Chapter 60: Critical Care Issues in Pregnancy

The mortality rate for critically ill obstetric patients ranges from 12% to 20%. A recently published retrospective study described the current leading diagnoses associated with ICU admission in obstetrics. ICU admissions related to abortions and ectopic pregnancy accounted for 10% of all ICU admissions among pregnant and postpartum women. Leading causes for antepartum admissions included obstetric-related hypertensive disease (23%), trauma (17%), and cardiac disease (13%). Delivery-related ICU admissions were overwhelmingly related to obstetric-related hypertensive disease (38%), hemorrhage (33%), and cardiac disease (18%). Postpartum admissions were most often attributed to cardiac disease (37%), obstetric-related hypertensive disease (21%), and cerebrovascular disease (20%).

Critical illness in obstetrics can be the result of pregnancy-specific conditions or due to commonly seen critical care diagnoses which may have unique-management considerations in pregnancy as a result of physiologic alterations and fetal concerns. Herein, we will review physiologic adaptations due to pregnancy by systems, general considerations for the critically ill pregnant patient, and management strategies for both pregnancy-specific conditions and critical medical conditions seen most commonly in gravid women.

Gestation in singleton pregnancies lasts an average of 40 weeks spanning from the first day of the last menstrual period to the estimated date of delivery. Previously, “term pregnancy” was defined as the period between 37 and 42 weeks gestation. However, recent data have shown improved neonatal outcomes with increasing gestation within this window. The American College of Obstetricians and Gynecologists (ACOG) and the Society of Maternal-Fetal Medicine now endorse the use of “early term” (37 0/7 through 38 6/7 weeks of gestation), “full term” (39 0/7 through 40 6/7 weeks of gestation), “late term” (41 0/7 through 41 6/7 weeks of gestation), and “postterm” (greater than 42 0/7 weeks of gestation) for classification.

Major adaptations in maternal physiology are required during gestation to sustain a healthy pregnancy. Many of these adaptations would be considered pathologic in a nonpregnant patient. Understanding of these changes is imperative in clinical decision making when pregnant women become ill.

Cardiovascular System

Pregnancy causes profound physiologic changes in the cardiovascular system. These adaptations begin very early in gestation, often before pregnancy is diagnosed, and are required to maximize oxygen delivery to the uteroplacental unit. In healthy women, these changes are generally well tolerated. However, in certain cardiac diseases, maternal morbidity and even mortality may occur.

Increased uterine volume elevates the diaphragm which displaces the heart up and to the left. The heart rotates along its long axis and the cardiac apex is deviated laterally. This results in an increased cardiac silhouette on routine radiography. Myocardial hypertrophy is observed due to the expanded blood volume and increasing afterload resulting in about a 12% increase in the overall size of the heart. Normal pregnancy can also result in changes in standard echocardiograms and electrocardiograms, including nonspecific T-wave changes and mitral/tricuspid regurgitation.

Cardiac output (CO) is the product of stroke volume and heart rate, both of which increase during pregnancy. The initial rise in heart rate occurs by 5 weeks gestation and continues to rise until it peaks at around 32 weeks gestation at 15 to 20 beats above the pregravid state (16%-20% increase in resting heart rate). The stroke volume begins to rise between 5 and 8 weeks gestation and reaches its maximum at 20 weeks, 20% to 30% above the pregravid state. CO is positional in the second half of pregnancy due the weight of the gravid uterus which compresses the inferior vena cava (IVC) and decreases venous return. The decrease in CO in the supine position compared to the lateral recumbent position is 10% to 30%. The IVC is completely occluded near term in the supine position; venous return from the lower extremities occurs through dilated paravertebral collateral circulation. There is selective distribution of the increased CO with uterine blood flow increasing 10-fold near term. Perfusion to the skin, breasts, and kidneys is also significantly increased.

Blood pressure is the product of CO and systemic vascular resistance (SVR). Despite the significant increase in CO early in gestation, systemic blood pressure is decreased until later in pregnancy as a result of decreased SVR that nadirs midpregnancy and then gradually rises until term. Progesterone-mediated smooth muscle relaxation contributes to the decrease in SVR. Central hemodynamic studies of pregnant women demonstrate a significant decrease in pulmonary vascular resistance. Mean arterial pressure, pulmonary capillary wedge pressure, central venous pressure, and left ventricular stroke work index are unchanged. Colloid osmotic pressure is decreased.

During the intrapartum and immediate postpartum period, the hemodynamic changes of the cardiovascular system reach new heights. CO increases dramatically during labor in part due to increased venous return from 300 to 500 mL autotransfusion that occurs at the onset of each contraction as blood is expressed from the uterus. In addition, mean arterial pressure (MAP) also rises in the first stage of labor and reaches a peak at the beginning of the second stage. The increase in CO and MAP are influenced by maternal pain and anxiety. Regional anesthesia has been shown to reduce the overall increase in CO, but a surge is still present with contractions. Immediately postpartum (10-30 minutes postdelivery) CO reaches its maximum and maternal heart rate declines. Approximately 1 hour postpartum CO returns to pregnancy baseline. Return to prepregnancy levels does not occur until 6 to 8 weeks postpartum.

Respiratory System

Physiologic and structural changes occur throughout the respiratory tract during pregnancy. The nasal mucosa becomes edematous and hyperemic with increased secretions due to a rise in circulating estrogen. These changes cause marked nasal stuffiness and an increased risk of epistaxis. Placement of nasogastric tubes or nasal airways can cause excessive bleeding if adequate lubrication is not used.

The structure of the thoracic cavity is markedly altered in pregnancy and cannot be entirely explained by the mechanical pressure of the gravid uterus. The subcostal angle increases from 68° to 103°, the transverse diameter of the chest expands by 2 cm, and the chest circumference expands by 5 to 7 cm. The resting level of the diaphragm is 4 cm higher at term that in the nongravid state. However, the diaphragmatic excursions are increased by 1 to 2 cm over nonpregnant values.

Intrinsic pulmonary function and static lung volumes are altered throughout the pregnancy. Elevation of the diaphragm decreases the volume of the lungs in the resting state which reduces the total lung capacity by 5% and the functional residual capacity (FRC) by 20%. FRC is the sum of expiratory reserve volume and residual volume; both decrease in pregnancy. Inspiratory capacity, the maximum volume that can be inhaled, increased by 5% to 10% because of the decrease in FRC. The vital capacity does not change (Table 60–1).

Increased progesterone levels during pregnancy leads to a state of chronic hyperventilation, which results in a decrease in PaCO₂ to below 30 mm Hg in normal women. Maternal pH does not change because there is a reciprocal decline in the bicarbonate concentration. Total body oxygen uptake at rest increases by 12% to 20%. This increased oxygen is needed to meet the high metabolic demands of pregnancy. The oxygen need is met by increased tidal volume alone because respiratory rate and pulmonary diffusing capacity do not change.

Hematologic System

Blood volume and composition change during pregnancy. Maternal blood volume begins to increase at about 6 weeks gestation and progresses until 30 to 34 weeks and then remains stable until delivery. Average blood volume expansion is 40% to 60% but this varies widely. The increase in blood volume results from a combined expansion of both plasma volume and red blood cell (RBC) mass. Without iron supplementation, RBC mass increases by about 18% by term, supplemental iron causes the increase to rise up to 30%. Plasma volume increases more than the RBC mass leading to a drop in maternal hematocrit, that is, dilutional. This so-called physiologic anemia of pregnancy reaches its nadir at 30 to 34 weeks gestation.

The white blood cell count increases to about 10,000/μL at term and the platelet count decreases slightly. Platelet counts greater than 120,000/μL are generally considered normal in pregnancy. In the third trimester, approximately 8% of gravidas will develop gestational thrombocytopenia with platelet counts between 70,000 and 150,000/μL.

