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Pregnancy and Primary Pulmonary Hypertension*: Successful Outcome With Epoprostenol Therapy FREE TO VIEW

Rosalyn Stewart, MD; Divina Tuazon, MD; Gayle Olson, MD; Alexander G. Duarte, MD
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*From the Department of Internal Medicine (Drs. Stewart, Tuazon, and Duarte), Division of Pulmonary and Critical Care Medicine, and the Department of Obstetrics and Gynecology (Dr. Olson), University of Texas Medical Branch, Galveston, TX.

Correspondence to: Alexander G. Duarte, MD, Division of Pulmonary and Critical Care Medicine, John Sealy Annex, 301 University Blvd, Galveston, TX 77555-0561; e-mail: aduarte@utmb.edu



Chest. 2001;119(3):973-975. doi:10.1378/chest.119.3.973
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Primary pulmonary hypertension (PPH) associated with pregnancy carries a high maternal mortality rate. Short-term epoprostenol infusion has been demonstrated to improve the hemodynamic profile in patients with PPH. We report a successful maternal-fetal outcome with epoprostenol therapy during pregnancy, cesarean section, and postpartum in a patient with PPH. Epoprostenol therapy did not produce any physical or developmental abnormalities in the fetus. A favorable maternal-fetal outcome may occur with a multidisciplinary approach.

Primary pulmonary hypertension (PPH) is a rare, progressive condition aggravated by the physiologic changes occurring during pregnancy and surgery. The maternal mortality rate associated with pregnancy and pulmonary hypertension ranges from 30 to 50%.12 The administration of IV epoprostenol has been well-demonstrated to improve hemodynamics in nonpregnant patients with PPH.3 We report a successful maternal-fetal outcome in a pregnant woman in whom PPH was diagnosed who was treated with IV epoprostenol before, during, and after undergoing cesarean section.

A 35-year-old, gravida (G2,P0) patient with a history of hypothyroidism presented at 26 weeks’ gestation with progressive exertional dyspnea and fatigue of several weeks duration. She also reported several recent syncopal episodes. Her first pregnancy was uncomplicated, and she denied prior cardiopulmonary disease, illicit drug use, or ingestion of anorexigens. On physical examination, her vital signs were as follows: BP, 90/60 mm Hg; heart rate, 105 beats/min; respiratory rate, 20 breaths/min; and oxygen saturation as measured by pulse oximetry, 92%. Jugular venous distension was present. Cardiac auscultation revealed a loud S2 and a grade 3/6 systolic murmur over the left lower sternal border that was accentuated on inspiration. Lung fields were clear to auscultation bilaterally. Extremities were without clubbing, and 1+ edema was present. An ECG was interpreted as representing normal sinus rhythm. A chest radiograph was unremarkable for parenchymal infiltrates, and a ventilation-perfusion scan was interpreted as revealing a low probability for a pulmonary embolism. Arterial blood gas measurements revealed the following: pH, 7.45; Pco2, 29 mm Hg; Po2, 79 mm Hg; and bicarbonate level, 20 mEq/L. An echocardiogram displayed a dilated right ventricle, paradoxical septal wall motion, and normal left ventricular wall motion.

The patient was admitted to labor and delivery and was prescribed bed rest, oxygen, diuretics, and heparin. Fetal heart tones were noted at 150 beats/min, and IM corticosteroids were administered to accelerate fetal lung development. Despite this therapy, the patient continued to report progressive dyspnea, and at 32 weeks’ gestation the placement of a pulmonary artery catheter (PAC) demonstrated moderate pulmonary hypertension (Table 1 ). IV epoprostenol therapy was initiated at 4 ng/kg/min, producing an improvement in the hemodynamic profile (Table 1). At 36 weeks’ gestation, while receiving IV epoprostenol, the premature rupture of membranes occurred followed by active labor. However, the progression of labor was inadequate, and a cesarean section was scheduled. Preoperatively, a PAC was placed and epidural anesthesia was administered. Subsequently, the cardiac output declined from 7.4 to 4.1 L/min and the epoprostenol infusion was increased to 10 ng/kg/min. The patient remained hemodynamically stable throughout the cesarean section and delivered a healthy male infant weighing 7 lbs with Apgar scores of 5 and 9, respectively, at 1 and 5 min. A bilateral tubal ligation was performed with patient consent. Following extubation, the PAC was maintained for 48 h to assist with IV fluid administration, and the hemodynamic profile remained stable with the patient receiving 10 ng/kg/min epoprostenol. On postoperative day 2, heparin therapy was resumed.

