Pregnancy and Obstetric Complications

C H A P T E R
19
Pregnancy and Obstetric Complications
DAVID L. HEPNER, MD n
BHAVANI SHANKAR KODALI, MD n
SCOTT SEGAL, MD, MHCM n
of regional anesthesia depends on the platelet count

Physiologic Changes of Pregnancy (consider at ≥70,000), provided no other coagulation
Nonobstetric Surgery abnormalities exist.
Maternal Safety
n Placenta accreta describes any abnormally firm adherence
Fetal Safety
to the myometrium, especially in those with a history of
Laparoscopic Surgery
placenta previa and previous cesarean section. Prompt hys-
In Vitro Fertilization
terectomy is the treatment of choice. Epidural anesthesia
Obstetric Anesthesia for Uncommon Conditions can be considered, with a low threshold to convert to gen-
Morbid Obesity
eral anesthesia.
Amniotic Fluid Embolism
n Less restrictive ACOG guidelines in 2010 emphasize patient
Pre-Eclampsia and Eclampsia
autonomy; trial of labor after cesarean is most safely under-
HELLP Syndrome
taken in a facility with appropriate staff but may occur at a
Pulmonary Edema in Pre-Eclampsia
smaller facility after risk/benefit analysis.
Abnormal Placentation and Massive Hemorrhage
n Transfusion of 1 unit FFP for 1 unit RBC is reasonable
Peripartum Cardiomyopathy
because many units of plasma are needed for coagulation
Cardiac Arrest and Cardiopulmonary Resuscitation
factor and fibrinogen replacement during postpartum
Conditions Complicating Regional Anesthesia bleeding with disseminated intravascular coagulation.
Regional Anesthesia and Anticoagulation
A postpartum hemorrhage algorithm facilitates the trans-
Local Anesthetic Allergy
fusion of blood products and communication with obste-
Latex Allergy
tricians and hematologists.
Conclusion n Peripartum cardiomyopathy is an idiopathic dilated car-
diomyopathy occurring antepartum or immediately
postpartum. Patients who recover ventricular function
promptly have a better prognosis; subsequent pregnancy
is risky. Continuous spinal or spinal-epidural analgesia is
KEY POINTS recommended.
n Airway changes throughout pregnancy worsen during n Cardiopulmonary resuscitation is largely unmodified from
labor and delivery as a result of mucosal edema. that in nonpregnant patients, but effective uterine displace-
n Anesthetic agents are not teratogenic; however, inhala- ment is essential. Emergency cesarean delivery should be
tion anesthetics and many intravenous agents may trigger initiated promptly (delivery within 5 minutes) for the ben-
developmental apoptosis and other neurologic insults that efit of both the fetus, even if of periviable gestational age,
could impact cognitive development. and the mother.
n Amniotic fluid embolism is associated with coagula- n Knowledge of pharmacokinetics and pharmacodynam-
tion abnormalities as well as hypoxia and cardiovascular ics of common anticoagulants used during pregnancy is
collapse. essential to avoid neuraxial techniques when significant
n HELLP (hemolysis, elevated liver enzymes, low platelets) anticoagulant effect may still be present. Guidelines should
is a more severe form of pre-eclampsia. Administration complement this knowledge.
537
Downloaded for Mehmet Fatih Polat (mfpolat@firat.edu.tr) at ULAKBIM Academic Firat Universitesi - Scival from ClinicalKey.com by Elsevier on April 23, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
538 ANESTHESIA AND UNCOMMON DISEASES
One study in a well-defined, continuously screened female

TABLE 19-1 n Physiologic Changes of Pregnancy
population between 18 and 44 years of age found a preg-
nancy rate of more than 10% per year.1 The anesthetic RESPIRATORY SYSTEM
care of pregnant women is common; 1% to 2% of preg- Minute ventilation ↑ 50%
nant women undergo nonobstetric surgery.2,3 Even unrec-
Functional residual capacity ↑ 20%
ognized pregnancy in outpatients occurs in about 1 in 300
women.4 The challenge to the anesthesiologist in caring Oxygen consumption ↑ 20%
for the obstetric patient centers on the physiologic changes Carbon dioxide production ↑ 20%
of pregnancy and the interactions with anesthetic drugs
and techniques. In addition, the urgency of care is often Apneic desaturation Faster
intensified by the presence of a viable fetus. This chap- Paco2 32 mm Hg
ter explores some of the more unusual clinical challenges,
Paco2 − Petco2 −1 to 0.75 mm Hg
both in obstetric anesthesia and analgesia, as well as in the
anesthetic care of the pregnant patient undergoing nonob- CARDIOVASCULAR SYSTEM
stetric procedures. Cardiac output ↑ 50%
Stroke volume ↑ 25%

PHYSIOLOGIC CHANGES OF PREGNANCY Heart rate ↑ 25%
Administration of safe anesthesia for any pregnant woman Systemic vascular resistance No change
necessitates a clear understanding of the physiologic changes
Blood pressure No change at term gestation
associated with pregnancy. Several changes have direct bearing
on anesthetic management of obstetric patients (Table 19-1).5,6 GASTROINTESTINAL SYSTEM
Airway effects in pregnancy could pose intubation difficulties; Barrier pressure ↓
metabolic and respiratory changes may expeditiously cause
Gastric emptying time No change
hypoxemia during apnea; gastrointestinal effects predispose
the parturient to regurgitation and aspiration; the growing Renal system:
uterus puts pressure on the aorta and inferior vena cava; and Plasma creatinine ↓
mechanical, hormonal, and biochemical factors can increase BRAIN
the spread of intrathecal and epidural local anesthetics in Minimal alveolar concentration ↓
pregnancy. Recent evidence suggests that airway changes are
METABOLIC
not limited to the duration of pregnancy and can continue
Free drug availability ↑
during labor and delivery.7,8
The implications of these physiologic changes on the coex- Plasma cholinesterase activity ↓
isting disease, or vice versa, must be evaluated in every pregnant
woman presenting with a coexisting disease or a complica-
tion of pregnancy. A coexisting disease, such as a cardiovascu-
lar lesion or a pulmonary condition, can translate physiologic considerations are maternal safety, fetal physiologic well-
changes into a clinically critical state, thereby contributing to being, avoidance of teratogenicity, and prevention of preterm
an increasing morbidity and mortality. In addition, pharma- labor (Box 19-1).
cokinetic and pharmacodynamic profiles are altered in preg-
nancy, and drug administration must be titrated carefully to
Maternal Safety
the desired effect. With the increase in blood volume there is a
greater volume of distribution; the low albumin and increased Maternal safety requires understanding of the altered physiol-
α-glycoprotein can also alter the free drug concentrations. ogy of pregnancy. The most important changes affecting the
Issues of fetal well-being, such as maintenance of uteroplacen- anesthetic management of these patients are the respiratory,
tal blood flow and oxygenation, prevention of fetal asphyxia, gastrointestinal (GI), and cardiovascular systems. Although
avoidance of teratogenic drugs, and prevention of preterm considerable controversy surrounds the physiology of gas-
labor, are essential to consider when taking care of the pregnant tric emptying and gastric acid production, pregnant patients
patient. Maintenance of uteroplacental blood flow is essential beyond the late second trimester should be considered at ele-
to fetal well-being. vated 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 pres-
NONOBSTETRIC SURGERY
sure [PCWP]), elevated cardiac output, physiologic anemia of
The anesthetic management of pregnant patients undergo- pregnancy, and aortocaval compression. Respiratory changes
ing nonobstetric procedures has been extensively reviewed affecting anesthetic management include the increased fragil-
in major textbooks of obstetric anesthesiology. The principal ity of the mucosa, upper airway edema, more difficult mask
Chapter 19 Pregnancy and Obstetric Complications 539
hypoxia and hypotension can adversely affect the fetus.

BOX 19-1 n GENERAL CONSIDERATIONS FOR Modest hypoxia is well tolerated by the fetus because of the
NONOBSTETRIC SURGERY IN PREGNANCY
high concentration of fetal hemoglobin and its affinity for O2.
Maternal Safety More severe hypoxia is associated with fetal desaturation and
Respiratory System asphyxia. Conversely, hyperoxia does not adversely affect the
Fragility of nasal mucosa
fetus, because of high placental shunt flow and inability of
Upper airway edema
Increased risk of difficult intubation
high maternal oxygen partial pressure (Po2) to increase mater-
Increased risk of desaturation nal O2 content significantly. High maternal O2 concentrations
may be given whenever indicated for maternal well-being.12
Gastrointestinal System
Increased risk aspiration (increased intragastric pressure and Conversely, the fetus poorly tolerates maternal hypoten-
decreased lower esophageal sphincter tone) sion if it is severe or prolonged.13 Uteroplacental blood flow
Cardiovascular System
is highly dependent on maternal systemic blood p ressure
Expansion of blood volume (normal filling pressures) (SBP), and decreases in SBP lead to fetal asphyxia. During
Elevated cardiac output nonobstetric surgery, causes of maternal hypotension
Physiologic anemia of pregnancy may include hypovolemia, deep general anesthesia, high
Fetal Safety spinal or epidural anesthesia, aortocaval compression,

Direct Effects of Anesthesia hemorrhage, positive-pressure hyperventilation, and sys-
Maternal hypoxia and hypotension leading to fetal acidosis temic hypotensive drugs. However, good fetal outcomes
Avoid uteroplacental vasoconstrictors (vasopressin, ketamine, high
have been reported after moderate deliberate hypotension
systemic local anesthetic concentrations)
during neurosurgery.14 Uteroplacental blood flow may also
Teratogenicity of Drugs
be impaired by systemic agents that produce uterine arterial
No specific link to any anesthetic drug
Caution with nitrous oxide
vasoconstriction or significantly increase myometrial tone.15
Inhalation anesthetics may cause “behavioral teratogenicity” Drugs that may cause these effects include large doses of
(behavioral abnormalities without structural defects) alpha-adrenergic agonists, vasopressin, ketamine, and high
Avoidance of Preterm Labor doses of local anesthetics. In contrast to classic animal stud-
ies, however, maternal administration of moderate-dose
phenylephrine during cesarean delivery has been associ-
ated with normal fetal blood gases.16 Minimal data exist on
ventilation, a 10-fold increased risk of difficult intubation, the choice of vasopressor during nonobstetric surgery, and
functional residual capacity (FRC) and oxygen (O2) consump- authorities recommend choosing the drug most appropriate
tion changes that predispose to desaturation during apnea, for maternal safety.17
and chronic respiratory alkalosis.6 Teratogenicity of maternally administered drugs has been
In addition, general anesthesia in pregnant patients must extensively reviewed elsewhere, and the reader is referred to
consider the altered response to anesthetic drugs. Minimal these sources for more information. To date, no anesthetic
alveolar concentration decreases in pregnancy, well before agent has been definitively shown to induce congenital abnor-
endorphins increase during labor.9 Indeed, increased sensi- malities in the developing fetus. However, associations between
tivity to intravenous (IV) and inhalation anesthetics occurs anesthetics and anomalies or abortion are strong enough to
during the first trimester. There is increased sensitivity to suc- dictate prudent use. Importantly, many drugs found to be ter-
cinylcholine,10 and patients receiving magnesium sulfate for atogenic in earlier animal or uncontrolled human epidemio-
preterm labor or pre-eclampsia are more sensitive to nonde- logic studies have proved safe when using more sophisticated
polarizing neuromuscular blocking drugs as well.11 Decreased methodology. This includes all common opioids, benzodiaz-
protein binding caused by lower concentrations of plasma epines, barbiturates, and local anesthetics.18,19
proteins, as well as increased volume of distribution from Inhalation anesthetics present a more complex picture. In
increased blood volume and weight (fat) gain, makes pharma- animals, prolonged exposure to more than 50% nitrous oxide
cokinetics of various drugs complex.6 The responses to many (N2O) induces fetal resorption and skeletal or visceral anoma-
anesthetic drugs, particularly those employed in some of the lies, depending on the timing of exposure.20–22 However, the
unusual situations described in this chapter, are unknown. etiology is complicated and not completely understood. N2O
Caution is therefore mandatory when any anesthetic agent is impairs 1-carbon metabolism through its action on vitamin
used in the pregnant patient. B12.23 This cannot explain all its effects, however, because sup-
plementation with folinic acid or methionine (which should
bypass many of the effects of inhibition of methionine synthase
Fetal Safety on DNA synthesis and methylation reactions) only partially
The fetus is potentially at risk by three mechanisms: direct reverses N2O effects on the developing fetus.24,25 Furthermore,
effects of anesthetic agents and techniques on fetal cardio- coadministration of isoflurane or halothane blocks many N2O
respiratory homeostasis, teratogenic effects of maternally effects, implicating α-adrenergic uterine vasoconstriction in
administered drugs, and induction of preterm labor. Maternal N2O pathophysiology of.26 Human epidemiologic studies of
healthy women exposed to N2O in the workplace have yielded laparoscopic cholecystectomy has become the most frequently
conflicting results. Positive studies show only a slight increase performed laparoscopic procedure during pregnancy.36 Other
in spontaneous abortion that may be explained by confound- types of laparoscopic surgeries performed safely during preg-
ing variables.27,28 Large epidemiologic investigations confirm nancy include appendectomy, ovarian cystectomy,37 man-
slight increases in early pregnancy loss and low birth weight agement of adnexal torsion,38 diagnostic laparoscopies for
but have yielded inconclusive or negative results regarding abdominal pain,39 splenectomy,40 heterotopic pregnancies,41
congenital anomalies. It is impossible to separate the effect and adrenal pheochromocytoma.42
of anesthesia from that of the surgical procedure or underly-
ing disease process requiring surgery in human epidemiologic PNEUMOPERITONEUM
studies.3 When faced with providing anesthesia for the pregnant patient
A more ominous and insidious effect of inhalation anesthet- undergoing laparoscopic surgery, the anesthesiologist must
ics has been termed behavioral teratogenicity. The term refers focus not only on maternal/fetal issues and prevention of pre-
to behavioral abnormalities occurring in the absence of obvi- term labor, but also on patient positioning during surgery and
ous structural defects. Even relatively brief intrauterine or early the physiologic and mechanical effects of the carbon dioxide
postnatal exposure to halogenated anesthetics, γ-aminobutyric (CO2) pneumoperitoneum. During laparoscopy, pneumoperi-
acid (GABA) agonists, or N-methyl-d-aspartate (NMDA) toneum can cause cardiovascular and respiratory alterations
antagonists in rodents has resulted in persistent defects in in nonpregnant patients, which become accentuated in the
memory and learning (maze solving).29,30 Studies in cell cul- parturient. Adding pneumoperitoneum to an enlarged uterus
ture and pathologic investigation of neonatal brains of rodents further limits diaphragm expansion and is associated with an
exposed in utero to isoflurane show widespread apoptosis and, increase in peak airway pressure, decrease in FRC, increased
specifically, defects in hippocampal synaptic function, effects ventilation/perfusion (V/Q) mismatching, increased alveolar-
that may explain the behavioral phenomena.29 These results arterial O2 gradient, decreased thoracic cavity compliance,
have yet to be confirmed in humans, although some epide- and increased pleural pressure.43 Pneumoperitoneum and
miologic evidence has demonstrated worrisome increases in Trendelenburg positioning moves the carina cephalad, which
cognitive dysfunction in infants and young children exposed can convert a low-lying tracheal tube to an endobronchial
to anesthetics,31 although thus far not to fetuses exposed dur- position. The Trendelenburg position increases intrathoracic
ing cesarean delivery.32 Until more definitive data on in utero pressure and accentuates all the respiratory-related physio-
exposure of fetuses to anesthetic agents are available, these logic changes.
results suggest caution in casually exposing the pregnant The combination of pregnancy and CO2 pneumoperito-
woman to these agents. neum predisposes the parturient to hypercapnia and hypox-
Preterm labor is associated with surgery in pregnancy. emia. Insufflation of CO2 results in CO2 absorption across the
Although halogenated anesthetics inhibit uterine contrac- peritoneum and into the maternal bloodstream. Elimination
tions, this effect is short lived and does not protect against depends on an increase in minute ventilation; however,
preterm labor. Intra-abdominal procedures and those occur- mechanical hyperventilation can reduce uteroplacental perfu-
ring during the third trimester are the most likely to be asso- sion, probably because of decreased venous return.44 Although
ciated with preterm labor. It is not clear from epidemiologic end-tidal CO2 concentration (ETco2, Petco2) correlates well
studies whether the surgery itself, or the underlying condition with arterial CO2 tension (Paco2) in healthy patients, these are
prompting it, is responsible.33 There is no evidence that any poor guides to Paco2 in sicker patients. Any increase in mater-
anesthetic technique either increases or decreases the chance nal Paco2 or decrease in Pao2 can affect fetal well-being.43
of preterm labor. However, tocolytic therapy with magne- The cardiovascular changes associated with CO2 insufflation
sium, cyclo-oxygenase inhibitors, calcium channel blockers, include reduction in cardiac index and venous return, which
or beta-adrenergic agonists can have important anesthetic can be exacerbated by reverse Trendelenburg positioning.45
implications. The observed increase in intracardiac filling pressures is prob-
ably secondary to an increase in intrathoracic pressure. The
combination of reverse Trendelenburg position, general anes-
Laparoscopic Surgery
thesia, and peritoneal insufflation can decrease the cardiac
Occasionally, pregnancy can be complicated by acute intra- index (CI) by as much as 50%.46
abdominal pathology, requiring surgical intervention. The hemodynamic effects of aortocaval compression by
Laparoscopic surgery is generally preferred to conventional the gravid uterus could further accentuate the hemodynamic
open procedures, and therefore the anesthesiologist must effects of pneumoperitoneum and reverse Trendelenburg posi-
be familiar with the physiologic implications and anesthetic tioning, resulting in significant hypotension.43,47 Steinbrook
management of pregnant women requiring laparoscopic pro- and Bhavani-Shankar47 studied the cardiac output changes
cedures. Laparoscopic procedures have become more popu- in four pregnant patients (17-24 weeks' gestation) undergo-
lar than open procedures because of decreased morbidity ing laparoscopic surgery using thoracic bioimpedance cardi-
and convalescence.34 Although pregnancy was considered ography.47 IV ephedrine (10 mg) was given if SBP decreased
a contraindication to the procedure less than 15 years ago,35 by more than 20% with respect to baseline. The authors noted
a 27% decrease in CI after 5 minutes of CO2 insufflation. CI physiologic range. They also recommended preoperative
remained 21% below baseline after 15 minutes of insuffla- and postoperative FHR and uterine activity monitoring and
tion. The authors' aggressive management of blood pressure no prophylactic tocolysis. No fetal loss or uterine injuries or
during anesthesia (treating any decrease in BP approaching spontaneous abortions occurred. There was no significant dif-
20% of baseline measurements with IV ephedrine to mini- ference in preterm delivery rate, Apgar scores, or birth weights
mize decreases in uterine blood flow) may have resulted in between the open and laparoscopic surgery groups. As in pre-
the somewhat smaller CI reduction during CO2 insufflation vious reports, the operative groups (both open and laparo-
in their pregnant patients (27%) compared with 30% to 50% scopic appendectomies and cholecystectomies) had a slightly
in nonpregnant subjects in most studies. Mean arterial pres- higher rate of preterm labor compared with the general popu-
sure (MAP) and systemic vascular resistance (SVR) increased lation. Furthermore, multiple case reports have reported suc-
in these study subjects during CO2 insufflation, which is simi- cessful outcomes with noninvasive monitoring.53,54
lar to that generally observed in nonpregnant subjects during Bhavani-Shankar et al.55 prospectively evaluated the Paco2-
laparoscopic surgery. ETco2 difference in eight parturients undergoing laparoscopic
cholecystectomy with CO2 pneumoperitoneum. The intra-
MONITORING abdominal pressures were maintained at about 15 mm Hg.
With the large number of physiologic changes associated These women underwent surgery with general anesthesia
with pregnancy, as well as the cardiovascular and pulmonary during the second and third trimester. After adjusting minute
changes induced by laparoscopic surgery, optimal periopera- ventilation to maintain the ETco2 at 32 mm Hg, ABGs (alpha-
tive monitoring is unclear. The main debate is whether peri- stat method) were measured at fixed surgical phases: before
operative monitoring of arterial blood gases (ABGs) and fetal insufflation, during insufflation, after insufflation, and after
and uterine activity is necessary in parturients undergoing lap- completion of surgery. The authors found no significant dif-
aroscopic surgery. The Society of American Gastrointestinal ferences in either mean Paco2-ETco2 gradient or Paco2 and
Endoscopic Surgeons (SAGES) published guidelines for lapa- pH during the various phases of laparoscopy. During the sur-
roscopic surgery during pregnancy that include perioperative gical phase the maximal Paco2-ETco2 difference detected was
monitoring of ABGs, as well as perioperative fetal and uter- 3.1 mm Hg (range, 1.1-3.1). It appears that ETco2 correlates
ine monitoring,48 as echoed by other authorities.39,49–51 Amos well with arterial CO2, and adjusting ventilation to maintain
et al.39 reported four fetal deaths in seven pregnant women ETco2 also maintains optimal maternal Paco2. These results
who underwent laparoscopic cholecystectomy or appendec- do not support the need for ABG monitoring during laparos-
tomy. During the same period, no fetal deaths occurred in copy in pregnant patients.
patients who underwent pelvic surgeries by laparotomy. Even Laparoscopic procedures have been performed safely
though no ABG data were collected, fetal demise could have during all trimesters of pregnancy. However, some authors
resulted from prolonged respiratory acidosis, despite main- advocate reserving semielective, nonobstetric surgery dur-
taining ETco2 in the physiologic range (low to mid-30s mm ing pregnancy only during the second trimester. During this
Hg). These concerns stem from previous studies indicating period, organogenesis is complete, and spontaneous abortions
that elevation in maternal Paco2 could impair fetal CO2 excre- are less common than in the first trimester. Furthermore, pro-
tion across the placenta and could exacerbate fetal acidosis. cedures during the third trimester have been associated with
Other risk factors were present for fetal loss in this series, how- more preterm labor and potential difficulty in visualization
ever, including perforated appendix and pancreatitis. with an enlarged uterus.36,38,56
Steinbrook et al.43 reported a case series of 10 pregnant
women, gestational age 9 to 30 weeks, undergoing laparo- ANESTHETIC TECHNIQUE
scopic cholecystectomy; ABGs or perioperative fetal and Table 19-2 summarizes recommended anesthetic and surgical
uterine activity were not monitored. The patients underwent interventions for laparoscopy during pregnancy.57
general anesthesia with controlled ventilation, with ETco2
maintained at 32 to 36 mm Hg. Fetal heart rate (FHR) and
In Vitro Fertilization
uterine activity were assessed preoperatively and immediately
postoperatively. All patients had an uneventful recovery and Infertility is defined as one year of frequent unprotected sex
did not need postoperative tocolysis, and no adverse maternal without achieving a pregnancy and is not an irreversible
or fetal outcomes were noted. Seven patients were followed to state. Infertility is becoming more common with the trend for
delivery and had normal infants. The authors concluded that advanced maternal age before conception.58,59 The progno-
standard monitors recommended by the American Society of sis for infertility caused by major causes and tubal and male
Anesthesiologists (ASA) are sufficient for the safety and well- factors has improved significantly with the introduction of
being of the parturient and the fetus. assisted reproductive technologies (ARTs).60 ART involves the
Based on a series of 45 laparoscopic cholecystectomies handling and manipulation of the oocyte and spermatozoa
and 22 laparoscopic appendectomies performed during all to achieve a successful pregnancy. In vitro fertilization (IVF),
three trimesters, Affleck et al.52 supported the use of nonin- the most common form of ART introduced in 1978,61 has
vasive monitors and maintenance of the ETco2 within the increased greatly, with a North American review reporting
outcome of IVF, such as stimulation protocol, embryo factor,