The biochemical characteristics of the blood change in pregnancy. Serum osmolality decreases by 10 mOsm/L early in pregnancy and then remains stable throughout gestation. Minor decreases in sodium, potassium, calcium, magnesium, and zinc occur. Chloride does not change, but bicarbonate markedly decreases. The plasma concentrations of albumin and total protein decrease in proportion to the plasma volume expansion. Alkaline phosphatase increases because of the production of the placental form of the enzyme. Serum lipids increase toward term, with the levels of cholesterol and triglycerides doubling during pregnancy.

Levels of many coagulation factors are altered in pregnancy. Fibrinogen levels increase to as high as 600 mg/dL near term. The prothrombin time, activated partial thromboplastin time, and thrombin time all fall slightly but usually remain within the lower range of normal limits for nonpregnant women. Bleeding time and whole blood clotting times do not change. There is a 5 to 6 fold increased risk for thromboembolic disease in pregnancy. This greater risk is caused by increased venous stasis, vessel wall injury, and changes to the coagulation cascade that lead to hypercoagulability. The overall risk of thromboembolism in pregnancy is estimated to be 1/1500 and accounts for 25% of the maternal deaths in the United States.

Renal System

The kidneys enlarge in size and weight during pregnancy due to increased renal vasculature, interstitial volume, and urinary dead space. The dead space is accounted for in the dilation of the collecting system. Pelvic calyceal dilation is greater on the right than the left. Anatomic changes are also observed in the bladder. The bladder trigone is elevated and increased vascularity is seen throughout the bladder, which increases the incidence of microhematuria.

Renal plasma flow and glomerular filtration rate (GFR) increase significantly early in pregnancy reaching their peak early in the third trimester. The creatinine clearance in pregnancy is increased to values of 150 to 200 mL/min. The increased GFR leads to a reduction in maternal plasma levels of creatinine, blood urea nitrogen, and uric acid. Serum creatinine falls from a nonpregnant level of 0.8 to 0.5 mg/dL by term.

Glucose excretion increases and glycosuria is common. This glycosuria is intermittent and not necessarily related to blood glucose levels or the stage of gestation. No significant increase in proteinuria occurs in a normal pregnancy in women without proteinuria before pregnancy. In women with preexisting proteinuria, the amount of proteinuria increases in both the second and third trimesters.

Other changes in the tubular function include an increase in the excretion of amino acids in the urine and an increase in calcium excretion. This increase in calcium excretion increases the risk of nephrolithiasis in the setting of urinary stasis mediated by progesterone. Finally, the kidney responds to the respiratory alkalosis of pregnancy by increased bicarbonate excretion.

Immune System

The fetus is a semiallograft and a successful pregnancy is dependent on either evasion of immune surveillance or suppression of the maternal-adaptive immune response. A major shift occurs away from cell-mediated cytotoxic immune responses toward increased humoral and innate immune responses.⁹ This shift decreases the maternal cytotoxic potential against fetal antigens. The decrease in cellular immunity leads to increased susceptibility to intracellular pathogens such as cytomegalovirus, herpes simplex virus, varicella, and malaria. The changes in the immunologic system of a pregnant woman are complex and not fully understood. Hormones, particularly progesterone, likely play a significant role.

Any pregnant patient requiring ICU level care should be in a facility with obstetric and neonatal teams for collaborative multidisciplinary care. The critically ill pregnant patient is at risk for labor and delivery, regardless of the initial inciting condition. In addition, postpartum patients continue to have pregnancy-related physiologic changes and are prone to specific pregnancy-related conditions such as bleeding, hypertensive disorders, venous thromboembolism, and infection from an obstetric source.

For patients who are still pregnant, in general the rule is for maternal stabilization prior to delivery of the fetus. In most cases, appropriate treatment of the mother will improve fetal status. Treatment required to stabilize the mother's critical status should be undertaken, even if such intervention is potentially disadvantageous to the fetus. Short- and long-term morbidity in surviving fetuses is directly related to maternal physiologic status.

There are cases where the obstetric team will be guiding the management of care toward intended delivery (preeclampsia, acute fatty liver, amniotic fluid embolus); however, it is important to know that even in cases where delivery is not recommended, spontaneous labor may ensue. A plan for potential delivery should be made with the obstetric team in case this occurs and should include preferred location, preferred mode (vaginal vs cesarean), need for analgesia or anesthesia and plan for advanced pediatric support for the newborn. Basic supplies should be made available at the ICU bedside. ICU teams must be aware of basic signs of labor including patient pain, leakage of fluid or mucus per vagina, any vaginal bleeding, palpable contractions (tightening at the uterine fundus). Although some of these may be difficult to discern in an intubated and sedated patient, close attention may allow early identification of signs and symptoms of labor in a critically ill patient and can allow for planning and mobilization of appropriate resources to optimize maternal and fetal outcome.

Critical illness can compromise the fetus as a result of maternal hypotension, hypoxemia, and acid-base imbalances. Fetal oxygenation is dependent upon uterine blood flow that is not autoregulated, thus can fall as a result of decrease in maternal systolic blood pressure. Uterine blood flow can also be reduced from vasoconstriction related to vasopressors, maternal hypercarbia or hypocarbia. Continuous fetal monitoring of fetuses who have reached viability may be recommended. The fetal heart rate pattern should be monitored by a physician or nurse experienced in fetal heart rate interpretation and information can be used to guide maternal resuscitative strategies.

Oxygen supplementation should be used early with goal maternal oxygen saturation (SaO₂) greater than 95% and PaO₂ greater than 70 mm Hg to maintain a favorable oxygen diffusion gradient from the maternal to the fetal side of the placenta. Early intubation after preoxygenation is recommended if adequate maternal oxygenation cannot be achieved noninvasively. The indications for intubation and ventilation are the same as for nonpregnant patients.

Endotracheal intubation in pregnant women is usually more difficult. Airway edema and hyperemia can contribute to difficult intubation and decreased lower esophageal tone leads to increased aspiration risk during endotracheal intubation. Selecting a size of 6 to 7 ET tube and applying cricoid pressure to prevent aspiration of gastric contents should be considered.

Ventilation of the pregnant patient is similar to that of nonpregnant patients, except that it should be directed to a slightly lower PCO₂ level because the normal pregnant state is a mild respiratory alkalosis with PCO₂ levels of 28 to 32 mm Hg. Excessive hyperventilation will lead to uterine vasoconstriction with decreased placental and fetal perfusion and should be avoided.

If indicated, chest tube should be placed 2 intercostal spaces above the usual landmark of the fifth intercostal space due to the elevation of the diaphragm and ideally should be done under ultrasound guidance.

Hypotension management in the parturient requires particular attention to body position and volume status. The uterus reaches the level of the maternal umbilicus by approximately 20 weeks of gestation when it is large enough to compress the IVC when the woman is supine and result in up to a 30% reduction in CO. Displacing the uterus to the left, off the vena cava, is critical to restoring CO. This is best accomplished by placing the woman on her left side, putting a wedge or rolled towel under her right side, or adjusting her platform to a 30° left lateral tilt.

Fluid resuscitation must be administered adequately because the addition of vasoconstricting agents will compromise uteroplacental flow if vasoconstriction is imposed on an insufficient circulating volume. All vasoactive agents have the potential to constrict uterine vessels and reduce blood flow to the placenta and fetus despite improving maternal blood pressures. Placental blood flow and uterine perfusion pressure are directly proportional to maternal systemic blood pressure and CO.

Attention should be paid to glycemic control, for fetal benefit, particularly if delivery is being considered. Aggressive venous thromboembolism prophylaxis should be initiated with sequential compression devices as well as pharmacoprophylaxis if no contraindication exists.

The American Heart Association publishes guidelines for cardiac arrest in special situations including pregnancy. During a maternal resuscitation, providers must consider the mother, the fetus, and anatomic and physiologic changes of pregnancy to optimize resuscitative efforts and outcome. Key interventions to prevent arrest in a critically ill pregnant woman include left lateral positioning, 100% oxygen, IV access above diaphragm and treatment of hypotension. Consideration of reversible causes of critical illness may allow initiation of early aggressive treatment.

