PRIMARY pulmonary hypertension (PPH) is rarely encountered in pregnant women, but carries a high risk of maternal morbidity and mortality. 1We report a case of PPH in a pregnant patient treated with antithrombotic drugs, inhaled pulmonary vasodilators, and epidural anesthesia for cesarean delivery; follow-up examination occurred at 6 months.

Two years previously, the 26-yr-old woman was diagnosed with PPH after cardiac decompensation, which occurred 5 months after uncomplicated delivery of a neonate. She refused treatment at that time. During her second pregnancy, at 15 weeks’ gestation, Doppler echocardiography showed a right atrial diameter of 6.2 cm (normal diameter, 2.2–4.1 cm), a short-axis end-diastolic diameter of the right ventricle of 5.1 cm (normal, 1.9–4.0 cm), a right ventricle with eccentric hypertrophy and fractional area shortening of 33%, and a small, normally contracting left ventricle.

The patient was lost to further follow-up examinations and reappeared at 31 weeks’ gestation, severely dyspneic at rest and with dilated neck veins and lower limb edema. Ultrasonograph showed a growth-retarded fetus. The patient’s systemic arterial pressure (AP) was 108/69 mmHg, with a regular heart rate of 94 beats/min. Electrocardiography showed a sinus rhythm, prominent P waves in V1–V3, and a partial right bundle branch block. Oxygen saturation by pulse oximetry (SpO2) of 88% increased to more than 94% with supplemented nasal oxygen. Hemoglobin was 11.4 g/dl, and platelet count was 177 103°/μl. Radial artery and thermodilution pulmonary artery catheters were inserted to test the response to nitric oxide (NO) and to oxygen breathing at inspiratory fraction (FIO2) of 1.0. Nitric oxide (40 ppm) failed to improve pulmonary hemodynamics, but oxygen breathing slightly decreased pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) and the catheters were removed. Dalteparin (Fragmin; Pharmacia-Upjohn, Stockholm, Sweden), a low-molecular-weight heparin, was administered subcutaneously at 5,000 and 7,500 IU/day. The patient received digoxin, magnesium for its tocolitic properties, and betamethasone at 31 weeks and 32 weeks of gestation to promote fetal lung maturation. Continued right-sided heart dilatation (atrial diameter = 6.3 cm, end-diastolic ventricular diameter = 5.4 cm) and a decrease of right ventricular fractional area shortening to 25% were found at 32 weeks’ gestation. Ultrasound biometry showed insufficient fetal growth, and the decision was made to proceed with cesarean delivery at 34 weeks’ gestation.

In the operating room, the patient was placed in a supine position with left uterine displacement. Radial artery, thermodilution pulmonary artery, and lumbar epidural (L2–3) catheters were placed during local anesthesia. After baseline measurements, 6 l/min O2by mask increased SpO2from 90 to 96%. The hemodynamic parameters, hemoglobin concentration, and platelet count obtained peripartum are summarized in table 1. Thromboelastography (reaction time, 6.0 mm; clot formation time, 2.0 mm; maximal amplitude, 76 mm; clot formation rate, 74°) and tests of platelet aggregation (65–86%) showed a coagulation profile typical for hypercoagulability of parturients near term. 2,3An epidural test dose of 3 ml lidocaine, 2% (60 mg), with 15 μg epinephrine was administered. Epidural anesthesia was induced slowly (70 min) with 300 mg plain lidocaine, 2%, 70 mg bupivacaine 0.5%, and 0.1 mg fentanyl. Epidural block finally spread to T5; the supine position with left-uterine displacement continued to be tolerated. The patient inhaled 20 μg aerosolized iloprost (Ilomedin; Schering, Berlin) diluted in 2 ml NaCl, 0.9%, for 4 min. A 1,590-g and 40-cm (< tenth percentile) infant was delivered by low transverse abdominal incision. Apgar scores were 7, 9, and 9 at 1, 5, and 10 min, respectively. Oxytocin was administered in the uterine wall and as a slow intravenous infusion. Tubal ligation was performed. Unfractioned heparin 5,000 IU was then administered subcutaneously. The patient received 2,400 ml lactated Ringer’s solution. Urine volume was 200 ml, and surgical blood loss was 400 ml. Coagulation tests after iloprost inhalation and delivery showed mild changes of reaction time (3.5–4.0 mm), clot formation time (2.0–2.5 mm), maximal amplitude (63–66 mm), clot formation rate (74–76°), and platelet aggregation (65–86%). The epidural catheter remained in situ .

Table 1. Effects of Epidural Anesthesia, Iloprost, and Cesarean Delivery on Hemodynamic Parameters, Hemoglobin, and Platelet Count

Baseline = 45 min after the epidural test dose; Iloprost = 20 μg inhaled over 4 min; CD = cesarean delivery; AP = systemic arterial pressure; PAP = pulmonary artery pressure; RAP = right atrial pressure; PCWP = pulmonary capillary wedge pressure; SVR = systemic vascular resistance; PVR = pulmonary vascular resistance; DO2= oxygen delivery; VO2= oxygen consumption; ExO2= oxygen extraction rate.

