bleeding in the mother and infant. [244] [245] The fetus has a smaller concentration of vitamin K–dependent factors, and, therefore, normal targeted maternal anticoagulation may lead to an exaggerated anticoagulation in the fetus. Nevertheless, warfarin continues to be the anticoagulant of choice in parturients with prosthetic heart valves, as there are no data documenting the benefits of subcutaneous unfractionated or low-molecular-weight heparin in this patient population.[244] There are reported cases of prosthetic heart valve thrombosis and of maternal and fetal deaths with the use of low-molecular-weight heparin. [246] [247]

Unfractionated heparin is a strongly acidic, anionic, sulfated mucopolysaccharide with a large molecular weight (3,000 to 30,000 daltons average) that prevents placental passage and makes it, along with other forms of heparin discussed later in the chapter, the anticoagulant of choice during pregnancy. [248] [249] It has a unique pentasaccharide sequence (only one third of heparin molecules) that is responsible for the anticoagulation properties by activating a conformational change in antithrombin III (AT III), leading to an accelerated interaction between AT III, thrombin (factor IIa) and factor Xa. Heparin leads to a similar inhibition of factors IIa and X (1:1 ratio). In addition, although to a lesser degree, unfractionated heparin catalyzes the inactivation of factors IIa, IXa, Xa, XIa, and XII. It also indirectly affects the thrombin-mediated activation of factors V and VIII, the end result being a decrease in important cofactors (Va and VIIIa) in the coagulation cascade.

Unfractionated heparin is cleared from the circulation rapidly, because high-molecular-weight species are cleared more rapidly than low-molecular-weight species. It has a saturable cellular mechanism of clearance via receptors on endothelial cells and macrophages, having a rapid saturable mechanism with low doses, a combination of rapid saturable and dose-dependent mechanisms with therapeutic doses, and a much slower first-order mechanism via the kidneys that is nonsaturable and dose independent with high doses. This dose-dependent mechanism of clearance leads to nonlinear pharmacodynamic properties that affect the intensity and duration of action of unfractionated heparin, noticed the most when very high doses are used.[250] In addition, the nonlinear pharmacodynamic properties of unfractionated heparin lead to an unpredictable bioavailability when injected subcutaneously, a condition that is easily noticed when low-dose subcutaneous injections are used. Its bioavailability ranges from 30% with low doses to 100% with very high doses (greater than 35,000 U). Although very high doses of subcutaneous unfractionated heparin have a bioavailability that is similar to an intravenous injection with peak levels 3 hours (range, 2 to 4 hours) after injection, its duration of action is much less predictable, with reported durations of greater than 24 hours after injection.[251] Other causes of an exaggerated response to unfractionated heparin include prolonged therapy and its use in debilitated patients. The half-life of intravenous unfractionated heparin is also affected, although to a lesser degree, by its nonlinear pharmacodynamic properties.

A knowledge of the pharmacodynamic properties of unfractionated heparin may be more important than following laboratory tests, as the activated partial thromboplastin time (aPTT) response to heparin during pregnancy is attenuated secondary to increased levels of factor VIII and fibrinogen, despite significantly elevated heparin levels. [250] [251] The use of small dose (≤5,000 U) subcutaneous unfractionated heparin for prophylaxis does not usually prolong the aPTT, and blood levels are not typically monitored. The use of subcutaneous unfractionated heparin for more than 5 days may lead to a decrease in the platelet count. However, the aPTT may be a better predictor of unfractionated heparin levels, compared with pharmacodynamic properties, when very high doses of subcutaneous injections are used. It is our recommendation to check the aPTT of a parturient taking high doses of subcutaneous unfractionated heparin on arrival at the labor floor and to wait for the result before performing a neuraxial technique. It has been our experience that the anticoagulant effect of high doses, as reflected by the aPTT, may persist for up to 28 hours after the last injection. In addition, a platelet count is recommended for any parturient who received unfractionated heparin for more than 4 days. It is important to realize that parturients at risk for deep venous or placental thrombosis are maintained on some form of heparin for most of the pregnancy. High doses of unfractionated heparin may be used throughout the pregnancy or, more commonly, after 36 weeks' gestation at the time when the low-molecular-weight heparin is discontinued.

The American Society of Regional Anesthesia (ASRA) developed guidelines for the performance of neuraxial techniques in the anticoagulated patient in 1996, and these guidelines were updated in 2003.[240] ASRA based these guidelines on the available scientific information, but in some cases this information may be sparse. In addition, guidelines are recommendations and not standards or absolute requirements. They are based on not only scientific information but also on synthesis of expert opinion and clinical feasibility data. Variances from recommendations may be acceptable based on the physician's judgment, and specific outcomes cannot be guaranteed by following these recommendations. [240] [241] Moreover, clinical and scientific information and evolving clinical practices may modify these guidelines with time.