Recommended modifications to basic life support (BLS) include patient positioning to optimize venous return and CO. Manual displacement can be accomplished by using a one-handed and two handed technique. A difficult airway should be anticipated due to pregnancy changes and optimal bag-mask ventilation and suctioning should be used while preparing for advanced airway management. Breathing should be supported to ensure adequate oxygenation and ventilation. Chest compressions should be performed the same as most current recommendations. Defibrillation may be utilized as indicated.

Recommended modifications to ACLS include anticipation of difficulty with airway and only attempting intubation with an experienced provider, with bag-mask ventilation with 100% oxygen prior to intubation. Medication and defibrillation should be utilized in the usual doses for the standard indications, however, internal/external fetal monitors should be removed prior to defibrillation. Consider and initiate appropriate therapy for reversible pregnancy-related etiologies for the arrest. Specifically, if the patient is on IV magnesium (a commonly used medication in obstetrics), magnesium should be stopped and IV calcium gluconate should be administered.

In maternal cardiac arrest, not immediately reversed by BLS and ACLS, prompt consideration for emptying the uterus must be undertaken. For this to be feasible, resuscitation teams must activate a protocol for possible cesarean delivery as soon as a maternal cardiac arrest is identified. In general, if the gravid uterus is at the level of the umbilicus (20 weeks size), the uterus may be causing aortocaval compression and impacting maternal hemodynamics. In this case, hysterotomy should be considered for maternal benefit, regardless of exact gestational age and fetal viability. This is an assessment that must be made promptly because the recommendation is to begin the cesarean within 4 minutes of arrest with the goal of delivering a viable fetus within 5 minutes.

Preeclampsia–Eclampsia

Essentials of diagnosis: hypertension, proteinuria, ± seizures (eclampsia).

Background

Preeclampsia is defined as new onset of hypertension and either proteinuria or end-organ dysfunction at more than 20 weeks gestational age in previously normotensive women or new onset proteinuria, severe hypertension, or symptoms in women with chronic hypertension. Preeclampsia is a common disorder with an incidence of approximately 15% in nulliparous women and 6% in multiparous women. The disease is also more common at extremes of age.

Hypertensive disorders in pregnancy are one of the leading causes of maternal death in the United States and worldwide. Approximately 75% of preeclampsia will be mild and self-limited. Of the remaining 25% that are severe, very few will require ICU care usually due to significant end-organ damage. Preeclampsia affects the cardiovascular, pulmonary, renal, hepatic, hematologic, and neurologic systems.

Early diagnosis of preeclampsia is imperative to optimize maternal and fetal outcomes. The only “cure” for preeclampsia is delivery, the timing of which is determined based on gestational age and severity of disease.

Clinical Features

Symptoms or Signs—Preeclampsia was historically diagnosed based on a triad of hypertension, proteinuria, and edema. Edema has been removed from the diagnostic criteria because of the frequent occurrence of edema in late pregnancy, but a sudden and dramatic weight gain still conveys a high likelihood of imminent preeclampsia. In 2013, ACOG removed proteinuria as an essential criterion for diagnosis of preeclampsia.

Preeclampsia is defined as with or without severe features. Preeclampsia without severe features, generally, does not cause long-term maternal end-organ damage and thus can be managed expectantly until a later gestational age, that is, 37 weeks. Preeclampsia with severe features can present with a wide variety of signs/symptoms and often requires delivery regardless of gestational age (Table 60–2).

Classically, the minimum criteria for diagnosis of mild preeclampsia are blood pressure greater than 140 mm Hg systolic or 90 mm Hg diastolic on 2 separate occasions greater than 4 hours apart and proteinuria defined as 300 mg of protein in a 24 hours urine collection or at least 30 mg/dL (1+) protein on a spot urine dipstick. There has been a shift to using a urine protein/creatinine ratio of more than or equal to 0.3 to diagnose proteinuria.

Recent guidelines published by the ACOG in December 2013 encourage new diagnostic criteria for preeclampsia excluding the requirement for proteinuria for diagnosis. The authors state that evidence suggests that kidney damage can occur in the setting of preeclampsia without significant proteinuria.

Laboratory Findings

Preeclampsia is generally a clinical diagnosis. Laboratory data are useful in following the course of the disease, particularly in the case of expectant management due to prematurity of the fetus. Serial monitoring of hemoglobin, platelet count, creatinine, liver function tests, lactate dehydrogenase (LDH), and creatinine are essential.

Management

Delivery—The only definitive management for preeclampsia is delivery of the fetus. In the case of severe preeclampsia, delivery is often expedited except in specific situations including extreme prematurity. Even in these cases, the delay is often brief and used to administer corticosteroids for fetal lung maturity or facilitate transfer to a tertiary care center.

Seizure Prophylaxis—Seizure prophylaxis should be administered to all patients in whom severe preeclampsia is diagnosed or suspected. Seizure prophylaxis is continued through delivery and 24 hours postpartum or until the patient has proven stable enough to attempt expectant management.

In the United States, magnesium sulfate is the most common medication administered for seizure prophylaxis. It is generally administered as an intravenous drip, but can be given intramuscularly if intravenous access is not available. The usual regimen includes a 4 to 6 g loading dose given over 30 minutes, followed by a continuous infusion of 2 g/h. The therapeutic range is wide with goal serum magnesium levels of 4.8 to 8.4 mg/dL.

Magnesium toxicity should be monitored for clinically in alert patients with physical exam (reflexes and cognitive status). Laboratory values can also be monitored. Magnesium is contraindicated in patients with myasthenia gravis and relatively contraindicated with pulmonary edema. It should be used with caution and consideration for dosage modification in the setting of significant renal dysfunction or oliguria. The second-line medication for treatment in these cases is phenytoin.

Control of Hypertension—Severe hypertension (BP > 160/110) should be controlled aggressively. Hydralazine and labetalol are the most common medications used to treat acute hypertension in pregnancy. Hydralazine is administered in 5 to 20 mg doses based on patient response at 30 minute intervals. Labetalol is administered starting at a 20 mg dose and can be doubled every 10 minutes up to an 80 mg dose and a maximum total of 220 mg.

The goal is to lower blood pressure out of the severe range, not to achieve a normal blood pressure. If repetitive IV doses of medication are unable to control the blood pressure, IV drips of nitroglycerin, nicardipine, or nitroprusside can be used in a monitored ICU setting. In the setting of refractory hypertension, delivery is required once the mother is stabilized. Nitroprusside administration can lead to fetal cyanide poisoning and thus should be used with caution prior to delivery of the fetus.

Physicians should exercise caution when using any vasodilators in patients with preeclampsia because patients are often intravascularly depleted making them susceptible to dramatic drops in blood pressure. Significant drops in blood pressure can lead to decreased uteroplacental perfusion and fetal compromise.

Hemodynamic Monitoring—Invasive monitoring is not contraindicated in pregnancy and can be considered in the case of refractory pulmonary edema or oliguria. Historically, it was thought that a pulmonary artery catheter may be favorable because central venous pressures are unreliable. Recently, echocardiography has been the favored method of monitoring for fluid status.

Pulmonary edema in preeclampsia may be due to left ventricular dysfunction secondary to high SVR, iatrogenic volume overload in the face of contracted intravascular space, decreased plasma colloid oncotic pressure, or pulmonary capillary membrane injury. Of note, in the event of respiratory compromise requiring intubation, it is important to note that patients often have laryngeal edema making intubation difficult. Advanced airway devices and a skilled anesthesiologist may be required.

Oliguria in preeclampsia is due to intravascular volume depletion (most common), relative volume overload with decreased left ventricular function secondary to high SVR, or renal arteriolar spasm. Echocardiographic assessment of cardiac function can help determine the cause of oliguria and course of treatment.

HELLP Syndrome—Preeclampsia can be complicated by hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. It is unclear if HELLP syndrome represents a separate clinical entity from preeclampia or is just a part of the spectrum of disease. Women with HELLP syndrome are generally older and multiparous and HELLP syndrome can occur in the absence of proteinuria or hypertension.