TABLE 19-2 n Suggested Anesthetic Plan for
Laparoscopic Surgery during Pregnancy
physician supervising the cycle, and patient selection.64,65 As
such, close scrutiny of other factors that may affect outcome,
Anesthetic including medications and techniques used to provide anes-
Consideration Intervention/Drug thesia, would be expected.66
In vitro fertilization produces a variable amount of pain
Premedication Sodium citrate, 30 mL orally;
metoclopramide, 10 mg
that many practitioners consider a significant disadvan-
intravenously tage.67 Abdominal pain levels have been correlated with
body mass index (BMI), number of follicles, and duration
of technique and may vary between patients. Although the
Induction Rapid-sequence induction
most widely used method for pain relief (95% of U.S. cen-
Ventilatory adjustments Keep end-tidal Pco2 between 32 and ters),68,69 conscious sedation is rarely effective in prevent-
34 mm Hg ing ovarian puncture pain. Lack of coverage for IVF by
Maintenance of Desflurane, fentanyl, oxygen most insurance companies70 and a concern for a decreased
anesthesia in air, and muscle relaxants pregnancy rate with anesthetic agents may account for
(e.g., vecuronium) the decreased use of general and regional techniques for
Positioning Left or right uterine displacement; IVF.62 However, state laws requiring that insurance compa-
gradual change to reverse nies provide partial or complete coverage for IVF,70 as well
Trendelenburg as similar embryo implantation and pregnancy rates with
Fetal heart rate 16 weeks, preoperative and the use of local anesthetics and short-acting general anes-
monitoring immediate postoperative period thetic agents,62 are likely to increase the use of general and
regional anesthesia. Therefore, it is important to understand
Insufflation technique Open trocar technique
the implications of anesthetic techniques on IVF as well as
Tocolysis Terbutaline, 0.25 mg the implications of ARTs on regional and general anesthesia
subcutaneously, if needed (Tables 19-3 and 19-4).
Hypotension Increments of ephedrine
ANESTHETIC ISSUES
Postoperative period Left or right uterine displacement,
Transvaginal ultrasound–guided oocyte retrieval (TUGOR)
oxygen supplements, fetal heart
monitoring averages 10 to 20 minutes and can be performed with the
patient under conscious sedation, paracervical block, neur-
Data from Bhavani-Shankar K, Steinbrook RA: Anesthetic considerations for axial blockade, or general anesthesia. Therefore, short-acting
minimally invasive surgery. In Brooks DC, editor: Current review of minimally
invasive surgery, ed 2, Philadelphia, 1998, Current Medicine, p 29. agents are desired to minimize recovery time. Monitored anes-
thesia care and conscious sedation rely on adequate local anes-
thesia. However, they are inadequate to anesthetize the ovary.
over 88,077 ART cycles since its inception.62,63 The majority Patient discomfort, motion caused by pain, and a deep level
of these cycles (63,639) consisted of IVF, with a delivery rate of sedation leading to airway obstruction are serious risks.
per retrieval of 29.8%.63 Overall, there was an increase of 7.5% In addition, significant discomfort may leave patients with
and 0.4% for cycles and deliveries per retrieval, respectively. bad memories and may discourage future attempts at IVF.
However, the high cost and the 70% failure rate have led repro- Therefore, we prefer to use neuraxial techniques or intrave-
ductive endocrinologists to analyze factors that may affect the nous general anesthesia (IVGA).
TABLE 19-3 n Different Types of Assisted Reproductive Technologies
Tugor Gift Zift/prost/tet
Average duration 10-20 minutes 60-90 minutes Two different procedures: embryo retrieval (10-20
minutes) followed by transfer (30-60 minutes)
24-48 hours after fertilization
Embryo transfer Fertilized oocyte on Unfertilized oocyte transferred Fertilized oocyte transferred 24-48 hours after
day 3 or 5 shortly after retrieval retrieval
Anesthetic options Multiple; general or Mainly general because of Two different anesthetics: intravenous general or short-
spinal preferred need for laparoscopy acting spinal preferred for embryo retrieval; general
anesthetic preferred for laparoscopy for transfer
TUGOR, Transvaginal ultrasound-guided oocyte retrieval; GIFT, gamete intrafallopian transfer; ZIFT, zygote intrafallopian transfer; PROST, pronuclear stage tubal
transfer; TET, tubal embryo transfer.
TABLE 19-4 n Anesthetic Options for Assisted Reproductive Technologies
General Anesthesia Neuraxial Blockade Paracervical Block Conscious Sedation
Benefits Fast induction and emergence Able to avoid intravenous Fast induction and emergence without the need for
agents if so desired anesthesia personal.
Drawbacks Conflicting results on effects of Longer induction and Ovaries are not Relies on adequate
different agents on embryo recovery times anesthetized; operator local anesthesia
implantation and pregnancy rates dependent; lidocaine that is difficult to
appears in follicular fluid achieve
A target-controlled propofol infusion delivered by non- the need for general anesthesia.74 Pregnancy rates are similar
anesthesiologists in the United Kingdom, initiated and super- between IVF-ET and GIFT; therefore the less invasive IVF-ET
vised by a consultant anesthesiologist, required considerable is more often performed. GIFT allows for the oocyte fertiliza-
medical input, especially in the early stages, to ensure the safe tion in vivo and may be acceptable for couples with religious
provision of care.71 Incremental alfentanil was used for anal- beliefs that preclude IVF. Other transfer options include zygote
gesia. The successful use of propofol and alfentanil by patient- intrafallopian transfer (ZIFT), pronuclear stage tubal transfer
controlled pump was previously reported in IV sedation for (PROST), and tubal embryo transfer (TET). Although fertiliza-
egg retrieval.72 The main concern with propofol is distin- tion is confirmed before embryo transfer, all these techniques
guishing among conscious sedation, monitored anesthesia care require TUGOR to aspirate the follicular fluid and laparoscop-
(MAC), and general anesthesia. An anesthesiologist or nurse ically guided transfer into the fallopian tube 24 to 48 hours
anesthetist under the supervision of the reproductive endo- after fertilization. Similar pregnancy rates and the need for
crinologist or anesthesiologist should be present at all times two procedures and anesthetics have led to a marked decline
with the use of MAC. Therefore, it is essential to maintain in the performance of these techniques.
verbal contact with patients during the use of conscious seda- In earlier reports of IVF when it was significantly longer,
tion. Even though propofol has been used by emergency med- general endotracheal anesthesia was used with a combination
icine physicians and gastroenterologists in the United States of inhalation agents, with or without N2O. General endotra-
for conscious sedation and by nonphysician providers in the cheal anesthesia is now rarely used, except in cases of lapa-
United Kingdom, no data describe propofol use by nurses roscopic oocyte retrieval or when dictated by the patient's
under reproductive endocrinologist supervision in the United condition. Concern about the use of N2O originated from
States. Therefore, we discourage the practice of propofol use earlier reports suggesting that it had a teratogenic effect and
by nonanesthesia providers for egg retrieval. caused fetal death in rats when used during organogenesis.75
Embryo transfer (ET) is a simple procedure that occurs on In addition, lower DNA and RNA content and morphologic
day 3 or 5 after TUGOR, relies on a fertilized oocyte, and rarely abnormalities were demonstrated in the embryos of pregnant
requires any anesthetic involvement. After speculum insertion rats exposed to N2O during organogenesis.76,77 This potential
into the vagina and examination of the cervix, a flexible cath- teratogenicity has been attributed in part to the inactivation
eter loaded with embryos and culture medium is advanced of methionine synthase. Short exposures to clinical concen-
past the cervical os and injected into the uterus. Conscious trations of N2O, isoflurane, and halothane had no deleterious
sedation or MAC may be necessary in cases of significant dis- effect on IVF and early embryonic growth up to the morula
comfort with speculum insertion, or when there is difficulty stage in the mouse.78 Despite the deleterious effect of N2O
advancing the flexible catheter past the cervical opening. in some rat studies, no significant differences between rates
Gamete intrafallopian transfer (GIFT) is an alternative to of fertilization or pregnancy were demonstrated in humans
IVF-ET that was more common before improved embryo undergoing laparoscopic oocyte retrieval and isoflurane/N2O
culture techniques and successful pregnancies with IVF-ET. or isoflurane/air general anesthesia.79 Inhaled agents have
After hormone stimulation and TUGOR, unfertilized oocytes not been shown to possess a teratogenic or embryo effect.80
are mixed with sperm and transferred shortly after retrieval Furthermore, halothane can protect against N2O-induced ter-
into the fallopian tube. Laparoscopy performed under gen- atogenicity and spontaneous abortions in rats.26 In addition,
eral anesthesia is preferred so as to have direct visualization higher pregnancy rates have been demonstrated in women
of the flexible catheter and fallopian tubes in GIFT. Although undergoing laparoscopic PROST under isoflurane/N2O com-
spinal anesthesia is rarely used for laparoscopic procedures pared with propofol/N2O anesthesia.81
because of concerns of shoulder discomfort and difficulty Propofol is an ideal induction and maintenance agent
breathing with CO2, one report highlights the safety of spi- because of its short-acting half-life and antiemetic proper-
nal anesthesia for laparoscopic oocyte retrieval.73 Another ties. However, early reports demonstrated that propofol dif-
technique is performed with a minilaparoscopic approach, fuses into follicular fluid, with greater levels observed with
reducing intraperitoneal pressure and CO2 and obviating higher doses.82,83 Even though follicular fluid concentrations
are higher in the last follicle than the first follicle, no differ- (COX), is an essential enzyme in prostaglandin synthesis and
ences were found in the ratio of mature to immature follicles primarily localized in the endometrial epithelium.97 Despite
or in fertilization, cleavage, or embryo cell number.83 In addi- these concerns, no animal or human data demonstrate any
tion, a report on the use of propofol for IVGA for TUGOR of changes produced by COX inhibitors on the embryo or on
donor oocytes demonstrated a lack of negative effect on the implantation rates. Furthermore, implantation does not occur
oocyte, as evaluated by cumulative embryo scores and rates until 3 to 5 days after egg retrieval. Some UK centers rou-
of implantation and pregnancy.84 Use of propofol (with N2O) tinely use NSAIDs without any known effects on endometrial
for transfer of fertilized embryos resulted in fewer pregnan- lining or implantation rates.98 We prefer to use NSAIDs for
cies compared with an isoflurane, N2O-based anesthesia.81 egg donors or for patients with pain refractory to significant
However, higher maternal serum concentrations were needed doses of opioids until further data are available. Future studies
in this study to provide anesthesia for laparoscopic PROST should help to clarify some of these concerns.
compared with the use of propofol for IVF-ET procedures.85 Nausea and vomiting are the most common complications
Another study on mouse oocytes found that high levels of proof general anesthesia but is reduced with the use of propo-
pofol in the follicular fluid may affect pregnancy rates.86 The fol, low doses of opioids, and the avoidance of inhaled anes-
use of thiopental and thiamylal for laparoscopic egg retrieval thetic agents. We prefer to avoid metoclopramide in patients
has also been associated with accumulation in follicular fluid87; undergoing IVF; the risk of affecting embryo implanta-
a comparison of thiopental and propofol used for laparoscopic tion and a successful pregnancy is greater than its benefit in
GIFT demonstrated similar pregnancy rates.88 A case-control patients not at significant risk for acid aspiration syndrome.
study comparing propofol IVGA to paracervical block showed Metoclopramide, a dopamine receptor antagonist, causes ele-
no difference in fertilization rates, embryo cleavage character- vated prolactin levels that may be associated with inhibition of
istics, or pregnancy rates between the two groups.89 Neither pulsatile gonadotropin-releasing hormone (GnRH) secretion,
group received premedication; both groups received 0.5 mg a hypoestrogenic state, and ovulatory dysfunction.99 Although
of alfentanil at anesthesia induction, and the propofol group not helpful for gastric motility, ondansetron use for the treat-
received a full induction dose (2 mg/kg), followed by a contin- ment or prevention of nausea and vomiting is not contrain-
uous infusion without additional anesthetic. The results of this dicated during IVF. Serotonergic agents, unlike serotonin
study are compelling because an IVGA group was compared (5-HT3) receptor antagonists such as ondansetron, may also
to a local anesthetic group without premedication. In addi- increase prolactin levels. We prefer to use a neuraxial tech-
tion, no studies demonstrate a teratogenic effect of propofol. nique for patients at increased risk for postoperative nausea
Overall, although it may appear in follicular fluid when used and vomiting or acid aspiration syndrome.
for IVGA for brief IVF procedures, data support that propofol During TUGOR, a transvaginal approach is used to punc-
has no adverse effect on pregnancy rates. ture the ovary and aspirate the follicular fluid. Both sym-
Fentanyl, alfentanil, and midazolam, when used as premed- pathetic and parasympathetic nerves supply the ovaries.
ications before TUGOR, reach low intrafollicular levels and Although most of the sympathetic nerves are derived from the
have no effect on rates of implantation or pregnancy.90,91 The ovarian plexus that accompanies the ovarian vessels, a minor-
absolute concentration of intrafollicular levels is extremely ity are derived from the plexus that surrounds the ovarian
low compared with plasma levels.91,92 Alfentanil had the low- branch of the uterine artery.100 Acute visceral pain is often dif-
est follicular fluid/plasma ratio (1:40) compared with mid- fuse in distribution, vague in location of origin, and referred to
azolam (1:20) and fentanyl (1:10).91 Remifentanil, a relatively remote areas of the body.101 Paracervical block (PCB) has been
new analgesic agent, has a fast onset and a very short recovery, utilized with and without conscious sedation for TUGOR
suitable for IVF procedures. A comparison of propofol/fen- to improve pain relief.68,102,103 PCB anesthetizes the vaginal
tanyl anesthesia to a midazolam/remifentanil technique found mucosa, uterosacral ligaments, and peritoneal membrane over
a decreased need for manual ventilation and a faster recovery the pouch of Douglas.102 Although the ovaries are not anes-
of function in the latter group. More patients in the propofol/ thetized, their pain sensitivity is the lowest compared with the
fentanyl group experienced intraoperative awareness and did rest of the internal female genital organs.101 PCB with 150 mg
not enjoy the anesthetic, but time to discharge did not vary.93 of lidocaine reduced abdominal pain by one half compared
Other studies have compared a propofol-based anesthetic with with placebo.102 The linear visual analog pain score (VAPS;
a sedative combination of ketamine and midazolam without 0-100 mm) decreased from 43.7 to 21.2 mm when evaluated
demonstrating a difference in the recovery profile, embryo 4 hours after TUGOR.102 Another study demonstrated no dif-
transfers, or pregnancy rates.94 Of note, there are sparse data ference in VAPS when 50 mg of lidocaine was compared with
on the safety of ketamine or remifentanil on ART. 100 and 150 mg for PCB.103 Assessing VAPS immediately after
Nonsteroidal anti-inflammatory drugs (NSAIDs), such as the procedure found median abdominal pain levels of 30 to
IV ketorolac, would be ideal for the acute visceral pain dur- 32 mm. Although small concentrations of lidocaine in the fol-
ing and after TUGOR. However, there is reluctance to use licular fluid can have adverse effects in mouse oocyte fertiliza-
them because prostaglandins (PGE2, PGF2α, PGI2) in the tion and embryo development,102,104 these levels do not affect
embryo and endometrium are important for implantation.95,96 embryo implantation or pregnancy rates.105 PCB alone is not
Prostaglandin H synthase, also known as cyclo-oxygenase sufficient to provide complete analgesia because of its 10%
to 15% failure rate and lack of interference with afferent sen- Male factor infertility is the most common form of infertil-
sory fibers originating from the ovarian plexus. This finding is ity.110 New variations of IVF include direct sperm harvesting
reflected in the 2.5 times higher vaginal and abdominal pain and a single sperm injection into the cytoplasm of the oocyte,
levels with PCB alone versus PCB with the addition of con- called intracytoplasmic sperm injection (ICSI). ICSI has greatly
scious sedation.68 increased pregnancy rates in patients with male factor infer-
Neuraxial techniques have also been used for TUGOR and tility caused by low sperm counts and is often combined with
are more likely to anesthetize the ovary, vaginal mucosa, and direct sperm aspiration from the epididymis or testicular
peritoneal membrane. A thoracic dermatomal level of the biopsy. Earlier reports described a more invasive, microepi-
tenth thoracic vertebra (T10) or higher is needed to anesthe- didymal sperm aspiration (MESA) with open surgical aspira-
tize the ovaries. Spinal anesthesia is more likely to be beneficial tion of the scrotum. Recent work has pioneered less invasive
because of its increased reliability and fast onset. It requires techniques, such as percutaneous epididymal sperm aspiration
minimal to no conscious sedation and can be tailored to mini- (PESA) and testicular epididymal sperm aspiration (TESA).
mize high sensory levels and motor blockade. The optimal spi- These two techniques have been done under local anesthesia
nal anesthetic should allow adequate surgical anesthesia with of the superior and inferior spermatic nerves and the genital
minimal side effects, a fast onset, a short recovery time, and a branch of the genitofemoral nerve, without premedication.111
similar rate of successful pregnancies as with other anesthetic We prefer to use spinal anesthesia or IVGA for these proce-
techniques. Earlier reports described the use of 60 mg of 5% dures to minimize patient discomfort and movement.
lidocaine for spinal anesthesia,106 but long recovery times and
the finding of transient neurologic symptoms caused some ANESTHETIC ISSUES
concerns. In an effort to decrease recovery times and keep In vitro fertilization consists of different stages, including
patients comfortable, Martin et al.107 decreased the dose to suppression therapy, stimulation therapy, trigger or ovula-
45 mg of lidocaine and evaluated the benefit of adding 10 μg tion therapy, egg retrieval, fertilization, postovulation therapy
of fentanyl to the spinal anesthetic. A comparison of these with progesterone, and embryo transfer. Therapy with leup-
studies demonstrated decreased time to ambulate, void, and rolide acetate (Lupron), a GnRH agonist, causes suppression
discharge in the lower-dose lidocaine group.106,107 The addi- of gonadotropins (follicle-stimulating hormone and luteiniz-
tion of fentanyl to the lidocaine resulted in improved analgesia ing hormone) and results in a lack of production of estrogen
during the procedure and, postoperatively, a decreased opioid and progesterone. Stimulation therapy is conducted with FSH-
consumption and no change in side effects or ability to ambu- and LH-containing human menopausal gonadotropin (hMG)
late, void, or be discharged. The addition of increased amounts and causes ovarian follicle growth. Human chorionic gonado-
of fentanyl to the spinal technique and surgical improvements tropin (hCG) causes ovulation to occur within 36 hours, and
leading to shorter egg retrieval led to a further decrease in the TUGOR is performed at this time. Supplemental progesterone
dose of lidocaine to 30 mg. is given after embryo transfer.
Although we have had a good success with the subarach- Stimulation therapy with gonadotropins (e.g., hMG or FSH
noid use of 30 mg of lidocaine combined with 25 μg of fen- preparations) may lead to very high estrogen levels and ovar-
tanyl, controversy about lidocaine and transient neurologic ian hyperstimulation.112 High estrogen levels place patients
symptoms led to the evaluation of bupivacaine as an alterna- at risk for thromboembolic phenomena. In its more severe
tive. However, a comparison of 30 mg of lidocaine with equi- form, ovarian hyperstimulation syndrome (OHSS) may lead
potent doses of bupivacaine (3.75 mg) demonstrated a longer to increased vascular permeability with leaky capillaries and
time to micturition and recovery with bupivacaine.108 Of note, findings such as weight gain, intravascular volume depletion,
patients undergoing IVF procedures demonstrate decreased ascites, pleural effusions, electrolyte changes, and renal dys-
serum albumin and α1-acid glycoprotein levels during supra- function. These patients usually experience a state of fibri-
physiologic estrogen states at oocyte retrieval. This may lead to nolysis, with higher fibrinogen, plasmin/α2-antiplasmin,
an increased free fraction of highly protein-bound drugs such thrombin/antithrombin complexes, and d-dimer levels than
as bupivacaine.109 However, this may only be significant when women with lower estrogen levels.113–115 In addition, tissue fac-
using larger doses of bupivacaine during epidural anesthe- tor increases with high estrogen levels and is a powerful trig-
sia, which is rarely used during IVF. At our institution, spinal ger of the extrinsic pathway of the coagulation cascade.115,116
anesthesia even with low doses of local anesthetic and opioid Treatment is usually supportive, with intravascular volume
is associated with longer times to voiding and discharge com- expansion, analgesics, bed rest, and thrombosis prophylaxis.
pared with IVGA. This finding and short surgical time led us to More invasive methods, such as paracentesis and thoracente-
use IVGA as our standard anesthetic for TUGOR. Spinal anes- sis, are more helpful for relief of symptoms, such as abdomi-
thesia with 30 mg of lidocaine and 25 μg of fentanyl is used at nal pain and shortness of breath. Conscious sedation is often
the patient's request, in those with significant gastroesophageal required for these procedures and should take into account
reflux disease (GERD) or morbid obesity, when the patient has the increased sensitivity to medications caused by intravas-
eaten and the oocytes must be retrieved before spontaneous cular volume contraction. Caution should be used if regional
ovulation occurs, and when indicated because of severe side anesthetic techniques are a consideration for these patients,
effects to IVGA, such as postoperative nausea and vomiting. because of the potential for anticoagulation.
The retrieval of oocytes from the follicles is not considered an section.120 Abnormal presentations, fetal macrosomia, and
elective procedure; failure to retrieve them may lead to sponta- prolonged labor are predisposing factors associated with
neous ovulation and a wasted cycle. In addition, failure to empty increased incidence of cesarean delivery among obese women.
the follicles may lead to OHSS with all its known complications. Evidence suggests that obese patients are at increased risk for
Our preference is to perform TUGOR under spinal anesthesia abnormal labor.121,122 Although not statistically significant, the
with minimal sedation in patients who did not follow preopera- incidence of cesarean delivery for failure to progress was much
tive fasting guidelines. Aspiration prophylaxis is recommended higher in the morbidly obese than the control group.
with sodium citrate and metoclopramide, despite the concerns There is high incidence of umbilical arterial pH less than
for increased prolactin levels with metoclopramide. 7.1 among obese women, regardless of whether they had a
Although the rate of success continues to increase with trial of labor or elective cesarean delivery.123 A significantly
ARTs, a significant number of cycles still do not result in a live higher incidence of Apgar score less than 5 at 1 minute or less
birth. Therefore, close scrutiny is expected of variables that than 7 at 5 minutes, of birth weight greater than 4500 g or
may affect oocyte retrieval or embryo transfer. It is essential less than 2500 g, of intrauterine growth retardation (IUGR),
to understand the impact of different anesthetic techniques and of neonatal intensive care unit (NICU) admission is
and medications on IVF and carefully study any data that found in infants born to obese versus nonobese parturients.124
links these factors with implantation or pregnancy rates. The Congenital anomalies in infants seems to be associated with
anesthetic may have an impact on ART, and vice versa. gravid obesity in the mothers; these infants are at a greater
risk for developing neural tube defects and other congenital
malformations.125
OBSTETRIC ANESTHESIA FOR UNCOMMON
CONDITIONS ANESTHETIC MANAGEMENT
An anesthesiologist should assess the patient at about 28
Morbid Obesity
weeks' gestation to determine the effect of pregnancy on vari-
A weight greater than 300 pounds (135 kg) in a gravida at term ous systems (Box 19-2). A multidisciplinary approach should
is considered morbid obesity.117 Pregnancy in obese patients be instituted, depending on the systemic findings. Careful
may have four important implications.118 First, some of the evaluation of airway should be performed, and the anesthetic
physiologic changes associated with pregnancy (e.g., increased plan should be formulated well in advance and communicated
blood volume and cardiac output, reduced FRC) may further to the patient as well as the obstetrician. Regional anesthesia
exacerbate deleterious effects produced by pathophysiologic is most appropriate for labor and delivery. Early initiation of
alterations of obesity. Second, obese patients are prone to epidural anesthesia is recommended, to provide ample time
acquire pregnancy-related diseases and complications (e.g., to negate difficulties encountered during epidural placements.
pre-eclampsia, gestational diabetes). Third, an increased inci- Continuous spinal anesthesia is a reasonable alternative.
dence of obstetric and perinatal complications is associated These two techniques provide satisfactory analgesia and anes-
with morbid obesity. Finally, a combination of these three fac- thesia as needed for cesarean delivery, urgent or otherwise.
tors may lead to the fourth implication: an unfavorable out- More recently, ultrasound is being used to increase the success
come of pregnancy. of regional anesthesia in morbidly obese pregnant women.126
Obese women should be strongly encouraged to lose weight If general anesthesia is contemplated, an assistant is advan-
before conceiving. This will decrease obstetric and perinatal tageous, and airway backup equipment should be available.
morbidity and mortality. Careful systemic evaluation should Difficult intubation should be anticipated, and a contingency
be performed at the first opportunity during pregnancy in backup plan should be initiated as needed. Great care must be
morbidly obese women to determine the systemic pathophysi- exercised in appropriately positioning morbidly obese preg-
ologic alterations of obesity. This includes the degree of respi- nant women for cesarean delivery. Hypoxia may occur in the
ratory impairment resulting in hypoxia, with consequences
such as pulmonary hypertension, right ventricular (RV) hyper-
trophy, and RV impairment. The left ventricle undergoes BOX 19-2 n ANESTHETIC CONSIDERATIONS IN
eccentric hypertrophy as a result of increased cardiac output, PREGNANT WOMEN WITH MORBID OBESITY
hypertension, and blood volume. The end result is a biventric-
Perform a preanesthetic evaluation during pregnancy.
ular hypertrophy. A bedside method to determine the degree Assess airway.
of hypoxemia is to measure the decrease in O2 saturation on Evaluate associated cardiorespiratory abnormalities of obesity.
assuming the supine position from an erect posture. If hypoxia Perform early epidural placement to ensure a good working catheter.
occurs in the supine position, further evaluation should be per- Consider continuous spinal technique if epidural anesthesia is
unsuccessful and airway is anticipated to be difficult.
formed to determine the RV functional changes.118 Pregnancy
Place several folded bedsheets stepwise from back to occiput, to
in morbidly obese women can exaggerate sleep apnea, resulting attain a good intubating position.
in pulmonary hypertension during pregnancy.119 Know that a large pannus may cause hemodynamic instability after
Increased BMI, increased prepregnancy weight, and induction of regional anesthesia.
excessive maternal weight gain increase the risk of cesarean
supine position, which may require elevation of the back rest