The ASRA guidelines for the anesthetic management of the patient receiving unfractionated heparin state that performance of a neuraxial technique should proceed for at least 1 hour before systemic intravenous anticoagulation with unfractionated heparin. Systemic intravenous anticoagulation with unfractionated heparin should be discontinued 2 to 4 hours before a neuraxial technique or epidural catheter manipulation (including removal).[240] In addition, the coagulation status should be evaluated with the aPTT, with a normalization being necessary before epidural catheter insertion or removal. Despite the limited risk for epidural hematoma formation when subcutaneous unfractionated heparin is combined with neuraxial techniques, we prefer to perform this technique either greater than 4 hours after the injection of subcutaneous heparin (half-life of 2 to 4 hours) or before its administration (≥1-hour interval). However, ASRA states that there does not appear to be an increased risk with neuraxial block in the presence of subcutaneous unfractionated heparin. The addition of other medications, such as nonsteroidal anti-inflammatory agents, aspirin, oral anticoagulants, and other forms of heparin that affect the coagulation cascade may increase the risk of epidural hematoma when subcutaneous unfractionated heparin is used concomitantly with a neuraxial technique. Our recommendation for the performance of neuraxial techniques following higher than usual doses or prolonged therapy was outlined previously.

Low-molecular-weight heparin (LMWH) has a molecular weight of 1,000 to 10,000 daltons, does not cross the placenta,[252] is formed by controlled depolymerization of unfractionated heparin, and has the same pentasaccharide sequence (potentiates action of antithrombin), but overall it has a lower number of chains with greater than 18 saccharide units (one half to one fourth of LMWH fragments), providing a greater anti–factor Xa to anti–factor IIa ratio. [251] [253] The 18 saccharide units are required for the inhibition of factor IIa but not for that of factor Xa. Different LMWH have different anti–factor Xa/factor IIa activity (e.g., 2.7:1 for enoxaparin vs. 2.1:1 for dalteparin) but have equivalent anticoagulation on clinical practice. [253] [254] Exogenous protamine completely reverses the anti–factor IIa activity of LMWH but only 60% of the anti–factor Xa activity, owing to a reduced binding to its components. There are few trials comparing LMWHs with functional or structural heterogeneity, although there is a report from the orthopedic population, where enoxaparin was similar to tinzaparin for deep venous thrombosis prophylaxis.[254] Enoxaparin is discussed here because it is the most widely used LMWH in the United States, the one referred in most manuscripts, review articles, and published guidelines, and the one that we currently use at our institution and are more familiar with.

LMWH has a lower binding to proteins and endothelial cells and dose-independent clearance compared with unfractionated heparin. The end result is a renal excretion that is dosage independent, a pharmacodynamic effect that is proportional to the dose used and more predictable, and a better bioavailability at low doses. In addition, LMWH has a similar bioavailability after subcutaneous and intravenous injection and is less immunogenic. Its dosage is adapted to body weight, and there is a risk of accumulation with obesity and renal failure.[254] The half-life of LMWH is 3 to 6 hours after subcutaneous injection, is independent of the dose, and is longer than that of unfractionated heparin. LMWH has a peak activity in 3 to 4 hours, low interpatient variability because of its more predictable dose response, and an increased popularity in its use with a once- or twice-a-day dosage that is very convenient for a parturient. LMWH has significant anti–factor Xa levels 12 hours after injection because of its longer half-life. There is a controversy over whether blood level testing with an anti–factor Xa assay is helpful in monitoring the response to LMWH and whether it is helpful prior to performing neuraxial techniques in the parturient anticoagulated with LMWH (see later). It is no surprise that LMWH is slowly replacing unfractionated heparin when prophylactic anticoagulation is needed in a parturient despite their similar efficacy; it is due to its improved bioavailability, longer half-life, more predictable dose response with a greater activity against factor Xa, and lower incidence of bleeding complications.[255]