Laboratory evidence of HELLP syndrome includes abnormal peripheral smears (burr cells, schistocytes, echinocytes), hemolysis (elevated indirect bilirubin, LDH > 600, low haptoglobin), elevated liver transaminases (2× upper limit of normal), and thrombocytopenia (plt < 100k). Severe thrombocytopenia (plt < 30k) occurs rarely and these patients may require platelet transfusion for delivery.

In the absence of liver rupture, treatment of HELLP syndrome is generally supportive other than delivery. Serial monitoring of laboratory values and magnesium administration for seizure prophylaxis are recommended. Additionally, dexamethasone 10 mg intravenously every 12 hours can be administered to speed the process of laboratory value improvement in the setting of severe thrombocytopenia. Corticosteroids have not been shown to improve maternal morbidity or mortality.

In the event of liver rupture, operative exploration should be expedited as this is a surgical emergency. Exploration should not be delayed for imaging studies. The maternal mortality rate associated with HELLP syndrome has been estimated to be 1% with most mortality occurring in the setting of liver rupture.

Eclampsia—Eclampsia is defined as the presence of grand mal seizures in women with preeclampsia without a seizure disorder or other attributable cause of seizures. Eclampsia carries of maternal mortality rate of 1% to 2% and a fetal mortality rate of 10%. Onset of seizures is often preceded by symptoms including a severe unrelenting headache, nausea, or vomiting. Seizures are usually self-limited and medication is not usually required to break the seizure activity.

Treatment of eclampsia is standard magnesium administration with a 4 to 6 g bolus and then a continuous infusion of 2 g/h. Magnesium should be administered expeditiously in the setting of eclampsia, however, the purpose is to prevent recurrent seizure. Magnesium is superior to phenytoin and diazepam for preventing additional seizures.

Once seizure activity is controlled, delivery should be affected. In many cases, labor can be induced safely and a vaginal delivery can be achieved. Magnesium prophylaxis should be continued throughout delivery and for 24 hours postpartum.

Additional Critical Care Events—Disseminated intravascular coagulation, hypertensive encephalopathy, acute myocardial infarction, acute renal failure, intracranial hemorrhage, and acute aortic dissection can also be associated with hypertensive disorders in pregnancy. In each of these settings, a multidisciplinary approach with critical care, obstetrics, anesthesia and in certain cases other services is required to provide adequate care.

Acute Fatty Liver of Pregnancy

Essentials of diagnosis: hepatic dysfunction and microvesicular fatty infiltration of hepatocytes.

Background

Acute fatty liver of pregnancy (AFLP) is a rare but life-threatening complication of pregnancy with an incidence between 1:7000 and 1:16,000. It occurs late in pregnancy or immediately postpartum, often as fulminant liver failure with sudden onset coagulopathy and encephalopathy in women with no history of liver disease. Microvesicular fatty infiltration of hepatocytes is seen on microscopy.

Historically, AFLP was thought to be universally fatal, but early recognition, aggressive stabilization of the mother, and prompt delivery have improved the prognosis. Maternal and fetal mortality are currently estimated at approximately 15%.

The exact etiology of AFLP remains unknown. In many cases, either the mother or fetus is found to have an autosomal mutation that causes deficiency of the long-chain 3-hydroxyacyl coenzyme-A dehydrogenase (LCHAD), a fatty acid beta-oxidation enzyme. The association of this mutation with AFLP is strong enough that screening for the LCHAD mutation is recommended in the infants of affected mothers. Additional risk factors include nulliparity, multiple pregnancy, male fetus, and coexisting preeclampsia.

Clinical Features

Symptoms or Signs—Patients often present with a history of 1 to 2 weeks of nausea, vomiting, anorexia, and malaise. On physical exam, patients are ill-appearing often with some degree of jaundice. Hypertension with or without proteinuria and transient diabetes insipidus with polydipsia and polyuria are also common.

In severe disease, ascites, progressive hepatic encephalopathy, hypoglycemia, coagulopathy, metabolic acidosis, and renal failure are also often seen. Intrauterine fetal demise occurs frequently, often prior to the diagnosis, likely due to hypoglycemia and uteroplacental insufficiency.

Laboratory Findings—Diagnosis of AFLP is suspected based on clinical presentation and dramatic laboratory changes (Table 60–3), but a definitive diagnosis cannot be made without a liver biopsy, confirming microvesicular fat infiltration of the hepatocytes.

Management

Care of a patient with suspected AFLP has 4 categories: diagnosis, stabilization, delivery, and support. During the diagnosis phase of management, intensive monitoring of the mother and the fetus are required. Because the fetal status can decline rapidly, if AFLP is suspected continuous external fetal monitoring should be applied until the diagnosis is ruled out or delivery is affected. Maternal hemodynamic and metabolic status should be monitored both clinically and with laboratory values.

The stabilization phase includes treatment of the complications of AFLP that are present. This includes establishing stable airway in an obtunded patient, normalizing intravascular volume, correcting electrolyte disturbances, treating hypoglycemia/hyperglycemia and correcting coagulation abnormalities with blood products. In certain cases, dialysis may be required for acute renal failure or desmopressin for diabetes insipidus.

Once the patient is stabilized, an expeditious delivery is recommended within 24 hours. The diagnosis of AFLP does not require a cesarean delivery. In fact, in the setting of significant coagulopathy, operative delivery may increase maternal morbidity and mortality. Regional anesthesia is often prohibited in cases of AFLP due to coagulopathy and thrombocytopenia. Care should be taken with medication choices if general anesthesia is required because certain medications can exacerbate liver failure.

Following delivery, care is supportive until the multisystem organ failure improves. This often requires ICU admission. Fluid balance, electrolyte status, and glycemic management are critical to survival. Blood glucose should be monitored hourly and electrolytes every 2 to 4 hours. Evidence of disseminated intravascular coagulation should be managed aggressively with blood products. Protein intake should be limited with the majority of caloric intake from glucose to decrease the nitrogenous waste. Colonic emptying should be facilitated with promotility agents to increase ammonia loss via stool. Neomycin 6 to 12 g or lactulose 20 to 30 g can also be administered daily to decrease colonic ammonia production. Occasionally, the liver damage from AFLP is so severe that transplantation is required.

Anaphylactoid Syndrome of Pregnancy/Amniotic Fluid Embolism

Essentials of diagnosis: hypotension, hypoxia, coagulopathy and frequently seizures/pulmonary edema/cardiac arrest.

Background

Amniotic fluid embolism (AFE) is a rare but catastrophic complication of pregnancy. The incidence is unknown but is thought to be between 1:8000 and 1:30,000 pregnancies. An AFE is a foreign substance (amniotic fluid with fetal squamous cells) that is introduced into the maternal circulation which causes an acute cardiovascular and pulmonary collapse with associated coagulopathy.

AFE usually occurs during labor, delivery or the first 30 minutes postpartum. The classic presentation is an acute cardiopulmonary arrest in a previously healthy woman laboring or immediately postpartum. Seventy percent of cases occur during labor. Cardiac arrest is common and amniotic fluid emboli account for 5% to 10% of all maternal deaths in the United States. Fetal mortality is approximately 21% and fetal neurologic complications occur in more than half of infants delivered to mothers with an AFE.

Risk factors for amniotic fluid emboli include increased maternal age, uterine overdistension, cesarean delivery, uterine rupture, placental abruption, severe cervical lacerations, and maternal trauma. Links have been suggested between AFE and meconium stained amniotic fluid, augmented labor, and hypertonic contractions but these reports have not been validated.

Clinical Features

Symptoms and Signs—The diagnosis of an AFE is made clinically with the spectrum of disease ranging from mild coagulopathy to sudden and complete cardiopulmonary collapse. Patients most often present with dyspnea, hypotension (100%), and hypoxia (93%). Coagulopathy (83%) and altered mental status (70%) are also common. Seizure activity occurs in approximately 33% of patients and significantly increases maternal morbidity and mortality. Constitutional symptoms (fever, chills, nausea, vomiting, and headache) are also present to varying degrees.

