Chapter 105. Critical Illness in Pregnancy

• Understanding the normal physiology of pregnancy is essential to evaluate the adequacy of cardiopulmonary function in the critically ill gravid woman.
• Pregnancy results in an increased cardiac output, which in late pregnancy may be diminished in the supine position by vena caval compression from the enlarged uterus.
• The reduced functional residual capacity (FRC) and increased oxygen consumption noted in normal pregnancy increase the risk of hypoxemia during intubation or hypoventilation.
• Hyperventilation during pregnancy results in a primary respiratory alkalosis and a compensatory metabolic acidosis with the following typical arterial blood gas values: PO2 >100 mm Hg, PCO2 27 to 32 mm Hg, and serum bicarbonate concentration 18 to 21 mEq/L.
• Fetal viability depends on adequate oxygen delivery. As a result of the dilutional anemia of pregnancy, cardiac output becomes the critical determinant of fetal oxygen delivery and must be maintained.
• Hemorrhage in pregnancy may be massive and require extraordinary fluid resuscitation.
• Vasoactive drugs should be used with caution in the pregnant patient, since they may reduce uterine blood flow.
• Control of increased afterload may require intravenous agents: Sodium nitroprusside should be used only for imminently life-threatening conditions, since cyanide toxicity may result in fetal injury or demise. Nicardipine is an intravenous calcium channel blocker that is preferable to nitroprusside, and experience with labetalol, a combined alpha-beta blocker, is growing and promising.
• Preeclampsia is a multisystem disorder characterized by hypertension, central nervous system dysfunction, coagulopathy, pulmonary edema, renal failure, and liver function abnormalities.
• Cardiopulmonary resuscitation must be modified in pregnancy and includes emergent cesarean section in selected patients.
• Pregnancy may represent a state of increased risk of pulmonary edema formation; acute hypoxemic respiratory failure is most often due to tocolytic therapy, and if due to tocolytics, usually resolves with supportive care.
• Successful management of critical illness in pregnancy requires continuous integration of the intensive care team with obstetric and neonatal consultants; mechanisms should exist for emergent involvement of the appropriate personnel.

Pregnancy greatly complicates critical illness, since assessment, monitoring, and treatment must take into account both maternal and fetal well-being. Knowledge of the normal changes in maternal respiratory, cardiac, and acid-base physiology in pregnancy is essential to distinguish between adaptive and pathologic changes.

This chapter begins with an overview of the changes in cardiovascular, respiratory, renal, and gastrointestinal physiology in normal pregnancy. Next, the determinants of fetal oxygen delivery are reviewed. The remainder of the chapter focuses on the disorders that can result in critical illness in pregnancy and the appropriate management of each. Finally, the importance of acid-base homeostasis, prophylaxis to prevent gastrointestinal bleeding, and early nutrition are discussed.

In many ways our understanding of the complex interaction between disease state and maternal/fetal physiology is incomplete. Thus we rely on an approach that assumes that measures that optimize maternal well-being are usually best for the fetus as well. Nonetheless, throughout critical illness, monitoring and management decisions must take into account fetal as well as maternal parameters. That is best achieved by expanding the typical critical care team consisting of nurse, respiratory therapist, and intensivist to include obstetrician and neonatologist as well.

Adaptation of the Circulation

In pregnancy, numerous circulatory adjustments occur that ensure adequate oxygen delivery to the fetus (Table 105-1). Early in pregnancy maternal blood volume increases, reaching a level 40% above baseline by the thirtieth week.1–3 This increase is due both to a 20% to 40% increase in the number of erythrocytes and a larger 40% to 50% increase in plasma volume. A mild dilutional anemia results, with a decrease in hematocrit of about 12%.1,2 The magnitude of the increase in blood volume is greater with multiple births. This extracellular volume expansion is associated with parallel decreases in colloid osmotic pressure and serum albumin concentration; both indices reach a plateau at 26 weeks, although there is a further decline in colloid osmotic pressure immediately postpartum.2 The extracellular volume expansion is caused by activation of the renin-angiotensin system with increased aldosterone production and results in mild peripheral edema in 50% to 80% of normal pregnancies.1,2

Coincident with the change in maternal blood volume is a 30% to 50% increase in cardiac output, most of which occurs in the first trimester and continues throughout gestation.4–6 The augmented cardiac output results from an increase in heart rate, and to a lesser degree stroke volume, with heart rate reaching a maximum of 15 to 20 beats per minute above resting nonpregnant levels by weeks 32 to 36.5,7 The increase in stroke volume is due both to an increase in preload caused by augmented blood volume and to a decrease in afterload caused by a 20% to 30% fall in systemic vascular resistance (SVR). The fall in SVR is attributed both to arteriovenous shunting through the low-resistance uteroplacental bed and vasodilation that may result from decreased vascular responsiveness to endogenous pressors and/or increased synthesis of vasodilators. Some studies suggest that since left ventricular end-diastolic pressure remains normal despite a rise in left ventricular end-diastolic volume,4,7 ventricular diastolic compliance may be increased. Others have postulated a decrease in ventricular compliance based on studies demonstrating increased left ventricular wall thickness and mass.5,6 While some authors have suggested that left ventricular performance improves during pregnancy;1 recent studies have noted no increase in ejection fraction as calculated from echocardiography.4,6 The exact contributions of increased heart rate and stroke volume, loading conditions, and ventricular performance to the increase in flow have not been conclusively determined.

During the course of pregnancy, cardiac output becomes more dependent upon body position, since the gravid uterus can cause significant obstruction of the inferior vena cava with reduced venous return. This effect is most notable in the third trimester. Vena caval obstruction is maximal in the supine position and much less pronounced in the left lateral decubitus position.1 During labor, uterine contraction can increase cardiac output 10% to 15% over resting pregnant levels by increasing blood return from the contracting uterus.2,8 This effect on cardiac output, however, may be tempered by blood loss during delivery.

Blood pressure decreases early in pregnancy owing to peripheral vasodilation as noted above. The peak decreases in systolic and diastolic pressures average 5 to 9 and 6 to 17 mm Hg, respectively, and occur at 16 to 28 weeks.9 Blood pressure then increases gradually, returning to prepregnancy levels shortly after delivery. A review of hypertension in pregnancy suggests that diastolic pressures of 75 mm Hg in the second trimester and 85 mm Hg in the third trimester should be considered the upper limits of normal.9

The normal adaptation of the circulatory system to pregnancy results in a physiologic third heart sound in the majority of pregnant patients. The chest radiograph reveals an enlarged cardiac silhouette. As will be discussed below, right ventricular, pulmonary artery, and pulmonary artery wedge pressures are unchanged from prepartum values in the healthy pregnant woman.10

Adaptation of the Respiratory System

Oxygen consumption increases 20% to 35% in normal pregnancy;11,12 during labor there is a further rise in oxygen consumption.13 The increase in oxygen consumption occurs because of fetal and placental needs, as well as maternal requirements resulting from increases in cardiac output and work of breathing.12 Increased oxygen consumption is associated with a 34% to 50% increase in carbon dioxide production by the third trimester, necessitating an increase in minute ventilation that begins in the first trimester and peaks at 20% to 40% above baseline at term.2,14 Alveolar ventilation is increased above the level needed to eliminate carbon dioxide, and partial pressure of carbon dioxide (PCO2) falls to a level of 27 to 32 mm Hg throughout pregnancy. The augmented alveolar ventilation is attributed to respiratory stimulation due to increased levels of progesterone, and results from a 30% to 35% increase in tidal volume (from 450 to 600 mL) while respiratory rate is unchanged.2,11,15 Renal compensation results in a maternal pH that is only slightly alkalemic, in the range of 7.40 to 7.45, with serum bicarbonate decreasing to 18 to 21 mEq/L11 (Table 105-2).

Maternal arterial partial oxygen pressure (PO2) is increased throughout pregnancy, to greater than 100 mm Hg, by virtue of augmented minute ventilation, but this increase does not significantly increase oxygen delivery. Mild hypoxemia and an increased alveolar-to-arterial oxygen gradient [(a-a)O2] may occur in the supine position.16 This likely results from airway narrowing or closure with resultant ventilation-perfusion mismatch related to a further decrease in the already reduced difference between functional residual capacity (FRC) and closing capacity that occurs in gravid individuals (see below).17 Whenever possible, arterial blood gas samples should be obtained in the seated position to avoid confounding effects from the mild positional hypoxemia of pregnancy (see Table 105-2).

FRC decreases progressively (10% to 25% at term) as a result of increased abdominal pressure from the enlarged uterus, which results in diaphragmatic elevation and decreased chest wall compliance.2,15 Expiratory reserve volume (ERV) and residual volume are decreased during the second half of pregnancy.15 Total lung capacity decreases minimally because the function of the diaphragm and thoracic muscles is unimpaired, and widening of the thoracic cage results in an increased inspiratory capacity.11,15 Vital capacity remains unchanged during pregnancy. Diffusing capacity is unchanged or slightly increased early in pregnancy and then decreases to normal or slightly below normal after the first trimester.18 Airway closure may occur near or above FRC in some women late in pregnancy.17,18 As discussed above, airway closure may be responsible, at least in part, for the positional hypoxemia noted late in pregnancy. The decreased FRC, when combined with the increased oxygen consumption found in pregnancy, makes the pregnant woman and fetus more vulnerable to hypoxia in the event of hypoventilation or apnea. This is an important consideration during endotracheal intubation.

Despite increases in levels of many hormones known to affect smooth muscle, the function of large airways does not appear to be altered in pregnancy. Forced expiratory volume in 1 second (FEV1), the ratio of FEV1 to forced vital capacity (FVC), and specific airways conductance are unchanged during pregnancy. The fact that flow-volume loops are also unaffected by pregnancy is further evidence of normal airway function.19 Lung compliance is unchanged.

Renal and Gastrointestinal Adaptation

Renal blood flow increases during the first and second trimesters to 60% to 80% above prepregnancy levels and then declines during the third trimester.2 The glomerular filtration rate rises early in pregnancy to 50% above baseline at 12 to 16 weeks and remains increased during pregnancy.20 This change means that serum creatinine during pregnancy (0.5 to 0.7 mg/dL) is somewhat lower than baseline. Therefore creatinine levels that would be normal in a nonpregnant patient can indicate renal dysfunction in pregnant patients.

Lower esophageal sphincter tone decreases during the first trimester of pregnancy and remains low until near term, perhaps as a result of increased plasma progesterone levels.2 The gravid uterus displaces the stomach, further reducing the effectiveness of the gastroesophageal sphincter. Basal gastric acid secretion and pH remain unchanged during pregnancy.21 Labor and narcotic analgesics given during labor delay gastric emptying time, significantly increasing the risk of aspiration.

Fetal Oxygen Delivery

Oxygen delivery to the fetal tissues depends on the oxygen content of uterine artery blood, as determined by maternal PO2, hemoglobin concentration and saturation, and uterine artery blood flow.2 As discussed above, the small increases in arterial PO2 attributable to hyperventilation have little effect on oxygen content, since maternal hemoglobin saturation is only marginally increased. However, the anemia of pregnancy reduces the oxygen content significantly, and thus the critically ill gravid patient is more dependent than the nonpregnant individual on cardiac output for maintenance of oxygen delivery.