of the operating table. Retraction of the pannus to facilitate BOX 19-3 n CONSIDERATIONS IN AMNIOTIC FLUID
EMBOLISM
surgery can result in exaggerated supine hypotensive syndrome
of pregnancy, which can result in cardiac arrest. A multidisci- Cardiorespiratory collapse may be the first sign of amniotic fluid
plinary approach is the key to a successful outcome of preg- embolism.
The patient occasionally presents with hypotension, seizures,
nancy in morbidly obese women.
dyspnea, and isolated coagulopathy.
Coagulopathy is an invariable accompaniment of amniotic fluid embolism.
Presence of squamous cells and other fetal debris (mucin, vernix,
Amniotic Fluid Embolism
lanugo) coated with leukocytes in the maternal circulation is the
Amniotic fluid embolism is one of the most intriguing com- hallmark of amniotic fluid embolism.
Initial pulmonary hypertension, hypoxia, left ventricular failure, and
plications of pregnancy. Its diagnosis is difficult and uncertain
coagulopathy are the primary events in amniotic fluid embolism.
at times, its pathophysiology is debatable, its treatment is diffi- Management is basically symptomatic and directed toward the
cult and often inadequate and nonspecific, and morbidity and maintenance of oxygenation, circulatory support, and correction of
mortality are high. Amniotic fluid or amniotic debris enters coagulopathy.
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 presentation of amniotic fluid embolus can vary with regard
high for patients who are symptomatic, at 61% to 86%.127,128 to timing, presenting symptoms, and subsequent course.136
The classic description of amniotic fluid embolism is pro- Therefore the differential diagnosis must be considered care-
found and unexpected shock, followed by cardiovascular col- fully while maintaining a high index of suspicion for amniotic
lapse and death in most patients.129 The syndrome was thought fluid embolism (Box 19-3).
most likely in multiparous women who had an unusually
strong or rapid labor.130 The use of uterine stimulants, meco- ETIOLOGY
nium staining of the amniotic fluid, or the presence of a large Intact fetal membranes isolate amniotic fluid from the mater-
or dead fetus was also believed to increase the risk. However, nal circulation. After delivery, uterine vessels on the raw sur-
a number of exceptions exist to this classic description. There face of the endometrium become exposed to amniotic fluid.
are several case reports of amniotic fluid emboli occurring Normally, uterine contractions are effective in collapsing
during cesarean delivery and therapeutic abortion, as well these veins. Therefore, in addition to ruptured membranes,
as occasional cases in the late postpartum period or rarely for amniotic fluid embolism to occur there must be a pres-
in nonlaboring patients.131–134 Other cases have been associ- sure gradient favoring the entry of amniotic fluid from the
ated with abdominal trauma, ruptured uterus, or intrapartum uterus into the maternal circulation.127 Although the placen-
amnioinfusion.135,136 tal implantation site is one potential portal of entry, particu-
Amniotic fluid may be trapped in the uterine veins dur- larly with partial separation of the placenta, this is otherwise
ing contraction of the uterus at delivery, then released into the unlikely if the uterus remains well contracted. On the other
circulation later, during normal postpartum uterine involu- hand, small tears in the lower uterine segment and endocervix
tion.137 This explains cases of amniotic fluid embolism occur- are common during labor and delivery and are now thought
ring in the late postpartum period. Delayed presentation could to be the most likely entry points.127,131 In support of this con-
also result from the initial onset being transient or subclinical cept, Bastien et al.138 reported a case of amniotic fluid embolus
and going unrecognized. This in turn could account for the where postmortem examination revealed marked plugging of
delayed or atypical presentation reported in the literature. both the cervical vasculature and the lungs by various amni-
otic fluid elements.
CLINICAL PRESENTATION The misconception that amniotic fluid routinely enters
Cardiorespiratory collapse was present in most patients with the maternal circulation at delivery arose from the belief that
amniotic fluid embolism, as seen in the Morgan series.127 the presence of squamous cells in the pulmonary vasculature
However, the presenting symptom in 51% of patients was signaled amniotic fluid entry into the maternal circulation.
respiratory distress. In the remainder, the first indication of a Studies now show that squamous cells can appear in the pul-
problem was hypotension in 27%, a coagulopathy in 12%, and monary blood of heterogeneous populations of both pregnant
seizures in 10%. On the other hand, Clark et al.128 found that, of and nonpregnant patients who have undergone pulmonary
those women presenting before delivery, 30% had seizures or artery (PA) catheterization.139,140 The presence of squamous
seizurelike activity, whereas 27% complained of dyspnea. Fetal cells is thought to have resulted from contamination by either
bradycardia (17%) and hypotension (13%) were the next most exogenous sources during specimen preparation or epithelial
common presenting features. Of the 13 patients who devel- cells derived from the entry site of the PA catheter.139 Because
oped symptoms after delivery, seven (54%) presented with it is difficult to differentiate adult from fetal epithelial cells,
an isolated coagulopathy manifested by postpartum hemor- the isolated finding of squamous cells in the pulmonary cir-
rhage. Several additional case reports have suggested that the culation of pregnant patients without amniotic fluid embolus
is most likely a contaminant and not indicative of maternal pulmonary vascular resistance further revealed that, with one
exposure to amniotic fluid. Furthermore, although squamous exception, all were either normal or in a range that was reflec-
cells may be present in both groups (clinical evidence with and tive of isolated LV failure. In an attempt to reconcile clinical
without amniotic fluid embolus), only the patients with amni- and animal experimental findings, Clark proposed a biphasic
otic fluid embolism had evidence of other fetal debris, such as model to explain the hemodynamic abnormalities that occur
mucin, vernix, and lanugo. In these patients, squamous cells with amniotic fluid embolus, suggesting that acute pulmo-
and other granular debris were frequently coated with leu- nary hypertension and vasospasm might be the initial hemo-
kocytes, suggesting a maternal reaction to foreign material. dynamic response. The resulting right-sided heart failure and
Where other occasional unidentifiable debris was detected, accompanying hypoxia could account for the cases of sudden
the material present in the patients who did not have an amni- death or severe neurologic impairment. Those patients who
otic fluid embolism was “clearly different” from that seen in survive the initial phase of pulmonary hypertension, which is
the sample.140 transient, proceed to the next stage of LV failure. Mechanisms
Additional confusion centers on the importance of tropho- that contribute to the later phase of LV failure include hypoxia,
blastic embolization to the maternal lung. Trophoblastic cells leftward shift of interventricular septum secondary to right-
are normally free floating in the intervillous space and there- sided heart failure (resulting in a decrease in cardiac out-
fore have direct access to the maternal circulation.127 Thus put, leading to impaired coronary artery perfusion), and the
their presence in the maternal peripheral or central vascular direct myocardial depressant effect of amniotic fluid itself.
circulation is neither surprising nor indicative of an amniotic Endothelin, which is in amniotic fluid in abundance, has been
fluid embolism. Further evidence that amniotic fluid does not cited as the cause of LV failure.145
normally enter the maternal circulation can be found from Other humoral factors, including proteolytic enzymes,
autopsies of parturients who died of various complications of histamine, serotonin, prostaglandins, and leukotrienes, may
pregnancy. A comparison of lung specimens from 20 toxemic contribute to the hemodynamic changes and consumptive
patients with an equal number who had clinical evidence of coagulopathy associated with amniotic fluid embolism.136
amniotic fluid embolus, using a specific stain for acid muco- Because of the clinical resemblance to sepsis and anaphylaxis,
polysaccharide, confirmed the presence of mucin in the lung Clark et al.128 suggested that the syndrome of amniotic fluid
secretions from all the amniotic fluid embolism patients; no embolism is caused by anaphylactoid reaction to amniotic
section from the toxemic patients stained positive.141 fluid and named the syndrome “anaphylactoid syndrome of
In summary, the presence of squamous or trophoblas- pregnancy.” Antigenic potential can vary in individuals and
tic cells in the maternal pulmonary vasculature must not be therefore can lead to different grades of the syndrome. For
equated with the entry of amniotic fluid into the maternal cir- example, women carrying a male fetus are more likely to be
culation. No evidence suggests or supports that amniotic fluid affected. Similarly, fluid containing thick meconium may be
embolism is a common physiologic event. more toxic than clear amniotic fluid. Human data have shown
that, although most patients dying of amniotic fluid emboli
PATHOPHYSIOLOGY have had clear amniotic fluid, there is a shorter time from the
Once the amniotic fluid enters the maternal circulation, a initial presentation to cardiac arrest and an increased risk of
number of physiologic changes occur that contribute to the neurologic damage or death in the presence of meconium or
syndrome observed. The pathophysiology is multifactorial, a dead fetus. Further indirect evidence for an immunologic
and the clinical presentation will depend on the predominant basis is the occurrence of fatal amniotic fluid emboli during
physiologic aberration. first-trimester abortions. This suggests that under the right
circumstances, maternal exposure to even small amounts of
HEMODYNAMIC CHANGES amniotic fluid can initiate the syndrome.128 Confirming the
Animal models have suggested that severe pulmonary hyper- theory of “anaphylactoid reaction” to amniotic fluid requires
tension was the major pathophysiologic change with amni- further research using tryptase markers.
otic fluid embolism.142 This was believed to result from either
critical obstruction of the pulmonary vessels by embolic mate- COAGULOPATHY
rial or pulmonary vasospasm secondary to the response of Consumptive coagulopathy is often associated with amni-
the pulmonary vasculature to fetal debris, resulting in acute otic fluid embolism. In Morgan's review,127 12% of patients
asphyxiation, cor pulmonale, and in turn sudden death or presented with a bleeding diathesis, with subsequent devel-
severe neurologic injury.131,142 However, human hemodynamic opment of a bleeding diathesis in an additional 37%. More
data do not support sustained periods of pulmonary hyperten- recent reviews, however, found an even higher incidence.
sion.143,144 In fact, left ventricular (LV) failure seems to be the Clark et al.128 reported that 83% of the cases in the national
pathognomonic feature in humans.136 registry had either clinical or laboratory evidence of consump-
Clark142 reviewed the available hemodynamic data from the tive coagulopathy. The remaining 17% died before the clotting
published cases of amniotic fluid embolus in humans and found status could be assessed by either clinical or laboratory tech-
only mild to moderate increases in PA pressure, whereas all nique. Similarly, in 15 cases of fatal amniotic fluid embolism
patients had evidence of severe LV dysfunction. Calculation of associated with induced abortion, two patients presented with
coagulopathy, and an additional 75% of initial survivors went it is clinically significant and strongly supportive of the diag-
on to develop disseminated intravascular coagulation (DIC).146 nosis of amniotic fluid embolus. This is particularly true if the
It now appears that amniotic fluid embolism is almost always squamous cells are coated with neutrophils or accompanied
associated with some form of DIC, with or without clinically by other fetal debris, such as mucin or hair. A more reliable
significant bleeding. Isolated DIC causing maternal hemor- method of confirming the diagnosis might center on the iden-
rhage may be the first indication of the problem in a small tification of other amniotic fluid elements in the maternal pul-
number of patients.147,148 The current laboratory evidence also monary vasculature, as opposed to squamous cells.140,152
supports that amniotic fluid embolus is associated with coag- Recent progress in the diagnosis of amniotic fluid embolus
ulation changes. Harnett et al.149 studied the effect of varying has centered on the attempt to develop simple, noninvasive,
concentrations of amniotic fluid (10-60 μL added to 330 μL sensitive tests using peripheral maternal blood. Kobayashi
of whole blood) on thromboelastographic variables and found et al.153 studied maternal serum sialyl Tn antigen levels in four
that amniotic fluid is procoagulant even with a 10-μL study women with clinical amniotic fluid embolism and compared
sample.149 them to both pregnant and nonpregnant controls. Sialyl, a
The etiology of the coagulopathy remains somewhat mucin-type glycoprotein that originates in fetal and adult
obscure; investigations have yielded inconclusive and con- intestinal and respiratory tracts, is present in both meconium
tradictory results. Although amniotic fluid contains activated and clear amniotic fluid. Using a sensitive antimucin anti-
coagulation factors II, VII, and X, their concentrations are body, TKH-2, the authors found no difference in the serum
well below those found in maternal serum at term.150 On the levels of pregnant patients throughout gestation or in the early
other hand, amniotic fluid has been shown to have a direct, postpartum period compared with healthy nonpregnant con-
factor X–activating property and thromboplastin-like effect; trols. However, the antigen levels were elevated in the amni-
both increase with gestational age. The thromboplastin-like otic fluid embolism group.153 Nonetheless, this test appears
effect is likely caused by substantial quantities of tissue fac- promising, although it needs further evaluation. Study of a
tor in amniotic fluid. Potential sources include sloughed fetal second marker of diagnosis that involves the measurement of
skin and epithelial cells derived from the fetal respiratory, zinc coproporphyrin, a characteristic meconium component,
GI, and genitourinary tract mucosa. Tissue factor activates found plasma concentrations were higher in patients with
the extrinsic pathway by binding with factor VII. This com- amniotic fluid embolus.154
plex in turn triggers clotting by activating factor X. Lockwood
et al.150 speculated that once clotting was triggered in the pul- MANAGEMENT
monary vasculature, local thrombin generation could then The management of the pregnant patient with amniotic fluid
cause vasoconstriction and microvascular thrombosis, as well embolism is basically symptomatic and directed toward the
as secretion of vascular endothelin. This vasoactive peptide maintenance of oxygenation, circulatory support, and cor-
can depress both myometrial and myocardial contractility rection of coagulopathy. Depending on the circumstances, a
and may primarily or secondarily contribute to the hemody- full cardiopulmonary resuscitation (CPR) protocol may be
namic changes and uterine atony generally associated with required. If the fetus is sufficiently mature and is undelivered
this syndrome. at the time of cardiac arrest, cesarean delivery should be insti-
tuted as soon as possible.
DIAGNOSIS Treatment of hemodynamic instability includes optimi-
There are no diagnostic criteria to confirm the presence of zation of preload with rapid volume infusion. Direct-acting
amniotic fluid embolism. The differential diagnosis includes vasopressors may be required in restoring aortic perfusion
air or thrombotic pulmonary emboli, septic shock, acute myo- pressure in the initial stages. Once this is attained, other
cardial infarction, cardiomyopathy, anaphylaxis, aspiration, inotropes such as dopamine and dobutamine can be added
placental abruption, eclampsia, uterine rupture, transfusion to improve myocardial function. When clinically feasible,
reaction, and local anesthetic toxicity.136 In the presence of PA catheterization can be instituted to help guide therapy.
central venous access, blood from the pulmonary vasculature Diuretics may be required to mobilize pulmonary edema
should be collected using the method described by Masson.130 fluid. Treatment of the coagulopathy associated with amniotic
He suggested that to minimize the possibility of maternal or fluid embolus involves blood component therapy. Amniotic
exogenous contamination, a more representative sample of the fluid embolism is associated frequently with massive hem-
pulmonary microvasculature can be obtained if blood is drawn orrhage, requiring replacement with packed red blood cells
from the distal lumen of a wedged pulmonary artery catheter. (PRBCs). O-negative or group-specific blood can be used if
After discarding the first 10 mL of blood, an additional 10 mL crossmatched blood is unavailable. Plasma and platelets are
is drawn, heparinized, and analyzed with Papanicolaou's given to replace the clotting factors. Ongoing therapy is gener-
method.151 The presence of components of amniotic fluid, ally guided by the clinical condition of the patient and labora-
including squamous cells and mucous strands, reinforces the tory evidence of coagulopathy.
diagnosis. Although pulmonary vasculature preparations may Although cryoprecipitate is not first-line therapy for
occasionally be contaminated by maternal squames, when treating coagulopathy, it may be useful in circumstances in
squamous cells are found in large numbers in such a sample, which fibrinogen is low and volume overload is a concern.
Cryoprecipitate was also found useful in a patient with severe Eclampsia remains a significant complication of pregnancy
acute respiratory distress syndrome (ARDS) secondary to in the United States. In a study of 399 consecutive women with
amniotic fluid embolus.155 After administration of cryopre- eclampsia, the mortality rate was 1%, and antepartum onset
cipitate, the patient's cardiopulmonary and hematologic sta- carried the greatest risk, especially before 32 weeks' gestation.
tus improved dramatically, suggesting that cryoprecipitate Postpartum eclampsia, however, was more likely to be associ-
may be useful when conventional medical therapy appears ated with neurologic deficits.163 Eclampsia remains a common
unsuccessful in maintaining blood pressure, oxygenation, and condition and a leading cause of maternal and perinatal mortal-
hemostasis. The recommendation was based on similar treat- ity in developing countries.164 Major maternal complications can
ment protocols for severely ill patients with multiple trauma, follow, including placental abruption, HELLP syndrome, DIC,
burns, and postoperative sepsis. These patients are believed to neurologic deficits, pulmonary aspiration, pulmonary edema,
have impaired clearance of circulating microaggregates and cardiopulmonary arrest, and acute renal failure (ARF).163
immune complexes by the reticuloendothelial system, leading Headache, visual disturbances, and epigastric or right upper
to cardiopulmonary insufficiency and DIC. Cryoprecipitate is quadrant (RUQ) pain are consistent with severe pre-eclampsia
rich in opsonic α2 surface-binding glycoprotein, also known and may forewarn of impending eclampsia. Seizures have an
as fibronectin, which facilitates the reticuloendothelial sys- abrupt onset, typically beginning as facial twitching and fol-
tem in the filtration of antigenic and toxic particulate mat- lowed by a tonic phase that persists for 15 to 20 seconds. This
ter. Depleted levels of this glycoprotein have been reported in progresses to a generalized clonic phase characterized by
severely ill patients, with marked improvement in the clinical apnea, which lasts approximately 1 minute. Breathing resumes
status after repletion of fibronectin levels.155 with a long stertorous inspiration, and the patient enters a
Isolated reports exist for other modalities of treatment for postictal state, with a variable period of coma. Pulmonary
amniotic fluid embolism. In one patient, a serine protein- aspiration of gastric contents may complicate a seizure. The
ase inhibitor, FOY, was used to treat associated DIC.156 Nitric number of seizures varies from 1 or 2 to as many as 100 in
oxide and aerosolized prostacyclin have been used to treat severe, untreated cases. The causes of eclampsia are poorly
refractory hypoxemia.157,158 Clark et al.128 suggested the use understood. It is generally believed that cerebral vasospasm
of high-dose corticosteroids and epinephrine as useful thera- and ischemia result in eclampsia. However, cerebral edema,
peutic adjuvants, in light of the similarities of amniotic fluid hemorrhage, and hypertensive encephalopathy have also been
embolism to anaphylaxis. In management of coagulopathy implicated in its pathogenesis.165,166
of amniotic fluid embolism, Leighton et al.159 recently deter- Until proved otherwise, the occurrence of seizures dur-
mined that patients receiving recombinant factor VIIa had sig- ing pregnancy should be considered eclampsia. Conditions
nificantly worse outcomes than cohorts who did not receive simulating eclampsia should be considered (e.g., encephali-
rVIIa, thus recommending that rVIIa be used in patients only tis, epilepsy, meningitis, cerebral tumor, and cerebrovascu-
when the hemorrhage cannot be stopped by massive blood lar accident) only after ruling out eclampsia167 (Box 19-4).
component replacement.159 Recent evidence from clinical Computed tomography (CT) may be normal or may show evi-
case reports also suggests that institution of cardiopulmo- dence of cerebral edema, infarction, or hemorrhage. Bleeding
nary bypass (CPB) may improve the outcome of patients with occurs more frequently in elderly gravidas with pre-existing
severe amniotic fluid embolism. Use of transesophageal echo-
cardiography (TEE) during circulatory collapse confirmed the
presence of intracardiac embolus, leading to CPB and emer-
BOX 19-4 n CONSIDERATIONS IN ECLAMPSIA
gent thrombectomy.160,161
Eclampsia can occur during the antepartum, intrapartum, and
postpartum periods.
Pre-Eclampsia and Eclampsia Headache, visual disturbances, and epigastric or right upper quadrant
pain may be symptoms of impending eclampsia.
Pre-eclampsia complicates 6% to 8% of all pregnancies. Other Seizures have an abrupt onset, beginning as facial twitching, followed
conditions (eclampsia, HELPP, pulmonary edema) are not as by a tonic phase and clonic phase.
common but may coexist with pre-eclampsia and contribute The CT scan may be normal or may show evidence of cerebral
to significant morbidity and mortality in pregnant women. edema, infarction, or hemorrhage.
Management involves maintenance of airway, oxygenation, and
Eclampsia is a life-threatening emergency that occurs sud-
ventilation.
denly, most often in the third trimester near term. In approxi- Propofol, midazolam, and succinylcholine may be required to facilitate
mately 60% of pre-eclamptic patients, convulsions and coma oxygenation and ventilation.
precede delivery. Most postpartum cases occur during the first 24 Magnesium sulfate is the preferred drug for the definitive treatment
hours, but seizures attributed to eclampsia have been reported as of seizures.
Eclamptic patients should undergo expeditious delivery.
late as 22 days after delivery. Approximately 50% of all patients have
Regional anesthesia to facilitate labor and delivery can be considered
evidence of severe pre-eclampsia. In the remaining half, the clas- in patients who are seizure free, conscious, and rational in behavior,
sic triad of pre-eclampsia (hypertension, proteinuria, and edema) with no evidence of increased intracranial pressure and absence of
may be absent or mildly abnormal.162 Incidence of eclampsia coagulopathy.
varies widely in the literature (1:100 to 1:3448 pregnancies).
hypertension and may result in death or permanent disability. be extubated at the conclusion of surgery if awake and con-
Other neurologic abnormalities include temporary blindness, scious. On the other hand, if general anesthesia was under-
retinal detachment, postpartum psychosis, and other transient taken in a woman who was not conscious initially, consider
neurologic deficits.151 The electroencephalogram (EEG) is also leaving the patient intubated and transferring her to inten-
abnormal, showing focal or diffuse slowing, as well as focal or sive care for BP control and controlled weaning from assisted
generalized epileptiform activity.166 ventilation while assessing neurologic recovery. Prolonged
Posterior reversible encephalopathy syndrome (PRES) has unconsciousness should prompt further evaluation with CT.
been associated with pre-eclampsia and eclampsia. This neu- Magnesium should be continued until BP normalizes and cen-
rotoxic state is accompanied by a unique brain imaging pat- tral nervous system (CNS) hyperexcitability disappears.
tern. The mechanism behind the developing vasogenic edema
and CT or magnetic resonance imaging (MRI) appearance of
PRES is not known. Two theories have historically been pro- HELLP Syndrome
posed: severe hypertension leads to failed autoregulation, with
subsequent hyperperfusion, endothelial injury, and vasogenic The HELLP (hemolysis, elevated liver enzymes, and low plate-
edema; or vasoconstriction and hypoperfusion lead to brain lets) syndrome is believed to be a clinical state that may rep-
ischemia and subsequent vasogenic edema.168 resent an advanced form of pre-eclampsia (Box 19-5). Based
on the platelet count, the HELLP syndrome is divided into
MANAGEMENT OF ECLAMPSIA three classes. Class I patients have a platelet count of less than
Supplemental oxygen should be delivered immediately during 50,000/mm3, class 2 is between 50,000 and 100,000/mm3, and
seizure. A soft nasopharyngeal airway may facilitate oxygen- class 3 is more than 100,000/mm3.170 The etiology of HELLP
ation during seizure. Ventilation may be assisted once seizures remains elusive. Its clinicopathologic manifestations result
end. Simultaneously, precautions should be observed to mini- from an unknown insult that leads to intravascular platelet
mize chances of gastric aspiration. Midazolam in incremental activation and microvascular endothelial damage.
doses up to 20 mg may be necessary, either to suppress sei- Hemolysis, defined as the presence of microangiopathic
zures or to facilitate further treatment in a combative patient. hemolytic anemia, is the highlight of the disorder. Sibai171
Occasionally, propofol and succinylcholine may be required noted a lack of consensus regarding the diagnostic features of
to facilitate oxygenation and ventilation. Immediate monitor- HELLP syndrome and suggested these diagnostic criteria: (1)
ing should include pulse oximetry, electrocardiogram (ECG), hemolysis, defined by an abnormal peripheral blood smear
and blood pressure (BP) recordings. Left uterine displacement and an increased bilirubin level (1.2 mg/dL or greater); (2) ele-
should be maintained throughout the resuscitative effort and vated liver enzymes, defined as an increased aspartate trans-
until delivery of the infant. aminase (aminotransferase, AST) level of at least 70 U/L and a
Magnesium sulfate is the preferred drug for the definitive lactate dehydrogenase (LDH) level greater than 600 U/L; and
treatment of seizures. After an immediate loading dose of 4 to (3) a low platelet count (<100,000/mm3). A diagnosis of full
6 g infused intravenously (IV) over 20 to 30 minutes, a mainte- HELLP syndrome is made only if all three criteria are present.
nance dose of 1 to 2 g/hr is initiated, assuming that the patient A diagnosis of partial HELLP syndrome is made if only one or
has adequate urine output. Hourly monitoring of urine output, two criteria are present, and a diagnosis of severe pre-eclampsia
regular evaluation of deep tendon reflexes, and observation of is made if none is present. Patients with full HELLP syndrome
respiratory rate should be implemented to guard against mag- are likely to have a higher incidence of stroke, cardiac arrest,
nesium toxicity. DIC, placental abruption, need for blood transfusion, pleural
Unless otherwise contraindicated, eclamptic patients effusion, ARF, and wound infections.172 Most cases of HELLP
should undergo expeditious delivery. The common indica- syndrome occur preterm, but 20% may present postpar-
tions for cesarean delivery include fetal distress, placental tum. Patients who develop HELLP postpartum have a higher
abruption, prematurity with an unfavorable cervix, persistent
seizures, and persistent postictal agitation.
Regional anesthesia to facilitate labor and delivery can be BOX 19-5 n CONSIDERATIONS IN HELLP SYNDROME
considered in patients who are seizure free, conscious, and
Hemolysis, elevated liver enzymes, and low platelets characterize the
rational in behavior, with no evidence of increased intracra-
HELLP syndrome.
nial pressure (ICP) and absence of coagulopathy. Moodley Classification is based on platelet count:
et al.169 found no difference in maternal and neonatal outcomes
n Class I (<50,000/mm3)
when comparing epidural anesthesia with general anesthe- n Class II (50,000-100,000/mm3)
sia for cesarean delivery in conscious women with eclampsia. n Class III (>100,000/mm3)
Unconscious or obtunded patients, or those with evidence of
Etiology remains elusive.
increased ICP, should have general anesthesia in line with neu- Delivery represents the only definitive treatment and should be
rosurgical anesthesia recommendations. Hyperventilation can undertaken immediately, with few exceptions.
be initiated soon after the delivery of the infant to minimize Dexamethasone increases the number of platelets significantly.
the effect of low Paco2 on the uterine arteries. The patient can
incidence of pulmonary edema and ARF.173 A recent analy-

sis of placental pathology found no significant differences BOX 19-6 n PULMONARY EDEMA IN PRE-ECLAMPSIA
between placentas obtained from patients with pre-eclampsia About 3% of women with severe pre-eclampsia develop pulmonary
or with HELLP, except for statistically more frequent retropla- edema.
cental hematoma in the pre-eclampsia group than the HELLP Pulmonary edema results from low colloid oncotic pressure, increased
intravascular hydrostatic pressure, and increased pulmonary
group.174
capillary permeability.
Studies show better maternal outcome with administration Edema is likely to occur 2 to 3 days postpartum.
of 10 mg of dexamethasone IV at 12-hour intervals until dis-
Treatment
ease remission is noted.175 Dexamethasone is continued until
n Management of underlying cause (overhydration, sepsis, cardiac
BP is 150/100 mm Hg or less, urine output is at least 30 mL/ failure)
hr for 2 consecutive hours without a fluid bolus or the use of n Administration of supplemental oxygen and diuretic with fluid
diuretics, platelet count is greater than 50,000/mm3, LDH level restriction

begins to decline, and the patient appears clinically stable. n Pulmonary artery catheter placement may occasionally facilitate
further management (vasodilators, inotropes).