Laboratory Findings—Lab values are nonspecific and do not aid in the diagnosis of AFE. Evidence of coagulopathy without previous blood loss is suggestive and significant hemorrhage is often seen acutely. Fetal squamous cells in the maternal pulmonary circulation at the time of autopsy are diagnostic but cannot always be identified due to prolonged courses following the acute event.

Management

AFE is a rare and unpredictable disorder of pregnancy. Treatment includes prompt initiation of basic and advanced cardiac life support. Continuous cardiac monitoring and pulse oximetry are required with invasive blood pressure monitoring. Coagulopathy must be managed promptly and aggressively with hemorrhage protocol combinations of packed red cells, fresh frozen plasma, cryoprecipitate, and platelets. In catastrophic cases where hemorrhage cannot be controlled, newer procoagulant agents should be used and a hysterectomy may be required. If an AFE is suspected before delivery, delivery should be prompt once the maternal condition is stabilized.

Peripartum Cardiomyopathy

Essentials of diagnosis: heart failure in last month of pregnancy or within 5 months of delivery, no history or other identifiable cause, LV systolic dysfunction.

Background

Peripartum cardiomyopathy (PPCM) occurs in about 1:2200 to 1:3200 pregnancies in the United States but is seen much more commonly globally. It is defined as heart failure in the last month of pregnancy or up to 5 months postpartum in the absence of known heart disease or another identifiable cause. It is characterized by left ventricular systolic dysfunction with an ejection fraction of < 45% or reduced fractional shortening.

Risk factors for peripartum cardiomyopathy include multiparity, black race, maternal age more than 30, hypertensive disorders of pregnancy, multiple gestation, long term tocolytic therapy (terbutaline), and maternal cocaine abuse. The exact etiology is unknown.

About half of patients will have complete resolution of symptoms after delivery with return of normal cardiac size and function. The remainder has continued dilation and often progressive heart failure. Future pregnancies are extremely high risk in women with a history of peripartum cardiomyopathy. In women without complete resolution of symptoms, future pregnancy mortality approaches 50%.

Clinical Features

Symptoms and Signs—Patients present with symptoms of heart failure. Some of the initial nonspecific symptoms may be confusing due to the prevalence of these symptoms in normal pregnancy.

Imaging studies show enlargement of the cardiac silhouette and pulmonary edema. Echocardiography shows decreased universal contractility and left ventricular enlargement without hypertrophy. Diagnostic criteria used include: Left ventricular ejection fraction less than 45% and/or fractional shortening of less than 30% and left ventricular end systolic dimension greater than 2.7 cm/m².

Laboratory Findings—Arterial blood gas shows hypoxemia with respiratory alkalosis. Urinalysis can show concentrated urine. CBC, serum chemistries and liver function tests should be unremarkable. Brain natriuretic peptide (BNP) levels typically increase 2 fold in healthy pregnancy and are usually elevated in heart failure, however limited data are available to support the use of this test in pregnancy. Elevated BNP has been observed in pregnant women with preeclampsia and other clinical conditions associated with volume overload.

Special Considerations—Systemic and pulmonary embolization can be seen more frequently than in other forms of cardiomyopathies.

Management

Treatment of PPCM is similar to that for other types of heart failure. The goal in management is to improve cardiac function by reducing afterload and preload and increasing contractility. It is important to remember to avoid angiotensin inhibition, which is contraindicated in pregnancy.

Initial stabilization may require intravenous diuretics or inotropic support. Loop diuretics serve to decrease preload and relieve pulmonary congestion. Digoxin may improve myocardial contractility and facilitate rate control when atrial fibrillation is present. Hydralazine is the vasodilator of choice and can be used to reduce afterload before delivery and angiotensin-converting enzyme inhibitors can be used postpartum. Beta blockade has also been shown to improve cardiac function and survival in chronic heart failure but should not be used in acute decompensated heart failure. Patients with acute decompensated heart failure with hypotension or persistent pulmonary edema despite initial measures may benefit from intravenous inotropic support with Dobutamine or Milrinone. An intra-aortic balloon pump, extracorporeal membrane oxygenation, and LV assist devices have been used successfully as a bridge for recovery or transplantation in patients with PPCM and should be considered in rapidly deteriorating patients who are not responding to medical therapy, including inotropic medications.

Anticoagulation with heparin should be considered if EF is significantly reduced, that is, less than 35% due to the high risk of thrombus formation and thromboembolism in the context of pregnancy-related hypercoaguabllity and stasis due to LV dysfunction.

Early delivery may be necessary if persistent hemodynamic instability is present, but if the mother is stabilized the goal is delivery at term. Cesarean delivery is reserved for obstetric indications. Early pain control is a key in patients with peripartum cardiomyopathy during labor as pain increases cardiac work and causes tachycardia. A carefully dosed epidural that provides adequate pain control and avoids hypotension is vital.

Background

Obstetric hemorrhage is the leading cause of maternal morbidity and mortality worldwide. It is defined as greater than 500 ml blood loss at the time of a vaginal delivery or greater than 1000 ml of blood loss at the time of cesarean birth. Massive hemorrhage is defined as greater than 1500 ml of blood loss. Rates of massive hemorrhage are increasing as the age and comorbidities of the pregnant population increases. Most obstetric ICU admissions will be due to hemorrhage. The most common causes of obstetric hemorrhage are uterine atony, placental abruption, and abnormal placentation (previa/accreta). Less common causes include genital tract lacerations, uterine inversion and coagulopathy.

Clinical Features/Management

1. Uterine atony

   1. Signs and symptoms include a boggy, soft uterus after delivery with the lower uterine segment often filled with clot.

   2. Risk factors include precipitous or prolonged labor, labor augmentation, overdistended uterus, grand multiparity, prior history of postpartum hemorrhage from uterine atony.

   3. Management include fundal massage and evacuation of the uterus are the first line in treatment of uterine atony. Retained products of conception can prolong the hemorrhage.

      Uterotonic drugs are administered during the fundal massage including intravenous oxytocin (10-40 units in 500-1000 ml normal saline), methylergonovine (0.2 mg intramuscularly), carboprost tromethamine (0.25 mg intramuscularly), or misoprostol (1000 mcg/rectum). Methylergonovine may be associated with increases in maternal blood pressure and therefore cannot be used in women with hypertension or preeclampsia. Prostaglandins can cause bronchospasm and therefore should be avoided in asthmatics.

      Obstetric balloon devices can also be used temporarily to tamponade uterine bleeding and slow postpartum hemorrhage. Patients may be observed for up to 24 hours with the balloon in situ before deflating and closely observing for recurrent bleeding.

      Surgical management options, including uterine compression sutures and uterine artery ligation, can also be pursued prior to hysterectomy.

      Additionally, in certain centers angiographic embolization can be performed, however this should not be considered first line therapy to control active obstetric hemorrhage.

2. Placental abruption

   1. Signs and symptoms include severe persistent abdominal pain differing from the classic crescendo-decrescendo labor pattern; ± vaginal bleeding; retroplacental clot on ultrasound; abnormal fetal heart rate tracing; coagulopathy; bluish “Couvelier's” uterus at the time of cesarean delivery.

   2. Risk factors include severe hypertension, preeclampsia, cocaine use, trauma, and rapid decompression of the uterus (ruptured membranes with polyhydramnios, delivery of the first twin).

   3. Management include the most important steps in the management of placental abruption are identifying the cause of the abruption, treating the underlying disorder and correction of coagulopathy. In the case of significant abruption, delivery should be affected as soon maternal hemodynamic stability is achieved.

3. Abnormal placentation (previa/accreta)

   1. Signs and Symptoms include placenta previa (placenta overlying the internal cervical os) often presents with painless third trimester bleeding and is usually diagnosed antepartum if adequate prenatal care is received. Placenta accreta occurs when the placenta invades the myometrium and fails to separate following delivery.