Numerous factors affect uterine artery blood flow. The uterine vasculature is maximally dilated under normal conditions and therefore is unable to adapt to stress by increasing flow through local vascular adjustment.22 This assertion is supported by investigations in a gravid ewe model of progressive anemia in which the hematocrit was lowered from 31% to 8%.23 There was no augmentation of flow to either the uterine or the placental beds, and consequently there was a progressive decline in oxygen delivery to the fetus. This finding suggests that the uterine bed is not readily able to increase fetal oxygen delivery by vascular autoregulation. Fetal oxygen delivery can be decreased by uterine artery vasoconstriction. Exogenous or endogenous sympathetic stimulation and maternal hypotension elicit uterine artery vasoconstriction. In addition, maternal alkalosis causes uterine artery vasoconstriction.2 The latter effect may be compounded by the resulting leftward shift of the maternal oxyhemoglobin saturation curve, which increases oxygen affinity, thereby reducing the PO2 in the uterine artery and decreasing the gradient that drives oxygen across the placenta.

In the placenta, a concurrent exchange mechanism driven by the difference in oxygen tension between maternal and fetal blood results in the transfer of oxygen from the maternal to the fetal circulation (Fig. 105-1).2 Complete equilibration does not occur, so the umbilical venous blood going to the fetus has a lower oxygen tension than the blood in the uterine vein. The oxygenated umbilical venous blood, which has a PO2 of 30 to 40 mm Hg, combines with deoxygenated fetal inferior vena caval blood, resulting in a fetal arterial PO2 of 20 to 25 mm Hg.2 In spite of the low umbilical vein and fetal arterial PO2 values, compensatory mechanisms maintain fetal oxygen delivery, and fetal oxygen content is relatively high. At all levels of PO2, fetal hemoglobin has a higher affinity for oxygen than maternal hemoglobin, being 80% to 90% saturated at a PO2 of 30 to 35 mm Hg.2 In addition, the fetus has a higher hemoglobin concentration (150 g/L) than does the adult and has a high systemic cardiac output, with both left and right ventricles delivering blood to the systemic circulation. Studies indicate that fetal tissue hypoxia does not occur until levels of hypoxemia are reached that would be catastrophic by adult criteria. Brief reductions by up to 50% in uterine blood flow are well tolerated in animal models.2 In a primate model of asphyxia, brain injury did not occur until fetal PO2 fell to 9 to 14 mm Hg.24 Protective responses to hypoxic stress also exist at the level of the fetal circulation. A reduction in oxygen supply by >50% in a sheep preparation caused some fetal tissues to shift to anaerobic metabolism, and the fetal cardiac output was redirected to the brain, heart, and adrenal glands.25 When fetal oxygen content is reduced by more than 75%, the oxygen supply is inadequate to most of the organism, including the central nervous system. Irreversible brain damage begins after 10 minutes without oxygen.2 This fact suggests that compensatory mechanisms, such as redistribution of fetal blood flow to vital organs, decreased oxygen consumption in response to hypoxic stress, and the successful prolonged dependence of certain tissue beds on anaerobic metabolism may occur.

In summary, during pregnancy oxygen delivery to maternal and fetoplacental tissue beds is highly dependent on adequate blood flow and maternal oxygen content. Maternal oxygen consumption increases progressively during gestation and rises further in labor. In late pregnancy or near term, the fetoplacental unit is unable to increase oxygen delivery by local vascular adjustment. The fetus, however, is protected from hypoxic insult by the avidity of fetal hemoglobin for oxygen relative to maternal hemoglobin, the high fetal hemoglobin content, the high fetal cardiac output, and the autoregulatory responses of the fetal circulation in response to hypoxic insult. These general physiologic characteristics of pregnancy have the following implications for management of critical illness:

1. Assessment of the adequacy of maternal blood flow must be made with an understanding that baseline flow is substantially increased, with further increases during active labor or with fever, infection, or pain.

2. Diminished placental blood flow represents a threat to fetal well-being and viability, especially if superimposed on maternal anemia, hypoxemia, or both. Maternal hypoxemia can be particularly damaging if it elicits vasodilation of nonplacental beds, as this results in redistribution of blood flow from the fetoplacental unit.

3. The delivery of oxygen to the fetoplacental unit can be optimized by maintaining or restoring adequate circulating volume and cardiac function, giving blood transfusions to increase oxygen carrying capacity, by putting the mother in the left lateral decubitus position to improve maternal cardiac output, and by giving supplemental oxygen to increase maternal oxygenation.

4. Delivery of the fetus may be the best option if gestational age permits. However, since labor represents a tremendous aerobic load for the mother, the team must judge whether labor should be avoided or postponed during periods of critical illness in which oxygen delivery is marginal.

5. One effective way to reduce aerobic requirements in the critically ill gravid patient is to assume the work of breathing in evolving respiratory failure. Thus early elective intubation and mechanical ventilation may be beneficial in selected patients.

6. Fetal monitoring is at present an inexact and evolving science and should be performed in conjunction with the obstetric team. Measurement of fetal heart rate is a useful but nonspecific indicator of well-being and a late sign of inadequate oxygen delivery. It is most accurate after 32 weeks of gestation and is best used as a screening tool. Although continuous transcutaneous PO2 measurement is feasible in the fetus, the results are difficult to interpret, and the low baseline value does not provide a wide margin for identifying evolving hypoxia. Fetal acid-base status can be measured by means of scalp blood sampling if membrane rupture and cervical dilation have occurred. A pH less than 7.2 suggests physiologic depression of the fetus.2 In general, the routinely obtained parameters of oxygen delivery and acid-base status in the mother are the best measures of the adequacy of oxygen delivery for both the fetus and the mother.

In pregnancy, circulatory impairment may be life-threatening, given the dependence of the mother and fetus on cardiac output for oxygen delivery. In the next section, common causes of hypoperfusion, such as hemorrhage, cardiac dysfunction, aortic dissection, trauma, and sepsis, are discussed. The pathophysiology and treatment of preeclampsia, which may occur as a result of uteroplacental hypoperfusion, is also explored. Venous thromboembolic disease in the setting of pregnancy is addressed in Chap. 27. Together these disorders account for a significant percentage of maternal deaths related to pregnancy (Table 105-3).26 Finally, modifications of cardiopulmonary resuscitation algorithms that are necessary in pregnancy are considered.

Hypoperfused States

The initial approach to the critically ill hypoperfused gravida is to distinguish between low-flow states caused by inadequate circulating volume, cardiac dysfunction, or trauma, and high-flow states such as septic shock, while taking into account the physiologic alterations associated with pregnancy. Most often the state of perfusion of the critically ill gravid patient can be determined by bedside assessment. Occasionally, the adequacy of intravascular volume remains unclear despite a careful history, physical examination, and review of routine laboratory data. Other patients are encountered who have obvious ventricular failure requiring the use of vasoactive drugs or respiratory failure requiring careful fluid management. In these instances right heart catheterization should be considered (Table 105-4), although a survival benefit from this invasive procedure has not been confirmed in obstetric patients.27 When this procedure is necessary in a pregnant patient, a subclavian or internal jugular approach should be used. Femoral vein catheterization is relatively contraindicated because of the obstruction of the vena cava by the uterus and the possible need for emergent delivery. In the healthy pregnant woman, right ventricular, pulmonary artery, and pulmonary capillary wedge pressures are unchanged from prepartum values.2,10 As discussed above, cardiac output is increased, and SVR and pulmonary vascular resistance are decreased during pregnancy (see Table 105-1). Assessment of left and right ventricular hemodynamics by echocardiography was shown to correlate with pulmonary artery catheter results in a heterogeneous group of critically ill obstetric patients.28 Thus in centers with sophisticated echocardiography techniques this may provide an alternative to invasive monitoring.

Hemorrhagic Shock

The common causes of hemorrhagic shock in pregnancy are listed in Table 105-5. When hemorrhage occurs in pregnancy, it can be massive and swift, necessitating immediate intervention. It is the second leading cause of both maternal death and admission to the ICU.26,29 Antepartum hemorrhage is most often caused by premature separation of the normal placental attachment site (abruptio placentae), disruption of an abnormal placental attachment (placenta previa), and spontaneous uterine rupture.

Abruptio placentae occurs in 1 of every 77 to 250 pregnancies, with an increased incidence in patients with hypertension (half from chronic hypertension, half from preeclampsia), high parity, cigarette smoking, cocaine use, and previous abruption.30–33 Maternal mortality, usually from postpartum hemorrhage, ranges from 0% to 5.2%, while fetal mortality is higher (between 5% and 36%).30 The cause of the premature placental separation is not well understood, but the initiating event may be a rupture of the spiral arterioles with formation of a hematoma, which then separates the placenta from its site of attachment.31 The severity of maternal blood loss is correlated with the extent and duration of abruption and fetal demise. Blood loss averages 2 to 3 L when abruption results in fetal death, and much of this blood can remain concealed within the uterus.30 Maternal complications include acute renal failure and disseminated intravascular coagulation (DIC), which occurs in up to 30% of patients with fetal death.2,30 Patients may initially present with painful vaginal bleeding and be misdiagnosed as having premature labor. The diagnosis is made using a combination of clinical information and ultrasound.

Placenta previa occurs in approximately 1 of 200 pregnancies and only infrequently causes massive hemorrhage because near-universal ultrasound examination during pregnancy leads to identification prior to delivery. Nonetheless, if vaginal examination results in disruption of the placenta over the cervical os, or if trophoblastic tissue invades the myometrium (placenta previa et accreta), the patient is at risk for massive hemorrhage at delivery.31 Placenta previa is more common in multiparas with prior cesarean delivery and in cigarette smokers.3,32,34 Fetal mortality is low, but it can be much higher if maternal shock occurs.

Uterine rupture occurs in approximately 1 of 2000 pregnancies.31 The most common setting in which rupture occurs spontaneously is the multipara with protracted labor. Other risk factors include prior cesarean section, operative (assisted) vaginal delivery, and use of uterotonic agents.34 In overt rupture, peritoneal signs may be observed. Nonetheless, substantial blood loss can occur in the absence of significant physical findings.

Common causes of postpartum hemorrhage include uterine atony, surgical obstetric trauma, uterine inversion, retained placental tissue, and coagulopathies due to DIC from amniotic fluid embolism, fetal death, and saline solution abortion.2,3 Uterine atony occurs after prolonged labor, overdistention of the uterus from multiple gestation or hydramnios, abruptio placentae, oxytocin administration, or cesarean section, or as a result of retained intrauterine contents or chorioamnionitis. Hemorrhage from surgical obstetric trauma may be due to cervical or vaginal lacerations or uterine incision for cesarean section.