When these occur, IV dexamethasone is decreased to 5-mg
n Tracheal intubation and ventilation may be required in the
doses 12 hours apart.175 minority of cases where respiratory failure complicates refractory
Compensated DIC may be present in all patients with the pulmonary edema.
HELLP syndrome.176 In addition, patients with this syndrome
may experience RUQ pain and neck pain, shoulder pain, or
relapsing hypotension caused by subcapsular hematoma and administration may prove beneficial if the colloid oncotic
intraparenchymal hemorrhage. Because abnormal liver func- pressure-PCWP gradient is lowered. In rare cases, tracheal
tion studies do not accurately reflect the presence of liver intubation and ventilation may be required if respiratory fail-
hematoma and hemorrhage, this subset of patients, particu- ure complicates refractory PE.183 ARDS can complicate severe
larly if associated with thrombocytopenia, should undergo pre-eclampsia, especially if pulmonary capillary permeability
CT examination of the liver.177 An abnormal hepatic imaging is increased.184
finding was noted in 77% of patients with a platelet count of
20,000/mm3 or less.
Abnormal Placentation and Massive Hemorrhage
Delivery represents the only definitive treatment of the
HELLP syndrome and should be undertaken immediately, Despite the overall decrease in maternal mortality, peripar-
with few exceptions. Conservative treatment that includes bed tum hemorrhage is still a major cause of maternal morbidity
rest, antithrombotic agents, and plasma volume expansion is and mortality, accounting for about 10% of maternal deaths.185
typically unsuccessful and often results in early maternal or Hemorrhage is one of the leading causes of maternal mortal-
fetal deterioration. In the presence of prematurity, cortico- ity in the United States and is the leading cause of maternal
steroids may be administered to accelerate lung maturity, fol- death in developing countries. Many conditions predispose to
lowed by delivery 48 hours later. Administration of high doses hemorrhage; abnormal placentation is one of the major causes
of corticosteroids may increase platelet numbers to allow and may be increasing at the fastest rate. An understanding
placement of a regional anesthetic, especially if a latency of of the risk factors, identification, and obstetric management
24 hours is achieved before delivery.178 of abnormal placentation may prove lifesaving for the mother
and fetus, because unexpected hemorrhage often occurs with
little or no warning and may be massive. General or regional
Pulmonary Edema in Pre-Eclampsia anesthesia could be used for cesarean delivery (Table 19-5).
Three percent of women with severe pre-eclampsia develop Unlike other places in the body where hemostasis depends
pulmonary edema (PE)179 (Box 19-6). PE results from low col- on vasospasm and blood clotting, hemostasis at the placental
loid oncotic pressure, increased intravascular hydrostatic pres- site depends on myometrial contraction and retraction. At term,
sure, and increased pulmonary capillary permeability.180 Many approximately 600 mL/min of blood flows through the placental
PE cases develop 2 to 3 days postpartum, and thus patients site.186 As the placenta separates, the blood from the implantation
with pre-eclampsia must remain under careful surveillance site may escape into the vagina immediately (Duncan mecha-
in the immediate postpartum period. The resolution of PE nism) or may be concealed behind the placenta and membranes
requires management of the underlying cause (e.g., overhy- (Schultze mechanism) until the placenta is delivered.
dration, sepsis, cardiac failure). Echocardiography may be
required to exclude cardiogenic causes.181,182 The initial treat- PLACENTA ACCRETA
ment of PE includes supplemental oxygen, fluid restriction, Adherent pieces of placenta prevent effective contraction of
and administration of a diuretic. In a subset of patients, if no the myometrium and may cause bleeding. Placenta accreta
resolution of PE is in sight, PA catheter placement may facili- describes any placental implantation in which there is abnor-
tate further management. This includes vasodilator therapy to mally firm adherence to the myometrium of the uterine wall.
reduce preload or afterload and administration of dopamine It is the result of deficient decidual development resulting in
or dobutamine in women with evidence of LV failure. Colloid implantation of the placenta into the myometrium without
Modern ultrasonographic techniques and MRI are providing

TABLE 19-5 n Anesthetic Considerations for Patients
with Abnormal Placentation
a more reliable diagnosis of adherent placenta.
The diagnosis should also be suspected during attempts at
General Anesthesia Regional Anesthesia manual removal of the placenta without success or with con-
tinued bleeding. Typical attempts at removal do not usually
Invasive Could be inserted Need for sedation succeed because a cleavage plane between the maternal pla-
monitors after induction when to minimize
patient unaware discomfort
cental surface and the uterine wall cannot be formed, and
continued traction on the umbilical cord may lead to uterine
Blood loss Controlled hypotension Sympathectomy inversion and life-threatening hemorrhage. Successful control
may help minimize likely to decrease
of the bleeding may be challenging; the bleeding is unlikely to
blood loss blood loss
respond to uterotonic agents or uterine massage because the
Comfort Patient is more Sedation likely will uterus is unable to contract with retained placental tissue.
comfortable in the be needed, and Once the level of suspicion is high, exploratory laparot-
setting of blood there should be
transfusions and a low threshold
omy should be performed in cases of a vaginal delivery. In
decreased blood for general both vaginal and cesarean deliveries, prompt hysterectomy is
pressure anesthesia the treatment of choice, because 85% of patients will require
a hysterectomy. In patients diagnosed with placenta accreta
Airway Protected Sedation, mental
status, and volume in whom attempts at removal of the placenta are stopped, the
resuscitation may maternal mortality is low (3%), with an average blood loss of
compromise airway approximately 3500 mL. There are several case reports of liga-
tion of hypogastric, uterine, and ovarian arteries. However,
all these techniques have a highly variable success rate, and
intervening decidua basalis. Whereas in placenta accreta the massive blood loss with potential maternal morbidity and
placental villi are attached to the myometrium, in placenta mortality is four times higher if conservative management is
increta the placental villi invade the myometrium, as opposed employed.
to placenta percreta, where the placental villi penetrate through Selective transcatheter embolization of the pelvic arteries
the myometrium. The abnormal adherence may involve all or is an alternative to more invasive procedures and has shown
a few of the cotyledons (total vs. partial placenta accreta). The promise as a technique to preserve the uterus and fertility.190
predominant histopathologic feature is the absence of decidua Embolization could be performed prophylactically when mas-
with direct attachment or invasion of the cotyledon into sive hemorrhage is suspected, to decrease the blood flow to
the myometrium. Decidua deficiency is also partly respon- the uterus, even when the plan is to perform a hysterectomy.
sible for placenta previa and may account for the high inci- Transcatheter embolization consists of the preoperative place-
dence of their coexistence.187 Other causes of placenta accreta ment of balloon catheters in the internal iliac arteries and is
include prior uterine surgery, infection, and trauma because performed in the interventional radiology suite. The bal-
of the adverse effects on the endometrium. Uterine trauma loons are inflated at the time that hemorrhage is expected and
may result from dilation and curettage (D&C), endometritis, should be deflated once hemostasis is achieved, to maximize
leiomyoma, Asherman's syndrome, or prior pregnancies. The blood flow to the lower extremities. The procedure could also
overall incidence of placenta accreta in the obstetric popula- be used as a treatment for unexpected massive hemorrhage
tion is 1:533,188 but is greatly increased in those with a history in a patient who wants to preserve fertility. When properly
of placenta previa (1:26), a previous cesarean section (1:10), or used, embolization appears to be safe and effective, is mini-
both.189 The greater the number of previous cesarean sections, mally invasive, and has often been beneficial in avoiding
the greater is the risk for placenta accreta. hysterectomy.
The incidence of placenta accreta ranges from 0.26% in an A low threshold should be used in performing a hyster-
unscarred uterus, 24% in the presence of placenta previa and ectomy once massive hemorrhage develops. If intraoperative
one prior cesarean section, to 67% with four or more prior bleeding persists after peripartum hysterectomy despite suture
cesarean deliveries and placenta previa. Placenta accreta has ligation or cautery, collagen-derived products with or without
overtaken uterine atony as the most common reason for a thrombin impregnation (Gelfoam, Surgicel, FloSeal) can be
postpartum hysterectomy. More recent data demonstrate that topically applied. This can be especially helpful where bleed-
the most important risk factors are age (odds ratio/OR 1.14), ing involves raw surfaces or is adjacent to areas of engorged
previous cesarean delivery (OR 8.62 if >2, not significant if vessels. In the event of DIC, whether dilutional or consump-
only 1), and placenta previa (OR 51.42). No increased inci- tive, pelvic packing may be required, with the patient (laparot-
dence of placenta accreta was found in patients with history omy closed or open) transferred to the ICU until the adequate
of D&C or abortion.188 A high index of suspicion should be replacement of blood and clotting factors with blood products
raised in the parturient with placenta previa or prior cesar- such as red blood cells, fresh-frozen plasma, cryoprecipitate,
ean section, especially with an anterior placenta, because the and platelets can be achieved. The packing would be removed
diagnosis of placenta accreta may be difficult by ultrasound. later once the patient is deemed stable.
Massive blood loss is common with placenta accreta. Even increased risk for uterine rupture, but its results may be life
though antepartum recognition and elective hysterectomy are threatening. The relative risk of uterine rupture is threefold
likely to decrease blood loss and morbidity, significant hemor- to fivefold with spontaneous labor and labor induced with-
rhage may result from the increased vascularity of the gravid out prostaglandins, but an astonishing 15-fold when there is
uterus. Two large-bore IV lines should be started, cross- induction of labor with prostaglandins compared with elec-
matched blood should be available, and consideration given tive repeat cesarean birth. The incidence of infant death was
to invasive monitoring, including arterial and central venous increased 10-fold in the presence of uterine rupture.195 ACOG
lines. A regional technique is permissible in a patient requir- discourages the use of prostaglandins for cervical ripening or
ing gravid hysterectomy, as long as no significant hemorrhage for the induction of labor in women attempting VBAC.197
has occurred and adequate volume resuscitation is main- The guidelines that restricted trial of labor after cesarean
tained.191 The most challenging cases occur with the retention (TOLAC) to a specific parturient population and only in
of an adherent placenta after delivery of a neonate in a patient centers with staff immediately available to perform cesarean
without risk factors for placenta accreta, because sudden mas- delivery led to a decline in VBAC rate to 8.5% in 2006. As a
sive blood loss can happen with multiple attempts at manual result, ACOG issued less restrictive VBAC guidelines in 2010
removal of the placenta. The anesthetic technique in this situa- that emphasize patient autonomy.198 Women who have had
tion is different because major hemodynamic changes may be two previous cesarean births, with an unknown uterine scar
present in the parturient. It is highly recommended to assess or with twin gestation, are now allowed to attempt TOLAC.
the ability of the anesthesiologist to both manage the airway Although TOLAC is most safely undertaken in a facility with
and volume-resuscitate the patient simultaneously. We per- staff immediately available to perform a cesarean section,
form epidural anesthesia in parturients at high risk or with resources may not be available or the parturient may attempt a
known placenta accreta, but we ensure low likelihood of a dif- TOLAC at a smaller facility after a thorough risk/benefit analy-
ficult airway, adequate IV access, and low threshold to con- sis and a discussion with the obstetrician. A joint ASA-ACOG
vert to general anesthesia. If hypovolemia is suspected, general statement leaves the definition of “immediately available per-
anesthesia induction should be considered, to have earlier sonnel and facilities” to the discretion of the institution, based
control of the airway.192 Other reasons for conversion to gen- on available resources and geographic location.199
eral anesthesia include generalized patient discomfort due to Risk factors for rupture of the uterus include a tumultuous
prolonged surgery, difficult surgical conditions, and earlier labor, prolonged labor, infection, previous uterine manipula-
airway control before swelling results with massive fluid resus- tions (D&C or evacuation), midforceps delivery, breech ver-
citation. We previously reported peripartum airway changes sion, and extraction and uterine trauma. Signs and symptoms
during cesarean hysterectomy and fluid resuscitation that of uterine rupture include sudden abdominal pain, shock, vag-
gradually resolved over the next 2 days.193 inal bleeding, fetal distress, change of uterine contour, and loss
of a uterine contraction pattern. Some obstetric authorities
UTERINE RUPTURE used to discourage epidural analgesia for VBAC because of the
Cesarean delivery is the most common surgery performed in concern of masking the abdominal pain. However, only a high
the United States, with the most common reason being elective and dense epidural anesthetic such as used for cesarean sec-
repeat cesarean section. The increased risks of bleeding, infection would blunt the pain of uterine rupture. Regional anes-
tion, thromboembolism, and cost with cesarean section led thesia can be safely employed, and although it does not have
to encouraging vaginal birth after a cesarean section (VBAC), an effect on the success rate of a vaginal delivery, it is more
with an increase in VBAC rate from 6.6% in 1985 to 30.3% likely to encourage parturients to attempt TOLAC. It is best
in 1996. However, this rate has declined in the past decade to use dilute solutions of local anesthetic with opioids because
because major complications (uterine rupture, hysterectomy, a sudden incidence of abdominal pain in an otherwise com-
injury to uterine arteries, bladder, and ureter) and neonatal fortable patient in labor (TOLAC) with epidural anesthesia
mortality were reportedly higher in women attempting VBAC should suggest uterine rupture. Also, abdominal pain is one of
compared with elective repeat cesarean sections.194,195 Uterine the least reliable signs of uterine rupture, because pain may be
rupture may occur at the site of a prior uterine scar, usually minimal, particularly when a previous cesarean scar dehisces.
a previous cesarean section scar. A classic cesarean scar goes The best diagnostic signs for uterine rupture are changes in
through uterine muscle and is more likely to dehisce than a contraction pattern, changes in configuration of the abdomen,
low transverse cesarean scar. It was always believed that the and fetal distress. Continuous FHR monitoring is paramount
risk of uterine rupture in patients attempting VBAC was less for its early diagnosis. Rapid recognition and management are
than 1%. However, this rate may be as high as 1.5% with a necessary to prevent maternal and fetal death. Except in par-
low transverse incision and higher with other types of inci- tial rupture of a previous low transverse uterine scar, which
sions. VBAC is allowed only in cases of a low transverse scar. can be repaired under a spinal or epidural anesthetic, emer-
The American College of Obstetricians and Gynecologists gency hysterectomy is usually needed. This is likely to require
(ACOG) recommends that physicians caring for parturients rapid anesthesia induction, even in the presence of shock, to
attempting VBAC should be immediately available to pro- allow control of the hemorrhage. Importantly, spontaneous
vide emergency care.196 Not only are these parturients at an uterine rupture of an unscarred uterus, although much less
common (1:15,000) than rupture of a previous uterine scar, will be needed for both coagulation factor and fibrinogen
is more serious and catastrophic. It results in high maternal replacement, so a 1:1 ratio would be reasonable to correct DIC
mortality (≥50%) and fetal mortality (up to 80%) with massive provided results are followed and product selection is modi-
blood loss, often exceeding 15 units in severe cases. fied accordingly. We decrease or stop the plasma transfusion
when the patient's coagulation values approach normal. In the
MANAGEMENT OF MASSIVE HEMORRHAGE absence of significant hemorrhage, transfusion of blood com-
Adequate surgical hemostasis and careful fluid and blood ponents is rarely necessary unless hemoglobin (Hb) concen-
replacement are essential to achieve good hemodynamic con- tration is less than 6 g/dL, the international normalized ratio
trol. Increases in maternal blood volume and coagulation (INR) is greater than 1.5, the platelet count is less than 50/mm3
proteins compensate for the average blood loss, and parturi- or there is evidence of platelet dysfunction and microvascu-
ents are often able to tolerate 1000 to 1500 mL of blood loss lar bleeding, or the fibrinogen concentration is less than 80 to
without major hemodynamic changes.200 However, obstetric 100 mg/dL in the presence of microvascular bleeding.202
hemorrhage can occur rapidly, especially when difficulties The administration of recombinant human factor VIIa can
in placental separation arise, because 600 to 700 mL of blood be considered if intraoperative bleeding persists after peripar-
flows through the placental intervillous spaces each minute. tum hysterectomy and blood product replacement. Release
DIC may occur with little or no warning, in part because of from the blood bank at the Brigham and Women's Hospital
the mixing of fetal and maternal blood and other cellular requires a hematology consult and approval. This can only
products, and intensifies blood loss.201 Physiologic changes be done if the fibrinogen level is greater than 100 mg/dL, so
of pregnancy may allow signs of significant hemorrhage to be plasma transfusion and lab draws are essential.
concealed until sudden hypotension and tachycardia occur. Some modalities for blood conservation are especially help-
Urine output, heart rate, and BP assessments are useful in esti- ful in parturients who are at high risk for hemorrhage, who
mating the volume status. Aggressive volume replacement is refuse blood products, and who are scheduled for a planned
essential to maintain tissue perfusion and oxygenation. Early procedure. These techniques include autologous donation
consideration should be given to colloids and blood prod- (parturient's own blood) before the scheduled procedure,
ucts, along with a request for assistance, a second large-bore acute normovolemic hemodilution immediately before the
IV line, and rapid infusion equipment for transfusion. A type procedure (parturient's own blood is removed and replaced
and crossmatch for at least 2 to 4 units of PRBCs should be with an equal proportion of crystalloid or colloid), and intra-
considered when the potential for significant blood loss is operative cell salvage. Although reinfusion of blood contain-
likely, such as in cases of placenta accreta. Uncrossmatched, ing amniotic fluid is possible, intraoperative cell salvage has
type O, Rh-negative blood is rarely necessary if sufficient pre- been safely used with leukocyte depletion filtration to remove
cautions are taken to order blood products in advance, except amniotic fluid.204,205 These techniques are still in evolution,
when massive hemorrhage is unexpected and occurs in a short especially in parturients, and future studies need to validate
period. their utility and safety.206,207 However, these blood conserva-
Although the ASA Task Force on Perioperative Blood tion techniques should always be considered in patients who
Transfusion and Adjuvant Therapies recommends the trans- refuse blood products.
fusion of PRBCs, platelets, and fibrinogen only after the care- In summary, retention of an adherent placenta and a rup-
ful assessment of volume status, surgical conditions, and tured uterus can present with little or no warning and should
laboratory monitoring,202 recent reports with trauma patients be in the differential diagnosis of postpartum hemorrhage.
support the transfusion of 1 unit fresh-frozen plasma (FFP) Massive blood loss is common, and the anesthesiologist should
for every 1 unit RBCs.203 We believe that it is reasonable to take be prepared to provide massive volume resuscitation. Regional
this approach with obstetric patients because the majority with anesthesia can be safely and effectively used, but some situ-
severe postpartum bleeding will be in DIC and will lack both ations warrant general endotracheal anesthesia. Therefore,
fibrinogen and clotting factors from both consumption and identification of risk factors, antepartum recognition of uter-
blood loss. At the beginning of an emergency, the blood bank ine rupture, and early planning with multidisciplinary team-
should be able to supply 4 units of already-thawed plasma work are important.
immediately, plus additional plasma within 15 to 20 minutes.
PRBCs are available promptly, and it takes about 45 minutes
Peripartum Cardiomyopathy
to have cryoprecipitate ready for transfusion. Four units of
plasma contains about the same amount of fibrinogen as a Peripartum cardiomyopathy (PPCM) occurs rarely, with
pool of 8 to 10 bags of cryoprecipitate in a much larger vol- an exact incidence that remains unknown. In part because
ume. We developed a postpartum hemorrhage (PPH) algo- the definition of PPCM is disputed, and perhaps because of
rithm together with our obstetric and blood bank colleagues reporting bias or epidemiologic differences in different areas
using a 1:1 FFP/RBC ratio for massive obstetric hemorrhage of the United States and in different countries, rates from 1:100
(Figure 19-1). More products are ordered based on frequent to 1:15,000 live births have been reported.208 The generally
laboratory results (CBC, PT, PTT, fibrinogen), aiming for the accepted incidence in the United States is 1:3000 to 1:4000.209
target values stated in the algorithm. Many units of plasma There is variation by ethnicity, with twofold to threefold
Step 1
Obstetric anesthesia (OB) Blood bank
1. Call blood bank, state: 1. State: “We will tube 2 RBC units immediately
• “Obstetric emergency/need emergency release” and prepare a cooler.”
• Patient name (Emergency release if applicable)
• Medical record number
• Location
• Attending physician 2. Check sample status – advise OB
3. Tube 2 RBCs immediately

(Emergency release if applicable)
2. Send runner to blood bank (BB) for cooler 4. Prepare a cooler for runner:
6 RBC units
4 FFP units
3. Arrange RBC pickup at tube station
4. Draw CBC, PT/PTT, fibrinogen 5. Thaw 1 pool CRYO

• Call lab to make super-stat
6. Thaw 4 more FFP
5. Receive coolers. Call BB to order additional

products
Step 2
OB Blood bank
Before labs come back, transfuse: 1. Tube 1st CRYO pool as soon as prepared,
1. RBCs based on estimated blood loss (EBL) notify OB
2. 1 FFP unit for each RBC
3. 1 CRYO pool
After labs come back, transfuse: 2. Issue additional products as ordered

1. CRYO to fibrinogen > 100 mg/dL
If first fibrinogen level is
<100 mg/dL Order 2 more CRYO pools
100-200 mg/dL Order 1 more CRYO pool
2. RBCs to Hct > 21%

3. Single donor platelets (SDP) to platelet
count > 50,000/L
4. Plasma to PT/PTT < 1.5 times control
Recombinant activated factor VII (rFVIIa, NovoSeven) is not recommended as first-line therapy in
postpartum hemorrhage or disseminated intravascular coagulation (DIC). Can be considered as a late
intervention; please consult hematology fellow before ordering.
FIGURE 19-1 Postpartum hemorrhage (PPH) algorithm. RBC, Red blood cells; CBC, complete blood count; PT/PTT, prothrombin/
partial thromboplastin time; FFP, fresh-frozen plasma; CRYO, cryoprecipitate; Hct, hematocrit.
higher incidence in African Americans than Caucasians, and However, a recent review of 23 cases of pregnancy-associated
a lower incidence in Hispanics.210 cardiomyopathy compared to 100 cases diagnosed in the
Although classically viewed as a nongenetic type of dilated final month of gestation or postpartum found them to be
cardiomyopathy (DCM), several investigations now show indistinguishable.211
familial clustering of PPCM and an association with fami- The diagnosis is one of exclusion, because there are
lies demonstrating genetic forms of DCM. PPCM is charac- no pathognomonic signs or definitive diagnostic tests.
terized by onset of cardiac failure typically occurring late in Criteria used for establishing the diagnosis were formu-
gestation or, most often, in the first few months postpartum. lated by a National Institutes of Health (NIH) consensus
DCM (29% vs. 9%).217 The wide discrepancy in myocarditis

BOX 19-7 n DIAGNOSIS OF PERIPARTUM may be caused by differences in timing of biopsy and criteria
CARDIOMYOPATHY
for diagnosis.208 Other hypothesized pathophysiologic mecha-
All the following must be present: nisms include abnormal cytokines (e.g., tumor necrosis factor
n Cardiac failure occurring in the last month of pregnancy, or within alpha [TNF-α], interleukin-6, Fas/APO-1), abnormalities of
5 months postpartum relaxin, selenium deficiency, and genetic factors. An exciting
n Absence of an identifiable cause for the cardiac failure recent hypothesis with immediate implications for possible
n Absence of heart disease before the last month of pregnancy
therapeutic interventions involves an abnormal cleavage prod-
n Echocardiographic evidence of left ventricular (LV) systolic
uct of prolactin. Mice with an induced deficiency of a tran-
dysfunction:
n LV ejection fraction <45% or
scription factor (STAT3) in myocytes develop PPCM thought
n Fractional shortening <30% or to arise from increased activity of cardiac cathepsin D, which
n LV end-diastolic dimension >2.7 cm/m2 cleaves prolactin into an antiangiogenic and proapoptotic hor-
mone that leads to myocyte damage. Preliminary data from a
Data from Pearson GD, et al: JAMA 283:1183-1188, 2000. small human trial of bromocriptine, which inhibits prolactin
release from the pituitary, demonstrated better LV functional
recovery, reduced mortality, and better functional status at 6
months.218
panel209 (Box 19-7). The European Society of Cardiology Treatment of peripartum cardiomyopathy is largely sup-
has recently embraced more liberal language regarding tim- portive and aimed at establishing normal hemodynamics,
ing of onset.212 avoiding further deterioration of cardiac function, and avoid-
The differential diagnosis of PPCM includes many other ing complications of heart failure, such as thromboembolism.
causes of the clinical signs, such as severe hypertension, dia- In the minority of cases appearing antepartum, consideration
stolic dysfunction, pulmonary or amniotic fluid embolism, must be given to possible adverse effects on the fetus. Sodium
exacerbation of valvular heart disease, infection, and toxic/ and water restriction and diuresis are initial steps. Digoxin has
metabolic disorders. A wide variety of “risk factors” have improved symptoms and is safe in pregnant patients. Beta-
been suggested, but because PPCM is so rare, few are widely adrenergic blockade, especially with vasodilating antagonists
accepted or strongly associated. The strongest factors include (e.g., carvedilol), improves hemodynamics and reduces mor-
maternal age over 30, African American ethnicity (Hispanics tality in idiopathic DCM, although efficacy in PPCM has not
appear relatively less susceptible), and multiple gestation; less been conclusively demonstrated.209,219 The addition of pent-
clear factors include multiparity, family history, long-term oxifylline (which decreases TNF-α) to conventional therapy
tocolysis, pre-eclampsia, cocaine abuse, malnutrition, and with diuretics and β-blockers significantly improved outcome
infection.208 In Africa, some populations demonstrate a much in PPCM patients.220 Angiotensin-converting enzyme (ACE)
higher incidence of PPCM (1%), apparently associated with inhibitors are recommended in other DCMs but cause renal
peripartum and postpartum consumption of large salt loads toxicity in the fetus or breastfed newborn. Hydralazine is
and high ambient temperature.213 the vasodilator of choice.209 Anticoagulation is generally rec-
The clinical presentation of PPCM is similar to other forms ommended if the left ventricular ejection fraction (LVEF) is
of DCM, although many symptoms are common in normal greatly decreased. Heparin, low-molecular-weight heparin,
pregnancies, often delaying the diagnosis in antepartum pre- and warfarin have been used; warfarin is generally reserved
sentations. Patients may complain of dyspnea, orthopnea, for postpartum patients because of teratogenic effects in early
cough or hemoptysis, generalized fatigue, and chest or abdom- pregnancy. However, use of warfarin in late pregnancy, when
inal pain. Physical findings include peripheral edema, crackles PPCM occurs, has not been shown to be harmful. All types
on pulmonary auscultation, jugular venous distention, a third of anticoagulants may be safely used in postpartum women,
heart sound, and a mitral regurgitation murmur.214 ECG and including breastfeeding mothers, because none is secreted in
chest films show typical signs of cardiomyopathy, including breast milk.209
tachycardia, atrial ectopy, nonspecific ST-segment and T-wave Other therapies of possible efficacy include maneuvers
changes, cardiomegaly (LV hypertrophy, left atrial enlarge- designed to ameliorate myocarditis, including immunosup-
ment), and pulmonary edema. As noted earlier, echocardiog- pressive drugs such as prednisone and azathioprine221 or
raphy shows signs of LV systolic dysfunction. intravenous immune globulin (IVIG).222 As noted earlier,
The pathophysiology of PPCM remains unknown. One inhibition of prolactin is a promising experimental therapy.
prevailing theory suggests that myocarditis of viral or auto- Cardiac transplantation has been described, including the use
immune origin is responsible for the LV failure. Some series of left ventricular assist devices (LVAD) as bridges to trans-
have found a high incidence (80%) of myocarditis on endo- plant.223 Because the course of LV recovery is variable but
myocardial biopsy,215 but others found an incidence of less often rapid, implantable cardioverter-defibrillators (ICDs)
than 10%, similar to age- and gender-matched controls with are best reserved for patients with persistent poor LV func-
idiopathic cardiomyopathy.216 Still others have found the inci- tion, and temporizing measures such as automatic external
dence of myocarditis to be greater in PPCM than in idiopathic defibrillators (AEDs) are used in high-risk patients early in
the course.210 Successful pregnancy after transplantation has