   2. Risk factors are similar for previa and accreta and include multiparity and prior uterine procedures (cesarean and curettage). Serial cesarean birth is the single greatest risk factor for abnormal placentation and all women with a prior cesarean delivery should undergo ultrasonographic evaluation for placenta accreta. Often the diagnosis of accreta is suspected on ultrasound based on the lack of integrity in the placenta myometrial border and/or placenta lakes. In cases where the suspicion is high, MRI may help further characterize the extent of invasion.

   3. Management include all cases of abnormal placentation should be delivered by cesarean with a skilled pelvic surgeon available. Early notification of the blood bank is imperative as massive transfusion may be required. Some literature has also described preoperative placement of embolization or balloon catheters prophylactically in the highest risk patients.

General Considerations

Obstetric hemorrhage is often underestimated. A stable airway and adequate intravenous access should be established early. Maternal hemodynamic collapse often does not occur until blood loss is greater than 2000 cc and coagulopathy is common. Hemorrhagic shock should be treated early and aggressively with 2:1 replacement with crystalloid and aggressive resuscitation with blood products is imperative. Most academic institutions have created an obstetric hemorrhage protocol to improve communication with the blood bank for release of products. When the hemorrhage protocol is activated packed red cells, fresh frozen plasma and platelets are released together, usually in a 6:4:1 or 4:4:1 ratio. Cryoprecipitate is often added after the first hemorrhage pack is transfused. Identification and correction of bleeding must be accomplished promptly. Newer therapies exist, with limited data regarding safety and effectiveness, which may be advocated for in intractable life-threatening hemorrhage include activated factor VII, prothrombin complex concentrate and tranexamic acid.

When a patient has endured a significant obstetric hemorrhage, she is at risk for significant comorbidities and complications related to the acute blood loss, massive transfusion and indicated therapies. By being aware of these risks, the critical care team can ensure proper posthemorrhage care, with early recognition and appropriate treatment of complications should they arise. Priorities in posthemorrhage management in the ICU include close observation of laboratory parameters (including CBC and coagulation profile) to assure adequate replacement once equilibration has occurred and avoidance of coagulopathy. Close observation is required for evidence of ongoing or recurrent bleeding. Infection is another risk that should be closely monitored for. Recognition of potential hypoperfusion injury to the brain, heart, kidneys and pituitary must be ensured. Additionally, risk for transfusion-related lung injury should be recognized and ventilatory status should be optimized. Aggressive venous thromboembolism prophylaxis must be initiated with sequential compression devices until hemostasis assured, and subsequently pharmacoprophylaxis added.

Thromboembolic Disease in Pregnancy

Background

Changes during normal pregnancy promote coagulation, decrease anticoagulation, and inhibit fibrinolysis. Venous thromboembolism (VTE) is the leading cause of maternal death in developed countries. The risk of VTE is increased 4× to 5× in pregnancy and the puerperium with an overall incidence of 1 in 1600 pregnancies. Most (~66%) of deep vein thromboses (DVT) occur during gestation while over half of pulmonary emboli (PE) occur postpartum. The mortality from VTE is higher in black pregnant patient compared with white ones.

Diagnosis

DVT and PE can present with a wide variety of signs and symptoms, many of which can be confused with normal pregnancy-related complaints including shortness of breath and lower extremity edema. Pregnant patients were excluded from the Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) study that described signs and symptoms of PE in nonpregnant patients. There are no validated clinical prediction guidelines for determining the pretest probability of PE in this population.

Significant clinical debate surrounds the decision between ventilation perfusion scans, computed tomography pulmonary angiography and magnetic resonance angiography for the diagnosis of PE in pregnancy. Every effort should be made to avoid unnecessary radiation exposure to the fetus while providing an accurate and timely diagnosis for the mother. In emergent situations, CT angiography is considered the gold standard for diagnosis of a PE in pregnancy.

American Congress of Obstetricians and Gynecologists (ACOG) committee guidelines state that fetal risks from radiation exposure are negligible when doses are less than 0.05 Gy. CTA delivers slightly lower fetal radiation doses and higher maternal doses of radiation (7.3 vs 0.9 mS) than V/Q scanning (0.003-0.131 mGy vs 0.32-0.74 mGy), in the first through third trimester. Using VQ scans as the initial diagnostic approach may necessitate a second diagnostic scan using CTA, which results in more overall radiation.

1. A normal arterial blood gas or alveolar-arterial difference is common with PE. Nonetheless, the presence of hypoxemia with normal chest radiograph should increase the clinical suspicion for PE.

2. D-dimer testing in pregnancy has limited value as no pregnancy-related normal values have been established and validated. Kovac and colleagues, proposed new values for D-dimer thresholds in pregnancy that should vary with trimesters: 286, 457, and 644 ng/mL in the first, second, and third trimesters, respectively, but these are not yet validated.

3. Compression ultrasound (CUS) is a noninvasive test with a sensitivity of 97% and a specificity of 94% for diagnosing symptomatic, proximal DVT in the general population. CUS appears to have a similar diagnostic accuracy in pregnant patients, with a false-negative rate of approximately 0.7%.⁷ The diagnosis of DVT during pregnancy is most often made by demonstrating poor compressibility of the proximal veins with the patient in the left lateral decubitus position. It is important to note that CUS may miss pelvic vein thromboses which are more common in pregnant and postpartum women.

4. Ventilation/perfusion (V/Q scan)—For those with a normal chest radiograph, V/Q scanning was can be used for the diagnosis of PE in pregnancy. Very low probability scans are associated with a 0% to 6% chance of having a PE. High probability scans are associated with a 56% to 96% chance of having a PE. Small studies describe perfusion (Q) scanning alone with decreases the radiation exposure to mother and fetus, for the diagnosis of PE in pregnancy. In such studies, Q scanning alone had a negative predictive value of 100% and only 7% of scans were nondiagnostic. An abnormal chest radiograph increases the probability of a moderate probability V/Q scan result and should prompt the clinician to avoid V/Q scan and directly proceed to CTPA.⁵

5. CT pulmonary angiograph (CTA) is considered the preferred tool for evaluating respiratory complaints and diagnosing PE in pregnancy due to better interobserver agreement for radiologists reading CT than nuclear scans and better imaging of other pulmonary pathology.

6. Magnetic resonance pulmonary angiography (MRPA) sensitivity and specificity for the diagnosis of PE during pregnancy has not been evaluated. Although no fetal teratogenicity of gadolinium has been observed in human studies, teratogenicity for high doses or prolonged exposures to gadolinium has been observed in animals, so that gadolinium is classified as a category C agent by the FDA.

Management

Adequate treatment of highly suspected or diagnosed VTE can be achieved using subcutaneous low-molecular-weight heparin (SC LMWH), intravenous unfractionated heparin (IV UFH), or subcutaneous unfractionated heparin (SC UFH). Neither UFH nor LMWH cross the placenta. Warfarin crosses the placenta and is not used for treatment of VTE in pregnancy because of the increased risk of birth defects if used during organogenesis and increased risk of fetal hemorrhage at delivery if used in the third trimester. Direct thrombin inhibitors have been demonstrated to cross the placenta in animal models and are not used in pregnant humans.

Subcutaneous LMWH, half-life of 6 hours, is preferred over IV UFH or SC UFH because it is easier to use and more efficacious with a better safety profile, findings extrapolated from clinical trials in nonpregnant patients. Initial doses of SC LMWH include dalteparin 200 units/kg once daily, tinzaparin 175 units/kg once daily, dalteparin 100 units/kg every 12 hours, or enoxaparin 1 mg/kg every 12 hours. While data is limited, many recommend the use of twice daily dosing of LMWH especially after the second trimester due to changes in volume of distribution and increased GFR rate. The dose can be titrated to an anti-Xa level of 0.6 to 1.0 IU/mL for twice daily administration. Controversy exists about monitoring anti-Xa activity in anticipation of the need for dose-escalation as pregnancy progresses. Once a therapeutic dose is achieved, some advocate the performance of periodic anti-Xa levels, particularly in patients at the extremes of body weight or those with altered renal function. The first anti-Xa level is generally measured 6 hours after the third or fourth dose if the dosing is every 12 hours, or 6 hours after the second or third dose if the dosing is once daily. Most adjustments should be an increase or decrease of 10% to 25%.