Three weeks later, the patient underwent a vasodilator trial with calcium-channel blockers but did not have a favorable response, hence, she was continued on epoprostenol therapy. Presently, she has resumed an active lifestyle as a housewife and mother. Furthermore, her 2-year-old son is in good health without any developmental delays.

An early case series reported a 50% mortality rate associated with pregnancy and PPH.1A more recent account noted a 30% mortality rate2 and partly attributed the decline in the mortality rate to earlier recognition, better understanding of the pathophysiology of pulmonary hypertension, along with improvements in medical therapy and critical-care obstetrics. Recognition of the elevated maternal-fetal mortality rate has led physicians to recommend effective contraception and, in the event of a pregnancy, early fetal termination.4The maternal mortality rate is related principally to the increased demands on the cardiopulmonary system during pregnancy. Under normal circumstances, increases in cardiac output in the range of 30 to 50%, blood volume in the range of 40 to 50%, and oxygen consumption of 20% are observed during pregnancy.56 Other physiologic changes include an increase in cardiac output during labor in patients receiving local anesthesia (pudendal block) and postpartum intravascular volume shifts resulting from blood loss or diuresis. These physiologic events place a great demand on the cardiovascular system, with the greatest incidence of mortality occurring during the first several postoperative days. This is likely related to changes in pulmonary vascular tone due to intravascular volume shifts, hypoxemia, elevated catecholamine levels, or thromboembolism. Identification of the hemodynamic changes has led to the use of anticoagulants, oxygen, and vasodilators in the management of these patients.

Several reports have demonstrated an improvement in hemodynamics and outcome in nonpregnant patients receiving vasodilator and anticoagulation therapy for the treatment of PPH.3,7 Subsequently, several reports have described the use of vasodilator therapy during parturition and postpartum with good outcomes.89 The majority of patients in these series had improvements in hemodynamics similar to our patient, leading one to speculate that a favorable short-term response to vasodilator therapy may be predictive of a favorable maternal outcome. Accordingly, we elected to use epoprostenol and heparin for several weeks prior to the expected date of delivery in order to maximize the benefits of this therapy. Furthermore, this therapy was continued in the postpartum period given the increased incidence of complications following labor and delivery. Another important point concerns the safety of the fetus following exposure to IV epoprostenol. Although there is little information on this subject, this report indicates that during the last trimester of pregnancy epoprostenol therapy does not result in any fetal deformities or growth retardation.

Several factors have been implicated as potential risk factors for maternal death, including mode of delivery, type and technique of anesthesia, and manner of maternal monitoring. A recent case series described successful outcomes in seven women with pulmonary hypertension following vaginal delivery.10 In contrast, greater morbidity and mortality has been associated with the performance of a cesarean section.2 To our knowledge, this is one of a small number of reports noting a successful maternal-fetal outcome following cesarean section in a patient with PPH.4,1112 An explanation for this observation has been offered and may be related to the selection of the anesthetic technique (epidural or general anesthesia), although it is not clear whether one technique is superior in the setting of pulmonary hypertension and parturition.11 Another explanation may lie in the fact that cesarean section is more likely to be performed in patients unable to deliver by the vaginal route who subsequently develop hemodynamic instability. While some authors have disputed the need for a PAC, we advocate its use intraoperatively and during the postpartum period.9 In this report, the epoprostenol infusion was titrated using pulmonary artery pressure and cardiac output measurements obtained with a PAC. An important component in the successful management of these patients involves a multidisciplinary team approach with an obstetrician, pulmonary or cardiology specialist, anesthesiologist, and experienced nursing staff.

In summary, PPH is likely to worsen during labor and delivery, resulting in a high maternal mortality rate. Early recognition and treatment with vasodilator and anticoagulation therapy may reduce the likelihood of complications. Elective cesarean section may be performed with intraoperative vasodilator administration. The IV epoprostenol dose not give rise to physical deformities or fetal growth retardation. A multidisciplinary approach to the management of patients with PPH during pregnancy is of great importance for a successful maternal-fetal outcome.

Abbreviations: PAC = pulmonary artery catheter; PPH = primary pulmonary hypertension

Table Graphic Jump Location
Table 1. Hemodynamic Measurements*
* 

PAP = pulmonary artery pressure; PVR = pulmonary vascular resistance; CO = cardiac output; CVP = central venous pressure; PAOP = pulmonary artery opening pressure.