been reported.224 However, deterioration of LV function is BOX 19-8 n CARDIOPULMONARY RESUSCITATION
IN PREGNANT PATIENTS
common in patients with incomplete recovery after the initial
presentation. Basic Life Support
Prognosis is poor unless rapid normalization of LVEF No change in technique of chest compressions.
Noninvasive ventilation complicated by anatomic and physiologic
occurs (<6 months). Mortality ranges from 25% to 50% in
changes of pregnancy.
patients with PPCM, although more recent series indicate bet- Early intubation recommended.
ter outcomes than historical series.209,225 Survivors whose ven- Left uterine displacement essential (folded clothing, linens, rescuer's
tricular function returned to normal have reduced contractile knees, Cardiff wedge).
reserve and may still experience further deterioration with Advanced Cardiac Life Support
subsequent pregnancies.226 No change in advanced cardiac life support (ACLS) protocols.
Anesthetic management of an undelivered parturient with No change in defibrillation techniques or voltages.
initial or recurrent PPCM has been described, but only in iso- Caution when using paddle electrodes on enlarged breasts to avoid
shocking rescuers.
lated case reports. In most patients, anesthesiologists have used
Obstetric anesthesiologist is logical “code leader.”
continuous spinal or combined spinal-epidural analgesia.227–231 Consider open-chest massage or cardiopulmonary bypass for
Invasive monitoring with an arterial catheter and a central reversible conditions not responding to conventional ACLS.
venous or PA catheter has generally been recommended as Delivery of Infant
well.227–232 Active anticoagulation may contraindicate regional Delivery within 5 minutes enhances intact neonatal survival.
anesthesia. One case report described general anesthesia with Delivery may improve success of maternal resuscitation.
target concentration–controlled propofol and remifentanil for Incision at 4 minutes of ACLS, with delivery at 5 minutes.
emergency cesarean section in a PPCM patient in active labor.233
Another described cesarean delivery with etomidate and suf-
entanil with good maternal and fetal outcomes.234 PPCM has pregnant basic life support (CPR) is essentially nonpregnant
also first appeared during anesthetic management for cesarean basic life support. Mouth-to-mouth, pocket mask, or bag/
delivery, requiring intraoperative resuscitation.235,236 The hemo- mask ventilation should be established immediately, followed
dynamic picture should guide the management of patients who as soon as possible by endotracheal intubation and ventila-
have recovered from a previous episode, although the limited tion. Noninvasive ventilation is complicated by the higher
cardiac reserve in these patients should be considered.232 O2 consumption, reduced chest compliance, pressure on the
diaphragm by the enlarged uterus, enlarged breasts, obesity,
and potential regurgitation of gastric contents associated with
Cardiac Arrest and Cardiopulmonary
pregnancy.237 Successful use of the laryngeal mask airway in
Resuscitation
the setting of failed airway in an obstetric emergency has been
Cardiac arrest occurs at an estimated rate of 1:20,000 to described.240 Chest compressions should begin promptly, fol-
1:30,000 late pregnancies.237,238 Unfortunately, maternal sur- lowed by advanced cardiac life support (ACLS) techniques, as
vival is rare, averaging just 7%.238 Causes of cardiac arrest the clinical situation dictates.
in pregnancy include hemorrhage, embolism (air, amniotic A vital aspect of CPR in pregnancy is the maintenance of
fluid), complications of pre-eclampsia, PPCM, pre-existing uterine displacement to facilitate venous return to the heart.
cardiac disease (e.g., coronary syndromes, valvular disease, Any convenient soft object (blanket, towel, pillow, cloth-
congenital defects, dysrhythmias), intracranial hemorrhage, ing) may be used as a wedge, placed under the patient's right
trauma, anaphylaxis, sepsis, local anesthetic toxicity, failed flank. Chest compressions have been found to be effective in
airway management, and hemodynamic effects of spinal and tilted patients up to 30 degrees, although less so than in supine
epidural anesthesia. Whereas the most common etiology patients.237 However, CPR is more effective when the patient
overall is hemorrhage, the most common conditions produc- is on a hard surface. For this reason, some suggest a purpose-
ing cardiac arrest in late pregnancy are embolism and hyper- built device known as the Cardiff wedge that tilts the patient
tension.239 As in any resuscitation situation, the fundamental on a rigid wooden structure with a lip on the dependent edge
goals are establishment of an effective airway and circulation to keep her from sliding off.241 A “human wedge” has also been
(basic CPR), followed by electrical and pharmacologic steps described in which the patient is tilted over the knees of a kneel-
to restore spontaneous circulation. The care of the pregnant ing person on the right side of the patient.242 A chair inverted
patient in cardiac arrest must also include consideration of the to rest on the seat and top of the back may also provide a firm,
physiologic changes of pregnancy and the welfare of the fetus, tilted support for the pregnant patient in cardiac arrest.238
if of viable gestational age (Box 19-8). Current American Heart Association (AHA) guidelines sug-
gest first attempting chest compressions in the supine position
BASIC LIFE SUPPORT with manual displacement of the uterus to the left, followed by
A fundamental principle in resuscitation of the arrested use of a wedge device if ineffective. Such manual displacement
pregnant patient is that the best way to care for both mother is as effective as tilting in nonarrest patients, and further, rescu-
and infant is to restore circulation to the mother.238 Thus, ers frequently overestimate the degree of tilt achieved.238
ADVANCED CARDIAC LIFE SUPPORT immediately, incision should occur at 4 minutes of arrest, and
The AHA recommends that no changes from standard ACLS delivery should be accomplished by 5 minutes.238,247 Follow-up
protocols be implemented when caring for pregnant patients. investigations by Katz et al.254 since their original recommen-
The reader is referred to standard texts to review such pro- dation247 continue to support better outcomes for both fetus
tocols.243 Unfortunately, studies indicate poor adherence and mother when cesarean delivery is initiated promptly.
to such guidelines in simulated cardiac arrest during preg- Some evidence suggests that perimortem cesarean delivery
nancy, and many recommend team drills to practice such has increased with improved awareness of these recommen-
infrequently used skills.244,245 In addition, special consider- dations, although timing usually exceeds 5 minutes, and over-
ations include theoretic concern regarding the appropriate all maternal and fetal outcomes remain poor.255
method for direct-current (DC) cardioversion. The enlarged A second reason to consider emergency cesarean delivery
breasts in pregnant patients may make access to the apex of during CPR is to improve the maternal condition.238,249,252–254
the heart difficult, particularly when the patient is severely This may be the case even when the fetus is previable, because
wedged. Furthermore, the anatomic and physiologic changes the mechanism of improvement may be both relief of aortoca-
of pregnancy may, in theory, alter the electrical properties of val compression and removal of the low-resistance uteropla-
the chest. However, measurements in pregnant women show cental circulation. The AHA recommends cesarean delivery
normal impedance.246 Others recommend caution to ensure even for very premature infants if the maternal condition does
that the left breast does not contact the hand of the person not appear immediately reversible, so that some chance of fetal
administering the shock.237 There is no known risk to the fetus survival is preserved and maternal resuscitation facilitated.238
of DC defibrillation or cardioversion. The AHA recommends
standard timing and energies for such maneuvers.238,243 Similar ADDITIONAL INTERVENTIONS
recommendations apply to pharmacologic interventions, Cardiopulmonary arrest during pregnancy is considered a
including large doses of α-agonists (epinephrine) to support possible indication for attempting open-chest cardiac mas-
the maternal circulation, even though these may theoretically sage, although the AHA does not specifically endorse its use.238
decrease uteroplacental blood flow.243 When anatomic factors limit the success of closed-chest CPR,
A logistical question concerns who should serve as the or the etiology of the arrest (e.g., PE, penetrating chest or
“code leader” for resuscitative efforts in pregnant patients. abdominal trauma) indicates this approach, thoracotomy and
Although the availability of various personnel and local open-chest cardiac massage may be considered. Retrospective
customs may dictate otherwise, we believe that a senior anes- data suggest invasive CPR is most likely to be successful when
thesiologist is the most appropriate clinician to fill this role. initiated relatively early in the resuscitation sequence. Also,
Anesthesiologists are skilled in airway management, IV access CPB has been successfully employed in select clinical situa-
techniques, and ACLS pharmacologic interventions. Other tions involving pregnant patients in cardiac arrest: hypother-
personnel often present at cardiac arrest situations, including mia from massive transfusion,256 bupivacaine cardiotoxicity,257
internists and surgeons, may not appreciate the physiologic and pulmonary embolism.250
changes of pregnancy and the impact on maternal resuscita-
tion as thoroughly as an obstetric anesthesiologist. Further, POSTRESUSCITATION CONSIDERATIONS
the obstetrician should attend to the fetal status and make Restoration of spontaneous circulation may be accompanied
preparations for possible emergency cesarean delivery. by other problems, depending on the etiology of the arrest.
Therapeutic hypothermia has been described but is not spe-
DELIVERY OF THE INFANT cifically endorsed by the AHA.238 Liver rupture has been
Significant controversy surrounds the decision on whether reported after CPR in pregnant patients.258 Hemostasis during
and when to perform an emergency cesarean delivery during cesarean section in the setting of cardiac arrest may initially
cardiac arrest in pregnant patients. There are two reasons to be straightforward, due to shunting of blood away from the
consider such a drastic intervention. First, there is substantial uterus, but subsequently cause further hemodynamic compro-
evidence from retrospective reviews that fetal outcome greatly mise after resuscitation.239 Management of brain-dead moth-
improves with cesarean delivery when maternal resuscitative ers with spontaneous circulation and undelivered infants has
efforts are not rapidly successful. In a review of 61 perimor- also been reported.259
tem cesarean sections performed in the 20th century through
the mid-1980s, Katz et al.247 reported 100% of the 42 infants
delivered within 5 minutes of maternal arrest survived with CONDITIONS COMPLICATING REGIONAL
no neurologic sequelae. As the interval from arrest to deliv- ANESTHESIA
ery lengthened, the chance of survival decreased and the
Regional Anesthesia and Anticoagulation
incidence of severe neurologic damage increased among sur-
vivors. When the interval exceeded 15 minutes, intact survival Pregnancy is a prothrombotic state with an increase in
was rare. Most authors continue to advocate early deliv- most coagulation factors (except XI and XIII, which are
ery of the viable infant when initial maternal resuscitation is decreased) and a decrease in clot inhibitors such as protein S.
unsuccessful.248–253 Preparations for operation should begin The hypercoagulable state of pregnancy is also characterized
by increased platelet hemostatic capacity, despite a decreased

TABLE 19-6 n Comparison of Unfractionated Heparin
platelet count. Fibrinogen increases by as much as 50%.100 and Low-Molecular-Weight Heparin
Prothrombin and the thrombin-antithrombin complex are
also elevated in normal pregnancies, whereas fibrinolysis Unfractionated Low-Molecular-
is diminished. This is demonstrated by elevated levels of Heparin Weight Heparin
plasminogen activator inhibitor 1 and 2.260 In addition, the
Molecular 3000 to 30,000 1000 to 10,000
increase in estrogen that accompanies pregnancy is a well- weight daltons daltons
known prothrombotic cause.261 The tendency toward exag-
gerated coagulation is worsened by anatomic factors, such Placental None None
passage
as the decrease of the blood flow in the lower extremities by
the gravid uterus, a condition worsened in the supine posi- Anti–factor Xa/ 1:1 Greater than 2:1
tion. Furthermore, the increased maternal vascular volume factor IIa ratio
and decreased ability to exercise lead to venous conges- Bioavailability About 30% Close to 100%
tion of the lower extremities and an impediment to venous
return. Maternal conditions such as preterm labor and pla- Half-life 1 to 2 hours 3 to 6 hours
centa previa may lead to prolonged periods of bed rest and Measurement of Activated plasma Anti–factor Xa
further predispose the patient to lower extremity venous activity thromboplastin activity
thrombosis. time
Hypercoagulable states are common in the general popula- Clearance Saturable cellular Renal
tion, with some reports demonstrating that 5% of whites are mechanism;
heterozygous for factor V Leiden, a point mutation of factor V dose dependent
that renders it resistant to activated protein C. Other, less com- Protamine Neutralizes Partial reversal
mon, but more severe hypercoagulable states include factor V response activity from reduced
Leiden homozygosity and deficiencies of protein S, protein binding
C, and antithrombin III.262 Many of the low-risk thrombo-
philias, such as heterozygosity for factor V Leiden, are silent
until pregnancy, when they may become manifest as a result anticoagulation may lead to an exaggerated anticoagulation in
of the imbalance between the prothrombotic and antithrom- the fetus. Nevertheless, warfarin continues to be the anticoag-
botic forces. Initial manifestations of prothrombotic condi- ulant of choice in parturients with prosthetic heart valves; no
tions during pregnancy may include the first presentation of data document the benefits of subcutaneous unfractionated
deep vein thrombosis, repeated missed abortions, and recur- heparin or LMWH in this patient population.270 Prosthetic
rent late fetal losses.263–265 Prophylactic anticoagulation may be heart valve thrombosis and maternal and fetal deaths have
indicated in some cases to prevent venous or placental throm- been reported with LMWH use.272,273
bosis, because improved placental blood flow is likely to lead Vitamin K is required for the formation of γ-carboxyglutamic
to better pregnancy outcomes. acid in the liver. The absence of this amino acid interferes with
Common anticoagulation options include warfarin, the synthesis of vitamin K–dependant factors (e.g., II, VII, IX,
unfractionated heparin, and low-molecular-weight heparin X). The prolongation of the prothrombin time (PT) is seen
(LMWH) (Table 19-6). Knowledge of the pharmacokinet- as early as 24 to 36 hours after the first warfarin dose, and it
ics and pharmacodynamics of these agents is essential for the usually reflects the absence of factor VII. Warfarin is usually
practitioner involved in the care of parturients, leading to a stopped 5 days before a regional anesthetic; it generally takes
better understanding of the implications on the obstetric and 4 days for INR to reach 1.5 in most patients. The INR should
anesthetic management. Current guidelines for regional anes- be measured before a neuraxial technique,266 with recom-
thesia and anticoagulation266,267 are better used to complement mended levels of 1.4 or less for single-shot spinal anesthesia
rather than to replace the understanding of the pharmacology and 1.2 or less for epidural anesthesia.267 Neuraxial catheters
of common anticoagulants during the puerperium. should be removed when the INR is less than 1.5.266
WARFARIN UNFRACTIONATED HEPARIN