IV UFH is preferred in critically ill patients and those likely to need delivery due to short half-life (1.5 hours) and easy reversibility with protamine. The impact of protamine on the fetus has not been widely studied, so the use of protamine should be reserved for cases of significant bleeding.

The dose consists of bolus of 80 units/kg, followed by a continuous infusion of 18 units/kg/h. The infusion is titrated every 6 hours to achieve a therapeutic activated partial thromboplastin time (aPTT), that corresponds to an anti-Xa level of 0.3 to 0.7 IU/mL. Once the target aPTT level is achieved, it should be rechecked once or twice daily.

Indications for insertion of an IVC filter are the same in pregnant and nonpregnant patients.

Women diagnosed with VTE within 4 weeks of expected delivery, who have high rate of mortality if therapeutic anticoagulation is stopped are transitioned from LMWH to UFH at approximately 36 weeks' gestation The IV UFH can be stopped 4 hours before delivery or when the patient goes into labor, with the PTT and anti-Xa levels used to monitor the coagulation status. In patients with extensive DVT or PE, scheduled induction of labor or cesarean delivery should be considered to minimize the duration of time without anticoagulation and a temporary IVC filter can be inserted. Neuraxial anesthesia is contraindicated in a therapeutically anticoagulated patient; timing delivery can allow patients to receive adequate anesthesia. After uncomplicated delivery heparin may be restarted 12 hours after a cesarean delivery or 6 hours after a vaginal birth.

Thrombolytic therapy. Despite the concern that thrombolytic therapy could lead to placental abruption, this complication has not been reported. Cesarean birth within 10 days is considered a relative contraindication to thrombolytic therapy; however, successful thrombolysis has been reported within an hour after vaginal and 12 hours after cesarean birth. In a review of 28 cases using thrombolysis in pregnancy, the complication rate was similar to that in nonpregnant patients.

There are case reports of successful use of thrombolytic therapy for massive PE during labor. Cesarean delivery in a patient with massive PE carries a high risk of maternal death and should be performed only in cases where the risks and benefits have been weighed and the mother is stable or perimortem.

In centers with interventional radiology expertise, pulmonary angiography with percutaneous mechanical clot fragmentation and placement of an IV filter may be attempted. Should mechanical and iv thrombolysis not be feasible or fail, ECMO with or without surgical embolectomy followed by cesarean delivery and placement of an IVC filter should be considered.

Severe Sepsis, Septic Shock, and Multiorgan Failure

Background

Severe sepsis and septic shock are not very common conditions, reported to occur in 0.002% to 0.01% of deliveries, but they do carry a high maternal morbidity and mortality with rates between 20% to 30% in pregnant patients with septic shock and multiple organ failure. Pregnancies complicated by severe sepsis are associated with increased rates of preterm labor, fetal infection, and preterm delivery.

Pregnancy predisposes women to specific infectious complications. The most common prenatal infections are chorioamnionitis, septic abortion, pyelonephritis, and pneumonia. The most common postpartum infections are endometritis, wound infection, necrotizing fasciitis, pelvic abscess, septic pelvic thrombophlebitis, and pyogenic sacroiliitis.

The outcome in severe sepsis is improved with early detection, prompt recognition of the infectious source, and early antibiotic therapy. However, there are no pregnancy-specific criteria for sepsis and sepsis criteria are affected by pregnancy physiology.

Diagnosis

Chorioamnionitis—Chorioamnionitis (CA) is an infection of the amniotic fluid, membranes, placenta, and/or decidua. It results from ascending polymicrobial infection in the setting of rupture of membranes or advanced cervical dilatation, rarely from hematogenous spread or invasive procedures such as amniocentesis, chorionic villus sampling or fetal surgery. Length of labor and ruptured membranes appear to be important risk factors. Signs include typical signs of sepsis associated with uterine tenderness ± foul or purulent amniotic fluid or vaginal discharge. Amniocentesis for amniotic fluid culture, gram stain, glucose concentration, WBC concentration, and leukocyte esterase level can be used to establish a microbiologic diagnosis of intra-amniotic infection

Early treatment with antibiotics covering gram-negative and anaerobic flora and evacuation of the uterus are imperative. The most commonly used antibiotics are ampicillin and gentamicin. Patients who undergo cesarean delivery in the presence of CA, are at increased risk of wound infection, endomyometritis, and venous thrombosis and usually require additional anaerobic antibiotic coverage.

Endometritis—Endometritis occurs postpartum, usually in the first week. It originates from bacterial ascension from the lower genital tract during labor. Symptoms are similar to chorioamnionitis. If there is no improvement within 24 to 48 hours, with broad-spectrum intravenous antibiotic therapy, imaging studies should be undertaken to search for a fluid collection or surgical site infection. The most common antibiotic regimens used to treat endometritis are single agent unasyn or combination ampicillin/gentamicin/clindamycin.

Septic Abortion—Septic abortion is now rare in the United States. Historically, septic abortions commonly occurred prior to national legalization of abortion. After the diagnosis of septic abortion is established, treatment with broad-spectrum antibiotics should be immediately instituted with evaluation for and removal of any retained products of conception. Surgical management should be pursued if the patient becomes hemodynamically unstable or shows no improvement with 24 to 48 hours of broad spectrum antibiotics. Hysterectomy and oophorectomy may be required if a dusky, devitalized uterus or pelvic tissue crepitus is encountered intraoperatively and/or clostridial infection is suspected.

Puerperal Mastitis—Puerperal mastitis is usually unilateral, presents in the first week postpartum, with septic symptoms, marked breast engorgement, erythema, and severe pain. Cases of toxic shock syndrome secondary to mastitis have been described and recently concern exists over the appearance of community-acquired methicillin-resistant S aureus (CA-MRSA). Milk from the affected breast should be aspirated and sent for culture and sensitivity before antibiotic treatment. Breast abscess may require surgical incision and drainage or aspiration. Breast feeding is safe and recommended during episodes of mastitis.

Acute Pyelonephritis—Acute pyelonephritis is common in pregnant patients due to pregnancy physiology; dilation of the ureters secondary to progesterone, lack of protective peristalsis, mechanical compression of the urinary system by the gravid uterus and bacteriuria. It manifests with sepsis symptoms, flank pain, nausea/vomiting, and/or costovertebral angle tenderness in the presence or absence of cystitis symptoms. Microscopic bacteriuria and pyuria on urinalysis are verified by a positive urine culture. Bacteriuria during pregnancy has a greater propensity to progress to pyelonephritis and therefore should be treated. E. coli Klebsiella, Enterobacter, Proteus, and gram-positive organisms, including group B Streptococcus account for approximately 70% of cases. Empiric treatment with a cephalosporin or broad-spectrum penicillin is recommended when pyelonephritis is suspected before a positive culture is confirmed. Failure to improve with first-line antibiotic treatment within 24 to 48 hours should prompt evaluation with ultrasound for obstructive urinary tract lesions, such as urinary calculi or perinephric abscess.

Pneumonia—Pneumonia (PNA) has increased morbidity and mortality in pregnancy. The most common pathogens are the same as those found in nonpregnant patients. Community-acquired MRSA can cause a necrotizing pneumonia or can be a super infection with influenza pneumonia. Standard antibiotics for treatment of PNA can be used in pregnancy with the exception of fluoroquinolones.

Influenza—Influenza in pregnant women is associated with a higher rate of morbidity and mortality. A rapid test can detect Influenza A and B, but the sensitivities differ seasonally. If suspicion is strong, culture should be performed. Oxygen, hydration, and neuraminidase inhibitors zanamivir (Relenza) and oseltamivir (Tamiflu) should be started immediately. Women with suspected or confirmed influenza who are pregnant or who have delivered within the previous 2 weeks should receive aggressive antiviral treatment and undergo close monitoring regardless of the results of rapid antigen tests.