Management

Patients at increased risk of bleeding should be identified early, so that intravenous access and blood typing can be achieved ahead of time. When massive hemorrhage occurs, the initial management of the patient is similar to that of the nonpregnant patient, and two or three large-bore (16-gauge or larger) venous catheters should be inserted. Immediate volume replacement with crystalloid should be instituted until blood is available, and supplemental oxygen should be administered. It is beneficial to position the patient in the left lateral decubitus position to prevent vena caval obstruction from worsening the reduction in venous return that results from massive hemorrhage. Fetal monitoring is important, as fetal distress in the setting of obstetric hemorrhage indicates hemodynamic compromise.2

If shock is not immediately reversed by volume resuscitation or is accompanied by respiratory dysfunction, elective intubation and mechanical ventilation is indicated, since hypoxemia superimposed on a low-flow state is particularly injurious to fetus and mother. Blood replacement with packed red blood cells should begin immediately. Massive obstetric hemorrhage is one setting in which initial resuscitation may require the use of unmatched type-specific blood until more complete cross-matching can be accomplished (see Chap. 68). Because critical illness in pregnancy is frequently associated with DIC, massive bleeding should prompt an evaluation for coagulopathy. If the peripheral blood smear, platelet count, prothrombin time (PT), partial thromboplastin time (PTT), or fibrinogen level suggests excessive factor consumption (DIC), measurement of plasma levels of fibrin degradation products and specific factors should be performed (see Chap. 69). Measurement of factor VIII levels is inexpensive and can be accomplished more quickly than a full DIC screen. Massive blood loss can result in a dilutional coagulopathy with secondary thrombocytopenia which needs to be corrected with appropriate blood product replacement.

Uterine atony is routinely treated with uterine massage, draining the bladder, and intravenous oxytocin.2,34 Oxytocin can cause hyponatremia by virtue of its antidiuretic effect. Alternatively, prostaglandin analogues such as carboprost tromethamine can be used to improve uterine contraction and decrease bleeding.2,34 Side effects include hypertension, bronchoconstriction, and intrapulmonary shunt with arterial oxygen desaturation. Ergot preparations such as methyl-ergonovine have been associated with cerebral hemorrhage and are contraindicated if the patient is hypertensive. Ultrasonography is used to diagnose retained intrauterine products of conception that require curettage. Embolization of the hypogastric, internal pudendal, or uterine artery with slowly absorbable gelatin sponge can sometimes control hemorrhage and allow subsequent recanalization of the embolized vessel.35 Surgical exploration to repair lacerations, ligate arteries, or remove the uterus is necessary in some cases.

Cardiac Dysfunction

Hypoperfusion from cardiac dysfunction is most often caused by congestive heart failure due to either preexisting myocardial or valvular heart disease, or to a cardiomyopathy arising de novo. However, the prevalence of heart disease during pregnancy is low, but its presence increases the likelihood of maternal and fetal morbidity and mortality. Patients with Eisenmenger syndrome, cyanotic congenital heart disease, or pulmonary hypertension have a high mortality rate (33% to 40%) during pregnancy.36 A recent study of 599 pregnancies in Canadian women with either congenital or acquired heart disease (40% had valvular heart disease) identified risk factors for adverse outcomes.37 Pulmonary edema, arrhythmia, stroke, or cardiac death complicated 13% of pregnancies. Predictors of maternal cardiac complications included prior cardiac events, poor functional class (New York Heart Association class III or IV) or cyanosis, left heart obstruction (aortic or mitral stenosis), and left ventricular systolic dysfunction. Adverse outcomes (<1% mortality) occurred in 27% of those with one risk factor and 62% of those with two or more risk factors. Neonatal complications (2% mortality) occurred in 20% of pregnancies and were associated with poor functional class or cyanosis, left heart obstruction, anticoagulation, smoking, and multiple gestation.

Prior subclinical heart disease may manifest itself for the first time during pregnancy owing to the physiologic changes of pregnancy described earlier. Peripartum cardiomyopathy (1 of every 1300 to 4000 deliveries) first presents in the last month of pregnancy or the first 6 months after parturition.38 Postulated risk factors include black race, older age, twin gestations, multiparity, anemia, preeclampsia, and postpartum hypertension. Bacterial endocarditis rarely complicates pregnancy, most often occurring in patients with preexisting cardiac abnormalities, although infection of previously normal valves has been reported in pregnancy, particularly in patients with a history of intravenous drug use.39 Myocardial infarction is extremely uncommon during pregnancy but should be considered in the hypoperfused patient with chest pain. Maternal mortality is high in patients delivering within 2 weeks of infarction.40 There is an increased incidence of aortic dissection during pregnancy, perhaps related to the increase in shear stress on the aorta from the increased heart rate and stroke volume associated with pregnancy and hormonal factors.40 Risk factors include hypertension, older age, multiparity, trauma, Marfan syndrome, Ehlers-Danlos syndrome, coarctation of the aorta, and bicuspid aortic valve. Aortic dissection presents most commonly during the third trimester, often as a tearing interscapular pain. Pulse asymmetry or aortic insufficiency may be noted on examination.

Management

It is essential to determine the cause of the underlying cardiac dysfunction and hypoperfusion. The chest radiograph may suggest the diagnosis; mediastinal widening is often noted in patients with aortic dissection. Echocardiography can help determine the volume status and detect valvular abnormalities, myocardial dysfunction, or ischemia. Transesophageal echocardiography and magnetic resonance imaging are the most sensitive and specific tests for detecting aortic dissection, although computed tomography of the chest is often done first given its ready availability.40 Once the cause of cardiac dysfunction is determined, the initial management of the hypoperfused cardiac patient should focus on volume status, and hypovolemia should be excluded as a cause of the low-flow state. As discussed above (see Table 105-4), right heart catheterization may be helpful in this regard, as well as in the further management of cardiogenic shock. Metabolic disturbances can worsen ventricular function in patients with a cardiomyopathy; therefore hypocalcemia, hypophosphatemia, acidosis, and hypoxemia should be avoided. Vasoactive drugs are reserved for situations in which hypovolemia has been corrected and maternal perfusion remains inadequate. If cardiogenic shock persists despite an adequate preload, dobutamine is the drug of choice. However, it should be reserved for life-threatening conditions because at least in animal models, it reduces placental blood flow.41 Infusion of dopamine in low doses [2 to 3 μg/(kg · min)] has been advocated to preserve splanchnic and renal perfusion. Its use in pregnancy has been limited, and recent studies demonstrated that it does not benefit critically ill patients with sepsis syndrome.42 Accordingly, we do not advocate its routine use in the critically ill pregnant patient, but it may be useful in treating oliguria associated with preeclampsia (see below). When cardiogenic shock is complicated by pulmonary edema, parenteral furosemide should be given; right heart catheterization may help to titrate therapy.

When cardiogenic shock persists despite inotropic drug support, afterload reduction with nicardipine should be considered.43 Intravenous sodium nitroprusside or nitroglycerin are second-line agents and when used the dose and duration of therapy should be minimized, and oral agents such as hydralazine or labetalol should be substituted as soon as possible to avoid nitroprusside toxicity. Angiotensin-converting enzyme inhibitors are absolutely contraindicated during pregnancy, because they have been found to cause fetal growth retardation, oligohydramnios, congenital malformations, and anuric renal failure in human neonates exposed in utero, as well as neonatal death.44

The hemodynamic alterations of labor and delivery, superimposed on those of pregnancy, make this an especially dangerous time for women with cardiac disease. The optimal method of delivery is an assisted vaginal delivery in the left lateral decubitus position.38 Epidural anesthesia will ameliorate tachycardia in response to pain, and its vasodilatory actions may be of benefit in patients with congestive heart failure.1 Since decreased SVR may lead to further decompensation in patients with aortic stenosis, hypertrophic cardiomyopathy, or pulmonary hypertension, general anesthesia may be preferred in these patients.1 The current consensus is that cesarean section should be reserved for cases with obstetric complications or fetal distress, although with improved surgical techniques and close hemodynamic monitoring, cesarean sections may be safer than in the past.1 Invasive monitoring may be required to follow shifts in volume status that occur from the tremendous “autotransfusions” produced by each uterine contraction and the blood loss that occurs with delivery.

Trauma

Death from trauma is a leading cause of nonobstetric maternal mortality. During pregnancy, hypoperfusion and shock may occur as a result of injury from motor vehicle accidents, falls, and assaults.45 The gravid woman is at greater risk of hemorrhage after trauma, as blood flow to the entire pelvis is increased. Some injuries are unique to pregnancy, including amniotic membrane rupture, abruptio placentae, uterine rupture, premature labor, and fetal trauma.45 In a series of patients with blunt abdominal trauma in late pregnancy, the most serious complications were placental abruption and uterine rupture and preterm labor was the most common.46 Rapid deceleration injury can cause abruptio placentae (20% to 40% of major injuries) as a result of deformation of the elastic uterus around the less elastic placenta. In most cases, vaginal bleeding will be present when abruption has occurred, although there are reports of occult abruption without vaginal bleeding following traumatic injury.46 Abruption can be complicated rapidly by DIC; therefore coagulation profiles should be monitored in all severely injured gravid patients. The cephalad displacement of abdominal contents in pregnancy increases the risk of visceral injury from penetrating trauma of the upper abdomen including splenic rupture. The urinary bladder is a target for injury because it is displaced into the abdominal cavity beyond 12 weeks of gestation.

The physiologic changes of pregnancy may make evaluation and treatment of the gravid trauma patient more difficult. Borderline tachycardia and supine hypotension (from obstruction of the vena cava by the uterus in late pregnancy) may be caused by pregnancy itself and thus may not indicate significant blood loss. Clinical signs of hypovolemia are not observed in trauma victims until intravascular volume is reduced by 15% to 20%. When hypovolemia is clinically evident in gravid patients, it signifies enormous blood loss because of the expanded blood volume associated with pregnancy. Pregnancy may mask findings of peritoneal irritation. In one series of 12 gravid patients undergoing peritoneal lavage for evaluation of blunt abdominal trauma, only 2 of the patients exhibited abnormal abdominal signs or symptoms.47 Nonetheless, 8 had positive lavage with confirmation of intra-abdominal bleeding or injury at laparotomy.

Blunt trauma rarely causes fetal injuries. Fetal skull fracture occurs most often in the third trimester, when the engaged fetal head is at risk of injury from maternal pelvic fractures.45 The risk of fetal death depends on the severity of maternal injury and hemodynamic compromise and on the extent of injury to the fetus.2 Maternal shock, pelvic fractures, severe head injury, and hypoxemia all increase the risk of fetal demise.

Management

Initially, maternal cardiopulmonary function and the extent of injury should be assessed. If required, emergent intubation should be performed by a skilled individual because of the increased risk of aspiration during pregnancy. Since maternal shock is a major cause of fetal demise, ensuring the adequacy of the maternal circulation is paramount. If significant hemorrhage is obvious, aggressive fluid replacement, as discussed above for hemorrhagic shock, is appropriate. Once the cervical spine is cleared, the patient should be placed in the left lateral position. Pelvic examination should be performed, provided there is no overt vaginal bleeding, to look for blood, urine, and amniotic fluid. Nitrazine paper can identify amniotic fluid and confirm rupture of the amniotic membranes. The diagnosis of pelvic or abdominal injury can usually be made by ultrasonography, computed tomography, or lavage.47–49 Because needle paracentesis is difficult to perform in the second and third trimesters, open peritoneal lavage is advised for assessing severe blunt abdominal trauma and confirming that intraperitoneal fluid noted on imaging studies is hemorrhagic. Once the mother is stabilized, cardiotocographic monitoring, including Doppler measurement of fetal cardiac activity and measurement of uterine activity, should be performed for 4 hours after the injury. When used in trauma patients who are beyond the twentieth week of pregnancy, cardiotocographic monitoring can identify placental abruption, fetal distress, and uterine contractions.45 Fetomaternal hemorrhage—that is, blood loss from the fetal to the maternal circulation—may be identified by the Kleihauer-Betke test, which identifies fetal hemoglobin in red blood cells. Rh sensitization of Rh-negative patients, neonatal anemia, fetal cardiac arrhythmias, and fetal exsanguination are potential complications of fetomaternal hemorrhage.45 Maternal Rh sensitization can be prevented by administration of RhO(D) immune globulin.

