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.
Table 105–4. Relative Indications for Right Heart Catheterization ||Download (.pdf)
Table 105–4. Relative Indications for Right Heart Catheterization
|Routine operative or labor/delivery monitoring for:|
| Severe pulmonary hypertension|
| Significant valvular heart disease|
| New York Heart Association class III or IV congestive heart failure|
|Hypertension or preeclampsia complicated by:|
| Pulmonary edema|
| Heart failure|
| Oliguric renal failure|
| Etiology is obscure|
| Volume resuscitation fails|
| Central venous pressure is elevated|
| Vasoactive drugs are required|
|Acute respiratory failure that is:|
| Accompanied by shock|
| Requires mechanical ventilation and positive end-expiratory pressure|
| Accompanied by pulmonary edema of unknown etiology|
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.
Table 105–5. Etiology of Hemorrhagic Shock in Pregnancy ||Download (.pdf)
Table 105–5. Etiology of Hemorrhagic Shock in Pregnancy
|Early||Late (Third Trimester)||Postpartum|
|Ectopic or abdominal pregnancy||Placenta previa or abruptio placentae||Surgical trauma|
|Abortion||Uterine rupture||Uterine inversion|
|Hydatidiform mole||Marginal sinus rupture||Retained placenta|
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.
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.
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.
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.
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.
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
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.
Table 105–6. Bacterial Infections Associated with Sepsis in Pregnancy and after Parturition ||Download (.pdf)
Table 105–6. Bacterial Infections Associated with Sepsis in Pregnancy and after Parturition
| Postpartum endometritis|
| Chorioamnionitis (intra-amniotic infection)|
| Septic abortion|
| Septic pelvic thrombophlebitis|
| Antepartum pyelonephritis|
| Abdominal wall or perineal incisions (necrotizing fasciitis)|
| Amniocentesis/chorionic villus sampling (septic abortion)|
| Infected cerclage (chorioamnionitis)|
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
Table 105–7. Pathogens Responsible for Severe Sepsis in Obstetric Patients ||Download (.pdf)
Table 105–7. Pathogens Responsible for Severe Sepsis in Obstetric Patients
| E. coli|
| Klebsiella-Enterobacter spp.|
| Proteus spp.|
| Serratia spp.|
| Pseudomonas spp.|
| Haemophilus influenzae|
| Clostridium perfringens|
| Fusobacterium spp.|
| Bacteroides spp.|
| Streptococci, groups A, B, and D|
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
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 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.
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
Table 105–8. Differential Diagnosis of Characteristic Features of Preeclampsia and Its Complications ||Download (.pdf)
Table 105–8. Differential Diagnosis of Characteristic Features of Preeclampsia and Its Complications
|Preeclampsia superimposed on chronic hypertension||Secondary hypertension (renal, pheochromocytoma)|
|Acute fatty liver of pregnancy||Sepsis|
|Elevated liver enzymes||Preeclampsia||Viral hepatitis|
|HELLP syndrome||Drug-induced hepatitis|
|Acute fatty liver of pregnancy|
|Cholestasis of pregnancy|
|Acute fatty liver of pregnancy||Hypovolemia/hemorrhage|
|Idiopathic postpartum renal failure||TTP/HUS|
|Pulmonary edema||Preeclampsia||Valvular heart disease|
|Peripartum cardiomyopathy||Ischemic heart disease|
|Tocolytic pulmonary edema||ARDS|
|Amniotic fluid embolism|
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.
Table 105–9. Drugs Used in the Management of Acute Hypertensive Crises in Pregnancy ||Download (.pdf)
Table 105–9. Drugs Used in the Management of Acute Hypertensive Crises in Pregnancy
|Nicardipine||5 mg/h increasing the infusion rate by 2.5 mg/h every 5 min (to a maximum of 15 mg/h)|
|Hydralazine||Initial dose: 5 mg IV bolus; then 5–10 mg every 20–30 min; side effects include tachycardia and headache|
|Labetalol||Small IV boluses, initially 20-mg, followed by 20 mg to 80 mg, given every 10–20 min until blood pressure is controlled or total dose is 300 mg; can use continuous infusion of 1–2 mg/min titrated up until blood pressure is controlled.|
|Diazoxide||For use in refractory patients; given in 30-mg miniboluses every 5 min|
|Sodium nitroprusside||May be used in standard doses [initially 0.25 μg/(kg. min)] for a short period (30 min) in acute crises; potential for fetal cyanide toxicity.|
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.
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