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2002 Selected Articles

Obstetric Embolic Disease

Jerry G. Ninia, MD

Ranging from the benign to the catastrophic, obstetric embolic disease accounts for the majority of nonabortive, pregnancy-related maternal mortality in the United States (Table 1).¹ Closely followed by hypertensive disorders and hemorrhage, embolic disease contributes to approximately 20% of cases of maternal death. Its predominance may be due to the difficulties inherent in every phase of management, prevention, recognition, and treatment. Obstetric embolic disease includes venous air embolism (VAE), superficial thrombophlebitis (STP), deep-vein thrombosis/pulmonary embolism (DVT/PE), amniotic fluid embolism (AFE), and septic pelvic thrombophlebitis (SPT).

VENOUS AIR EMBOLISM

In general, VAE is transient, benign, and common–especially in association with cesarean delivery. It occurs in more than 65% of patients undergoing cesarean delivery with regional anesthesia, and in more than 90% of patients receiving general anesthesia.² Patient positioning during abdominal delivery may affect the incidence of VAE, so that steep Trendelenburg and uterine exteriorization should be avoided. Signs of VAE include hypotension and hypoxemia in 10% and 30% of patients, respectively.³ Symptoms include chest pain in 23% of patients.³ Seldom used in clinical practice, precordial Doppler monitoring can be implemented intraoperatively to detect VAE. Monitoring of expired nitrogen is another way to assess for VAE.² A massive air embolus can be treated with position changes, 100% forced inspiratory oxygen (FIO₂), rapid administration of intravenous (IV) fluids, and expediting delivery while minimizing instrumentation. Additionally, cases of fatal VAE have been reported following antepartum oral sex.⁴

SUPERFICIAL THROMBOPHLEBITIS

With an incidence approaching 7% of all pregnancies, STP is quite common. Patients present with pain and localized tenderness over a firm reticular vein or varicosity. Telangiectasias may be involved as well. While the risk of subsequent DVT is low, a Doppler or duplex scan may be included in the evaluation. Care must be taken to rule out cellulitis as well. Treatment includes moist heat, leg elevation, compression, and ambulation. Nonsteroidal anti-inflammatory agents (NSAIDs) may be used for analgesia, with resolution usually occurring within 2 to 3 weeks.

DEEP-VEIN THROMBOSIS/ PULMONARY EMBOLISM

Deep-vein thrombosis occurs in 0.3% of pregnancies, with the condition being more common in women aged 35 years or more and in postpartum patients delivered by cesarean section. Additionally, the left leg is involved more often. On physical examination, the "typical" symptoms of pain, swelling, edema, and Homan’s sign may be unreliable, so a Doppler or duplex scan may be necessary to confirm the diagnosis. These studies work well for evaluating the femoral and popliteal veins. Although more expensive and invasive, venography is better suited to evaluate the vasculature below the knee, as well as Dodd’s, Boyd’s, and Cockett’s perforating veins. Finally, venography incurs a radiation exposure of 21 mrads, which is well below the safe level of 10 R for exposure during pregnancy.

When treated, fewer than 5% of DVTs progress to PE, with a 1% mortality. If unrecognized, up to 25% of DVTs will progress to PE, with a 15% mortality.⁵ Diagnosis is often accomplished with ventilation-perfusion ratio (V/Q) scanning, but antepartum pulmonary angiography may be used with abdominal shielding. Heparin therapy increases thrombolysis by activating antithrombin III. It is a bulky molecule that does not cross the placenta, nor is it secreted in breast milk. Unfractionated heparin is often administered in a dose of 500 U/kg/d to maintain the activated partial thromboplastin time (aPTT) at 1.5 to 2 times the baseline value. Its safety in treating antepartum as well as postpartum DVT/PE is widely acknowledged. With long-term use, however, care must be taken to watch for osteoporosis and thrombocytopenia. Type I heparin-induced thrombocytopenia (ie, heparin-associated thrombocytopenia) is reversible and nonimmune. Type II heparin-associated thrombocytopenia is severe, rare and immune-mediated. It can occur 1 to 2 weeks after starting therapy, and confers a paradoxical increased risk of thrombosis. These complications are less common with the use of low-molecular-weight heparins (LMWH).

With proper dosing, several LMWH products have been found to be even safer and more effective than unfractionated heparin for both prophylaxis and treatment of DVT and PE.⁶ It is neither necessary nor useful to monitor the aPTT when using LMWH. These products are most active in the tissues, and do not exert most of their effects on coagulation factors. Due to pharmacologic differences, dosing is highly product-specific.