If maternal death occurs despite aggressive resuscitation and the fetus is alive and undelivered, a postmortem cesarean section should be considered. A review of over 150 cases revealed that the outcome was significantly related to the length of time between maternal death and delivery and to the gestational age of the fetus.50

Septic Shock

Sepsis is another important cause of hypoperfusion in pregnancy, accounting for 13% of maternal deaths in the United States in the 1990s.26 The diagnosis of sepsis in the febrile gravid patient can be obscured by the normal hemodynamic changes of pregnancy (i.e., increased cardiac output and decreased SVR). An awareness of the usual settings and patients at risk for sepsis will increase the chance of recognizing this life-threatening state. Animal data suggest pregnancy may cause increased vulnerability to the systemic effects of bacteremia and endotoxemia.51 In addition, pregnant patients have an increased susceptibility to infection with Listeria monocytogenes and disseminated herpesvirus, varicella, and coccidioidomycosis infections, perhaps owing to a decreased cell-mediated immune response during pregnancy.2

The common causes of sepsis in pregnancy include septic abortions, antepartum pyelonephritis, chorioamnionitis, and postpartum infections (puerperal sepsis) (Table 105-6).52 Septic abortion is more often seen in countries where access to abortion is limited. Chorioamnionitis or intra-amniotic infection complicates up to 1% of all pregnancies. It occurs most commonly after prolonged rupture of membranes or prolonged labor, or after invasive procedures such as amniocentesis or cervical cerclage, but occasionally it reflects hematogenous spread from maternal bacteremia.53 Patients present with fever, tachycardia (both maternal and fetal), uterine tenderness, and foul-smelling amniotic fluid.

Sepsis in obstetric patients usually occurs postpartum. Clinical settings that increase the risk of postpartum sepsis include cesarean section, prolonged rupture of membranes, and prior instrumentation of the genitourinary tract.52,54 Infection usually occurs at the placental site, resulting in endometritis. Patients with endometritis may present with fever, abdominal pain and tenderness, and purulent lochia. Episiotomy sites and cesarean section incisions are less common sources of postpartum infection. Rarely, life-threatening wound infection with group A streptococci results in necrotizing fasciitis, while Clostridium species may cause gas gangrene of the uterus.2,52 The bacteria that must be considered include Staphylococcus aureus and S. epidermidis; groups A, B, and D streptococci; Escherichia coli; Proteus mirabilis; Enterobacter spp.; Klebsiella spp.; Pseudomonas spp.; anaerobic streptococci and Bacteroides spp.; and Clostridium perfringens (Table 105-7).52 Rarely, toxic streptococcal syndrome may occur as a result of infection with pyrogenic exotoxin A–producing group A streptococci in patients with necrotizing fasciitis or may unexpectedly follow an uncomplicated pregnancy and delivery.2 Patients present with an influenza-like prodrome and gastrointestinal symptoms followed by shock and multiple organ system dysfunction. If a patient deteriorates while receiving appropriate antibiotic therapy, surgical exploration with possible hysterectomy are indicated.2

The hemodynamic profile in septic shock is similar to that of the nonpregnant septic patient.54 In a study by Lee and colleagues of 10 obstetric patients with septic shock, right heart catheterization of the 8 surviving patients revealed a high cardiac index and heart rate with a low blood pressure and a decreased systemic vascular resistance index (SVRI). Analysis of left ventricular function curves revealed that 50% of the patients had evidence of myocardial depression despite an increased cardiac index. The greatest improvement in SVRI occurred in the eight surviving women; their initial SVRI was 885 ± 253 dyne · s/(cm5 · m2), and it rose to 1672 ± 413 dyne · s/(cm5 · m2) following resolution of their hyperdynamic state. It is important to remember that pregnancy itself results in a 25% decrease in vascular resistance from the prepregnancy level of 900 to 1500 dyne · s/cm5, a decrease in blood pressure, and a 20% increase in heart rate. Thus three useful signs of sepsis—tachycardia, hypotension, and low systemic vascular resistance—must be interpreted with caution in the gravid patient, particularly in the third trimester. However, a rapid change in hemodynamic parameters suggests infection. Complications of sepsis in pregnancy include pulmonary capillary leakage with subsequent acute respiratory distress syndrome (ARDS) and DIC.54

Management

The septic gravid patient requires thorough culturing and evaluation of pelvic sites. Empiric antibiotic therapy, designed to cover what is typically a polymicrobial infection involving gram-positive, gram-negative, and anaerobic organisms, as discussed above, should be given until specific bacteriologic cultures are available. Reasonable regimens to cover the above organisms should include at least two antibiotics such as clindamycin and a third-generation cephalosporin; in certain patients it is necessary to expand the initial regimen to include a semisynthetic penicillin, an aminoglycoside, or another broad-spectrum agent.52 If possible, however, it is best to avoid aminoglycosides in patients with sepsis antepartum, because these agents can be ototoxic and nephrotoxic to the fetus. Chorioamnionitis associated with sepsis is unlikely to respond to antibiotic therapy alone, and delivery of the fetus is required.2 Postpartum deterioration in septic patients receiving adequate antibiotic coverage suggests a localized abscess, a resistant organism, or septic pelvic thrombophlebitis.2 Surgical drainage of appropriate pelvic and abdominal sources, with possible hysterectomy, may be required, particularly in patients with myometrial microabscesses or gas gangrene from clostridial species. Computed tomography or magnetic resonance imaging of the pelvis may help in the diagnosis of septic pelvic thrombophlebitis, which is treated with antibiotics and anticoagulation.2 Venous ligation or surgical excision is sometimes required.

Patients who have evidence of adequate tissue perfusion and oxygen delivery may not require fluid or vasoactive drugs for the treatment of tachycardia and moderate hypotension. Lactic acidosis or end-organ dysfunction is an indication for volume resuscitation, but given the risk of precipitating low-pressure pulmonary edema, right heart catheterization may be helpful to allow titration of volume therapy. Mechanical ventilatory support should be instituted if needed. If hypoperfusion persists despite volume replacement, the use of vasoactive agents such as dobutamine to increase forward flow may be of value in patients who have markedly abnormal ventricular performance. Since there are no clear benefits from inotropic agents in patients with high-flow states whose cardiac function is near normal, these drugs should be withdrawn if adverse effects are noted. Elevated temperature should be controlled with acetaminophen and a cooling blanket, because fever is detrimental to the fetus. The role that vasopressin might play in the pregnant patient with septic shock remains undefined, but institution of an infusion at 40 mU/h is reasonable in the patient with refractory shock.

Naloxone has not proven useful in septic shock, and recent trials of immunotherapeutic agents directed against bacterial antigens or exotoxins have to date not added to the armamentarium available to treat these patients.55 As in the nonpregnant septic patient, corticosteroids should be given if adrenal insufficiency is documented.56 The corticotropin stimulation test may be difficult to interpret in the pregnant woman because baseline cortisol may be elevated in pregnancy and stimulation tests have not been studied in this population. Recombinant protein C has not been systematically evaluated in pregnant patients and it is impossible to make informed commentary on its risk/benefit profile in this setting. At present, the essentials of treatment are early appropriate antibiotics, surgical treatment if necessary, and meticulous supportive care.

Preeclampsia

Preeclampsia is a unique disorder of pregnancy that complicates 5% to 10% of all pregnancies, accounting for a substantial proportion of obstetric ICU admissions (38% in a recent series in the United States) and 10% to 15% of maternal deaths.3,26,57 It occurs most often in nulliparous women after the twentieth week of gestation, typically near term, and may even occur postpartum. It is characterized by hypertension, proteinuria, and generalized edema; however, these features may be mild and may not occur simultaneously, making the diagnosis of early disease difficult in some cases. Hyperuricemia is also present in almost all cases of preeclampsia and may be useful in differentiating preeclampsia from both preexisting chronic hypertension and gestational hypertension.44 Multiple other organ systems may be involved, as discussed below. Risk factors for the development of preeclampsia, besides the primigravid state, include both preexisting and gestational hypertension, maternal or paternal family history of preeclampsia, preexisting renal disease, diabetes mellitus, multiple gestation, hydatidiform mole, and antiphospholipid antibody syndrome.2,58 Preeclampsia may progress to a convulsive and potentially lethal phase, termed eclampsia, without warning. Eclampsia occurs in more than 0.2% of all deliveries, with an incidence of 1.5% in twin deliveries.59 An especially fulminant complication of preeclampsia is the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), which occurred in 0.3% of deliveries in one large clinical series.60 Maternal and fetal morbidity and mortality are significant if eclampsia or the HELLP syndrome develops or if preeclampsia develops prior to 34 weeks of gestation.44 In one large study of women with eclampsia, perinatal mortality was 8.6%, with placental abruption accounting for four of the six perinatal deaths; there were no maternal deaths.59 In a recent review of women with HELLP syndrome, perinatal mortality was 12.6%.60 While there were no maternal deaths, life-threatening complications such as placental abruption often with associated DIC, pulmonary edema, and ARDS, cerebral hemorrhage, and hepatic hematoma occurred in 10.3% of patients.

Although the exact etiology of preeclampsia is unknown, nearly all maternal organ systems are affected. The common pathologic feature is vascular endothelial damage that may be due to mediator release as a result of placental ischemia.61 Maternal vascular endothelial dysfunction results in increased loss of fluid from the intravascular compartment, increased sensitivity to pressor agents and activation of the coagulation cascade.62 Increased endothelin production and decreased release of nitric oxide may also be important in the development of this disorder.63 The reduction in placental perfusion and increased circulating concentrations of markers of endothelial activation and intravascular coagulation occurs before the onset of clinical disease.9,62 Cardiac output and plasma volume are reduced in preeclampsia, while SVR is increased.44 In one study, right heart catheterization of 44 untreated preeclamptic patients revealed low normal right atrial and pulmonary capillary wedge pressures (Ppw), a reduced cardiac output, and a markedly elevated systemic vascular resistance.9 A study of 41 preeclamptic patients found that the majority of the patients had a normal Ppw, normal to high cardiac index, and upper normal to moderately elevated SVR compared to historical controls.64 The eight patients with pulmonary edema had a high wedge pressure.

