Perioperative management for parturients with pulmonary hypertension: experience with 30 consecutive cases

Abstract

Pregnancy with pulmonary hypertension is considered to be associated with increased maternal and neonatal mortality. We retrospectively reviewed all parturients with pulmonary hypertension who registered at our hospital between 1999 and December 2008. We collected information about patient characteristics, including maternal age, gravida and para, pulmonary hypertension category, New York Heart Association (NYHA) functional class, pulmonary artery pressure, mode of delivery and type of anesthesia, use of anticoagulation and advanced therapy (nitric oxide, prostacyclin analogus, bosentan or sildenafil). The overall maternal mortality was 16.7% in puerperium, and there were four fetal/neonatal deaths (13%). Logistic regression could not identify any factors, including modes of anesthesia, mode of delivery, and categories and severity of pulmonary hypertension, that were significant predictors of mortality. Maternal mortality in parturients with pulmonary hypertension is high and women with pulmonary hypertension who become pregnant warrant a multidisciplinary approach.

Keywords

pulmonary hypertension / pregnancy / anesthesia

Introduction

A mean pulmonary arterial pressure higher than 25 mmHg at rest or more than 30 mmHg with exercise associated with a mean pulmonary-capillary wedge pressure and left ventricular end-diastolic pressure of less than 15 mmHg [1] is defined as pulmonary hypertension. Its etiology can be idiopathic or secondary to congenital heart disease, valvular heart disease, HIV infection, portal hypertension, or thyroid disorders [2]. Pregnancy with pulmonary hypertension is a rare condition, and can result in increased maternal and neonatal mortality.

Pregnancy induces many physiologic changes. Cardiovascular stress caused by pregnancy, labor, delivery and post-delivery can result in different degrees of cardiac failure. Cardiac output increases by approximately 50% due to elevated blood volume and reduction in systemic vascular resistance. For parturients with pulmonary hypertension, pulmonary artery pressure tends to rise linearly with cardiac output, and symptoms of right heart failure may occur. Hypercoagulability may be deleterious to patients with pulmonary hypertension, in case thrombus forms or embolises in pulmonary circulation. So women with pulmonary hypertension should avoid pregnancy.

During the past decade, management of parturients with hypertension has improved due to early recognition, further understanding of cardiopulmonary pathophysiology, new drugs targeting at pulmonary vasculature, better obstetric and anesthetic management and multidisciplinary approach [3,4]. However, mortality rates still remain disappointingly high.

Although it is highly recommended for patients with pulmonary arterial to use effective contraception and terminate pregnancy as early as possible if it occurs, some still choose to become pregnant. Since data on pregnancy in these women were rare, we summarized pregnancies with pulmonary hypertension, described the etiology and severity of pulmonary hypertension, obstetric and infant outcomes during and after pregnancy.

Materials and methods

We reviewed all charts of 30 pregnant women with pulmonary hypertension at Peking Union Medical College Hospital from January 1999 to December 2008. Institutional Review Board approval was obtained. The following data was collected, including maternal age, gestational age, parity status, New York Heart Association (NYHA) function class, pulmonary hypertension etiology and treatment, mode of delivery and anesthetic management, maternal and neonatal outcome.

Cases were classified into four groups according to the etiology of pulmonary arterial hypertension. When no apparent cause of pulmonary arterial hypertension was defined, the case was classified as idiopathic pulmonary arterial hypertension. Patients with congenital heart disease associated with pulmonary arterial hypertension were included in the congenital heart disease group. Patients with rheumatic heart disease associated with pulmonary arterial hypertension were classified as rheumatic heart disease group. Cases were classified as other-etiology group when pulmonary arterial hypertension was secondary to connective tissue disease, systemic vasculitis, pulmonary thrombo-embolism or chronic hepatitis.

Neonatal assessment included Apgar score and mortality rate.

Statistical analysis

Patients’ characteristics, peripartum management and outcome of pregnancies were presented separately for each group. Numerical values were presented as median (range) and categories variables as number (percentage) per group. Categorical data were compared by theχ² test with Yates’ correction for small numbers. Univariable logistic regression was used to identify predictors of maternal death between demographic and clinical variable, including modes of anesthesia, mode of delivery, and categories and severity of pulmonary hypertension. P<0.05 was considered statistically significant.

Results

Thirty parturients with pulmonary hypertension were managed during this period. The majority were transferred from local clinics at near-term gestation. They did not have regular prenatal or cardiac consultation. After admission, all parturients were managed with absolute rest and supplementary oxygen. Digoxin or furosemide was given as required. A multidisciplinary team, including obstetricians, cardiologists, anesthesiologists and pediatricians, made a care plan for each parturient based on cardiac function, responses to therapy and maturity and safety of the fetus.