The safety and efficacy of LMWH in pregnancy is supported by a review of 624 high-risk parturients with a prior incidence of thrombosis receiving enoxaparin prophylaxis. [256] [257] This study demonstrated a congenital anomaly rate of 2.5%, which is not greater than that in the general population, and a 1.1% fetal death rate unrelated to enoxaparin. There was only one enoxaparin-related hemorrhage and a 1.3% incidence of recurrent maternal venous thrombotic events, which is very low for this high-risk population. The overall conclusion of this study, supported by an ACOG committee opinion,[257] is that LMWH is safe and efficacious for the prevention of thrombosis in parturients who are at a high risk for this complication. [256] [257] Typical prophylactic doses of LMWH during pregnancy are 40 mg subcutaneously (1 mg is equivalent to 100 units) of enoxaparin per day, or 30 mg subcutaneously twice a day. These dosages are used in parturients with a remote history of thrombosis but without a thrombophilia, low-risk thrombophilia, recurrent pregnancy loss, or a history of fetal demise. Prophylactic doses are usually discontinued at 36 weeks' gestation and changed to subcutaneous unfractionated heparin. High-dose therapy typically ranges from 1.0 to 1.5 mg/kg of subcutaneous enoxaparin twice a day and is indicated for the management of acute thrombosis, a remote history of thrombosis, and the presence of antiphospholipid antibodies or a high-risk thrombophilia. High-dose therapy is usually continued until 24 hours before induction of labor or a planned cesarean section.

LMWH does not usually influence the aPTT but has an effect on anti–factor Xa values. An anti–factor Xa chromogenic assay measures the activity against factor Xa but not that against factor IIa.[258]Although minimal anticoagulation is equivalent to values below 0.2 U/mL, prophylactic levels of 0.1 to 0.2 U/mL may suffice.[258] It is not usually measured for prophylactic doses owing to the predictable dose response of LMWH. It may be prudent to check assay values in cases of obesity, low body weight, or renal failure, because LMWH has a renal elimination and is affected by changes in body weight.[258] [259] It has been recommended to check anti–factor Xa levels while using high doses during pregnancy owing to increases in glomerular filtration rate, clotting factor concentration, weight, and volume of distribution.[260] Testing may also be useful with prolonged therapy and in parturients at high risk of bleeding or thrombosis.[259] Whether this assay confers any improved efficacy and safety has not been confirmed, and critics point out that there is interassay variability.[261] Further investigation is needed on this topic. The peak activity of LMWH is already reduced by the end of the first trimester, further reduced by the beginning of the third trimester, and returns to normal postpartum.[260] Overall there is a volume expansion as a term pregnancy approaches, leading to subtherapeutic levels. Occasionally, LMWH is changed to intravenous unfractionated heparin in very high risk patients and then discontinued 4 to 6 hours before the time of delivery. This may create a problem if the patient requires a surgical procedure or the placement of a regional anesthetic, because a combination of both agents may result in an unpredictable anti–factor Xa and aPTT response. We recommend to check both tests before a cesarean section or neuraxial technique under this circumstance.

Epidural hematoma is the most feared complication of neuraxial techniques and is much more likely in the setting of an inherited clotting abnormality or the use of anticoagulants while performing these techniques. While a review of the literature in 1994 found 61 cases over an 88-year period, 1906-1994,[262] in 2003 a Food and Drug Administration (FDA) MedWatch found 60 cases over a 9-year period associated with the use of neuraxial anesthesia and LMWH therapy.[263] There was one case of an epidural hematoma in a parturient receiving LMWH. The timing of the administration of LMWH, the removal of the epidural catheter, and the development of the hematoma are unclear, and the patient had a temporary lower extremity motor weakness that resolved spontaneously without any surgical intervention. The 1994 review had only five cases in parturients (8.2% of cases),[262] results that go along with the pregnancy-associated prothrombotic state and its associated resistance to anticoagulation. These factors counteract the epidural venous plexus engorgement, with an increased incidence of intravascular epidural catheters, present during pregnancy. An analysis of the obstetric cases demonstrates that the majority occurred when the anticoagulant dosing was in close proximity to the placement of a neuraxial technique or when patients were taking other medications that alter coagulation. In addition, a review from the United Kingdom found no cases of epidural hematoma in over 9000 epidurals placed in parturients who were taking aspirin as possible prophylactic treatment for preeclampsia. Although aspirin was not found to be beneficial for the prevention of preeclampsia, it was not associated with a significant increase in placental hemorrhages or in bleeding during preparation for epidural anesthesia.[264] Of note, the decreased incidence of epidural hematoma during pregnancy should not modify the recommendations regarding the use of neuraxial techniques in parturients with clotting abnormalities or in those being anticoagulated. In addition, it has been documented that epidural catheter placement is as important as its removal, because both situations could lead to epidural hematoma in the anticoagulated patient.[262]

Epidural hematoma is a very rare complication of neuraxial techniques, with an incidence ranging from 1:220,000 after spinal anesthesia to 1:150,000 after epidural anesthesia.[262] It is more common in the presence of LMWH, with an incidence as high as 1:3,000 after a continuous epidural catheter and 1:40,000 after a spinal anesthetic.[253] It is important to use very low concentrations of local anesthetic to detect any change in the patient's neurologic state. In addition, close follow-up of the neurologic status is essential after the removal of an epidural catheter. Clinical symptoms of epidural hematoma include radicular back pain, bowel or bladder dysfunction, and sensory or motor deficits. [265] [266] Interestingly, and different from common wisdom, severe radicular back pain is rarely the presenting symptom. Magnetic resonance imaging is the best diagnostic test for a suspected epidural hematoma, and early decompressive laminectomy is the treatment of choice.