Preeclampsia may be mild or severe. Markers of disease severity that should alert the physician to an increased risk of complications include systolic or diastolic blood pressures of ≥160 and ≥110 mm Hg, respectively (especially after 24 hours of hospitalization), proteinuria ≥2 g in 24 hours or ≥100 mg/dL in a random specimen, oliguria, or pulmonary edema.2,9 Especially worrisome symptoms and signs in any patient with preeclampsia include headache, blurred vision, scotomata, altered consciousness, clonus, epigastric or right upper quadrant pain, increasing serum creatinine level, consumptive coagulopathy with thrombocytopenia and/or microangiopathic hemolytic anemia, and even mildly elevated values on liver function tests.2,9

Maternal complications of severe preeclampsia include seizures (eclampsia); cerebral hemorrhage or edema; renal dysfunction; pulmonary edema; placental abruption with DIC; the HELLP syndrome; and hepatic infarction, failure, subcapsular hemorrhage, or rupture.44,65 The etiology of eclamptic seizures is presumed to be related to cerebral vasospasm, ischemia, or edema and hypertensive encephalopathy.2 Although the risks of eclampsia are higher when the above markers of disease severity are present, in one large clinical series 20% of eclamptic patients had a blood pressure below 90 mm Hg or no proteinuria prior to experiencing convulsions.44 Though it is rare, cerebral edema is a cause of death in patients with preeclampsia. It may result from severe hypertension and large volumes of fluid administered to treat the oliguria and decreased plasma oncotic pressure frequently noted in preeclampsia.66 Renal dysfunction may result from intravascular volume depletion, renal ischemia, and glomerular disease characterized by swollen glomerular endothelial cells known as glomeruloendotheliosis.20,67 Acute renal failure is rare and most often is seen in patients with the HELLP syndrome, placental abruption, massive hemorrhage, or coagulopathy.2 Pulmonary edema is uncommon, having an incidence of 2.9% in patients with severe preeclampsia.68 Contributing factors include increased left ventricular afterload, myocardial dysfunction, decreased colloid osmotic pressure, vigorous fluid therapy, and in some cases increased capillary permeability.2 It most commonly occurs after parturition. In a subgroup of patients, antepartum pulmonary edema develops.69 These patients are typically obese and chronically hypertensive with secondary left ventricular hypertrophy. The increased intravascular volume of pregnancy and the hemodynamic derangements of preeclampsia cause diastolic dysfunction with an elevated Ppw and pulmonary edema.

The HELLP syndrome is characterized by multiorgan dysfunction arising from an endothelial abnormality with secondary fibrin deposition and organ hypoperfusion.2 A microangiopathic hemolytic anemia and consumptive coagulopathy develop. When DIC occurs, it is often in the setting of placental abruption, sepsis, or fetal demise.2 The liver involvement is characterized by periportal or focal parenchymal necrosis with elevated liver function tests. Intrahepatic hemorrhage or subcapsular hematoma occurs in 2% of patients and may progress to hepatic rupture.60,65

The HELLP syndrome occurs in 4% to 20% of patients with preeclampsia.61 There is an increased incidence in white women and in one series 45% of the patients were multiparous.2,60 Patients are more often preterm than those with uncomplicated eclampsia. In up to 30% of patients, the HELLP syndrome develops after parturition; typically it appears within 48 hours, but it has been reported up to 7 days postpartum. Presenting symptoms are usually nonspecific, the most common being malaise, epigastric or right upper quadrant pain, nausea, vomiting, and edema. Patients less frequently present with jaundice, gastrointestinal bleeding, or hematuria. Signs and symptoms of preeclampsia may be mild or absent upon initial presentation. Complications include acute renal failure, ARDS, hemorrhage, hypoglycemia, hyponatremia, and nephrogenic diabetes insipidus. Fetal growth restriction and prematurity are the major causes of perinatal morbidity and mortality. Maternal mortality ranges from 0% to 24%, with higher perinatal mortality (8% to 60%).

Laboratory values that suggest the diagnosis include:61 (1) hemolysis demonstrated by an abnormal peripheral smear; (2) increased levels of bilirubin (≥1.2 mg/dL) or lactate dehydrogenase (≥600 U/L); (3) increased liver enzyme levels with an elevated serum level of glutamic oxaloacetic transaminase (≥70 U/L); and (4) thrombocytopenia with a platelet count of <100,000/μL. Isolated thrombocytopenia that progresses may be one of the first clues to the diagnosis.

Management

The principles of management of preeclampsia include early diagnosis, close medical observation, and timely delivery. Delivery is curative in most cases. The differential diagnosis of preeclampsia includes thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), acute fatty liver of pregnancy, and idiopathic postpartum renal failure (Table 105-8) (see Chap. 70). Once the diagnosis is made, further management is based on an evaluation of the mother and fetus. Mild preeclampsia may be managed on an outpatient basis if hypertension is mild, the fetus is doing well, and compliance is good.44 The patient will require close monitoring, since this condition can worsen suddenly. The presence of symptoms and proteinuria increases the risk of placental abruption and eclampsia. These patients and those with disease progression should be hospitalized and observed closely. In patients who have mild preeclampsia at term and have a favorable cervix, labor should be induced. There is no consensus regarding the utility of bed rest, antihypertensive therapy, or anticonvulsant prophylaxis in this group of patients. Based on a number of clinical trials, there is no clear benefit to antihypertensive drug treatment in women with mild gestational hypertension or preeclampsia.44

Because severe eclampsia can progress rapidly, delivery is recommended in these patients. Immediate delivery is appropriate when there are signs of impending eclampsia, multiorgan involvement, or fetal distress, and in patients who are more than 34 weeks pregnant.44 Early in gestation, conservative management with close monitoring to improve neonatal survival and morbidity may be appropriate in selected cases at tertiary perinatal centers. The objective of antihypertensive therapy is to prevent cerebral complications such as encephalopathy and hemorrhage. A sustained diastolic blood pressure of 110 mm Hg or greater should be treated to keep the mean arterial pressure between 105 and 126 mm Hg and the diastolic pressure between 90 and 105 mm Hg. While hydralazine 5 mg IV every 20 minutes to a total dose of 20 mg has been the traditional treatment, blood pressure control in the ICU setting is best obtained with either intravenous labetalol or nicardipine.43 A loading dose of labetalol 20 mg is recommended, followed by either repeated incremental doses of 20 to 80 mg at 10- to 15-minute intervals or an infusion starting at 1 to 2 mg/min and titrated up until the target blood pressure is achieved.43 Since calcium channel blockers may be potentiated by magnesium infusion, care should be taken to avoid hypotension when the two medications are used together.3 Acute nicardipine infusion can induce severe maternal tachycardia.70 (Table 105-9). Nitroprusside is relatively contraindicated, and angiotensin-converting enzyme inhibitors are absolutely contraindicated, in pregnancy. Diuretics should be used with caution, as they may aggravate the reduction in intravascular volume that is often seen in preeclampsia. Volume expansion may decrease SVR and improve oliguria; however, the increased risk of pulmonary or cerebral edema makes fluid administration difficult without a right heart catheter in place.3,71 Antihypertensive therapy has no effect on the progression of disease and does not prevent complications such as HELLP.

Magnesium sulfate prophylaxis has been shown to be better than placebo, phenytoin, or nimodipine in the prevention of eclampsia.72–74 In a recent large study, magnesium sulfate was superior to both phenytoin and diazepam for the treatment and prevention of recurrent convulsions in women with eclampsia.75 Magnesium sulfate should be given to all women with either preeclampsia or eclampsia and for a minimum of 24 hours postpartum. Aspirin has no role in the treatment of preeclampsia.

The preeclamptic patient with oliguria may benefit from judicious volume loading and low-dose dopamine therapy.76 Invasive monitoring is recommended to prevent pulmonary and cerebral edema. Pulmonary edema is managed conventionally. Patients with delayed postpartum resolution of the HELLP syndrome with persistent thrombocytopenia, hemolysis, or organ dysfunction may benefit from plasmapheresis with fresh frozen plasma.2,77 Many of these patients may actually have TTP or HUS, which can be difficult to distinguish from the HELLP syndrome. In two studies, administration of corticosteroids resulted in improved maternal platelet counts and liver function test results and in a trend toward better fetal outcome.78 No significant effect in delaying delivery was noted. Management of intrahepatic hemorrhage with subcapsular hematoma includes administration of blood products, delivery, and control of liver hemorrhage.65 Embolization of the hepatic artery is often successful, but evacuation of the hematoma and packing of the liver may be required.

Cardiopulmonary Resuscitation

Pregnancy can interfere with the performance of adequate cardiopulmonary resuscitation (CPR). If cardiopulmonary arrest occurs, the physiologic changes of pregnancy must be taken into account when performing CPR, including the increased metabolic rate and cardiac output and decreased oxygen reserve typical of the pregnant patient. The gravid uterus may impede venous return and distal arterial perfusion by compressing the inferior vena cava and aorta. In late pregnancy, the gravid uterus acts like an abdominal binder; the resulting elevation of intrathoracic pressure may limit the ability to create forward flow during CPR.

These considerations have prompted some pregnancy-specific modifications of the usual approach to CPR.79,80 The key modification is that the pregnant patient should receive standard CPR while in the left lateral decubitus position to decrease aortocaval compression by the uterus. That can be accomplished by using a table that provides a lateral tilt, by placing a wedge under the patient's right hip, or by manually displacing the uterus to the left.2 Otherwise, standard resuscitative measures using currently approved protocols should be followed. Defibrillation (after removal of fetal monitoring devices to prevent arcing) and pharmacologic therapy should be employed as clinically indicated.

If standard closed-chest CPR cannot generate a pulse, especially in late pregnancy, open-chest massage and emergency cesarean section should be considered. In one case report, the mother could not be resuscitated until the fetus was delivered; both subsequently survived.81 To facilitate this plan, obstetric, internal medicine, and anesthesiology staff need to be apprised early of any acute deterioration in the circulation of a critically ill gravida. Delivery within 4 to 5 minutes of the arrest will improve the chance of a good outcome for both mother and fetus.79

During pregnancy, ventilatory failure may occur as a result of a chronic lung disease such as cystic fibrosis or asthma and may require mechanical ventilation. A more common cause of respiratory compromise in pregnant women is acute hypoxemic respiratory failure related to amniotic or venous air embolism, tocolytic-induced pulmonary edema, aspiration, or pneumonia. This section focuses on the management of both ventilatory and hypoxemic respiratory failure in the gravid patient.82

Ventilatory Failure

With improved medical care, patients with chronic lung diseases such as cystic fibrosis are surviving to childbearing age, presenting new management problems for the intensivist. Asthma, however, remains the most common pulmonary problem encountered in pregnancy, affecting 1% to 4% of all gravidas. When these conditions require mechanical support, ventilator management necessitates careful attention to the special needs of mother and fetus.

Mechanical Ventilation

If ventilatory failure is imminent, intubation and mechanical ventilation should be performed electively. The indications for intubation and mechanical ventilation are not significantly changed by pregnancy, although the normal PCO2 of 27 to 32 mm Hg during pregnancy should be considered when deciding on mechanical ventilation.3 Several difficulties in airway management should be anticipated in the critically ill pregnant patient (Table 105-10). Pharyngeal, laryngeal, and vocal cord edema are common, and the highly vascular upper airway may bleed from even minor intubation-related trauma.83 Relatively small endotracheal tubes (6- to 7-mm diameter) may be necessary, and nasotracheal intubation is best avoided because of this upper airway narrowing.2 There may be an increased risk of aspiration during pregnancy because of delayed gastric emptying, increased intra-abdominal pressure from compression by the gravid uterus, and diminished competence of the gastroesophageal sphincter.84 Use of cricoid pressure to minimize the risk of pulmonary aspiration is recommended. Approximately 40% of maternal deaths associated with general anesthesia in England and Wales from 1976 to 1978 were related to difficulties with endotracheal intubation.85 Control of the airway should be achieved in an early and elective fashion by a skilled individual. Noninvasive mask ventilation for acute respiratory failure has not been studied in pregnancy. In the awake patient needing temporary ventilatory assistance, noninvasive positive pressure ventilation is a reasonable first step. Theoretical limitations to this therapy include pregnancy-related upper airway edema and increased risk of aspiration.