Management

Interventions that improve maternal hemodynamic stability and oxygen delivery to the fetus result in improved maternal and fetal outcomes. Operative intervention on behalf of the fetus in an unstable mother increases maternal morbidity and mortality. To date, no “evidence-based” recommendations are specific to the pregnant patient with septic shock.

1. Vasopressors can vasoconstrict uterine blood vessels, reducing fetal blood flow. First line in the management of hypotension is administration of intravenous fluids (normal saline 20 mg/kg) and placing the patient in the left lateral decubitus position to prevent compression of the IVC by the gravid uterus. Hypotension that persists requires vasopressor therapy. Although norepinephrine can reduce uterine blood flow, there is no data to suggest that norepinephrine has an adverse effect on fetal well-being, therefore it is often the first line therapy. Vasopressin may be added in patients with refractory shock at a rate of 0.01 to 0.04 UI/min

2. Bedside critical care ultrasound is emerging as a useful tool in the assessment of the hypotensive critically ill patient. Transthoracic echocardiography (TTE) may assist in the differentiation of life-threatening hypotension in the critically ill obstetric patient by allowing the rapid identification of right ventricular versus left ventricular heart failure, pericardial effusion and fluid status.

3. Little evidence exists regarding the management of ARDS specifically in pregnancy, and thus, treatment approaches must be drawn from studies performed in a general patient population. Initial management is the same regardless of the cause of the acute respiratory failure with supplemental oxygen with goal is to maintain the oxyhemoglobin saturation 95% or more and arterial oxygen tension (PaO₂) more than 70 mm Hg, to maintain fetal oxygenation. Mechanical ventilation may be required. Ventilatory goals are different in pregnant patients. The target PaCO₂ is 30 to 32 mm Hg, since this is the normal level during pregnancy; more respiratory alkalosis should be avoided because it may decrease uterine blood flow. Maternal permissive hypercapnia may also be deleterious to the fetus because of resultant fetal respiratory acidosis.

4. Sedation is required to tolerate mechanical ventilation. The literature suggests that use of benzodiazepines and narcotics are safe in pregnancy. Transient neurologic deficits and respiratory depression have been reported in neonates born to mothers medicated in the later stages of pregnancy. Propofol classified as a pregnancy category B agent, crosses the placenta and may be associated with neonatal respiratory depression. Data on the clinical use of propofol for pregnant critically ill patients is limited to case reports, so its use should be limited until more prospective data is available.

5. Extracorporeal membrane oxygenation (ECMO) is a technique that provides support to selected patients with severe respiratory failure. Little data exists regarding the long term outcomes for infants born after the use of ECMO during pregnancy. However during the 2009 H1N1 influenza epidemic, ECMO was used with a good impact on survival for pregnant women.

6. Acute Kidney Injury is often reversible in pregnancy. Ischemic ATN is usually precipitated by abruptio placentae or postpartum hemorrhage and, less commonly, by AFE and sepsis. The diagnosis of postrenal AKI in the pregnant patient is particularly challenging due to the physiologic dilatation of the collecting system that normally occurs in the second and third trimesters and determining the presence of abnormal findings on renal ultrasonography is more difficult.

Pulmonary Edema

Historically, approximately 50% of the cases of pulmonary edema were attributed to tocolytic therapy or cardiac disease, peripartum cardiomyopathy, mitral stenosis, with the rest due to preeclampsia, eclampsia or iatrogenic volume overload.

The use of tocolytics including calcium channel blockers, to inhibit preterm labor is associated with the pulmonary edema in 0.25% to 5% of treated patients. It is more common among multiple gestations and use of multiple tocolytic agents simultaneously.

The standard therapeutic approach includes discontinuation of potentially contributing tocolytics, supplemental oxygen, fluid restriction, and diuresis. Diuretics should be used with caution in the setting of preeclampsia due to intravascular volume depletion.

Arrhythmia

Arrhythmias are more common in women with heart disease. Arrhythmia with significant hemodynamic effect should be treated urgently and aggressively. If the mother's own perfusion is compromised significantly, uterine vascular constriction will occur. ECG should be done to document the rhythm before treatment and secondary causes for arrhythmia should be ruled out (dehydration, hyperthyroidism, drugs, sepsis, pulmonary emboli).

Paroxysmal supraventricular tachycardia is the most common nonsinus tachycardia in women of childbearing age. Adenosine, verapamil or metoprolol intravenous are highly effective in terminating the rhythm. Paroximal Atrial Fibrillation and Atrial flutter with rapid ventricular response occur more frequently in young women mostly due to successful congenital heart disease treatment. The treatment should be the same as in nonpregnant women, although with a heightened sense of urgency. Intravenous verapamil, metoprolol or diltiazem are usually successful at slowing the ventricular rate. If this is not achieved, cardioversion should be performed.

Ventricular tachycardia does occur in pregnancy especially in patients with history of structural heart disease. Acute treatment should include the usual medications or cardioversion as needed to protect the mother.

All drugs used to treat an arrhythmia cross the placenta resulting in fetal exposure, and most are categorized as Food and Drug Administration (FDA) class C. All beta-blockers have the potential for influencing fetal and newborn size, but only atenolol is singled out as being FDA class D. Digoxin, verapamil, diltiazem, and adenosine have their usual efficacy without adversely affecting the fetus. Experience during pregnancy is greater with quinidine than with all the other antiarrhythmic drugs. Lidocaine has been used without any recognized teratogenic effects, although there has been some concern about fetal bradycardia. A reported series, used Amiodarone in 26 women to treat fetal arrhythmias and also for maternal arrhythmias had no recognized adverse fetal effects. Cardioversion preceeded by moderate sedation has been used in pregnancy without any reported adverse fetal effects.

Symptomatic bradycardia is rare in pregnancy. Temporary and permanent pacing can be performed during pregnancy if required with minimizing irradiation, for maternal and fetal benefit.

Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA) occurs in approximately 1% to 3% of diabetic women who become pregnant and represents a medical emergency with high maternal and fetal mortality. Prompt recognition and resuscitative therapy markedly improves outcome. It can occur in the newly diagnosed diabetic patient, and the hormonal changes of pregnancy, a state of relative insulin resistance may become the background for this phenomenon. The blood glucose levels in pregnant women with DKA are usually lower than those in nonpregnant women with DKA.

The presentation of DKA is similar in pregnant and nonpregnant women, with symptoms of nausea, vomiting, thirst, polyuria, polydipsia, tachypneea, change in mental status.

Maternal hyperglycemia results in fetal hyperglycemia and fetal osmotic diuresis. Maternal acidemia decreases uterine blood flow with a resultant decrease in placental perfusion leading to decreased oxygen delivery to the fetus. Fetal acidosis and fetal volume depletion may occur, which jeopardizes the viability of the fetus. Other than fetal heart rate monitoring, which is used to assess and monitor the fetus, DKA is treated similarly in pregnant and nonpregnant patients.

Asthma affects 3% to 8% of pregnant women. Clinical severity of asthma in pregnancy seems to follow the severity before the pregnancy with exacerbations 20% to 36% of pregnancies, most frequently between weeks 14 and 24.

The diagnosis and treatment of acute asthma during pregnancy does not differ from the management in nonpregnant patients. Intensive monitoring of both mother and fetus is essential. Pregnant patients with acute asthma should rest in a seated, rather than supine, position. A severe asthma attack presents more of a risk to the fetus than the use of asthma medications because of the potential for fetal hypoxia, so therapy β2-agonists, anticholinergics, and systemic corticosteroids should be used as indicated to treat exacerbations.

Evidence based data about the management of refractory status asthmaticus in obstetric patients is minimal. Review of 3 case reports with a total of 10 cases, 2 of which were past 32 weeks, revealed 2 patients who underwent cesarean delivery and improved dramatically after the procedure.

Critical illness in obstetrics may occur due to pregnancy-specific conditions, rarely encountered by the intensivist physician, or due to commonly seen critical care diagnoses with unique-management considerations in pregnancy. A multidisciplinary collaborative approach will help to optimize maternal and fetal outcomes in these high-risk pregnancies.