The previously mentioned ASRA guidelines were developed in part because of the increased incidence of epidural hematoma associated with the use of LMWH and neuraxial techniques.[240] These guidelines recommend discontinuing prophylactic doses of LMWH at least 10 to 12 hours before a regional technique, and a single-dose spinal anesthetic is the preferred technique. Therapeutic doses should be discontinued at least 24 hours before a regional technique, and LMWH should not be started until 2 hours after epidural catheter removal. The presence of blood at the time of epidural catheter placement may increase the risk of bleeding into the epidural space and necessitates a delay of 24 hours before LMWH administration. Although epidural catheters are not usually kept for postoperative pain management in parturients, in part because of the excellent and prolonged analgesia with neuraxial morphine, it is important to be careful when these catheters are kept in place in parturients who require LMWH prophylaxis or therapy. Epidural catheters can be safely continued while using prophylactic doses, as long as the LMWH is not started before 6 to 8 hours postoperatively and the catheter is removed 10 to 12 hours after the last LMWH dose. Epidural catheters should be removed in parturients receiving therapeutic doses, and the first dose should not be given earlier than 24 hours postoperatively. ASRA does not recommend the use of the anti–factor Xa assay because, according to the published guidelines, the anti–factor Xa level is not predictive of the risk of bleeding.[240] We consider this item controversial, because it is well known that the anti–factor Xa activity of LMWH is affected by body weight, renal dysfunction, pregnancy, and prolonged therapy. [259] [267] We do not routinely check this assay in parturients taking prophylactic doses of LMWH if the last dose was greater than 24 hours before the placement of a neuraxial technique. However, we do measure this test in the presence of therapeutic doses of LMWH, or if the last prophylactic dose of LMWH was less than 24 hours from a regional technique. Our target dose is less than 0.1 U/mL, as this dose is associated with minimal anticoagulation. We are aware that although high levels of this assay would most likely preclude a regional technique, there are no data to support the safety of neuraxial techniques with lower levels. We encourage more senior anesthesiologists to perform the block, and we prefer to use midline neuraxial techniques to minimize the risk of intravascular epidural catheters.

Newer anticoagulants are being compared to traditional anticoagulants, such as unfractionated heparin, and are being used with an increased frequency, in part because of their similar safety profile and ease of administration. Fondaparinux, one of these agents, is a synthetic pentasaccharide that gained FDA approval at the end of 2001. It selectively binds to antithrombin, inducing a conformational change that significantly increases the anti–factor Xa activity without inhibition of factor IIa. [268] [269] [270] It does not cross react with antibodies against heparin/platelet factor 4 complexes and, therefore, is unlikely to lead to thrombocytopenia. It has a very long half-life of about 18 hours, a fact that must be known by practitioners of regional anesthesia. It takes at least 4 days to completely eliminate this agent from the circulation, and regional anesthesia should be avoided during this time period. It may be reasonable to check anti–factor Xa activity before the performance of a neuraxial technique. It may also be reasonable to administer fondaparinux 2 hours after an atraumatic single spinal needle pass or epidural catheter removal.[240] We have already seen a parturient as a high-risk anesthesia consult because she was taking fondaparinux, 2.5 mg/day. She had a history of antiphospholipid antibodies and deep venous thrombosis, requiring thromboprophylaxis during her pregnancy, and was allergic to LMWH. Therapeutic doses range from 5 to 10 mg. [268] [269]

In summary, it is important to use appropriate neuraxial techniques, to avoid multiple anticoagulants, and to exercise caution in proper parturient selection. Finally, and perhaps most importantly, a knowledge of the pharmacokinetics and pharmacodynamics of commonly used anticoagulants during pregnancy is essential to avoid the use of neuraxial techniques at a time when a significant anticoagulant effect may still be present. In addition, an understanding of the mechanism of action, side effect profile, and half-life of newer anticoagulants is quite important. The use of guidelines should not be used as a substitute but to complement this knowledge.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier

Local Anesthetic Allergy

A true IgE-mediated anaphylactic reaction to an anesthetic agent, while often life threatening, is quite rare under anesthesia. The incidence varies between 1:3,500 and 1:20,000, with neuromuscular blocking drugs and latex being the most common offending agents. A recent review on allergic reactions during anesthesia in France during a 2-year period found no cases of local anesthetic allergy.[271]Local anesthetics belong to the ester or amide type. Whereas ester local anesthetics are metabolized to p-aminobenzoic acid (PABA), amide local anesthetics are metabolized in the liver to a variety of compounds. Methylparaben is a preservative that may be present in amide or ester local anesthetics and can have some cross reactivity with PABA. An IgE-mediated reaction to a local anesthetic, most likely due to the PABA metabolite from esters or methylparaben, accounts for less than 1% of all reactions to local anesthetics.[272] Almost all cases of questionable allergic reactions to local anesthetics are due to a vasovagal episode, systemic injection of local anesthetic with central nervous system manifestations, or intravascular injection of epinephrine, with its associated cardiovascular manifestations. Furthermore, most allergic reactions to local anesthetics are due to a type IV delayed hypersensitivity reaction that presents as a contact dermatitis.[272]

Cross reactivity to other local anesthetics should be considered in cases where a true IgE-mediated reaction to an amide or ester group local anesthetic is suspected or confirmed by prior testing. Skin tests should then be conducted, not only for the suspected agent but also for other local anesthetics, including agents of both types, to identify a safe alternative.[273] There is even a report of an IgE-mediated reaction to ropivacaine in a patient with a history of an anaphylactic reaction to other amide local anesthetics, including lidocaine, bupivacaine, and mepivacaine.[273] This particular patient tolerated procaine, an ester local anesthetic, well. Skin tests are conducted by intradermally injecting small quantities of local anesthetic and watching for a wheal and flare response. Should a positive response be observed, then a skin prick test followed by a subcutaneous injection is recommended, because the results are equivocal in many cases.[274] The Chandler methodology for provocative skin testing[275] can be performed over a 1- to 2-hour period by a trained allergist by incrementally performing subcutaneous injections of a local anesthetic while observing the patient closely on a monitored unit for any signs of an allergic reaction.

The history of a local anesthetic allergy in an obstetric patient is more complicated, because skin testing is not recommended during pregnancy unless the results obtained will lead to a significant implication on treatment.[276] Regional anesthesia is much safer in parturients when compared with general anesthesia,[277] and regional analgesia is by far the most effective means of analgesia during labor and delivery. Although the best time to conduct skin testing is before pregnancy, it has been argued that provocative challenge skin testing can be conducted during pregnancy to rule out the possibility of a true local anesthetic allergy. [278] [279] The timing of the testing during pregnancy is also controversial, because an allergic reaction due to skin testing before fetal viability may lead to untoward effects on the fetus. Other risks include the possibility of fetal sensitization and the fact that it remains unclear whether a response to skin testing is modified by pregnancy.[280] Therefore, in the event that testing has not been performed during pregnancy, we recommend that a very thorough history be conducted first to rule out other causes of an adverse local anesthetic reaction. In addition, it is important to elicit a family history, as genetic linkage has been postulated.[280] Other options for anesthesia and analgesia should be considered, and a very thorough informed consent process with the patient is strongly recommended while conducting a risk benefit analysis. An awareness of the risks of skin testing during pregnancy should also be discussed with the patient and made only in close collaboration with an allergist and the obstetrician. Should the decision to proceed with skin testing be made, the timing should be close to the date of delivery to maximize fetal well-being.

In summary, most cases of reactions to local anesthetics are not allergic and should not preclude their use. However, even though a life-threatening anaphylactic reaction to a preservative-free local anesthetic is quite uncommon, it has been reported and should be taken seriously and followed closely if confirmed or strongly suspected ( Box 19-6 ).

BOX 19-6 

Differential Diagnosis of Local Anesthetic Allergy



Vasovagal episode



Systemic local anesthetic injection



Central nervous system



Systemic epinephrine



Cardiac toxicity



Type IV cell-mediated reaction



Contact dermatitis



Type I cell-mediated reaction




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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Pregnancy is a common and nonpathologic condition. However, the altered physiology of pregnancy complicates the anesthetic care of even healthy pregnant patients. When unusual conditions of pregnancy further alter the physiologic state, the anesthesiologist faces additional challenges. Although nearly every disease entity may complicate pregnancy, the scope of this chapter is not sufficient to cover them all. In these situations, basic principles of management of the pregnant patient should apply and have been summarized in this chapter, as well as some of the more important specific conditions specific to pregnant patients.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


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