The overall median age of parturients was 27 years (range 21-37 years) and 24 patients (80%) were primiparas. There were 8 cases of parturients with idiopathic pulmonary hypertension (iPH), 7 cases of congenital heart disease-associated pulmonary hypertension(CAD-PH), 10 cases of rheumatic heart disease-associated pulmonary hypertension(RH-PH) and 5 cases of pulmonary hypertension due to other etiology(o PH). Characteristics of these parturients were presented in Table 1.

Cardiac function of 17 parturients (57%) deteriorated to NYHA class III–IV during pregnancy. Three patients were hospitalized at 16, 18 and 23 weeks of gestation for therapeutic abortion because of severe hemodynamic instability, and only one survived.

There was only one successful vaginal delivery. 18 cesarean sections were performed under epidural anesthesia or combined spinal-epidural anesthesia, and 11 cesarean deliveries were performed under general anesthesia.

No patients need transfusion during their stay at hospital. All patients who had general anesthesia were monitored in ICU after the surgical delivery.

The overall maternal mortality of parturients with pulmonary hypertension was 17% (5/30) and no significant difference in mortality was seen between four subgroups (P = 0.109). The mortality rate of parturients with Eisenmenger’s syndrome was 50% (2/4). Logistic regression could not identify any risk factor, including modes of anesthesia, mode of delivery, and categories and severity of pulmonary hypertension, that was a significant predictor of mortality.

There was one neonatal death and three stillbirths. 16 infants were preterm. And of the 26 live births, none had an Apgar score less than 5 at 1 min and all live-born infants survived.

Discussion

The problems posed by pulmonary hypertension in adults are still challenging in clinic. Thus maternal and neonatal outcomes in this specific population require comprehensive assessment and collaboration between obstetricians, physicians, pediatricians and anesthesiologists.

Maternal mortality

There are five maternal deaths in 30 pregnancies (17%), indicating the high maternal mortality associated with pulmonary hypertension, but less than the 30%-50% mortality rate reported previously [5-7]. The mortality of patients with Eisenmenger’s syndrome was 50%, which was similar to previous report [8]. We also found women with pulmonary hypertension secondary to congenital heart disease are prone to have a higher mortality, which was also reported recently in a review [9].

There were 3 cases of early worsening at 16, 18 and 23 weeks’ gestation, and only one survived after pregnancy termination, suggesting that early pulmonary hypertension deterioration during pregnancy may lead to higher maternal mortality and prompt therapeutic abortion is needed.

Logistic regression failed to find any risk factors. It may be caused by following reasons. First, the number of patients enrolled was relatively small, so its statistical power is limited. Second, selection bias was unavoidable in this study, and the results may only reflect part of the truth.

Mode of delivery

Mode of delivery for patients with pulmonary hypertension remains controversial. Some recommend scheduled caesarean section since it can reduce the risk of hemodynamic instability during urgent cesarean section [10,11]. Vaginal delivery, however, is associated with fewer bleeding and infectious complications [12,13], but the Valsalva maneuver, associated with pushing, may increase right ventricular pressure, which should be avoided in these parturients. In our series, all but one were delivered by caesarean section, which is recommended in recent reports [9,14].

Fetal and neonatal outcomes

Maternal pulmonary hypertension is associated with an increased risk of fetal and neonatal complications, including stillbirth, neonatal death, fetal intrauterine growth retardation and preterm delivery [14]. There were three stillbirths and one neonatal death, which is also similar as reported [14]. Sixteen out of 30 women were delivered preterm, all for maternal reasons. This high preterm rate reflects reported trends [14]. All live-born infants survived and it seems that improvements in neonatal care make iatrogenic preterm delivery for maternal interest possible.

Anesthetic methods

The choice of anesthetic method for cesarean section in parturients with pulmonary hypertension is also controversial. Both general anesthesia [15,16] and neuraxial anesthesia [17-19] had been successfully used. For patients who were NYHA class I–II we chose neuraxial anesthesia. For patients who were NYHA class III–IV we usually chose general anesthesia for better cardiovascular control. We prefer to choose anesthetic agents associated with less vasodilation and cardiac depression such as midazolam and fentanyl. Inotropes (dobutamine or dopamine) were used if indicated. From our experience, the main principles were to avoid increase of pulmonary vascular resistance and to maintain left ventricular afterload and right ventricular contractility.

Intra-operative monitoring

Standard monitoring was used intra-operatively. Arterial and central venous lines were used for patients with hemodynamic instability. Fluid therapy was guided by heart rate, mean arterial pressure, central venous pressure and urine output. Pulmonary arterial catheter was not routinely used.

Oxytocin

Oxytocin, a systemic vasodilator, should be used with caution in parturients with pulmonary hypertension. An infusion of oxytocin can lower systemic vascular resistance and increase pulmonary vascular resistance, resulting in a drop in cardiac output. In our study, oxytocin was administrated slowly after delivery, titrating according to heart rate and blood pressure. No major postpartrum hemorrhage happened.