The initial ventilator settings should be aimed at achieving eucapnia, which in this patient population is a PCO2 of 28 to 35 mm Hg. Respiratory alkalosis should be avoided, since studies in animal models suggest that hyperventilation can reduce fetal oxygenation and decrease uteroplacental flow.2,86 Alkalosis can usually be avoided with tidal volumes in the range of 10 mL/kg and respiratory rates of 15 to 18 breaths per minute (bpm). In the asthmatic patient (see below), the use of a lower tidal volume and respiratory rate minimizes the adverse effects of intrinsic positive end-expiratory pressure (PEEP) (see Chap. 38).

The patient with acute pulmonary edema (see below) should be ventilated with a small tidal volume (4 to 6 mL/kg) and a high respiratory rate (24 to 30 bpm).87 While recent studies of nonpregnant adults managed with mechanical ventilation for ARDS have shown improved survival when low (∼6 mL/kg) tidal volumes were used—even if this was associated with hypercapnia—the safety of this permissive hypercapnia in pregnancy remains to be determined. In one animal model, acute hypercapnia during mechanical ventilation was associated with fetal distress. During any mechanical ventilatory period, continuous fetal monitoring should be conducted, usually accomplished by heart tone determination, and if acute ventilatory changes are associated with any evidence of challenge to the fetus, they should be avoided. It is important to note that pregnancy, particularly in the third trimester, can result in significant chest wall stiffness resulting from the gravid uterus, and high airway pressures may not signal lung stiffness or overdistension per se. Taken together, these observations would suggest an approach to acute hypoxemic respiratory failure in pregnancy that would begin with careful fetal monitoring, instituting low tidal volumes, avoiding acute rises in partial arterial pressure of carbon dioxide (PaCO2) and increasing tidal volume if they occur in association with fetal distress, and allowing plateau airway pressures to be somewhat higher than the 30 cm H2O often recommended for individuals without such abdominal distension.

When a diffuse lung lesion is present and toxic levels of oxygen would be needed, sufficient PEEP should be imposed to correct arterial hypoxemia at a nontoxic fraction of inspired oxygen (FiO2 <0.6). In the pregnant patient, we aim to keep the PaO2 >90 mm Hg, a value higher than that used in the nonpregnant patient, to prevent fetal distress. To minimize the decrease in venous return that occurs with positive pressure ventilation, it is important that the pregnant patient be managed in a lateral position whenever possible. Measures to avoid atelectasis in the ventilated gravid patient include PEEP, sighs, and alternating the position between left lateral and right lateral.

In patients with severe lung lesions requiring toxic concentrations of oxygen and high levels of PEEP, and in patients with hemodynamic instability, muscle relaxation and sedation will decrease oxygen consumption and assist in stabilization. Nondepolarizing neuromuscular blocking agents including cisatracurium, pancuronium, vecuronium, and atracurium, produce no adverse fetal effects with short-term use.2 Of these, cisatracurium is preferred because it does not depend on renal or hepatic function for elimination. Benzodiazepines may increase the risk of cleft palate and other major birth defects when used early in pregnancy, although this has not been conclusively demonstrated. If enzodiazepines are necessary for sedation, the lowest dose and shortest duration of use are recommended. Propofol, pregnancy category B hypnotic agent (see Chap. 14), may be considered, however no data exist on its use in the first or second trimesters in humans. Narcotic analgesics such as morphine sulfate and fentanyl may be used safely during pregnancy. These agents all cross the placenta; therefore if given near the time of delivery, immediate intubation of the neonate may be required.

Fetal viability can be maintained throughout pregnancy with mechanical ventilation, even when maternal death occurs. Mechanical ventilation is most appropriate when instituted early in the course of progressive ventilatory failure, to stabilize mother and fetus and then permit identification of reversible factors to allow either safe withdrawal of mechanical support or controlled delivery. These complex decisions are best made in collaboration with the critical care physician, obstetrician, and neonatologist.

Chronic Lung Disease

Most chronic pulmonary diseases that can result in ventilatory failure, such as cystic fibrosis, kyphoscoliosis, neuromuscular diseases, pulmonary fibrosis, and chronic obstructive pulmonary disease (COPD), are uncommon in pregnant women. Despite the increased ventilatory demands that occur in pregnancy, ventilatory failure is rare. In one study, several women with a preconception vital capacity of 40% to 70% predicted due to lung resection or collapse for tuberculosis, carried their pregnancy to term and had few respiratory symptoms.88 Although several authorities suggest that a vital capacity of at least 1 L is essential for a safe and successful pregnancy,89 one patient has been reported to have completed pregnancy with a vital capacity of only 0.8 L (25% of predicted) and a PCO2 of 45 mm Hg.90 Thus severe reduction in lung volume to a level that would represent impairment of ventilatory function in a nonpregnant individual does not in itself preclude a successful conception and pregnancy.

Patients with severe restrictive lung disease and progressive ventilatory insufficiency during pregnancy may benefit from nocturnal positive pressure ventilation and oxygen administration. One patient with severe kyphoscoliosis and a forced vital capacity of 580 mL, a PO2 of 59 mm Hg, and a PCO2 of 52 mm Hg at 25 to 28 weeks of gestation avoided mechanical ventilation by using nocturnal positive pressure ventilation with a tight-fitting mask during weeks 28 to 30 of pregnancy, until delivery could be accomplished by cesarean section.91 This approach may be applicable to other pregnant patients with chronic ventilatory impairment. Pulse oximetry should be used to screen patients with marginal ventilatory function for nocturnal hypoxemia.

Asthma

The course of asthma during pregnancy is variable: In approximately 35% of pregnant asthmatic women the asthma does not change; in 36% it improves; and in 28% it worsens.92 Patients with more severe asthma are more likely to experience worsening of their asthma during pregnancy. Asthma typically worsens during the second and third trimester with improvement during the last month of pregnancy. Adverse maternal outcomes in pregnant women with asthma have been noted including preterm labor, pregnancy-induced hypertension and preeclampsia, chorioamnionitis, and cesarean delivery. Adverse fetal outcomes include preterm birth and infants small for gestational age.93 Treatment of the gravid patient with asthma by a specialist reduces the likelihood of preterm birth, low birth weight infants, and perinatal mortality, suggesting that control of asthma and prevention of acute exacerbations are crucial to a good outcome.94,95

Management

The management of the pregnant patient with status asthmaticus is similar to that of the nonpregnant patient, with a few exceptions.2 Even the usually mild hypoxemia seen in asthma should be treated aggressively in the gravid patient because it is detrimental to the fetus. Oxygenation therefore should be assessed even in mild attacks. Since the baseline PCO2 is decreased in pregnancy and probably falls further with an acute asthma attack, an arterial blood gas determination that shows a PCO2 of >35 mm Hg during status asthmaticus should alert the clinician to impending ventilatory failure. However, experience with nonpregnant patients with status asthmaticus and mild hypercapnia has suggested that many can be managed without mechanical ventilatory support.

Most drugs used to treat asthma are considered safe for use during pregnancy.94,95 Inhaled bronchodilators are standard therapy. A study of inhaled β-agonists in 259 pregnancies (most subjects used metaproterenol) noted no difference in the incidence of congenital malformations, premature births, low birth weight, poor Apgar scores, or perinatal mortality when compared with asthmatic subjects not using inhaled bronchodilators.96 Use of parenteral β-agonists is generally limited to situations in which inhaled agents have been ineffective, since epinephrine causes vasoconstriction of the uteroplacental circulation in animal studies, and there is one report of an increased incidence of congenital malformations in humans who used this drug in the first trimester, and terbutaline may inhibit labor and cause pulmonary edema if given near term.3 Inhaled corticosteroids have been shown to decrease the incidence of asthma attacks and hospital readmissions in studies of pregnant women with asthma.87Budesonide is the inhaled corticosteroid of choice with triamcinolone being absolutely contraindicated due to cleft palate formation in rabbits. Oral corticosteroids have been associated with a twofold increase in the incidence of preeclampsia, and in one study an increased risk of cleft palate (0.4% absolute incidence). Systemic corticosteroids remain recommended therapy for the treatment of acute asthma exacerbations and patients with severe asthma.97 Although there is a risk of causing fetal adrenal insufficiency, this is a rare occurrence. Heliox, a low-density mixture of helium and oxygen, may decrease the work of breathing and preclude intubation and mechanical ventilation when given to subjects in status asthmaticus (see Chap. 40). Despite isolated reports of congenital cardiovascular anomalies in infants born to asthmatic women taking theophylline, it has an extensive safety record in pregnancy, with the only fetal risk being neonatal theophylline toxicity when the drug is given at the time of delivery.3 Pregnancy decreases theophylline clearance in the third trimester, so dose adjustment may be necessary.83

Acute Hypoxemic Respiratory Failure

Pregnancy creates an increased susceptibility to acute hypoxemic respiratory failure caused by a variety of disorders, including those that result in pulmonary edema, such as amniotic fluid embolism, β-adrenergic tocolytic therapy, and aspiration (Table 105-11). Other causes of hypoxemic respiratory failure include venous air embolism and respiratory infections.

Amniotic Fluid Embolism

Amniotic fluid embolism occurs in 1 of every 8000 to 80,000 pregnancies, and is estimated to account for over 10% of peripartum maternal deaths.98 The mortality rate is very high (80% to 90%) with many of the deaths occurring within 1 hour of the onset of symptoms.98,99

The two most important risk factors are advanced maternal age (mean = 32 years) and multiparity. Other, less well established risk factors include amniotomy, cesarean section, insertion of intrauterine fetal or pressure monitoring devices, and term pregnancy in the presence of an intrauterine device. The use of uterine stimulants, tumultuous labor, excessive fetal size, and intrauterine fetal death have not been substantiated as important risk factors.83 It is important to note that while most cases occur during labor and delivery, amniotic fluid embolism may be associated with uterine manipulation during first- and second-trimester abortions or trauma and has been reported to occur spontaneously at 20 weeks of gestation.100

The classic presentation of amniotic fluid embolism, seen in more than 50% of cases, is the abrupt onset of severe dyspnea, tachypnea, and cyanosis during labor or soon after delivery, frequently in association with cardiovascular collapse, hypoxemia, and seizures.100 Shock and bleeding each are the initial presentation in 10% to 15% of cases. Bleeding secondary to DIC occurs in up to 50% of patients who survive the first 30 to 60 minutes. Most of the remaining patients will have evidence of DIC on laboratory tests. Amniotic fluid embolism is frequently complicated by pulmonary edema; it was found in 70% of the cases on chest radiograph.100