Warfarin, a competitive inhibitor of vitamin K, is rarely used Unfractionated heparin is a strongly acidic, anionic, sulfated
during pregnancy because it readily crosses the placenta, is a mucopolysaccharide with a high molecular weight (average
first-trimester teratogen, and may cause fetal intracranial hem- 3000-30,000 daltons) that prevents placental passage and that
orrhage during the third trimester.268–270 It is most important makes it, along with other forms of heparin discussed later, the
to avoid warfarin during weeks 6 to 12, the period of organ- anticoagulant of choice during pregnancy.274,275 Unfractionated
ogenesis, and the last 2 weeks of pregnancy to diminish the heparin has a unique pentasaccharide sequence (only one
risk of warfarin embryopathy and bleeding in the mother and third of heparin molecules) that is responsible for the antico-
infant.270,271 The fetus has a smaller concentration of vitamin agulation properties by activating a conformational change in
K–dependent factors, and therefore normal targeted maternal antithrombin III (AT-III), leading to an accelerated interaction
between AT-III, thrombin (factor IIa), and factor Xa. Heparin pregnancy. High doses of unfractionated heparin may be used
leads to a similar inhibition of factors IIa and X (1:1 ratio). In throughout the pregnancy or, more frequently, after 36 weeks'
addition, although to a lesser degree, unfractionated heparin gestation at the time when LMWH is discontinued.
catalyzes the inactivation of factors IIa, IXa, Xa, XIa, and XII. The American Society of Regional Anesthesia (ASRA)
It also indirectly affects the thrombin-mediated activation of developed guidelines for the performance of neuraxial tech-
factors V and VIII, the end result being a decrease in impor- niques in the anticoagulated patient in 1996, and these guide-
tant cofactors (Va and VIIIa) in the coagulation cascade. lines were updated in 2003 and 2010.266 ASRA based these
Unfractionated heparin is cleared from the circulation rap- guidelines on the available scientific information, but in some
idly, because high-molecular-weight species are cleared more cases this information may be sparse. In addition, guidelines
rapidly than low-molecular-weight species. It has a saturable are recommendations and not standards or absolute require-
cellular mechanism of clearance through receptors on endo- ments. They are based not only on scientific information
thelial cells and macrophages, with a rapid saturable mech- but also on synthesis of expert opinion and clinical feasibil-
anism at low doses, a combination of rapid saturable and ity data. Variances from recommendations may be acceptable
dose-dependent mechanisms at therapeutic doses, and a based on the physician's judgment, and specific outcomes can-
much slower first-order mechanism through the kidneys that not be guaranteed by following these recommendations.266,267
is nonsaturable and dose independent with high doses. This Moreover, clinical and scientific information and evolving
dose-dependent mechanism of clearance leads to nonlinear clinical practices may modify these guidelines with time.
pharmacodynamic properties that affect the intensity and The ASRA guidelines for the anesthetic management of
duration of action of unfractionated heparin, most noticeable the patient receiving unfractionated heparin state that per-
when high doses are used.276 In addition, the nonlinear phar- formance of a neuraxial technique should proceed for at least
macodynamic properties of unfractionated heparin lead to an 1 hour before systemic IV anticoagulation with unfraction-
unpredictable bioavailability when injected subcutaneously, a ated heparin. Systemic IV anticoagulation with unfractionated
condition that is easily noticed when low-dose subcutaneous heparin should be discontinued 2 to 4 hours before a neur-
(SC) injections are used. Its bioavailability ranges from 30% axial technique or epidural catheter manipulation (includ-
with low doses to 100% with very high doses (>35,000 U). ing removal).266 In addition, the coagulation status should be
Although very high doses of SC unfractionated heparin have evaluated with aPTT, which must normalize before epidural
a bioavailability similar to IV injection, with peak levels at catheter insertion or removal. Despite the limited risk for epi-
3 hours (range, 2-4 hours) after injection, its duration of action dural hematoma formation when SC unfractionated heparin
is much less predictable, reported as longer than 24 hours is combined with neuraxial techniques, we prefer to perform
after injection.277 Other causes of an exaggerated response to this technique either longer than 4 hours after injection of
unfractionated heparin include prolonged therapy and its use SC heparin (half-life, 2-4 hours) or before its administration
in debilitated patients. The half-life of IV unfractionated hepa- (≥1-hour interval). However, ASRA states that there does not
rin is also affected, although to a lesser degree, by its nonlinear appear to be an increased risk with neuraxial block in the pres-
pharmacodynamic properties. ence of SC unfractionated heparin unless higher-than-average
Knowledge of the pharmacodynamic properties of unfrac- doses (>10,000 daily or >twice daily) are used. Administration
tionated heparin may be more important than laboratory tests. to small or weak patients may result in a prolongation of the
The activated partial thromboplastin time (aPTT) response to aPTT. The addition of other medications (e.g., NSAIDs, aspi-
heparin during pregnancy is attenuated secondary to increased rin, oral anticoagulants) and other forms of heparin that affect
levels of factor VIII and fibrinogen, despite significantly ele- the coagulation cascade may increase the risk of epidural
vated heparin levels.276,277 The use of small-dose (≤5000 U) SC hematoma when SC unfractionated heparin is used concomi-
unfractionated heparin for prophylaxis does not usually pro- tantly with a neuraxial technique.
long aPTT, and blood levels are not typically monitored. The
use of SC unfractionated heparin for more than 5 days may LOW-MOLECULAR-WEIGHT HEPARIN
lead to a decrease in the platelet count. However, the aPTT Low-molecular-weight heparin (1000-10,000 daltons) does
may be a better predictor of unfractionated heparin levels, not cross the placenta,278 is formed by controlled depolymer-
compared with pharmacodynamic properties, when very ization of unfractionated heparin, and has the same penta-
high SC doses are used. We recommend checking the aPTT saccharide sequence (potentiates action of antithrombin).
of a parturient receiving high-dose SC unfractionated heparin Overall, however, LMWH has a lower number of chains with
on arrival at the labor floor and waiting for the result before greater than 18 saccharide units (one half to one fourth of
performing a neuraxial technique. The anticoagulant effect LMWH fragments), providing a greater anti–factor Xa/anti–
of high doses, as reflected by the aPTT, may persist for up to factor IIa ratio.277,279 The 18 saccharide units are required for
28 hours after the last injection. In addition, a platelet count the inhibition of factor IIa but not factor Xa. Different LMWHs
is recommended for any parturient who received unfraction- have different anti–factor Xa/factor IIa activity (e.g., 2.7:1 for
ated heparin for more than 4 days. It is important to realize enoxaparin vs. 2.1:1 for dalteparin) but have equivalent antico-
that parturients at risk for deep vein or placental thrombo- agulation on clinical practice.279,280 Exogenous protamine com-
sis are maintained on some form of heparin for most of the pletely reverses the anti–factor IIa activity of LMWH but only
60% of the anti–factor Xa activity, because of reduced binding High-dose therapy is usually continued until 24 hours before
to its components. There are few trials comparing LMWHs induction of labor or a planned cesarean section.
with functional or structural heterogeneity, although there is a Low-molecular-weight heparin does not usually influ-
report from the orthopedic population, where enoxaparin was ence the aPTT but has an effect on anti–factor Xa values. An
similar to tinzaparin for deep vein thrombosis prophylaxis.280 anti–factor Xa chromogenic assay measures the activity against
Enoxaparin is discussed here because it is the most widely factor Xa but not that against factor IIa.284 Although minimal
used LMWH in the United States and the one most often cited anticoagulation is equivalent to values below 0.2 U/mL, pro-
in the literature. phylactic levels of 0.1 to 0.2 U/mL may suffice.285 It is not
Low-molecular-weight heparin has a lower binding to pro- usually measured for prophylactic doses because of the pre-
teins and endothelial cells and dose-independent clearance dictable dose response of LMWH. It may be prudent to check
compared with unfractionated heparin. The end result is a assay values in patients with obesity, low body weight, or renal
renal excretion that is dosage independent, a pharmacody- failure, because LMWH has renal elimination and is affected
namic effect that is proportional to the dose used and more by changes in body weight.284,285 Monitoring anti–factor Xa
predictable, and a better bioavailability at low doses. In addi- levels while using high doses of LMWH during pregnancy
tion, LMWH has a similar bioavailability after SC and IV injec- is recommended because of increases in glomerular filtra-
tion and is less immunogenic. Its dosage is adapted to body tion rate, clotting factor concentration, weight, and volume
weight, and there is a risk of accumulation with obesity and of distribution.286 Testing may also be useful with prolonged
renal failure.280 The half-life of LMWH is 3 to 6 hours after SC therapy and in parturients at high risk of bleeding or throm-
injection, is independent of the dose, and is longer than that bosis.285 Whether this assay confers any improved efficacy and
of unfractionated heparin. LMWH has peak activity in 3 to safety has not been confirmed, and interassay variability is an
4 hours and low interpatient variability because of its more issue.287 Further investigation is needed on this topic.
predictable dose response; its once-daily or twice-daily dosage The peak activity of LMWH is already reduced by the end of
is convenient for a parturient. LMWH has significant anti– the first trimester, further reduced by the beginning of the third
factor Xa levels 12 hours after injection because of its longer trimester, and returns to normal postpartum.286 Overall, there
half-life. It is controversial whether blood testing with an anti– is a volume expansion as a term pregnancy approaches, leading
factor Xa assay is helpful in monitoring response to LMWH to subtherapeutic levels. Occasionally, LMWH is changed to IV
or helpful before performing neuraxial techniques in the par- unfractionated heparin in high-risk patients and then discon-
turient anticoagulated with LMWH (see later). Despite their tinued 4 to 6 hours before delivery. This may create a problem
similar efficacy, LMWH is replacing unfractionated heparin if the patient requires a surgical procedure or placement of a
when prophylactic anticoagulation is needed in a parturient regional anesthetic, because a combination of both agents may
because of LMWH's improved bioavailability, longer half-life, result in an unpredictable anti–factor Xa and aPTT response.
more predictable dose response with greater activity against
factor Xa, and lower incidence of bleeding complications.281 EPIDURAL HEMATOMA
The safety and efficacy of LMWH in pregnancy is sup- Epidural hematoma is the most feared complication of neur-
ported by a review of 624 high-risk parturients with a prior axial techniques and is much more likely in the patient with
incidence of thrombosis receiving enoxaparin prophy- an inherited clotting abnormality or with use of anticoagu-
laxis.282,283 The congenital anomaly rate was 2.5%, (no greater lants. Although a review found 61 cases over an 88-year period
than in general population), with 1.1% fetal mortality unre- (1906–1994),288 in 2003 a U.S. Food and Drug Administration
lated to enoxaparin. There was only one enoxaparin-related (FDA) MedWatch found 60 cases over a 9-year period associ-
hemorrhage and a 1.3% incidence of recurrent maternal ated with the use of neuraxial anesthesia and LMWH ther-
venous thrombotic events (low for this high-risk popula- apy.289 There was one case of an epidural hematoma in a
tion). The study's conclusion, supported by an ACOG com- parturient receiving LMWH. The timing of LMWH admin-
mittee opinion,283 is that LMWH is safe and efficacious for istration, removal of the epidural catheter, and development
the prevention of thrombosis in high-risk parturients. Typical of the hematoma are unclear, and the patient had a temporary
prophylactic doses of LMWH during pregnancy are 40 mg lower extremity motor weakness that resolved spontaneously
subcutaneously (1 mg is equivalent to 100 units) of enoxa- without surgical intervention.
parin once daily, or 30 mg subcutaneously twice daily. These The 1994 review had only five cases in parturients (8.2%
dosages are used in parturients with a remote history of of cases),288 results that support the pregnancy-associated pro-
thrombosis but without a thrombophilia, low-risk thrombo- thrombotic state and its associated resistance to anticoagu-
philia, recurrent pregnancy loss, or a history of fetal demise. lation. These factors counteract the epidural venous plexus
Prophylactic doses are usually discontinued at 36 weeks' ges- engorgement during pregnancy, with an increased incidence
tation and changed to SC unfractionated heparin. High-dose of intravascular epidural catheters. An analysis of the obstet-
therapy typically ranges from 1 to 1.5 mg/kg of SC enoxapa- ric cases demonstrates that the majority occurred when the
rin twice daily and is indicated for the management of acute anticoagulant dosing was close to the placement of a neurax-
thrombosis, remote history of thrombosis and presence of ial technique or when patients were taking other medications
antiphospholipid antibodies, or a high-risk thrombophilia. that alter coagulation.
In addition, a UK review found no cases of epidural hema- association with an increased risk of epidural hematoma. The
toma in more than 9000 epidurals placed in parturients who first dose of LMWH should not be given earlier than 24 hours
were taking aspirin as possible prophylactic treatment for pre- postoperatively and not until 2 hours have elapsed since cath-
eclampsia. Although not found beneficial for the prevention eter removal.
of pre-eclampsia, aspirin was not associated with a signifi- The ASRA does not recommend the use of the anti–factor
cant increase in placental hemorrhages or in bleeding during Xa assay because this level is not predictive of bleeding risk.266
preparation for epidural anesthesia.290 Of note, the decreased However, anti–factor Xa activity of LMWH is affected by
incidence of epidural hematoma during pregnancy should body weight, renal dysfunction, pregnancy, and prolonged
not modify the recommendations regarding the use of neur- therapy.285,293 Therefore the dosage during pregnancy should
axial techniques in parturients with clotting abnormalities or take all these factors into account. We do not routinely check
in those being anticoagulated. In addition, it has been docu- this assay in parturients because no data support the safety of
mented that epidural catheter placement is as important as its neuraxial techniques with lower levels. We encourage more
removal, because both situations could lead to epidural hema- senior anesthesiologists to perform the block, and we prefer to
toma in the anticoagulated patient.288 use midline neuraxial techniques to minimize the risk of intra-
Epidural hematoma is a rare complication of neuraxial vascular epidural catheters.
techniques, with an incidence ranging from 1:220,000 after
spinal anesthesia to 1:150,000 after epidural anesthesia.288 It is OTHER AGENTS: FONDAPARINUX
more common in the presence of LMWH, with an incidence Newer anticoagulants are being compared to traditional anti-
as high as 1:3000 after a continuous epidural catheter and coagulants, such as unfractionated heparin, and are being
1:40,000 after a spinal anesthetic.279 It is important to use very used with an increased frequency, in part because of their sim-
low concentrations of local anesthetic to detect any change ilar safety profile and ease of administration.
in the patient's neurologic state. In addition, close follow-up Fondaparinux is a synthetic pentasaccharide that gained
of the neurologic status is essential after the removal of an FDA approval in 2001. It selectively binds to antithrombin,
epidural catheter. Clinical symptoms of epidural hematoma inducing a conformational change that significantly increases
include radicular back pain, bowel or bladder dysfunction, the anti–factor Xa activity without inhibition of factor IIa.294–
and sensory or motor deficits.291,292 Interestingly, and counter 296
Fondaparinux does not cross-react with antibodies against
to common wisdom, severe radicular back pain is rarely the heparin–platelet factor 4 complexes and therefore is unlikely
presenting symptom. MRI is the best diagnostic test for a sus- to lead to thrombocytopenia. It has a long half-life of about
pected epidural hematoma, and early decompressive laminec- 18 hours, which may be prolonged with renal failure, a per-
tomy is the treatment of choice. tinent fact for regional anesthesia. It takes at least 4 days to
The ASRA guidelines were developed in part because of eliminate this agent completely from the circulation, and
the increased incidence of epidural hematoma associated regional anesthesia should be avoided during this period.
with the use of LMWH and neuraxial techniques.266 These Fondaparinux is administered 2 hours after an atraumatic,
guidelines recommend discontinuing prophylactic doses of single spinal needle pass or epidural catheter removal.266
LMWH at least 10 to 12 hours before a regional technique, Indications for fondaparinux thromboprophylaxis d uring
and a single-dose spinal anesthetic is the preferred technique. pregnancy include allergic reactions to LMWH and deep
Therapeutic doses should be discontinued at least 24 hours vein thrombosis during LMWH therapy. Prophylactic doses
before a regional technique, and LMWH should not be started range from 2.5 to 5 mg and therapeutic doses from 7.5 to
until 2 hours after epidural catheter removal. The presence of 10 mg.294,295
blood at the time of epidural catheter placement may increase
the risk of bleeding into the epidural space and necessitates ANTIPLATELET MEDICATIONS
a delay of 24 hours before LMWH administration. Although Maternal age has increased with the use of ARTs, and some
epidural catheters are not usually kept for postoperative pain parturients may present with more comorbidities, including
management in parturients, in part because of the excellent coronary artery disease. Therefore, antiplatelet agents now
and prolonged analgesia with neuraxial morphine, it is impor- warrant discussion here. Aspirin (acetylsalicylic acid, ASA)
tant to be careful when these catheters are kept in place in par- and NSAIDs produce an acetylation of COX, leading to an
turients who require LMWH prophylaxis or therapy. Catheter inhibition of platelet aggregation. This inhibition lasts 1 to
management depends on total daily dose, timing of the first 3 days for NSAIDs and up to 7 to 10 days for ASA, which
postoperative dose, and dosing schedule.266 Epidural catheters produces a permanent defect in platelet aggregation. Several
can be safely continued while using prophylactic single daily reports have documented the use of neuraxial techniques in
dosing, as long as the LMWH is not started before 6 to 8 hours the presence of antiplatelet medications without any untow-
postoperatively, the second postoperative dose is no sooner ard effects, as mentioned earlier.290 Current recommendations
than 24 hrs after the first dose, and the catheter is removed state that use of neuraxial techniques in pregnant patients
10 to 12 hours after the last LMWH dose. Epidural catheters taking antiplatelet medications alone does not represent an
should be removed in parturients receiving twice-daily dos- increased risk for epidural hematoma.240 Antiplatelet drugs
ing before initiation of thromboprophylaxis because of its may augment the effect of other anticoagulants, however, and
therefore caution should be exercised when considering a Early emergency decompressive laminectomy, ideally
neuraxial technique on patients receiving more than one med- within 12 hours, is the treatment of choice for an epidural
ication that affects coagulation.266,267 hematoma. Recent UK data demonstrate that adherence to
Ticlopidine (Ticlid) and clopidogrel (Plavix) belong to a newer these precautions has reduced the risk of epidural hematoma
class of antiplatelet agents, the thienopyridines. These medi- to an acceptable level.297
cations cause selective inhibition of adenosine diphosphate– Knowledge of the pharmacokinetics and pharmacody-
mediated platelet activation.266,267 They bind irreversibly namics of common anticoagulants used during pregnancy
to platelets and inhibit platelet adhesion, aggregation, and is essential to avoid neuraxial techniques when a significant
secretion. These medications are frequently used in patients anticoagulant effect may still be present. In addition, under-
with coronary stents. Clopidogrel has a potency that is 40 to standing the mechanism of action, side effect profile, and half-
100 times greater than ticlopidine. Oral administration results life of newer anticoagulants is important. Guidelines should
in peak plasma levels after 2 hours. Clopidogrel's effect on not be used as a substitute but rather as a complement to this
platelet function lasts 5 days, versus ticlopidine's effect of 10 to knowledge.
15 days. Although ASRA recommends discontinuation of
ticlopidine for 14 days and clopidogrel for 7 days before neur-
Local Anesthetic Allergy
axial blockade,266 Nordic guidelines recommend discontinua-
tion of no less than 5 days before central neuraxial blockade.267 A true immunoglobulin E (IgE)–mediated anaphylactic reac-
Platelet GP IIb/IIIa inhibitors block the final common tion to an anesthetic agent, although often life threatening,
pathway to platelet aggregation. Time to normal platelet is rare in the patient under anesthesia. The incidence varies
aggregation ranges from 8 hours for eptifibatide and tirofiban between 1:3500 and 1:20,000, with neuromuscular blocking
to 24 to 48 hours for abciximab. Neuraxial techniques should drugs and latex being the most common offending agents.
be avoided until platelet function has recovered.266 A review of allergic reactions during anesthesia in France dur-
Other medications interfere with primary or secondary ing a 2-year period found no cases of local anesthetic allergy.298
hemostasis, but data are incomplete and guidelines lacking or Local anesthetics belong to the ester or amide type. Whereas
limited. Examples include direct thrombin inhibitors (hiru- ester local anesthetics are metabolized to p-aminobenzoic acid
dins and argatroban), synthetic Xa inhibitors (danaparoid), (PABA), amide local anesthetics are metabolized in the liver to
oral Xa inhibitors (rivaroxaban and apixiban), oral direct a variety of compounds. Methylparaben is a preservative that
thrombin inhibitors (dabigatran) and thienopyridines (prasu- may be present in amide or ester local anesthetics and can have
grel). Knowledge of the pharmacokinetics and pharmacody- some cross-reactivity with PABA. An IgE-mediated reaction
namics of these drugs is the best guide for the use of neuraxial to a local anesthetic, most likely caused by the PABA metabo-
techniques in patients taking these medications. lite from esters or methylparaben, accounts for less than 1% of
all reactions to local anesthetics.299 Almost all cases of ques-
SUMMARY tionable allergic reactions to local anesthetics result from a
It is important to use appropriate neuraxial techniques, to vasovagal episode, systemic injection of local anesthetic with
avoid multiple anticoagulants, and to exercise caution in CNS manifestations, or intravascular injection of epinephrine,
proper parturient selection. The decision to perform neuraxial with its associated cardiovascular manifestations. Further,
anesthesia should utilize a risk/benefit analysis. Low concen- most allergic reactions to local anesthetics are caused by a type
tration local anesthetic techniques should be used to facili- IV delayed hypersensitivity reaction that presents as a contact
tate lower extremity neurologic assessment during neuraxial dermatitis.299
anesthesia and analgesia. It is important to remember that Cross-reactivity to other local anesthetics should be con-
epidural hematomas have been reported at epidural catheter sidered when a true IgE-mediated reaction to an amide or
withdrawal in patients with altered coagulation, and there- ester group local anesthetic is suspected or confirmed by prior
fore neurologic examination should be continued for a time testing. Skin tests should then be conducted, not only for the
after catheter removal. Soft, flexible catheters are preferred for suspected agent but also for other local anesthetics, including
an epidural technique because they have a lower incidence of agents of both types, to identify a safe alternative.300 There is
venous cannulation. Appropriate use of neuraxial techniques, even a report of an IgE-mediated reaction to ropivacaine in
proper patient selection, timing of a regional technique in a patient with a history of an anaphylactic reaction to other
relation to an anticoagulant, avoidance of multiple medica- amide local anesthetics, including lidocaine, bupivacaine, and
tions that alter the coagulation cascade, and use of less trau- mepivacaine. This patient tolerated procaine, an ester local
matic techniques (e.g., subarachnoid) are likely to decrease the anesthetic, well. Skin tests are conducted by intradermally
incidence of bleeding complications. In addition, the use of injecting small quantities of local anesthetic and watching for
opioid and dilute solutions of local anesthetic and thorough a wheal and flare response. A positive response should be fol-
neurologic checks may assist in the early diagnosis of an epi- lowed by a skin prick test and then SC injection, because the
dural hematoma. Symptoms to look for include severe back results are equivocal in many cases.301 The Chandler method-
pain that is often radiating, leg weakness or sensory changes ology for provocative skin testing302 can be performed over
unrelated to the block, and bladder or bowel changes. a 1- to 2-hour period by a trained allergist incrementally
performing SC injections of a local anesthetic while observ- Obstetric and gynecologic examinations and latex condom use
ing the patient closely on a monitored unit for any signs of an sensitize women to latex.308 For this reason, patients undergo-
allergic reaction. ing obstetric and gynecologic procedures account for almost
The history of a local anesthetic allergy in an obstetric 50% of latex-mediated reactions.309 Oxytocin-induced uter-
patient is more complicated, because skin testing is not rec- ine contractions may cause the release of latex particles in the
ommended during pregnancy unless the results obtained will uterus into the systemic circulation.
lead to a significant implication for treatment.303 Regional High-risk groups for latex allergy include those with occu-
anesthesia is much safer in parturients compared with general pational exposure to latex (e.g., health care workers), atopic
anesthesia,304 and regional analgesia is by far the most effec- individuals, spina bifida patients, patients with multiple sur-
tive means of analgesia during labor and delivery. Although geries (e.g., genitourinary abnormalities), and people allergic
the best time to conduct skin testing is before pregnancy, to tropical fruits (e.g., bananas, avocados, papaya, kiwi, pears).
some believe provocative challenge skin testing can be con- These fruits contain proteins that cross-react with latex,
ducted during pregnancy to rule out a true local anesthetic resulting in the latex-fruit syndrome. Latex-mediated reactions
allergy.305,306 The timing of the testing during pregnancy is also include irritant contact dermatitis, type IV cell-mediated reac-
controversial, because an allergic reaction caused by skin test- tions (allergic contact dermatitis), and type I IgE-mediated
ing before fetal viability may lead to untoward effects on the hypersensitivity reactions (anaphylaxis).
fetus. Other risks include the possibility of fetal sensitization, Anaphylaxis during pregnancy is managed medically the
and it remains unclear whether a response to skin testing is same as in nonpregnant patients with a few modifications.
modified by pregnancy. The first step in the treatment of an anaphylactic reaction con-
Therefore, in the event that testing has not been performed sists of the withdrawal of the likely causative drug and early
during pregnancy, a thorough history should be conducted use of epinephrine.310 Epinephrine interrupts the effects of the
first to rule out other causes of an adverse local anesthetic preformed mediators and prevents more mediator release.
reaction. In addition, it is important to elicit a family history Epinephrine is considered the drug of choice in the treatment
because genetic linkage has been postulated.307 Other options of anaphylaxis during pregnancy; no alternative more com-
for anesthesia and analgesia should be considered, and a thor- pletely treats the physiologic manifestations of anaphylaxis.
ough informed consent process with the patient is strongly Some concern surrounds the use of epinephrine during preg-
recommended while conducting a risk/benefit analysis. The nancy because of its potential to reduce uterine blood flow, a
risks of skin testing during pregnancy should also be dis- result of its effect on uterine vascular resistance through its
cussed with the patient, in collaboration with an allergist and α-mediated blood vessel vasoconstriction in the placenta.308
the obstetrician. If skin testing is planned, the timing should However, only when given in excessive doses does epinephrine
be close to the date of delivery to maximize fetal well-being. decrease uteroplacental blood flow. Appropriate epinephrine
Most cases of reactions to local anesthetics are not aller- dosage—a starting dose of 0.1 to 0.2 μg/kg in the treatment
gic and should not preclude their use. However, even though of mild to moderate hypotension, titrated to response—will
a life-threatening anaphylactic reaction to a preservative- increase SVR, cardiac output, and uteroplacental perfusion.
free local anesthetic is uncommon, it has been reported and Doses of 0.1 to 0.5 mg IV are used in the presence of cardio-
should be taken seriously and followed closely if confirmed or vascular collapse.
strongly suspected (Box 19-9). The best position for the parturient is left uterine dis-
placement, avoiding the supine, sitting, or standing position,
because such positioning alone can precipitate cardiac arrest
Latex Allergy
from aortocaval compression, with resultant supine hypoten-
More recently, anaphylaxis has been reported to occur imme- sive syndrome or massive vasodilation.311
diately after latex exposure. This trend is likely correlated to Other important steps in the treatment of anaphylaxis
the higher level of sensitization to latex in high-risk patients. include airway support with 100% oxygen to compensate for
the increased O2 consumption, and IV crystalloid replace-
ment (2-4 L) to compensate for the peripheral vasodilation.
BOX 19-9 n DIFFERENTIAL DIAGNOSIS OF LOCAL Bronchospasm may be initially treated with bronchodilators
ANESTHETIC ALLERGY (nebulized albuterol, ipratropium bromide). When cardiovas-
Vasovagal episode
cular collapse and bronchospasm occur together, epineph-
Systemic local anesthetic injection rine remains the first-line therapy to correct cardiovascular
n Central nervous system reaction homeostasis and treat hypotension and bronchospasm at the
Systemic epinephrine same time. The epinephrine total dosage requirement may be
n Cardiac toxicity
correlated with the severity of the reaction.
Type IV cell-mediated reaction
n Contact dermatitis
Even though anaphylaxis is uncommon during pregnancy,
Type I cell-mediated reaction it is important to recognize it rapidly and treat it effectively;
n Anaphylaxis the maternal hypoxia and hypotension that can result from
anaphylaxis may be catastrophic to both mother and fetus.
Prevention is the most important part of management to management of hypotension during spinal anesthesia for cesarean deliv-
decrease the incidence of anaphylaxis. Patients who experi- ery, Anesth Analg 94:920–926, table of contents, 2002.
17. Oxford CM, Ludmir J: Trauma in pregnancy, Clin Obstet Gynecol
ence anaphylaxis during pregnancy should have a follow-up 52:611–629, 2009.
assessment from an allergy/immunology specialist to confirm 18. Shepard TH, Lemire RJ: Catalog of teratogenic agents, ed 11, Baltimore,
the trigger for anaphylaxis and prevent recurrence. 2004, Johns Hopkins University Press.
19. Teiling AK, Mohammed AK, Minor BG, et al: Lack of effects of prenatal
exposure to lidocaine on development of behavior in rats, Anesth Analg
CONCLUSION 66:533–541, 1987.
20. Mazze RI, Wilson AI, Rice SA, et al: Reproduction and fetal develop-
Pregnancy is a common and nonpathologic condition. ment in rats exposed to nitrous oxide, Teratology 30:259–265, 1984.
However, the altered physiology of pregnancy complicates 21. Baden JM, Fujinaga M: Effects of nitrous oxide on day 9 rat embryos
the anesthetic care of even healthy pregnant patients. When grown in culture, Br J Anaesth 66:500–503, 1991.
unusual conditions of pregnancy further alter the physiologic 22. Lane GA, Nahrwold ML, Tait AR, et al: Anesthetics as teratogens: nitrous
oxide is fetotoxic, xenon is not, Science 210:899–901, 1980.
state, the anesthesiologist faces additional challenges. Basic 23. Chanarin I: Cobalamins and nitrous oxide: a review, J Clin Pathol
principles of management of the pregnant patient are sum- 33:909–916, 1980.
marized in this chapter, along with various diseases that may 24. Keeling PA, Rocke DA, Nunn JF, et al: Folinic acid protection against
complicate pregnancy and select conditions specific to preg- nitrous oxide teratogenicity in the rat, Br J Anaesth 58:528–534, 1986.
nant patients. 25. Fujinaga M, Baden JM: Methionine prevents nitrous oxide-induced terato-
genicity in rat embryos grown in culture, Anesthesiology 81:184–189, 1994.
26. Mazze RI, Fujinaga M, Baden JM: Halothane prevents nitrous oxide
teratogenicity in Sprague-Dawley rats; folinic acid does not, Teratology
REFERENCES 38:121–127, 1988.
1. Wiesen AR, Gunzenhauser JD: Laboratory-measured pregnancy rates 27. Brodsky JB, Cohen EN: Health experiences of operating room person-
and their determinants in a large, well-described adult cohort, Mil Med nel, Anesthesiology 63:461–464, 1985.
169:518–521, 2004. 28. Spence AA: Environmental pollution by inhalation anaesthetics, Br J
2. Brodsky JB, Cohen EN, Brown BW Jr, et al: Surgery during pregnancy Anaesth 59:96–103, 1987.
and fetal outcome, Am J Obstet Gynecol 138:1165–1167, 1980. 29. Jevtovic-Todorovic V, Hartman RE, Izumi Y, et al: Early exposure to com-
3. Mazze RI, Kallen B: Reproductive outcome after anesthesia and oper- mon anesthetic agents causes widespread neurodegeneration in the devel-
ation during pregnancy: a registry study of 5405 cases, Am J Obstet oping rat brain and persistent learning deficits, J Neurosci 23:876–882, 2003.
Gynecol 161:1178–1185, 1989. 30. Levin ED, Bowman RE: Behavioral effects of chronic exposure to low
4. Manley S, de Kelaita G, Joseph NJ, et al: Preoperative pregnancy test- concentrations of halothane during development in rats, Anesth Analg
ing in ambulatory surgery: incidence and impact of positive results, 65:653–659, 1986.
Anesthesiology 83:690–693, 1995. 31. Jevtovic-Todorovic V, Olney JW: PRO: anesthesia-induced develop-
5. Farraghar R, Bhavani-Shankar K: Obstetric anesthesia. In Healy TEJ, mental neuroapoptosis—status of the evidence, Anesth Analg 106(6):
Knight PR, editors: Wylie and Churchill Davidson's a practice of anesthe- 1659–1663, 2008.
sia, ed 7, London, 2003, Arnold, pp 923–940. 32. Sprung J, Flick RP, Wilder RT, et al: Anesthesia for cesarean delivery and
6. Chang B: Physiological changes of pregnancy. In Chestnut DHC, editor: learning disabilities in a population-based birth cohort, Anesthesiology
Obstetric anesthesia: principles and practice, Philadelphia, 2004, Elsevier, 111:302–310, 2009.
pp 15–36. 33. Mazze RI, Kallen B: Appendectomy during pregnancy: a Swedish regis-
7. Boutonnet M, Faitot V, Katz A, et al: Mallampati class changes dur- try study of 778 cases, Obstet Gynecol 77:835–840, 1991.
ing pregnancy, labour, and after delivery: can these be predicted? Br J 34. Cunningham AJ, Brull SJ: Laparoscopic cholecystectomy: anesthetic
Anaesth 104:67–70, 2011. implications, Anesth Analg 76:1120–1133, 1993.
8. Kodali BS, Chandrasekhar S, Bulich LN, et al: Airway changes during 35. Fitzgibbons R Jr: Laparoscopic cholecystectomy, JAMA 266:269, 1991.
labor and delivery, Anesthesiology 108:357–362, 2008. 36. Lachman E, Schienfeld A, Voss E, et al: Pregnancy and laparoscopic sur-
9. Chan MT, Mainland P, Gin T: Minimum alveolar concentration of hal- gery, J Am Assoc Gynecol Laparosc 6:347–351, 1999.
othane and enflurane are decreased in early pregnancy, Anesthesiology 37. Andreoli M, Servakov M, Meyers P, et al: Laparoscopic surgery during
85:782–786, 1996. pregnancy, J Am Assoc Gynecol Laparosc 6:229–233, 1999.
10. Leighton BL, Cheek TG, Gross JB, et al: Succinylcholine pharmacody- 38. Barnard JM, Chaffin D, Droste S, et al: Fetal response to carbon dioxide
namics in peripartum patients, Anesthesiology 64:202–205, 1986. pneumoperitoneum in the pregnant ewe, Obstet Gynecol 85:669–674, 1995.
11. Kussman B, Shorten G, Uppington J, et al: Administration of magnesium 39. Amos JD, Schorr SJ, Norman PF, et al: Laparoscopic surgery during
sulphate before rocuronium: effects on speed of onset and duration of pregnancy, Am J Surg 171:435–437, 1996.
neuromuscular block, Br J Anaesth 79:122–124, 1997. 40. Hardwick RH, Slade RR, Smith PA, et al: Laparoscopic splenectomy in
12. Khazin AF, Hon EH, Hehre FW: Effects of maternal hyperoxia on the pregnancy, J Laparoendosc Adv Surg Tech A 9:439–440, 1999.
fetus. I. Oxygen tension, Am J Obstet Gynecol 109:628–637, 1971. 41. Wang PH, Chao HT, Tseng JY, et al: Laparoscopic surgery for heterotopic
13. Brann AW Jr, Myers RE: Central nervous system findings in the new- pregnancies: a case report and a brief review, Eur J Obstet Gynecol Reprod
born monkey following severe in utero partial asphyxia, Neurology Biol 80:267–271, 1998.
25:327–338, 1975. 42. Demeure MJ, Carlsen B, Traul D, et al: Laparoscopic removal of a right
14. Newman B, Lam AM: Induced hypotension for clipping of a cerebral adrenal pheochromocytoma in a pregnant woman, J Laparoendosc Adv
aneurysm during pregnancy: a case report and brief review, Anesth Surg Tech A 8:315–319, 1998.
Analg 65:675–678, 1986. 43. Steinbrook RA, Brooks DC, Datta S: Laparoscopic cholecystectomy dur-
15. Li H, Gudmundsson S, Olofsson P: Acute increase of umbilical artery ing pregnancy: review of anesthetic management, surgical consider-
vascular flow resistance in compromised fetuses provoked by uterine ations, Surg Endosc 10:511–515, 1996.
contractions, Early Hum Dev 74:47–56, 2003. 44. Levinson G, Shnider SM, DeLorimier AA, et al: Effects of maternal
16. Lee A, Ngan Kee WD, Gin T: A quantitative, systematic review of ran- hyperventilation on uterine blood flow and fetal oxygenation and acid-
domized controlled trials of ephedrine versus phenylephrine for the base status, Anesthesiology 40:340–347, 1974.
45. Wahba RW, Beique F, Kleiman SJ: Cardiopulmonary function and lapa- 71. Edwards JA, Kinsella J, Shaw A, et al: Sedation for oocyte retrieval using
roscopic cholecystectomy, Can J Anaesth 42:51–63, 1995. target controlled infusion of propofol and incremental alfentanil deliv-
46. Joris JL, Noirot DP, Legrand MJ, et al: Hemodynamic changes during ered by non-anaesthetists, Anaesthesia 65:453–461, 2010.
laparoscopic cholecystectomy, Anesth Analg 76:1067–1071, 1993. 72. Dell RG, Cloote AH: Patient-controlled sedation during transvagi-
47. Steinbrook RA, Bhavani-Shankar K: Hemodynamics during laparo- nal oocyte retrieval: an assessment of patient acceptance of patient-
scopic surgery in pregnancy, Anesth Analg 93:1570–1571, table of con- controlled sedation using a mixture of propofol and alfentanil, Eur J
tents, 2001. Anaesthesiol 15:210–215, 1998.
48. Society of American Gastrointestinal Endoscopic Surgeons: Guidelines 73. Silva PD, Kang SB, Sloane KA: Gamete intrafallopian transfer with spinal
for laparoscopic surgery during pregnancy, Surg Endosc 12:189–190, anesthesia, Fertil Steril 59:841–843, 1993.
1998. 74. Pellicano M, Zullo F, Fiorentino A, et al: Conscious sedation versus gen-
49. Cruz AM, Southerland LC, Duke T, et al: Intraabdominal carbon dioxide eral anesthesia for minilaparoscopic gamete intra-fallopian transfer: a
insufflation in the pregnant ewe: uterine blood flow, intraamniotic pres- prospective randomized study, Hum Reprod 16:2295–2297, 2001.
sure, and cardiopulmonary effects, Anesthesiology 85:1395–1402, 1996. 75. Lane GA, Nahrwold ML, Tait AR, et al: Anesthetics as teratogens: nitrous
50. Hunter JG, Swanstrom L, Thornburg K: Carbon dioxide pneumoperi- oxide is fetotoxic, xenon is not, Science 210:899–901, 1980.
toneum induces fetal acidosis in a pregnant ewe model, Surg Endosc 9: 76. Hansen DK, Grafton TF: Effect of nitrous oxide on embryonic macromolec-
272–277, discussion 277–279, 1995. ular synthesis and purine levels, Teratog Carcinog Mutagen 8:107–115, 1988.
51. Bhavani-Shankar K, Mushlin PS: Arterial to end-tidal gradients in preg- 77. Baden JM, Fujinaga M: Effects of nitrous oxide on day 9 rat embryos
nant subjects, Anesthesiology 87:1596, 1997. grown in culture, Br J Anaesth 66:500–503, 1991.
52. Affleck DG, Handrahan DL, Egger MJ, et al: The laparoscopic manage- 78. Lee EJ, Bongso A, Kumar A: Evaluation of inhalational anaesthetics on
ment of appendicitis and cholelithiasis during pregnancy, Am J Surg murine in vitro fertilization, Ann Acad Med Singapore 23:479–485, 1994.
178:523–529, 1999. 79. Rosen MA, Roizen MF, Eger EI, et al: The effect of nitrous oxide on
53. Elerding SC: Laparoscopic cholecystectomy in pregnancy, Am J Surg in vitro fertilization success rate, Anesthesiology 67:42–44, 1987.
165:625–627, 1993. 80. Kennedy GL, Smith SH, Keplinger ML, et al: Reproductive and terato-
54. Soper NJ, Hunter JG, Petrie RH: Laparoscopic cholecystectomy during logic studies with isoflurane, Drug Chem Toxicol 1:75–88, 1977.
pregnancy, Surg Endosc 6:115–117, 1992. 81. Vincent RDJ, Syrop CH, Van Voorhis BJ, et al: An evaluation of the effect
55. Bhavani-Shankar K, Steinbrook RA, Brooks DC, et al: Arterial to end- of anesthetic technique on reproductive success after laparoscopic pro-
tidal carbon dioxide pressure difference during laparoscopic surgery in nuclear stage transfer: propofol/nitrous oxide versus isoflurane/nitrous
pregnancy, Anesthesiology 93:370–373, 2000. oxide, Anesthesiology 82:352–358, 1995.
56. Curet N, Allen D, Josloff R, et al: Laparoscopy during pregnancy, Arch 82. Coetsier T, Dhont M, De Sutter P, et al: Propofol anaesthesia for ultra-
Surg 131:546, 1996. sound guided oocyte retrieval: accumulation of the anaesthetic agent in
57. Bhavani-Shankar K, Steinbrook RA: Anesthetic considerations for mini- follicular fluid, Hum Reprod 7:1422–1424, 1992.
mally invasive surgery. In Brooks DC, editor: Current review of mini- 83. Ben-Shlomo I, Moskovich R, Golan J, et al: The effect of propofol anes-
mally invasive surgery, ed 2, Philadelphia, 1998, Current Medicine, p 29. thesia on oocyte fertilization and early embryo quality, Hum Reprod
58. Mosher WD, Pratt WF: Fecundity and infertility in the United States: 15:2197–2199, 2000.
incidence and trends, Fertil Steril 56:192–193, 1991. 84. Rosenblatt MA, Bradford CN, Bodian CN, et al: The effect of a pro-
59. Collins JA: Unexplained infertility: evaluation and treatment, Philadelphia, pofol-based sedation technique on cumulative embryo scores, clinical
1995, Saunders. pregnancy rates, and implantation rates in patients undergoing embryo
60. Meldrum DR: Female reproductive aging: ovarian and uterine factors, transfers with donor oocytes, J Clin Anesth 9:614–617, 1997.
Fertil Steril 59:1–5, 1993. 85. Tillman Hein HA, Putman JM: Is propofol a proper proposition for
61. Steptoe PC, Edwards RG: Birth after the reimplantation of a human reproductive procedures? J Clin Anesth 9:611–613, 1997.
embryo, Lancet 2:336, 1978. 86. Janssenwillen C, Christiaens F, Camu F, et al: The effect of propofol on
62. Tsen LC: Darwin to desflurane: anesthesia for assisted reproductive pathogenetic activation, in vitro fertilization and early development of
technologies, Anesth Analg 94S:109–114, 2002. mouse oocytes, Fertil Steril 67:769–774, 1997.
63. Society for Assisted Reproductive Technology in the United States: 87. Endler GC, Stout M, Magyar DM, et al: Follicular fluid concentrations of
1999 results generated from the American Society for Reproductive thiopental and thiamylal during laparoscopy for oocyte retrieval, Fertil
Medicine/Society for Assisted Reproductive Technology Registry, Fertil Steril 48:828–833, 1987.
Steril 78:918–931, 2002. 88. Pierce ET, Smalky M, Alper MM, et al: Comparison of pregnancy rates
64. Lu MC: Impact of “non-physician factors” on the “physician factor” of following gamete intrafallopian transfer (GIFT) under general anesthe-
in vitro fertilization success: is it the broth, the cooks, or the statistics? sia with thiopental sodium or propofol, J Clin Anesth 4:394–398, 1992.
Fertil Steril 71:998–1000, 1999. 89. Christiaens F, Janssenwillen C, Van Steirteghem A, et al: Comparison
65. Karande VC, Morris R, Chapman C, et al: Impact of the “physician factor” of assisted reproductive technology performance after oocyte retrieval
on pregnancy rates in a large assisted reproductive technology program: under general anaesthesia (propofol) versus paracervical local anaes-
do too many cooks spoil the broth? Fertil Steril 71:1001–1009, 1999. thetic block: a case-controlled study, Hum Reprod 13:2456–2460, 1998.
66. Jennings JC, Moreland K, Peterson CM: In vitro fertilisation: a review of 90. Chopineau J, Bazin JE, Terrisse MP, et al: Assay for midazolam in liquor
drug therapy and clinical management, Drugs 52:313–343, 1996. folliculi during in vitro fertilization under anesthesia, Clin Pharm
67. Awonuga A, Waterstone J, Oyesanya O, et al: A prospective random- 12:770–773, 1993.
ized study comparing needles of different diameters for transvaginal 91. Soussis I, Boyd O, Paraschos T, et al: Follicular fluid levels of midazolam,
ultrasound-directed follicle aspiration, Fertil Steril 65:109–113, 1996. fentanyl, and alfentanil during transvaginal oocyte retrieval, Fertil Steril
68. Hung Yu Ng E, Kwai Chi Chui D, Shan Tang O, et al: Paracervical block 64:1003–1007, 1995.
with and without conscious sedation: a comparison of the pain levels 92. Shapira SC, Chrubasik S, Hoffmann A, et al: Use of alfentanil for in vitro
during egg collection and the postoperative side effects, Fertil Steril fertilization oocyte retrieval, J Clin Anesth 8:282–285, 1996.
75:711–717, 2001. 93. Casati A, Valentini G, Zangrillo A, et al: Anaesthesia for ultrasound
69. Ditkoff EC, Plumb J, Selick A, et al: Anesthesia practices in the United guided oocyte retrieval: midazolam/remifentanil versus propofol/fen-
States common to in vitro fertilization (IVF) centers, J Assist Reprod tanyl regimens, Eur J Anaesthesiol 16:773–778, 1999.
Genet 14:145–147, 1997. 94. Ben-Shlomo I, Moskovich R, Katz Y, et al: Midazolam/ketamine sedative
70. Jain T, Harlow BL, Hornstein MD: Insurance coverage and outcomes of combination compared with fentanyl/propofol/isoflurane anaesthesia
in vitro fertilization, N Engl J Med 347:661–667, 2002. for oocyte retrieval, Hum Reprod 7:1757–1759, 1999.
95. Marshburn PB, Shabanowitz RB, Clark MR: Immunohistochemical 119. Lewis DF, Chesson AL, Edwards MS, et al: Obstructive sleep apnea
localization of prostaglandin H synthase in the embryo and uterus of during pregnancy resulting in pulmonary hypertension, South Med J
the mouse from ovulation through implantation, Mol Reprod Dev 25: 91:761–762, 1998.
309–316, 1990. 120. Sebire NJ, Jolly M, Harris JP, et al: Maternal obesity and pregnancy out-
96. Van der Weiden RM, Helmerhorst FM, Keirse MJ: Influence of pros- come: a study of 287,213 pregnancies in London, Int J Obes Relat Metab
taglandins and platelet activating factor on implantation, Hum Reprod Disord 25:1175–1182, 2001.
6:436–442, 1991. 121. Johnson JW, Longmate JA, Frentzen B: Excessive maternal weight and preg-
97. Van Voorhis BJ, Huettner PC, Clark MR, et al: Immunohistochemical nancy outcome, Am J Obstet Gynecol 167:353–370, discussion 370–372,
localization of prostaglandin H synthase in the female reproductive tract 1992.
and endometriosis, Am J Obstet Gynecol 163:57–62, 1990. 122. Peckham CH, Christianson RE: The relationship between prepregnancy
98. Bokhari A, Pollard BJ: Anaesthesia for assisted conception: a survey of weight and certain obstetric factors, Am J Obstet Gynecol 111:1–7, 1971.
UK practice, Eur J Anaesthesiol 16:225–230, 1999. 123. Chauhan SP, Magann EF, Carroll CS, et al: Mode of delivery for the mor-
99. Monroe SE, Levine L, Chang RJ, et al: Prolactin-secreting pituitary adeno- bidly obese with prior cesarean delivery: vaginal versus repeat cesarean
mas. V. Increased gonadotroph responsivity in hyperprolactinemic women section, Am J Obstet Gynecol 185:349–354, 2001.
with pituitary adenomas, J Clin Endocrinol Metab 52:1171–1178, 1981. 124. Perlow JH, Morgan MA, Montgomery D, et al: Perinatal outcome