McCaffrey, RN, Dunn, LJ (1964) Primary pulmonary hypertension in pregnancy.Obstet Gynecol Surv19,567-591. [CrossRef] [PubMed]
 
Weiss, BM, Zemp, L, Seifert, B, et al Outcome of pulmonary vascular disease in pregnancy: a systematic overview from 1978 through 1996.J Am Coll Cardiol1998;31,1650-1657. [CrossRef] [PubMed]
 
McLaughlin, VV, Genthner, DE, Panella, MM, et al Reduction in pulmonary vascular resistance with long term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension.N Engl J Med1998;338,273-277. [CrossRef] [PubMed]
 
Elkayam, U, Dave, R, Bokhari, SWH Primary pulmonary hypertension and pregnancy. Elkayam, U Gleicher, N eds.Cardiac problems in pregnancy1998,183-190 Wiley-Liss. New York, NY:
 
Ueland, K Pregnancy and cardiovascular disease.Med Clin North Am1977;61,17-41. [PubMed]
 
Weiss, BM, Hess, OM Pulmonary vascular disease and pregnancy: current controversies, management strategies, and perspectives.Eur Heart J2000;21,104-115. [CrossRef] [PubMed]
 
Rich, S, Kaufmann, E, Levy, PS The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension.N Engl J Med1992;327,76-81. [CrossRef] [PubMed]
 
Noontens, M, Rich, S Successful management of labor and delivery in primary pulmonary hypertension.Am J Cardiol1993;71,1124-1125. [CrossRef] [PubMed]
 
Easterling, TR, Ralph, DD, Schmucker, BC Pulmonary hypertension in pregnancy: treatment with pulmonary vasodilators.Obstet Gynecol1999;93,494-498. [CrossRef] [PubMed]
 
Smedstad, KG, Cramb, R, Morison, DH Pulmonary hypertension and pregnancy: a series of eight cases.Can J Anaesth1994;41,502-512. [CrossRef] [PubMed]
 
O’Hare, R, McLoughlin, C, Milligan, K, et al Anesthesia for caesarean section in the presence of severe primary pulmonary hypertension.Br J Anaesth1998;81,790-792. [CrossRef] [PubMed]
 
Badalian, SS, Silverman, RK, Aubry, RH, et al Twin pregnancy in a woman on long term epoprostenol therapy for primary pulmonary hypertension.J Reprod Med2000;45,149-152. [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1. Hemodynamic Measurements*
* 

PAP = pulmonary artery pressure; PVR = pulmonary vascular resistance; CO = cardiac output; CVP = central venous pressure; PAOP = pulmonary artery opening pressure.

References

McCaffrey, RN, Dunn, LJ (1964) Primary pulmonary hypertension in pregnancy.Obstet Gynecol Surv19,567-591. [CrossRef] [PubMed]
 
Weiss, BM, Zemp, L, Seifert, B, et al Outcome of pulmonary vascular disease in pregnancy: a systematic overview from 1978 through 1996.J Am Coll Cardiol1998;31,1650-1657. [CrossRef] [PubMed]
 
McLaughlin, VV, Genthner, DE, Panella, MM, et al Reduction in pulmonary vascular resistance with long term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension.N Engl J Med1998;338,273-277. [CrossRef] [PubMed]
 
Elkayam, U, Dave, R, Bokhari, SWH Primary pulmonary hypertension and pregnancy. Elkayam, U Gleicher, N eds.Cardiac problems in pregnancy1998,183-190 Wiley-Liss. New York, NY:
 
Ueland, K Pregnancy and cardiovascular disease.Med Clin North Am1977;61,17-41. [PubMed]
 
Weiss, BM, Hess, OM Pulmonary vascular disease and pregnancy: current controversies, management strategies, and perspectives.Eur Heart J2000;21,104-115. [CrossRef] [PubMed]
 
Rich, S, Kaufmann, E, Levy, PS The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension.N Engl J Med1992;327,76-81. [CrossRef] [PubMed]
 
Noontens, M, Rich, S Successful management of labor and delivery in primary pulmonary hypertension.Am J Cardiol1993;71,1124-1125. [CrossRef] [PubMed]
 
Easterling, TR, Ralph, DD, Schmucker, BC Pulmonary hypertension in pregnancy: treatment with pulmonary vasodilators.Obstet Gynecol1999;93,494-498. [CrossRef] [PubMed]
 
Smedstad, KG, Cramb, R, Morison, DH Pulmonary hypertension and pregnancy: a series of eight cases.Can J Anaesth1994;41,502-512. [CrossRef] [PubMed]
 
O’Hare, R, McLoughlin, C, Milligan, K, et al Anesthesia for caesarean section in the presence of severe primary pulmonary hypertension.Br J Anaesth1998;81,790-792. [CrossRef] [PubMed]
 
Badalian, SS, Silverman, RK, Aubry, RH, et al Twin pregnancy in a woman on long term epoprostenol therapy for primary pulmonary hypertension.J Reprod Med2000;45,149-152. [PubMed]
 
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