The mechanisms of respiratory and circulatory failure in amniotic fluid embolism remain controversial. Amniotic fluid and particulate matter (lanugo hairs, meconium, fat, or fetal squames) may enter the maternal venous circulation via endocervical veins or uterine tears or at the placental site itself.11 In some animal studies, filtered amniotic fluid has been found to be relatively innocuous in less than massive amounts. This finding suggests that cellular and other debris present in the fluid embolism may either mechanically obstruct the maternal pulmonary vasculature, leading to the development of pulmonary hypertension, or trigger a maternal systemic reaction. Others believe that vasoconstrictor arachidonic acid metabolites present in the amniotic fluid itself may elicit pulmonary hypertension.83 Circulatory failure has been ascribed to various pathophysiologic processes, and these may vary over time. Initially, acute right heart strain from acute pulmonary hypertension may occur. Acute elevation of pulmonary artery and central venous pressures with subsequent hypotension have been observed in animal models of amniotic fluid embolism.100 Elevation of Ppw, minimal increase in the pulmonary vascular resistance, and depressed left ventricular performance have been observed in human patients with amniotic fluid embolism, suggesting that left ventricular dysfunction contributes to circulatory collapse.99 In addition, a component of pulmonary capillary leakage must exist, as severe pulmonary edema occurs at a Ppw <19 mm Hg.99

Management

The treatment of patients with amniotic fluid embolism and cardiovascular collapse is supportive and is aimed at ensuring adequate oxygenation, stabilizing the circulation, and controlling bleeding. The initial management should include intubation, administration of 100% oxygen, and mechanical ventilation with a small tidal volume (4 to 6 mL/kg) and rapid rate (24 bpm). Early sedation and muscle relaxation may allow complete rest of the respiratory muscles and confer hemodynamic stability. PEEP is then added to achieve a PaO2 of >90 mm Hg at an FiO2 <0.6. Pulmonary artery catheterization allows measurement of the cardiac output and Ppw, which can be used to guide hemodynamic adjustments aimed at minimizing Ppw (to reduce vascular leak) while providing an adequate cardiac output. Pulmonary arterial blood can be examined cytologically for evidence of abnormal amniotic fluid components—fetal squamous cells, lanugo hairs, etc. However, demonstration of these amniotic fluid elements in the maternal pulmonary circulation is not sufficient to make this diagnosis, since small numbers of fetal squamous cells have been observed in patients without clinical evidence of amniotic fluid embolism.82 Vasoactive drugs are frequently necessary to reverse hypotension. Once DIC is established, factor replacement and heparin therapy, which are controversial, should be undertaken only in conjunction with a hematology consultant.30 Intravenous corticosteroid therapy has been reported to be of benefit in limited case reports.101

Tocolytic Therapy

Pulmonary edema associated with β-adrenergic agents given to inhibit preterm labor is seen in as many as 4.4% of patients receiving these drugs.102 Most of the reported cases have resulted from use of intravenous β-mimetics such as ritodrine, terbutaline, isoxuprine, and salbutamol. There is an increased incidence in women with multiple gestations, concurrent infection, and those receiving corticosteroid therapy.3 Most women have intact membranes at the time of presentation. Pulmonary edema typically develops during tocolytic therapy or within 24 hours after the discontinuation of these drugs. When pulmonary edema develops postpartum, the vast majority of cases are encountered within 12 hours of delivery.102

The pathogenesis of this disorder remains unknown. Pulmonary edema has never been associated with similarly high doses of β-adrenergic agonists during the treatment of asthma. Therefore, some alteration related to pregnancy may predispose women to this complication. Left ventricular function was normal in those patients assessed with echocardiography and invasive monitoring.102 The observation that Ppw is normal in most patients who have pulmonary artery catheters placed has led to speculation that these drugs or occult infection produce a pulmonary capillary leak.3,102 Several facts suggest that increased circulatory volume may also play a major role: (1) large volumes of crystalloid are often given in response to the reflex tachycardia resulting from sympathomimetic drugs; (2) the intravascular volume expansion and reduced colloid oncotic pressure characteristic of pregnancy increase susceptibility to hydrostatic edema; (3) sodium and water excretion may be impaired in the supine pregnant patient; (4) tocolytic agents may increase arginine vasopressin secretion and thus impair water balance; and (5) the response to diuresis is prompt in these patients.102

Most patients complain of chest discomfort and dyspnea, manifest tachypnea, have tachycardia with crackles on lung auscultation, and have pulmonary edema on chest radiography (Table 105-12). A positive fluid balance is often noted in the hours to days preceding the onset of symptoms. In the largest collected series, the mean arterial PO2 when breathing room air was 50.4 ± 2.9 mm Hg with a PCO2 of 28.1 ± 2.1 mm Hg.102 The history and clinical findings should help in distinguishing this disorder from acute thromboembolic disease, acid aspiration, and amniotic fluid embolism.

Management

The course of this disease is usually benign, and invasive hemodynamic monitoring is usually not required. In a large series there were only two maternal deaths (3%); fetal survival was 95%.102 Treatment should consist of discontinuation of tocolytic therapy, oxygen administration, and diuresis. Response is usually rapid, with resolution of tachypnea and hypoxemia often occurring within hours.

Aspiration

Aspiration is an uncommon but well-described and ominous complication of the peripartum period.84 Factors that increase the risk of aspiration in the pregnant woman include the increased intragastric pressure that results from external compression by the enlarged uterus, relaxation of the lower esophageal sphincter due to progesterone, delayed gastric emptying during labor, and depressed mental status and vocal cord closure from analgesia. Injury due to aspiration of gastric contents is related to the volume of aspirated material, its acidity, the presence of particulate material, the bacterial burden of the aspirated material, and host resistance to subsequent infection. The early injury is a chemical pneumonitis, the severity of which is determined primarily by the acidity and volume of the aspirate. Diffuse lung injury with the development of ARDS may occur early in the course. A late complication of aspiration is the evolution to bacterial pneumonia, which tends to be focal and polymicrobial and occurs 24 to 72 hours after the event.

Management

Prevention of this dread complication should be the primary goal of all physicians assessing and managing the patient's airway. Once aspiration has occurred, treatment is supportive and is similar to that for the nonpregnant individual, as discussed elsewhere in this text (see Chap. 51). Antibiotics should be given only if bacterial pneumonia develops.

Venous Air Embolism

Although a rare occurrence, venous air embolism may account for 1% of all maternal deaths.103 It occurs during normal labor, delivery of women with placenta previa, criminal abortions using air, orogenital sex, and insufflation of the vagina during gynecologic procedures.103 Air is thought to enter subplacental venous sinuses, then to embolize through the venous circulation, and finally to obstruct pulmonary blood flow when it reaches the right ventricle. Two other mechanisms may be important in the pathophysiology of this disorder—the obstruction of pulmonary arterioles by fibrin microemboli and the recruitment and activation of polymorphonuclear leukocytes by aggregated proteins; both the fibrin microemboli and the aggregated proteins would be produced by the turbulent air-blood interface. Symptoms include cough, dyspnea, dizziness, tachypnea, tachycardia, and diaphoresis. Sudden hypotension is usually followed by respiratory arrest. A mill wheel murmur or bubbling sound is occasionally heard over the precordium. Right heart strain, ischemia, and arrhythmias have been noted on the electrocardiogram. Patients who survive the initial cardiopulmonary collapse may develop noncardiogenic pulmonary edema.

Management

When venous air embolism is suspected, the patient should be placed immediately in the left lateral decubitus position to direct the air embolus away from the right ventricular outflow tract. The patient should be ventilated with 100% oxygen in an effort to decrease the size of the embolus by removing nitrogen.103 Hyperbaric therapy has been an effective way to treat air embolism in diving medicine. Anticoagulation with heparin to treat fibrin microemboli and administration of high-dose corticosteroids to decrease pulmonary edema formation have been proposed, but their usefulness in this disorder remains untested.103

Respiratory Infections

The incidence of pneumonia in pregnancy may be increasing, reflecting a decline in the general health of a segment of the population of childbearing women and infection with human immunodeficiency virus (HIV).104 In a large retrospective review of pneumonia during pregnancy, pneumonia complicated 1 out of every 1287 deliveries.105 The incidence may be even higher in urban areas, with one study reporting pneumonia in 1 of every 367 deliveries at a large city hospital. Obstetric complications included preterm labor in 44% and preterm delivery in 36% in one large study of pneumonia during pregnancy.105 In addition, 20% of the cases had respiratory failure requiring mechanical ventilation; maternal mortality was 4%, while fetal mortality was 12%. Underlying maternal disease, such as the acquired immunodeficiency syndrome (AIDS) and cystic fibrosis, were associated with maternal medical complications and preterm delivery. The spectrum of organisms that causes bacterial pneumonia is similar to that in the nonpregnant population (Table 105-13).83,104 An increased incidence of influenza pneumonia was noted among pregnant patients during the 1918–1919 and 1957–1958 influenza pandemics. Autopsy reports noted the cause of death as respiratory insufficiency from fulminant influenza pneumonia rather than from secondary bacterial infection as is usually the case in the nonpregnant population.103 However, pregnancy has not been demonstrated to be a risk factor for severe influenza infection except during those pandemic years. Primary infection with varicella zoster virus progresses to pneumonia more often in adults than in children. Some investigators have noted an increased rate of progression to pneumonia and an increased mortality in pregnant patients, but the validity of this claim has not been proved conclusively. Coccidioidomycosis is the fungal infection most commonly associated with increased risk of dissemination during pregnancy, especially if it is contracted in the third trimester or immediately postpartum.104 The decreased cell-mediated immunity thought to occur during pregnancy may predispose the pregnant patient to disseminated varicella and coccidioidomycosis. Infection with Mycobacterium tuberculosis during pregnancy occurs. Whether pregnancy adversely influences the course of active tuberculosis is a matter of debate.106 It is clear that with appropriate chemotherapy, the prognosis for pregnant women with tuberculosis is excellent. There is no evidence for increased activation of quiescent disease during pregnancy. In vivo studies suggest that pregnancy does not affect the response to tuberculin skin testing, and this test can be performed safely during pregnancy.106 Maternal and fetal mortality from advanced tuberculosis was high in the era before effective chemotherapy. At present, the outcome for mother and child is excellent except in rare cases of congenital or neonatal tuberculosis.

HIV infection in the pregnant patient is complicated by the risk of perinatal transmission to the fetus, preterm delivery, and opportunistic infection, especially pneumonia.107 Testing for HIV infection and antiretroviral therapy to prevent vertical transmission are currently the standard of care in the pregnant patient. Pneumocystis carinii pneumonia (PCP) may complicate pregnancy and may be especially virulent in this setting. It is the most common cause of AIDS-related death in pregnant women in the United States, with respiratory failure requiring mechanical ventilation occurring in 59% of patients and with a mortality rate of 50%.108 Fetal mortality is also high and appears to be worse if PCP occurs during the first or second trimester. The clinical presentation is not altered by pregnancy.