100. Cunningham F, Gant N, Leveno K, et al: Williams obstetrics, ed 21, New in pregnancy complicated by massive obesity, Am J Obstet Gynecol
York, 2001, McGraw-Hill. 167:958–962, 1992.
101. Koninckx PR, Renaer M: Pain sensitivity of and pain radiation from the 125. Waller DK, Mills JL, Simpson JL, et al: Are obese women at higher risk
internal female genital organs, Hum Reprod 12:1785–1788, 1997. for producing malformed offspring? Am J Obstet Gynecol 170:541–548,
102. Hung Yu Ng E, Shan Tang O, Kwai Chi Chui D, et al: A prospective, ran- 1994.
domized, double-blind and placebo-controlled study to assess the effi- 126. Chin KJ, Perlas A, Chan V, et al: Ultrasound imaging facilitates spi-
cacy of paracervical block in the pain relief during egg collection in IVF, nal anesthesia in adults with difficult surface anatomic landmarks,
Hum Reprod 14:2783–2787, 1999. Anesthesiology 115:94–101, 2011.
103. Hung Yu Ng E, Miao B, Chung Ho P: A randomized double-blind study 127. Morgan M: Amniotic fluid embolism, Anaesthesia 34:20–32, 1979.
to compare the effectiveness of three different doses of lignocaine used in 128. Clark SL, Hankins GD, Dudley DA, et al: Amniotic fluid embolism: anal-
paracervical block during oocyte retrieval, J Assist Reprod Genet 20:8–12, ysis of the national registry, Am J Obstet Gynecol 172:1158–1167; discus-
2003. sion 1167–1169, 1995.
104. Schnell VL, Sacco AG, Savoy-Moore RT, et al: Effects of oocyte exposure 129. Steiner PE, Lushbaugh CC: Landmark article, Oct. 1941. Maternal pul-
to local anesthetics on in vitro fertilization and embryo development in monary embolism by amniotic fluid as a cause of obstetric shock and
the mouse, Reprod Toxicol 6:323–327, 1992. unexpected deaths in obstetrics, JAMA 255:2187–2203, 1986.
105. Wikland M, Evers H, Jakobsson AH: The concentration of lidocaine in 130. Masson RG: Amniotic fluid embolism, Clin Chest Med 13:657–665,
follicular fluid when used for paracervical block in a human IVF-ET 1992.
programme, Hum Reprod 5:920–923, 1990. 131. McDougall RJ, Duke GJ: Amniotic fluid embolism syndrome: case
106. Manica VS, Bader AM, Fragneto R, et al: Anesthesia for in vitro fertiliza- report and review, Anaesth Intensive Care 23:735–740, 1995.
tion: a comparison of 1.5% and 5% lidocaine for ultrasonically guided 132. Dudney TM, Elliott CG: Pulmonary embolism from amniotic fluid, fat,
oocyte retrieval, Anesth Analg 77:453–456, 1993. and air, Prog Cardiovasc Dis 36:447–474, 1994.
107. Martin R, Tsen LC, Tzeng G, et al: Anesthesia for in vitro fertilization: the 133. Lawson HW, Atrash HK, Franks AL: Fatal pulmonary embolism dur-
addition of fentanyl to 1.5% lidocaine, Anesth Analg 88:532–536, 1999. ing legal induced abortion in the United States from 1972 to 1985, Am J
108. Tsen LC, Schultz R, Martin R, et al: Intrathecal-low dose bupivacaine Obstet Gynecol 162:986–990, 1990.
vs. lidocaine for in-vitro fertilization procedures, Reg Anesth Pain Med 134. Sterner S, Campbell B, Davies S: Amniotic fluid embolism, Ann Emerg
26:52–56, 2001. Med 13:343–345, 1984.
109. Tsen LC, Arthur GR, Datta S, et al: Estrogen-induced changes in pro- 135. Maher JE, Wenstrom KD, Hauth JC, et al: Amniotic fluid embolism
tein binding of bupivacaine during in vitro fertilization, Anesthesiology after saline amnioinfusion: two cases and review of the literature, Obstet
87:879–883, 1997. Gynecol 83:851–854, 1994.
110. Hull M, Glazener CM, Kelly NJ, et al: Population study of causes, treat- 136. Davies S: Amniotic fluid embolus: a review of the literature, Can J
ment, and outcome of infertility, BMJ 291:1693–1697, 1985. Anaesth 48:88–98, 2001.
111. Gorgy A, Meniru GI, Naumann N, et al: The efficacy of local anesthe- 137. Courtney LD: Coagulation failure in pregnancy, BMJ 1:691, 1970.
sia for percutaneous epididymal sperm aspiration and testicular sperm 138. Bastien JL, Graves JR, Bailey S: Atypical presentation of amniotic fluid
aspiration, Hum Reprod 13:646–650, 1998. embolism, Anesth Analg 87:124–126, 1998.
112. Rein MS, Barbieri RL: The infertile couple. part I, ed 7, St Louis, 1999, 139. Clark SL, Pavlova Z, Greenspoon J, et al: Squamous cells in the maternal
Mosby. pulmonary circulation, Am J Obstet Gynecol 154:104–106, 1986.
113. Kodama H, Fukuda J, Karube H, et al: Status of the coagulation and 140. Lee W, Ginsburg KA, Cotton DB, et al: Squamous and trophoblastic cells
fibrinolytic systems in ovarian hyperstimulation syndrome, Fertil Steril in the maternal pulmonary circulation identified by invasive hemody-
66:417–424, 1996. namic monitoring during the peripartum period, Am J Obstet Gynecol
114. Kodama H, Fukuda J, Karube H, et al: Characteristics of blood hemo- 155:999–1001, 1986.
static markers in a patient with ovarian hyperstimulation syndrome who 141. Roche WD Jr., Norris HJ: Detection and significance of maternal pulmo-
actually developed thromboembolism, Fertil Steril 64:1207–1209, 1995. nary amniotic fluid embolism, Obstet Gynecol 43:729–731, 1974.
115. Magnani B, Tsen LC, Datta A, et al: Do short-term changes in estrogen 142. Clark SL: New concepts of amniotic fluid embolism: a review, Obstet
levels produce increased fibrinolysis? Am J Clin Pathol 112:485–491, 1999. Gynecol Surv 45:360–368, 1990.
116. Aune B, Oian P, Osterud B: Enhanced sensitivity of the extrinsic coagu- 143. Clark SL, Cotton DB, Gonik B, et al: Central hemodynamic alterations in
lation system during ovarian stimulation for in vitro fertilization, Hum amniotic fluid embolism, Am J Obstet Gynecol 158:1124–1126, 1988.
Reprod 9:1349–1352, 1993. 144. Clark SL, Montz FJ, Phelan JP: Hemodynamic alterations associated with
117. Hood DD, Dewan DM: Anesthetic and obstetric outcome in morbidly amniotic fluid embolism: a reappraisal, Am J Obstet Gynecol 151:617–
obese parturients, Anesthesiology 79:1210–1218, 1993. 621, 1985.
118. Bhavani Shankar K, Lee-Paritz A: Anesthesia for pregnant obese parturi- 145. El Maradny E, Kanayama N, Halim A, et al: Endothelin has a role in early
ents. In Datta S, editor: Anesthesia and obstetric management of high-risk pathogenesis of amniotic fluid embolism, Gynecol Obstet Invest 40:14–
pregnancy, ed 3 New York, 2003, Springer, pp 53–66. 18, 1995.
146. Guidotti RJ, Grimes DA, Cates W Jr.: Fatal amniotic fluid embolism dur- 171. Sibai BM: The HELLP syndrome (hemolysis, elevated liver enzymes, and
ing legally induced abortion, United States, 1972 to 1978, Am J Obstet low platelets): much ado about nothing? Am J Obstet Gynecol 162:311–
Gynecol 141:257–261, 1981. 316, 1990.
147. Choi DM, Duffy BL: Amniotic fluid embolism, Anaesth Intensive Care 172. Audibert F, Friedman SA, Frangieh AY, et al: Clinical utility of strict
23:741–743, 1995. diagnostic criteria for the HELLP (hemolysis, elevated liver enzymes,
148. Davies S: Amniotic fluid embolism and isolated disseminated intravas- and low platelets) syndrome, Am J Obstet Gynecol 175:460–464, 1996.
cular coagulation, Can J Anaesth 46:456–459, 1999. 173. Sibai BM, Ramadan MK, Chari RS, et al: Pregnancies complicated by
149. Harnett M, Datta S, Bhavani-Shankar K: How does amniotic fluid effect HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets):
coagulation? Anesthesiology 94:A45, 2001. subsequent pregnancy outcome and long-term prognosis, Am J Obstet
150. Lockwood CJ, Bach R, Guha A, et al: Amniotic fluid contains tissue factor, Gynecol 172:125–129, 1995.
a potent initiator of coagulation, Am J Obstet Gynecol 165:1335–1341, 1991. 174. Mehrabian F, Mohammadizadeh F, Moghtaderi N, et al: Comparison of
151. Masson RG, Ruggieri J: Pulmonary microvascular cytology: a new diag- placental pathology between severe preeclampsia and HELLP syndrome,
nostic application of the pulmonary artery catheter, Chest 88:908–914, Arch Gynecol Obstet 285:175–181, 2012.
1985. 175. Magann EF, Martin JN Jr.: Critical care of HELLP syndrome with corti-
152. Lee KR, Catalano PM, Ortiz-Giroux S: Cytologic diagnosis of amni- costeroids, Am J Perinatol 17:417–422, 2000.
otic fluid embolism: report of a case with a unique cytologic feature and 176. De Boer K, Buller HR, ten Cate JW, et al: Coagulation studies in the
emphasis on the difficulty of eliminating squamous contamination, Acta syndrome of haemolysis, elevated liver enzymes and low platelets, Br J
Cytol 30:177–182, 1986. Obstet Gynaecol 98:42–47, 1991.
153. Kobayashi H, Ohi H, Terao T: A simple, noninvasive, sensitive method 177. Barton JR, Sibai BM: Hepatic imaging in HELLP syndrome (hemoly-
for diagnosis of amniotic fluid embolism by monoclonal antibody sis, elevated liver enzymes, and low platelet count), Am J Obstet Gynecol
TKH-2 that recognizes NeuAc α2-6GalNAc, Am J Obstet Gynecol 174:1820–1825, discussion 1825–1827, 1996.
168:848–853, 1993. 178. O'Brien JM, Shumate SA, Satchwell SL, et al: Maternal benefit of cor-
154. Kanayama N, Yamazaki T, Naruse H, et al: Determining zinc copropor- ticosteroid therapy in patients with HELLP (hemolysis, elevated liver
phyrin in maternal plasma: a new method for diagnosing amniotic fluid enzymes, and low platelet count) syndrome: impact on the rate of
embolism, Clin Chem 38:526–529, 1992. regional anesthesia, Am J Obstet Gynecol 186:475–479, 2002.
155. Rodgers GP, Heymach GJ 3rd: Cryoprecipitate therapy in amniotic fluid 179. Fox DB, Troiano NH, Graves CR: Use of the pulmonary artery catheter
embolization, Am J Med 76:916–920, 1984. in severe preeclampsia: a review, Obstet Gynecol Surv 51:684–695, 1996.
156. Taenaka N, Shimada Y, Kawai M, et al: Survival from DIC following 180. Benedetti TJ, Kates R, Williams V: Hemodynamic observations in severe
amniotic fluid embolism: successful treatment with a serine proteinase preeclampsia complicated by pulmonary edema, Am J Obstet Gynecol
inhibitor; FOY, Anaesthesia 36:389–393, 1981. 152:330–334, 1985.
157. Van Heerden PV, Webb SA, Hee G, et al: Inhaled aerosolized prosta- 181. Desai DK, Moodley J, Naidoo DP, et al: Cardiac abnormalities in pul-
cyclin as a selective pulmonary vasodilator for the treatment of severe monary oedema associated with hypertensive crises in pregnancy, Br J
hypoxaemia, Anaesth Intensive Care 24:87–90, 1996. Obstet Gynaecol 103:523–528, 1996.
158. Capellier G, Jacques T, Balvay P, et al: Inhaled nitric oxide in patients 182. Mabie WC, Hackman BB, Sibai BM: Pulmonary edema associated with
with pulmonary embolism, Intensive Care Med 23:1089–1092, 1997. pregnancy: echocardiographic insights and implications for treatment,
159. Leighton BL, Wall MH, Lockhart EM, et al: Use of recombinant factor Obstet Gynecol 81:227–234, 1993.
VIIa in patients with amniotic fluid embolism: a systematic review of 183. Dildy GA 3rd, Cotton DB: Management of severe preeclampsia and
case reports, Anesthesiology 115:1201–1208, 2011. eclampsia, Crit Care Clin 7:829–850, 1991.
160. Firstenberg MS, Abel E, Blais D, et al: Temporary extracorporeal circu- 184. Catanzarite V, Willms D, Wong D, et al: Acute respiratory distress syn-
latory support and pulmonary embolectomy for catastrophic amniotic drome in pregnancy and the puerperium: causes, courses, and outcomes,
fluid embolism, Heart Surg Forum 14:E157–E159, 2011. Obstet Gynecol 97:760–764, 2001.
161. Lee PH, Shulman MS, Vellayappan U, et al: Surgical treatment of an 185. Chichakli LO, Atrash HK, MacKay A, et al: Pregnancy-related mortal-
amniotic fluid embolism with cardiopulmonary collapse, Ann Thorac ity in the United States due to hemorrhage: 1979-1992, Obstet Gynecol
Surg 90:1694–1696, 2011. 94:721–725, 1999.
162. Gambling D: Hypertensive disorders. In Chestnut D, editor: Obstetric 186. Hepner DL, Gaiser RR: The patient with retained placenta, Anesthesiol
anesthesia: principles and practice, Philadelphia, 2004, Elsevier, pp News 23:20–29, 1997.
794–835. 187. Breen JL, Neubecker R, Gregori CA, et al: Placenta accreta, increta, and
163. Mattar F, Sibai BM: Eclampsia. VIII. Risk factors for maternal morbidity, percreta: a survey of 40 cases, Obstet Gynecol 49:43–47, 1977.
Am J Obstet Gynecol 182:307–312, 2000. 188. Wu S, Kocherginsky M, Hibbard JU: Abnormal placentation: twenty-
164. Usta IM, Sibai BM: Emergent management of puerperal eclampsia, year analysis, Am J Obstet Gynecol 192:1458–1461, 2005.
Obstet Gynecol Clin North Am 22:315–335, 1995. 189. Clark SL, Koonings PP, Phelan JP: Placenta previa/accreta and prior
165. Barton JR, Sibai BM: Cerebral pathology in eclampsia, Clin Perinatol cesarean section, Obstet Gynecol 66:89–92, 1985.
18:891–910, 1991. 190. Ornan D, White R, Pollak J, et al: Pelvic embolization for intractable
166. Kaplan PW, Repke JT: Eclampsia, Neurol Clin 12:565–582, 1994. postpartum hemorrhage: long-term follow-up and implications for fer-
167. Witlin AG, Friedman SA, Egerman RS, et al: Cerebrovascular disor- tility, Obstet Gynecol 102:904–910, 2003.
ders complicating pregnancy—beyond eclampsia, Am J Obstet Gynecol 191. Chestnut DH, Dewan DM, Redick LF, et al: Anesthetic management
176:1139–1145; discussion 1145–1148, 1997. for obstetric hysterectomy: a multi-institutional study, Anesthesiology
168. Bartynski WS: Posterior reversible encephalopathy syndrome. Part 2. 70:607–610, 1989.
Controversies surrounding pathophysiology of vasogenic edema, AJNR 192. Kamani AA, Gambling DR, Christilaw J, et al: Anaesthetic management
Am J Neuroradiol 29:1043–1049, 2008. of patients with placenta accreta, Can J Anaesth 34:613–617, 1987.
169. Moodley J, Jjuuko G, Rout C: Epidural compared with general anaes- 193. Bhavani-Shankar K, Lynch EP, Datta S: Airway changes during cesarean
thesia for caesarean delivery in conscious women with eclampsia, Br J hysterectomy, Can J Anaesth 47:338–341, 2000.
Obstet Gynaecol 108:378–382, 2001. 194. McMahon MJ, Luther ER, Bowes WA, et al: Comparison of a trial of labor
170. Martin JN Jr., Rinehart BK, May WL, et al: The spectrum of severe pre- with an elective second cesarean section, N Engl J Med 335:689–695, 1996.
eclampsia: comparative analysis by HELLP (hemolysis, elevated liver 195. Lydon-Rochelle M, Holt VL, Easterling TR, et al: Risk of uterine rupture
enzyme levels, and low platelet count) syndrome classification, Am J during labor among women with a prior cesarean delivery, N Engl J Med
Obstet Gynecol 180:1373–1384, 1999. 345:3–8, 2001.
196. American College of Obstetricians and Gynecologists: Vaginal birth 219. Sliwa K, Skudicky D, Bergemann A, et al: Peripartum cardiomyopathy:
after previous cesarean delivery. ACOG practice bulletin No 5. Clinical analysis of clinical outcome, left ventricular function, plasma levels of
management guidelines for obstetrician-gynecologists, Int J Gynaecol cytokines and Fas/APO-1, J Am Coll Cardiol 35:701–705, 2000.
Obstet 66:197–204, 1999. 220. Sliwa K, Skudicky D, Candy G, et al: The addition of pentoxifylline to
197. American College of Obstetricians and Gynecologists: Induction of labor conventional therapy improves outcome in patients with peripartum
for vaginal birth after cesarean delivery. ACOG Committee Opinion No cardiomyopathy, Eur J Heart Fail 4:305–309, 2002.
271, Obstet Gynecol 99:679–680, 2002. 221. Midei MG, DeMent SH, Feldman AM, et al: Peripartum myocarditis and
198. American College of Obstetricians and Gynecologists: Vaginal birth cardiomyopathy, Circulation 81:922–928, 1990.
after previous cesarean delivery. ACOG Practice Bulletin No 115, Obstet 222. Bozkurt B, Villaneuva FS, Holubkov R, et al: Intravenous immune glob-
Gynecol 116:450–463, 2010. ulin in the therapy of peripartum cardiomyopathy, J Am Coll Cardiol
199. American College of Obstetricians and Gynecologists: optimal goals 34:177–180, 1999.
for anesthesia care in obstetrics. ACOG Committee Opinion No 433. 223. Lewis R, Mabie WC, Burlew B, et al: Biventricular assist device as a
ACOG Committee on Obstetric Practice, Obstet Gynecol 113:1197– bridge to cardiac transplantation in the treatment of peripartum cardio-
1199, 2009. myopathy, South Med J 90:955–958, 1997.
200. Hepner DL, Gutsche BB: Obstetric hemorrhage, Curr Rev Clin Anesth 224. Carvalho AC, Almeida D, Cohen M, et al: Successful pregnancy, delivery
22:213–224, 1998. and puerperium in a heart transplant patient with previous peripartum
201. Azeez Pasha SA, Kooheji AJ, Azeez A: Anesthetic management of peri- cardiomyopathy, Eur Heart J 13:1589–1591, 1992.
partum hemorrhage, Semin Anesth Periop Med Pain 19:225–236, 2000. 225. Felker GM, Jaeger CJ, Klodas E, et al: Myocarditis and long-term sur-
202. Nuttall GA, Brost BC, Connis RT, et al: Practice guidelines for periopera- vival in peripartum cardiomyopathy, Am Heart J 140:785–791, 2000.
tive blood transfusion and adjuvant therapies: an updated report by the 226. Sliwa K, Forster O, Zhanje F, et al: Outcome of subsequent pregnancy
American Society of Anesthesiologists Task Force on Perioperative Blood in patients with documented peripartum cardiomyopathy, Am J Cardiol
Transfusion and Adjuvant Therapies, Anesthesiology 105:198–208, 2006. 93:1441–1443, A10, 2004.
203. Ickx BE: Fluid and blood transfusion management in obstetrics, Eur J 227. Velickovic IA, Leicht CH: Continuous spinal anesthesia for cesarean sec-
Anaesthesiol 27:1031–1035, 2010. tion in a parturient with severe recurrent peripartum cardiomyopathy,
204. Waters JH, Biscotti C, Potter PS, et al: Amniotic fluid removal during Int J Obstet Anesth 13:40–43, 2004.
cell-salvage in the cesarean section patient, Anesthesiology 92:1531– 228. Connelly NR, Chin MT, Parker RK, et al: Pregnancy and delivery in a
1536, 2000. patient with recent peripartum cardiomyopathy, Int J Obstet Anesth
205. Catling SJ, Williams S, Fielding AM: Cell salvage in obstetrics: an evalu- 7:38–41, 1998.
ation of the ability of cell salvage combined with leucocyte depletion fil- 229. Velickovic IA, Leicht CH: Peripartum cardiomyopathy and cesarean
tration to remove amniotic fluid from operative blood loss at caesarean section: report of two cases and literature review, Arch Gynecol Obstet
section, Int J Obstet Anesth 8:79–84, 1999. 270:307–310, 2004.
206. Weiskopf RB: Erythrocyte salvage during cesarean section (editorial), 230. Kaufman I, Bondy R, Benjamin A: Peripartum cardiomyopathy and
Anesthesiology 92:1519–1521, 2000. thromboembolism; anesthetic management and clinical course of an
207. Camann WC: Cell salvage during cesarean delivery: is it safe and valu- obese, diabetic patient, Can J Anaesth 50:161–165, 2003.
able? Maybe, maybe not! (editorial), Int J Obstet Anesth 8:75–76, 1999. 231. Shnaider R, Ezri T, Szmuk P, et al: Combined spinal-epidural anesthesia
208. De Beus E, van Mook WN, Ramsay G, et al: Peripartum cardiomyop- for cesarean section in a patient with peripartum dilated cardiomyopa-
athy: a condition intensivists should be aware of, Intensive Care Med thy, Can J Anaesth 48:681–683, 2001.
29:167–174, 2003. 232. Gambling DR, Flanagan ML, Huckell VF, et al: Anaesthetic management
209. Pearson GD, Veille JC, Rahimtoola S, et al: Peripartum cardiomyopathy: and non-invasive monitoring for caesarean section in a patient with car-
National Heart, Lung, and Blood Institute and Office of Rare Diseases diomyopathy, Can J Anaesth 34:505–508, 1987.
(National Institutes of Health) workshop recommendations and review, 233. McCarroll CP, Paxton LD, Elliott P, et al: Use of remifentanil in a patient
JAMA 283:1183–1188, 2000. with peripartum cardiomyopathy requiring caesarean section, Br J
210. Elkayam U: Clinical characteristics of peripartum cardiomyopathy in Anaesth 86:135–138, 2001.
the United States: diagnosis, prognosis, and management, J Am Coll 234. Bilehjani E, Kianfar AA, Toofan M, et al: Anesthesia with etomidate and
Cardiol 58:659–670, 2011. remifentanil for cesarean section in a patient with severe peripartum car-
211. Elkayam U, Akhter MW, Singh H, et al: Pregnancy-associated cardiomy- diomyopathy: a case report, Middle East J Anesthesiol 19:1141–1149, 2008.
opathy: clinical characteristics and a comparison between early and late 235. Wake K, Takanishi T, Kitajima T, et al: Cardiac arrest during emergency
presentation, Circulation 111:2050–2055, 2005. cesarean section due to peripartum cardiomyopathy: a case report,
212. Sliwa K, Hilfiker-Kleiner D, Petrie MC, et al: Current state of knowledge Masui 52:1089–1091, 2003.
on aetiology, diagnosis, management, and therapy of peripartum car- 236. Malinow AM, Butterworth JF, Johnson MD, et al: Peripartum cardiomy-
diomyopathy: a position statement from the Heart Failure Association opathy presenting at cesarean delivery, Anesthesiology 63:545–547, 1985.
of the European Society of Cardiology Working Group on Peripartum 237. Morris S, Stacey M: Resuscitation in pregnancy, BMJ 327:1277–1279, 2003.
Cardiomyopathy, Eur J Heart Fail 12:767–778, 2010. 238. Vanden Hoek TL, Morrison LJ, Shuster M, et al: Cardiac arrest in spe-
213. Boomsma LJ: Peripartum cardiomyopathy in a rural Nigerian hospital, cial situations. Part 12. 2010 American Heart Association guidelines
Trop Geogr Med 41:197–200, 1989. for cardiopulmonary resuscitation and emergency cardiovascular care,
214. Lee W, Cotton DB: Peripartum cardiomyopathy: current concepts and Circulation 122(18 Suppl 3):829–861, 2010.
clinical management, Clin Obstet Gynecol 32:54–67, 1989. 239. Luppi CJ: Cardiopulmonary resuscitation in pregnancy: what all nurses
215. Sanderson JE, Olsen EG, Gatei D: Peripartum heart disease: an endo- caring for childbearing women need to know, AWHONN Lifelines 3:41–45,
myocardial biopsy study, Br Heart J 56:285–291, 1986. 1999.
216. Rizeq MN, Rickenbacher PR, Fowler MB, et al: Incidence of myocarditis 240. Keller C, Brimacombe J, Lirk P, et al: Failed obstetric tracheal intubation
in peripartum cardiomyopathy, Am J Cardiol 74:474–477, 1994. and postoperative respiratory support with the ProSeal laryngeal mask
217. O'Connell JB, Costanzo-Nordin MR, Subramanian R, et al: Peripartum airway, Anesth Analg 98:1467–1470, table of contents, 2004.
cardiomyopathy: clinical, hemodynamic, histologic and prognostic 241. Rees GA, Willis BA: Resuscitation in late pregnancy, Anaesthesia 43:
characteristics, J Am Coll Cardiol 8:52–56, 1986. 347–349, 1988.
218. Sliwa K, Blauwet L, Tibazarwa K, et al: Evaluation of bromocriptine 242. Goodwin AP, Pearce AJ: The human wedge: a manoeuvre to relieve aor-
in the treatment of acute severe peripartum cardiomyopathy: a proof- tocaval compression during resuscitation in late pregnancy, Anaesthesia
of-concept pilot study, Circulation 121:1465–1473, 2010. 47:433–434, 1992.
243. American Heart Association: 2010 guidelines for CPR and ECC,
267. Breivik H, Bang U, Jalonen J, et al: Nordic guidelines for neurax-