Of the various LMWH products available, three are commonly used in the United States, and all are administered by subcutaneous injection. Enoxaparin (Lovenox) is approved for both DVT prophylaxis and treatment. It is given in a dose of 1 mg/kg every 12 hours for treatment. For patients undergoing abdominal surgery, the prophylactic dose is 40 mg four times a day, with the first dose given 2 hours prior to surgery. Dalteparin (Fragmin) is approved for postoperative DVT prophylaxis in abdominal surgery, with once-daily dosing of 2,500 U Ardeparin (Normiflo) is approved for postoperative DVT prophylaxis in patients undergoing hip and knee surgery. It is administered in a dose of 50 U/kg. The clinical effects of the LMWH products can be reversed with 1 mg of protamine sulfate.

Inhalation heparin therapy will be clinically available in the near future, but its use in treating DVT/PE is yet to be studied. Warfarin blocks vitamin K and the vitamin K-dependent coagulation factors II, VII, IX, and X. Its teratogenicity in pregnancy is well known, as it may cause nasal hypoplasia and skeletal defects with first-trimester exposure and intracranial bleeding with second- and third-trimester exposure.^7,8 Thus, its antepartum use is contraindicated. It may be used postpartum, however, even in women who are breast-feeding.

AMNIONIC FLUID EMBOLISM

A rare phenomenon, AFE occurs in only 1/20,000 to 3/100,000 live births.⁹ It is associated with an 80% maternal mortality, usually within 5 hours of onset. Survivors often suffer neurologic sequelae. Although not pathognomonic, fetal squames may be found in the maternal pulmonary vasculature at autopsy.¹⁰

The etiology of AFE is unclear. Administering IV injections into amniotic fluid appears to be benign, and does not give rise to embolic disease. Additionally, the amount of squames and particulate matter found in the mother’s lungs does not correlate with the severity of the clinical presentation. Because the clinical diagnosis of AFE is based on exclusion of other possible causes, the condition is more like an "anaphylaxis of pregnancy" characterized by profound hypotension, hypoxia, and coagulopathy. These changes are the result of a breach in the maternal-fetal physiologic barrier during labor and delivery.

Definitive treatment of AFE is elusive, and there are no data to suggest that any type of intervention improves the prognosis. Prompt recognition based on a high index of clinical suspicion is important. Initial measures include protecting the maternal airway and providing 100% FIO₂, cardiopulmonary support, and liberal use of IV fluids. Prompt fetal delivery may improve maternal survival.¹¹ Coagulopathies must be treated aggressively with blood products. Surgical intensive care is required to manage the sequelae of hemodynamic collapse, including cardiac and renal failure, pulmonary edema, and adult respiratory distress syndrome (ARDS).

Septic Pelvic Thrombophlebitis

Septic pelvic thrombophlebitis (SPT) is a rare condition associated with the postpartum period. Postpartum endometritis may spread throughout the pelvic venous system, including the inferior vena cava. The embolic disease process is more common in the right ovarian vein, whereas left ovarian vein disease with renal vein involvement is less common.^12,13 Patients often present with pain and fever in the postpartum period. There may be initial clinical improvement with antibiotic therapy, but patients with SPT will continue to "spike" fevers daily, usually in the evening, despite the resolution of pain. Computed tomographic (CT) scanning or magnetic resonance imaging (MRI) studies are best for diagnosis. Care must be taken to rule out ureteral obstruction or urinoma. Patients respond quickly to heparin anticoagulant therapy, and long-term anticoagulation is seldom needed. Most clinicians continue antibiotic therapy along with anticoagulation, although research has failed to show a quicker resolution of the febrile course.¹⁴

CONCLUSION

With a broad spectrum of clinical presentations and severity, obstetric embolic disease can be trivial or fatal. Early recognition is crucial in reducing the potential for morbidity and mortality. This is especially true for AFE, whose complex pathogenesis and serious maternal and fetal implications continue to be associated with high death rates. Exciting new treatments for thromboembolic disease are on the horizon, including inhalation heparin therapy as well as synthetic prophylactic and therapeutic agents. Further study should continue to reduce the incidence of these conditions with increased safety and efficacy.

Jerry G. Ninia, MD, is a clinical assistant professor of obstetrics and gynecology at the State University of New York-Stony Brook School of Medicine, and a member of the board of directors of the American College of Phlebology.

REFERENCES

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