Management

The choice of antibacterial agents to treat pneumonia during pregnancy should take account of potential fetal toxicity. The penicillins, cephalosporins, and erythromycin (except for the estolate, which increases the risk of cholestatic jaundice in pregnancy) are considered safe.103,104Tetracycline and chloramphenicol are contraindicated, and sulfa-containing regimens should be avoided near term except for the treatment of PCP, as discussed below.83,104Amantadine has been shown to be teratogenic at very high but not at lower doses in animals; its use has not been studied in pregnant women.103 Favorable results have been obtained using acyclovir to treat pregnant women with varicella pneumonia.83 No teratogenic effects have been noted in animal studies of acyclovir.103 It is important to initiate therapy with acyclovir early to affect outcome favorably. Thus acyclovir should be started at the first sign of respiratory system involvement in pregnant patients with cutaneous varicella infection.103 Amphotericin B should be used to treat disseminated coccidioidal infections in pregnancy. Fluconazole and likely other azole antifungals are teratogenic and best avoided.109 No adverse effects on the fetus have been reported for amphotericin. Active tuberculosis during pregnancy should be treated with isoniazid, rifampin, and ethambutol plus pyridoxine until drug susceptibility testing is complete.110 All three of these medications cross the placenta, but none has been shown to have teratogenic effects. In patients with sensitive organisms, isoniazid and rifampin should be continued for 9 months. Although pyrazinamide is recommended for routine use in pregnant women by the World Health Organization, in which case the treatment duration is shortened to 6 months, the drug has not been routinely used in the United States due to lack of data regarding safety. Streptomycin is the only antituberculosis drug with documented harmful effects on the human fetus and it should not be used during pregnancy.110 PCP should be treated with trimethoprim-sulfamethoxazole.104 Treatment with trimethoprim-sulfamethoxazole, compared with other therapies, may result in improved outcome.108 Corticosteroids are added if clinically indicated as for the nonpregnant patient.104

Acute Renal Failure

The incidence of acute renal failure associated with pregnancy is between 0.02 and 0.05%.20 The differential diagnosis of acute renal failure in pregnancy can be found in Table 105-14.2 As discussed above, acute renal failure may complicate preeclampsia, the HELLP syndrome, and acute fatty liver of pregnancy. Acute tubular necrosis may occur from hemorrhage or sepsis. Acute cortical necrosis is associated with placental abruption, septic abortion, prolonged intrauterine retention of a dead fetus, hemorrhage, and amniotic fluid embolism.20 Acute oliguric renal failure necessitating dialysis typically results. Arteriography may demonstrate loss of the cortical circulation, and renal biopsy can confirm the diagnosis. While renal function often improves, end-stage renal failure is the eventual outcome.20 Idiopathic postpartum acute renal failure is an unusual complication of pregnancy and may occur days to weeks after a normal pregnancy and delivery.20 The etiology is unknown. The disorder may be a variant of HUS or TTP, since it is clinically and pathologically similar to these entities although without hemolysis or thrombocytopenia, and many patients respond to treatment with prednisone administration and plasmapheresis.2 In general, the treatment of acute renal failure in pregnancy is similar to that in the nonpregnant patient, with supportive care and dialysis as necessary. Renal dysfunction associated with preeclampsia and the HELLP syndrome should respond to delivery of the fetus, while TTP and HUS require plasmapheresis with fresh frozen plasma.77

Acute Liver Failure

Acute liver failure is an uncommon complication of pregnancy.65 The differential diagnosis and characteristics of liver diseases in pregnancy can be found in Table 105-15.78 In pregnancy, de novo liver function test abnormalities are uncommon and occur in less than 5% of pregnancies in the United States.65 Serum alkaline phosphatase increases during the first 7 months of pregnancy peaking at two to four times normal at term. As discussed above, serum albumin concentrations decrease in pregnancy. Levels of serum aminotransferases and bilirubin are unchanged in normal pregnancy.

Liver failure rarely complicates preeclampsia and the HELLP syndrome; subcapsular hematoma and rupture are more common complications, as discussed above. Acute fatty liver of pregnancy is estimated to occur in 1 of 13,000 deliveries.65 Risk factors include male fetus, multiple gestations, and a first pregnancy. Mean onset is at 36 weeks' gestation, although the disorder can be seen as early as 26 weeks and postpartum. Patients present with nonspecific symptoms such as headache, nausea and vomiting (70%), right upper quadrant or epigastric pain (50% to 80%), malaise, and anorexia.78 The onset of acute fatty liver of pregnancy may be similar to the onset of preeclampsia, with peripheral edema, hypertension, and proteinuria. Jaundice may follow 1 to 2 weeks later. Cholestasis with mild-to-moderate elevations in serum aminotransferases are the rule. Ultrasound may show increased echogenicity. Computed tomographic abdominal scans are more sensitive and may demonstrate decreased attenuation, although this imaging exposes the fetus to significant radiation. Liver biopsy is sometimes necessary to make the diagnosis but must be undertaken with caution because these patients often have a coagulopathy. The biopsy is characterized by microvesicular fatty infiltration detected only on frozen sections.65 Acute fatty liver of pregnancy progresses to fulminant hepatic failure complicated by encephalopathy, renal failure, pancreatitis, hemorrhage, DIC, seizures, coma, and death.78 Because deterioration may occur rapidly, expectant management is generally not advised. The treatment is delivery of the fetus. Jaundice, liver dysfunction, and DIC may worsen for a few days after delivery but then should improve. Maternal and fetal mortality has improved with early delivery and is less than 20%. Full maternal recovery is to be expected. Because long-chain 3-hydroxyacyl-coenzyme dehydrogenase deficiency in the fetus has been reported to be associated with acute fatty liver of pregnancy in seven of ten women in a recent study, infants may have hypoglycemia, hypotonia, acute or chronic skeletal and cardiac muscle dysfunction, and sudden infant death syndrome.

While early mortality can be reduced in the critically ill gravid patient by the therapies outlined above, malnutrition, nosocomial infection, and gastrointestinal hemorrhage often complicate a prolonged ICU stay and account for much of the later morbidity and mortality. Several of these issues are discussed below with the aim of establishing the best milieu for recovery from critical illness.

Acid-Base Status

As previously discussed, pregnancy results in a compensated respiratory alkalosis in which PCO2 and bicarbonate concentration average 30 mm Hg and 18 to 20 mEq/L, respectively. During labor this respiratory alkalosis worsens because of maternal hyperventilation. Nonetheless, current evidence suggests that the resulting alkalemia is not clinically relevant. In one study, fetal oxygen delivery was not impaired when mothers hyperventilated in labor, as fetal PO2 decreased by only 4 mm Hg despite significant increases in maternal and fetal plasma pH.111 Fetal compensation may result from the facts that the alkalosis-induced leftward shift of the fetal hemoglobin saturation curve may preserve fetal oxygen-carrying capacity and that carbon dioxide diffuses rapidly across the placenta, allowing quick re-establishment of acid-base homeostasis. Unlike spontaneous hyperventilation, however, respiratory alkalosis from excessive mechanical ventilation can cause fetal asphyxia in animal models as a result of decreased uteroplacental blood flow.86 Furthermore, maternal metabolic alkalosis has been shown in animal models to significantly decrease placental blood flow and fetal carotid PO2.112 Since severe respiratory and metabolic alkaloses in the critically ill are often a result of medical treatment—excessive mechanical ventilation, nasogastric suction, diuretic use, and corticosteroid administration—close monitoring of maternal acid-base status should allow prevention or early correction of the alkalosis.

Acidosis may be detrimental to the fetus and should be avoided. Decreased ventilation, with elevation of PCO2 even to prepregnancy levels, will result in respiratory acidosis. Early intubation and mechanical ventilation are indicated in gravidas before hypercapnia and severe respiratory acidosis develop.

Maternal metabolic acidosis occurs in normal labor and delivery, presumably as a result of hyperventilation and other muscle activity.113 Lactic acid is produced, and these maternal fixed acids pass rapidly to the fetus. In early labor, fetal pH averages 7.30 and PCO2 averages 45 mm Hg, with a fall in pH to 7.20 immediately after delivery.114 The pH falls owing to a metabolic acidosis, which resolves over the first 60 minutes of neonatal life. When a maternal metabolic acidosis develops as a result of illness, treatment should be directed at the underlying process after it is determined whether the anion gap is normal or increased. The use of bicarbonate to correct pH is controversial for both pregnant and nonpregnant patients, as is discussed in Chap. 77. When bicarbonate is given, serum carbon dioxide levels rise, and carbon dioxide diffuses rapidly across the placenta. The rise in fetal bicarbonate levels is slower, because this charged species equilibrates more slowly across the placenta. Thus infused bicarbonate may increase acidosis intracellularly or in fetal tissue beds. For this reason, if correction of an underlying acidosis or delivery are likely to be achieved within hours, treatment with bicarbonate is not recommended. Controlled mechanical ventilation to correct metabolic acidosis is indicated when the patient cannot generate sufficient respiratory compensation or the work of breathing will further aggravate the acidosis. This measure should make it possible to provide enough ventilation to minimize acidosis.

Prevention of Gastrointestinal Hemorrhage

Pregnancy is not known to result in abnormal gastric acid secretion or to increase the vulnerability of the upper gastrointestinal mucosa to ulceration, but critical illness is often complicated by gastric erosion and severe bleeding. A number of interventions are currently used as prophylaxis against this common complication.

Antacids and sucralfate act by mixing with and neutralizing the gastric contents or by directly coating the gastric mucosa. Because the enlarging uterus may divide the stomach into antral and fundal pouches, complete mixing of gastric contents is unlikely.115 Therefore these agents may fail to provide prophylaxis against gastric ulceration. Histamine-receptor blockers such as cimetidine and ranitidine are category B medications, as are the proton pump inhibitors, and are the medications of choice in pregnant critically ill patients to reduce the risk of gastrointestinal hemorrhage.

Nutrition

Total parenteral nutrition (TPN) has been used in pregnant patients for extended periods for disorders such as inflammatory bowel disease, esophageal stricture, and malignancy. Its use in acute malnutrition associated with critical illness is less well described.116 Animal studies find that the mother is favored over the fetus during starvation, and in human beings maternal body stores are maintained at the expense of fetal growth during semistarvation.3 For these reasons, aggressive and early nutritional support should be instituted. Patients who have not resumed normal oral intake within 3 days of the onset of critical illness should receive nutritional support. The gut should be used if possible, and feedings given as a bolus by nasogastric tube or as infusions by a soft duodenal feeding tube. Caloric requirements during pregnancy are close to 40 kcal/(kg/d). Sepsis, trauma, burns, and recent surgery are likely to increase this requirement. If severe liver disease is not present, it is recommended that 1.5 g/(kg/d) of protein be given and that approximately 20% of calories be provided as lipids. A variety of enteral feeding supplements can meet these goals at tolerable infusion rates. Finally, electrolyte disorders are common in these patients, and careful attention must be paid to serum calcium, phosphate, and magnesium levels, with additional supplements given as necessary.

Patients who do not tolerate enteral feeding will require TPN. The same guidelines for total calories and for the distribution of calories among lipids, carbohydrates, and protein can be used. There is a theoretical concern that the use of intravenous fat emulsions in pregnancy could result in placental infarction due to fat emboli.117 However, this complication has not been reported and fat emulsions are used in our institution.

FDA Drug Classification

Since pregnant patients being treated for critical illness may require multiple pharmacologic interventions, intensivists in the United States should be aware of the Food and Drug Administration use-in-pregnancy ratings. Commonly prescribed medications in the intensive care unit are listed in Table 105-16. Category A drugs are those that have undergone adequate controlled studies in pregnant women and have not demonstrated a risk to the fetus. Category B drugs are those with no evidence of fetal risk in human beings (if animal studies demonstrate risk, human findings do not, or if human studies are inadequate, animal findings are negative). Category C agents are those in which risk cannot be ruled out (human studies are lacking, and animal studies are either positive for fetal risk or lacking; still, potential benefits may outweigh risk). Category D includes agents with positive evidence of fetal risk by virtue of investigational or postmarketing human data (still, in critical illness potential benefits may outweigh risks). Category X includes drugs contraindicated in pregnancy.