Advanced pulmonary arterial hypertension therapy

Over the past decade, special agents dilating pulmonary vasculature, including prostacyclin analogs, phosphodiesterase inhibitors, and endothelin-receptor antagonists, have been introduced to pulmonary hypertension management. However, these agents were not commonly used because of high cost. Similarly, inhaled nitric oxide which may be of benefit in acute situations is not yet available in our hospital.

Conclusions

In conclusion, the overall mortality rate of pregnant women with pulmonary hypertension is high. Mode of delivery and anesthetic choice should be based on patients’ clinical status, etiology of pulmonary hypertension, the safety of fetus, the experience of anesthesiologists and also obstetric factors. It is strongly recommended that women with pulmonary hypertension should avoid pregnancy. Management of pregnant patients with pulmonary hypertension requires a multidisplinary team corporation with careful monitoring.

References

[1] Gaine SP, Rubin LJ. Primary pulmonary hypertension. Lancet1998; 352(9129): 719–725

[2] Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med2004; 351(14): 1425–1436

[3] Weiss BM, Hess OM. Pulmonary vascular disease and pregnancy: current controversies, management strategies, and perspectives. Eur Heart J2000; 21(2): 104–115

[4] Warnes CA. Pregnancy and pulmonary hypertension. Int J Cardiol2004; 97(Suppl 1): 11–13

[5] Weiss BM, Zemp L, Seifert B, Hess OM. Outcome of pulmonary vascular disease in pregnancy: a systematic overview from 1978 through 1996. J Am Coll Cardiol1998; 31(7): 1650–1657

[6] Yentis SM, Steer PJ, Plaat F. Eisenmenger’s syndrome in pregnancy: maternal and fetal mortality in the 1990s. Br J Obstet Gynaecol1998; 105(8): 921–922

[7] Simonneau G, Galiè N, Rubin LJ, Langleben D, Seeger W, Domenighetti G, Gibbs S, Lebrec D, Speich R, Beghetti M, Rich S, Fishman A. Clinical classification of pulmonary hypertension. J Am Coll Cardiol2004; 43(12 Suppl): S5–S 12

[8] Gleicher N, Midwall J, Hochberger D, Jaffin H. Eisenmenger’s syndrome and pregnancy. Obstet Gynecol Surv1979; 34(10): 721–741

[9] Curry RA, Fletcher C, Gelson E, Gatzoulis MA, Woolnough M, Richards N, Swan L, Steer PJ, Johnson MR. Pulmonary hypertension and pregnancy—a review of 12 pregnancies in nine women. BJOG2012; 119(6): 752–761

[10] Ghai B, Mohan V, Khetarpal M, Malhotra N. Epidural anesthesia for cesarean section in a patient with Eisenmenger’s syndrome. Int J Obstet Anesth2002; 11(1): 44–47

[11] Olofsson C, Bremme K, Forssell G, Ohqvist G. Cesarean section under epidural ropivacaine 0.75% in a parturient with severe pulmonary hypertension. Acta Anaesthesiol Scand2001; 45(2): 258–260

[12] Diller GP, Gatzoulis MA. Pulmonary vascular disease in adults with congenital heart disease. Circulation2007; 115(8): 1039–1050

[13] Steer PJ. Pregnancy and contraception. In: Gatzoulis MA, Swan L, Therrien J, Pantely GA. Adult Congenital Heart Disease: A Practical Guide. Oxford: BMJ Publishing, Blackwell Publishing, 2005:16–35

[14] Bédard E, Dimopoulos K, Gatzoulis MA. Has there been any progress made on pregnancy outcomes among women with pulmonary arterial hypertension? Eur Heart J2009; 30(3): 256–265

[15] Monnery L, Nanson J, Charlton G. Primary pulmonary hypertension in pregnancy; a role for novel vasodilators. Br J Anaesth2001; 87(2): 295–298

[16] Coskun D, Mahli A, Korkmaz S, Demir FS, Inan GK, Erer D, Ozdogan ME. Anaesthesia for caesarean section in the presence of multivalvular heart disease and severe pulmonary hypertension: a case report. Cases J2009; 2(1): 9383

[17] Robinson DE, Leicht CH. Epidural analgesia with low-dose bupivacaine and fentanyl for labor and delivery in a parturient with severe pulmonary hypertension. Anesthesiology1988; 68(2): 285–288

[18] Khan MJ, Bhatt SB, Kryc JJ. Anesthetic considerations for parturients with primary pulmonary hypertension: review of the literature and clinical presentation. Int J Obstet Anesth1996; 5(1): 36–42

[19] Rimaitis K, Aliuškevičienė A, Adukauskienė D, Rimaitis M, Macas A. Cesarean delivery in severe pulmonary hypertension: a case report. Medicina (Kaunas)2012; 48(3): 159–162

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