Table 1. Effects of Epidural Anesthesia, Iloprost, and Cesarean Delivery on Hemodynamic Parameters, Hemoglobin, and Platelet Count
Table 1. Effects of Epidural Anesthesia, Iloprost, and Cesarean Delivery on Hemodynamic Parameters, Hemoglobin, and Platelet Count

In the intensive care unit, continuous oxygen by mask and intermittent iloprost inhalations six times daily were continued. Cardiac output decreased during the first 12 h to 5.4 l/min, and then ranged between 4.1 and 6.4 l/min. Systolic PAP (82–95 mmHg) remained initially below systolic AP, but in the further course exceeded intermittently the AP level without clinical consequences. Systemic vascular resistance (SVR) increased from 567 to 1,180 dyn · s−1· cm−5, and PVR increased from 395 to 890 dyn · s−1· cm−5. Positive fluid balance of 1,600 ml was reduced to 600 ml with furosemide. Postoperative analgesia was provided with intravenous paracetamol and morphine. Thromboelastographic and platelet aggregation tests remained unchanged postpartum, and the epidural catheter was removed 28 h after insertion (25 h after the last heparin dose). Subcutaneous dalteparin administration, 5,000 IU twice daily, was resumed 2 h later. On postpartum day 2, the pulmonary artery catheter was removed. Oral anticoagulation was started on postpartum day 8, and dalteparin was discontinued on postpartum day 10. Home treatment with inhaled iloprost and evaluation for lung transplantation were considered, but the patient’s understanding of and potential compliance with the treatment were considered to be inadequate. She was discharged on postpartum day 21, receiving coumarin and digoxin. The newborn required continuous positive airway pressure for 5 days, then recovered and progressed uneventfully.

After discharge, the patient discontinued her medication, became severely dyspneic and cyanotic, and was readmitted to the hospital 1 month later. Six months after delivery of the infant, the patient’s clinical condition was stable. Doppler echocardiography showed an atrial diameter of 7.4 cm, an end-diastolic ventricular diameter of 5.7 cm, a low (20%) fractional area shortening of the right ventricle, and a newly patent foramen ovale with right-to-left shunt.

Pregnancy in patients with PPH carries a 30% risk of maternal mortality, as compared with a 30–40% rate in Eisenmenger syndrome, and a more than 50% rate in secondary vascular pulmonary hypertension. 1,4–6Acute and prolonged treatment with inhaled NO and intravenous and inhaled prostaglandins, such as prostacyclin (PGI2), improve pulmonary endothelial cell function, abnormal platelet aggregation, right-sided heart hemodynamics, and life expectancy in patients with PPH. Side effects, such as bleeding caused by inhibition of platelet aggregation, predominant decrease of SVR and hypoxemia, and complications associated with the drug-delivery system, occasionally limit the intravenous PGI2application. NO treatment may also be complicated by platelet inhibition or methemoglobinemia, formation of toxic nitrate metabolites, and technical requirements for its application. 7–11Aerosolized PGI2and its synthetic analog iloprost are more easily administered, do not affect SVR, and more effectively reduce PAP in patients with pulmonary hypertension, compared with intravenous PGI2and inhaled NO. 9,10The experiences with NO and PGI2in pregnant patients are currently limited to a few cases. 1,12–16A patient with Eisenmenger syndrome was treated successfully with NO peripartum; however, methylene blue was necessary because of severe methemoglobinemia. The patient died when NO was discontinued, despite intravenous infusion of PGI2. 12In a case of scleroderma, pulmonary hypertension was unresponsive to NO, and the patient died 9 days after delivery of an infant. 13However, a woman with human immunodeficiency virus infection and pulmonary hypertension was successfully treated with oxygen and NO for several weeks peripartum. 14Treatment with intravenous PGI2was recommended for 12–15 months before conception in patients with PPH. 15When PPH was diagnosed during pregnancy, one patient responded favorably to PGI2and furosemide, but another failed to respond, and died before delivery of a neonate. 15Another PPH patient was treated with intravenous PGI2, but bleeding after operative delivery necessitated gradual change to aerosolized PGI2; the bleeding ceased and the patient recovered. 16 

The echocardiographic and invasive measurements in our patient showed a severe form of PPH with progressive dilation of the right side of the heart. The diameters of the right atrium and right ventricle far exceeded the values found in healthy parturients at term and postpartum. 17The patient’s response to NO at 31 weeks’ gestation was inadequate, but oxygen breathing resulted in some improvement in pulmonary hemodynamics. In the operating room, supplemented oxygen and epidural anesthesia provided a stable cardiovascular condition, with a systolic AP greater than the systolic PAP. Inhaled iloprost decreased PAP before delivery and again in the intensive care unit, when PAP started to exceed AP (table 1). The observed changes in PAP and PVR were moderate and coinfluenced by other factors (e.g. , oxygen, epidural anesthesia, volume infusion, delivery and bleeding, and furosemide), but iloprost may have prevented a further increase of PAP and right-sided heart decompensation peripartum.

The use of antithrombotic drugs in pregnant patients with pulmonary hypertension is controversial because of a low incidence of cases, more frequent reports of bleeding than of thromboembolism, concomitant coagulation defects, and subtle differences between PPH, Eisenmenger syndrome, and other types of secondary pulmonary hypertension. 1,4–6Gestational hypercoagulability and increased pulmonary thrombogenicity of PPH indicate a thromboembolic prophylaxis peripartum. 1,7,11Therefore, a low-molecular-weight heparin was administered for 4 weeks peripartum, followed by oral anticoagulation. The major concern of the treatment represented the insertion and removal of the epidural catheter and inhalation of iloprost, with its potential to induce platelet dysfunction and, eventually, epidural hematoma. The mild changes of thromboelastographic parameters and platelet aggregation tests excluded the adverse coagulation effect of iloprost in this patient.

This case report confirms the importance of early hospital admission and individually tailored medical treatment in pregnant PPH patients. The use of antithrombotic drugs and selective pulmonary vasodilators are warranted in late pregnancy and particularly after delivery of an infant, to prevent the pulmonary hypertensive crisis and right-sided heart failure. Inhaled iloprost appears to be a promising option to reduce PAP without compromising platelet function, an important characteristic for patients requiring regional anesthesia.

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