Circulation 122(Suppl 3):2010. ial blocks in disturbed haemostasis from the Scandinavian Society of
244. Lipman SS, Daniels KI, Carvalho B, et al: Deficits in the provision of Anaesthesiology and Intensive Care Medicine, Acta Anaesthesiol Scand
cardiopulmonary resuscitation during simulated obstetric crises, Am J 54:16–41, 2010.
Obstet Gynecol 203:179-e1–179-e5, 2010. 268. Ginsberg JS, Chan WS, Bates SM, et al: Anticoagulation of pregnant
245. Lipman SS, Daniels KI, Arafeh J, et al: The case for OBLS: a simulation- women with mechanical heart valves, Arch Intern Med 163:694–698,
based obstetric life support program, Semin Perinatol 35:74–79, 2011. 2003.
246. Nanson J, Elcock D, Williams M, et al: Do physiological changes in 269. Chan WS, Anand S, Ginsberg JS: Anticoagulation of pregnant women
pregnancy change defibrillation energy requirements? Br J Anaesth 87: with mechanical heart valves: a systematic review of the literature, Arch
237–239, 2001. Intern Med 160:191–196, 2000.
247. Katz VL, Dotters DJ, Droegemueller W: Perimortem cesarean delivery, 270. Hung L, Rahimtoola SH: Prosthetic heart valves and pregnancy,

Obstet Gynecol 68:571–576, 1986. Circulation 107:1240–1246, 2003.
248. Finegold H, Darwich A, Romeo R, et al: Successful resuscitation after 271. Ginsberg JS, Hirsh J: Use of antithrombotic agents during pregnancy,
maternal cardiac arrest by immediate cesarean section in the labor room, Chest 114:524S–530S, 1998.
Anesthesiology 96:1278, 2002. 272. Rowan JA, McCowan LM, Raudkivi PJ, et al: Enoxaparin treatment in
249. Baraka A, Kawkabani N, Haroun-Bizri S: Hemodynamic deteriora- women with mechanical heart valves during pregnancy, Am J Obstet
tion after cardiopulmonary bypass during pregnancy: resuscitation by Gynecol 185:633–637, 2001.
postoperative emergency cesarean section, J Cardiothorac Vasc Anesth 273. Lev-Ran O, Kramer A, Gurevitch J, et al: Low-molecular-weight hepa-
14:314–315, 2000. rin for prosthetic heart valves: treatment failure, Ann Thorac Surg 69:
250. Ilsaas C, Husby P, Koller ME, et al: Cardiac arrest due to massive pulmo- 264–265, 2000.
nary embolism following caesarean section: successful resuscitation and 274. Ginsberg JS, Greer I, Hirsh J: Use of antithrombotic agents during preg-
pulmonary embolectomy, Acta Anaesthesiol Scand 42:264–266, 1998. nancy, Chest 119:122S–1231S, 2001.
251. Parker J, Balis N, Chester S, et al: Cardiopulmonary arrest in pregnancy: 275. Nelson-Piercy C, Letsky EA, de Swiet M: Low-molecular-weight heparin
successful resuscitation of mother and infant following immediate caesar- for obstetric thromboprophylaxis: experience of sixty-nine pregnancies
ean section in labour ward, Aust N Z J Obstet Gynaecol 36:207–210, 1996. in sixty-one women at high risk, Am J Obstet Gynecol 176:1062–1068,
252. Awwad JT, Azar GB, Aouad AT, et al: Postmortem cesarean section fol- 1997.
lowing maternal blast injury: case report, J Trauma 36:260–261, 1994. 276. Morris TA: Heparin and low-molecular-weight heparin: background
253. Cordero DR, Toffle RC, McCauley CS: Cardiopulmonary arrest in preg- and pharmacology, Clin Chest Med 24:39–47, 2003.
nancy: the role of caesarean section in the resuscitative protocol, W V 277. Hirsh J, Warkentin TE, Shaughnessy SG, et al: Heparin and low-molec-
Med J 88:402–403, 1992. ular-weight heparin: mechanism of action, pharmacokinetics, dosing,
254. Katz V, Balderston K, DeFreest M: Perimortem cesarean delivery:
monitoring, efficacy, and safety, Chest 119:64S–94S, 2001.
were our assumptions correct? Am J Obstet Gynecol 192:1916–1920; 278. Dimitrakakis C, Papageorgiou P, Papageorgiou I, et al: Absence of

discussion 1920–1921, 2005. transplacental passage of low-molecular-weight heparin enoxaparin,
255. Dijkman A, Huisman CM, Smit M, et al: Cardiac arrest in pregnancy: Haemostasis 30:243–248, 2000.
increasing use of perimortem caesarean section due to emergency skills 279. Horlocker TT, Heit JA: Low-molecular-weight heparin: biochemistry,
training? Int J Obstet Gynaecol 117:282–287, 2010. pharmacology, perioperative prophylaxis regimens, and guidelines for
256. Litwin MS, Loughlin KR, Benson CB, et al: Placenta percreta invading regional anesthetic management, Anesth Analg 85:874–885, 1997.
the urinary bladder, Br J Urol 64:283–286, 1989. 280. White RH, Ginsberg JS: Low-molecular-weight heparins: are they all the
257. Long WB, Rosenblum S, Grady IP: Successful resuscitation of bupiva- same? Br J Haematol 121:12–20, 2003.
caine-induced cardiac arrest using cardiopulmonary bypass, Anesth 281. Lensing AW, Prins MH, Davidson BL, et al: Treatment of deep venous
Analg 69:403–406, 1989. thrombosis with low-molecular-weight heparins: a meta-analysis, Arch
258. Lau G: A case of sudden maternal death associated with resuscitative Intern Med 1555:601–607, 1995.
liver injury, Forensic Sci Int 67:127–132, 1994. 282. Lepercq J, Conard J, Borel-Derlon A, et al: Venous thromboembolism
259. Mallampalli A, Powner DJ, Gardner MO: Cardiopulmonary resusci- during pregnancy: a retrospective study of enoxaparin safety in 624
tation and somatic support of the pregnant patient, Crit Care Clin 20: pregnancies, Br J Obstet Gynaecol 108:1134–1140, 2001.
747–761, x, 2004. 283. American College of Obstetricians and Gynecologists: Safety of lovenox in
260. Suzuki S, Morishita S: Platelet hemostatic capacity (PHC) and fibrino- pregnancy. Committee Opinion No 276, Obstet Gynecol 100:845–846, 2002.
lytic inhibitors during pregnancy, Semin Thromb Hemost 24:449–451, 284. Aguilar D, Goldhaber SZ: Clinical uses of low-molecular-weight hepa-
1998. rins, Chest 115:1418–1423, 1999.
261. Carr BR, Ory H: Estrogen and progestin components of oral contracep- 285. Laposata M, Green D, Van Cott EM, et al: The clinical use and laboratory
tives: relationship to vascular disease, Contraception 55:267–272, 1997. monitoring of low-molecular-weight heparin, danaparoid, hirudin and
262. Heijboer H, Brandjes DP, Buller HR, et al: Deficiencies of coagulation- related compounds, and argatroban. College of American Pathologists
inhibiting and fibrinolytic proteins in outpatients with deep-vein throm- Conference XXXI on Laboratory Monitoring of Anticoagulant Therapy,
bosis, N Engl J Med 323:1512–1516, 1990. Arch Pathol Lab Med 122:799–807, 1998.
263. Bare SN, Poka R, Balogh I, et al: Factor V Leiden as a risk factor for mis- 286. Casele HL, Laifer SA, Woelkers DA, et al: Changes in the pharmacoki-
carriage and reduced fertility, Aust N Z J Obstet Gynaecol 40:186–190, netics of the low-molecular-weight heparin enoxaparin sodium during
2000. pregnancy, Am J Obstet Gynecol 181:1113–1117, 1999.
264. Ray JG, Laskin CA: Folic acid and homocyst(e)ine metabolic defects and 287. Kitchen S: Problems in laboratory monitoring of heparin dosage, Br J
the risk of placental abruption, pre-eclampsia and spontaneous preg- Haematol 111:397–406, 2000.
nancy loss: a systematic review, Placenta 20:519–529, 1999. 288. Vandermeulen EP, Van Aken H, Vermylen J: Anticoagulants and spinal-
265. Ridker PM, Miletich JP, Buring JE, et al: Factor V Leiden mutation as a epidural anesthesia, Anesth Analg 79:1165–1177, 1994.
risk factor for recurrent pregnancy loss, Ann Intern Med 128:1000–1003, 289. Wedel DJ: Anticoagulation and regional anesthesia, Anesth Analg

1998. 96:114S–1147S, 2003.
266. Horlocker TT, Wedel DJ, Rowlingson JC, et al: Regional anesthesia in 290. CLASP Collaborative Group: A randomised trial of low-dose aspirin for
the patient receiving antithrombotic or thrombolytic therapy: American the prevention and treatment of pre-eclampsia among 9364 pregnant
Society of Regional Anesthesia and Pain Medicine evidence-based women. Collaborative Low-dose Aspirin Study in Pregnancy, Lancet
guidelines (third edition), Reg Anesth Pain Med 35:64–101, 2010. 343:619–629, 1994.
291. Horlocker TT: Complications of regional anesthesia, Anesth Analg

301. Finucane BT: Allergies to local anesthetics—the real truth, Can J Anaesth
98:S56–S63, 2004. 50:869–874, 2003.
292. Horlocker TT, Wedel DJ: Neurologic complications of spinal and epi- 302. Chandler MJ, Grammer LC, Patterson R: Provocative challenge with
dural anesthesia, Reg Anesth Pain Med 25:83–98, 2000. local anesthetics in patients with a prior history of reaction, J Allergy
293. Sephton V, Farquharson RG, Topping J, et al: A longitudinal study of Clin Immunol 79:883–886, 1987.
maternal dose response to low-molecular-weight heparin in pregnancy, 303. Bernstein IL, Storms WW: Practice parameters for allergy diagnos-
Obstet Gynecol 101:1307–1311, 2003. tic testing. Joint Task Force on Practice Parameters for the Diagnosis
294. Buller HR, Davidson BL, Decousus H, et al: Subcutaneous fondaparinux and Treatment of Asthma. The American Academy of Allergy, Asthma
versus intravenous unfractionated heparin in the initial treatment of and Immunology and the American College of Allergy, Asthma and
pulmonary embolism, N Engl J Med 349:1695–1702, 2003. Immunology, Ann Allergy Asthma Immunol 75:543–625, 1995.
295. Treatment of proximal deep vein thrombosis with a novel synthetic 304. Hawkins JL, Koonin LM, Palmer SK, et al: Anesthesia-related deaths
compound (SR90107A/ORG31540) with pure anti–factor Xa activity: a during obstetric delivery in the United States, 1979–1990, Anesthesiology
phase II evaluation. The Rembrandt Investigators, Circulation 102:2726– 86:277–284, 1997.
2731, 2000. 305. Palmer CM, Voulgaropoulos D: Management of the parturient with a
296. Diuguid DL: Choosing a parenteral anticoagulant agent, N Engl J Med history of local anesthetic allergy, Anesth Analg 77:625–628, 1993.
345:1340–1342, 2001. 306. Balestrieri PJ, Ferguson JE 2nd: Management of a parturient with a his-
297. Cook TM, Counsell D, Wildsmith JA: Major complications of central tory of local anesthetic allergy, Anesth Analg 96:1489–1490, 2003.
neuraxial block: report on the Third National Audit Project of the Royal 307. Hepner DL, Castells MC, Tsen LC: Should local anesthetic allergy testing be
College of Anaesthetists, Br J Anaesth 102:179–190, 2009. routinely performed during pregnancy? Anesth Analg 97:1853–1854, 2003.
298. Mertes PM, Laxenaire MC, Alla F: Anaphylactic and anaphylactoid 308. Chaudhuri K, Gonzales J, Jesurun CA, et al: Anaphylactic shock in
reactions occurring during anesthesia in France in 1999–2000. Groupe pregnancy: a case study and review of the literature, Int J Obstet Anesth
d'Etudes des Reactions Anaphylactoides, Anesthesiology 99:536–545, 17:350–357, 2008.
2003. 309. Draisci G, Zanfini BA, Nucera E, et al: Latex sensitization: a special risk
299. Hepner DL, Castells MC: Anaphylaxis during the perioperative period, for the obstetric population? Anesthesiology 114:565–569, 2011.
Anesth Analg 97:1381–1395, 2003. 310. Dewachter P, Mouton-Faivre C, Emala CW: Anaphylaxis and anesthesia:
300. Morais-Almeida M, Gaspar A, Marinho S, et al: Allergy to local anes- controversies and new insights, Anesthesiology 111:1141–1150, 2009.
thetics of the amide group with tolerance to procaine, Allergy 58: 311. Pumphrey RS: Fatal posture in anaphylactic shock, J Allergy Clin

827–828, 2003. Immunol 112:451–452, 2003.

Pregnancy and Obstetric Complications

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Pregnancy and Obstetric Complications

Uploaded by

Copyright:

Available Formats

C H A P T E R

of regional anesthesia depends on the platelet count

One study in a well-defined, continuously screened female

Stroke volume ↑ 25%

hypoxia and hypotension can adversely affect the fetus.

outcome of IVF, such as stimulation protocol, embryo factor,

TABLE 19-3 n Different Types of Assisted Reproductive Technologies

Tugor Gift Zift/prost/tet

TABLE 19-4 n Anesthetic Options for Assisted Reproductive Technologies

General Anesthesia Neuraxial Blockade Paracervical Block Conscious Sedation

supine position, which may require elevation of the back rest

incidence of pulmonary edema and ARF.173 A recent analy-

diuretics, platelet count is greater than 50,000/mm3, LDH level restriction

further management (vasodilators, inotropes).

Modern ultrasonographic techniques and MRI are providing

Obstetric anesthesia (OB) Blood bank

3. Tube 2 RBCs immediately

4. Draw CBC, PT/PTT, fibrinogen 5. Thaw 1 pool CRYO

5. Receive coolers. Call BB to order additional

After labs come back, transfuse: 2. Issue additional products as ordered

2. RBCs to Hct > 21%

DCM (29% vs. 9%).217 The wide discrepancy in myocarditis

the course.210 Successful pregnancy after transplantation has

by increased platelet hemostatic capacity, despite a decreased

WARFARIN UNFRACTIONATED HEPARIN

291. Horlocker TT: Complications of regional anesthesia, Anesth Analg

You might also like

TABLE 19-3 n Different Types of Assisted Reproductive Technologies