Eisenmenger syndrome during pregnancy: A true anesthetic challenge

Abstract

Eisenmenger syndrome (ES) is a rare congenital heart disease (CHD) that occurs in persons with large intracardiac anatomical defects which may go undetected for many years, consequently results in reduced life expectancies and high mortality in the third and fourth decade of life. Pregnancy in patients with CHD and pulmonary arterial hypertension (PAH) is presaged with challenges, and perioperative management of such cases remains a topic of debate. Our case had both, atypical presentation, not diagnosed until her third trimester of third pregnancy and a quick progression to a severe stage with PAH and CorPulmonale. The atypical presentation being persistent polycythemia, raising clinical suspicion and thorough clinical examination revealing differential cyanosis and clubbing of hands and feet in pre-anesthesia checkup (PAC). A multidisciplinary approach clinched the diagnosis, and the use of a novel integrated method for perioperative management incorporating all available literature and modern interventions highlighted the critical role of anesthesiologists at a tertiary care setup.

Introduction

Pregnancy is a delicately balanced altered physiological condition characterized by multiple homeostatic changes. The presence of a coexisting congenital cardiac lesion can tip the scales against the mother as well as the fetus. Eisenmenger syndrome (ES) is one such rare irreversible condition due to untreated acyanotic congenital heart disease (CHD), resulting in right to left intracardiac shunt and leading to hypoxemia, cyanosis, heart failure, erythrocytosis, hyperviscosity and cerebrovascular accidents culminating in death eventually.¹ About 8 % patients with CHD and 3 % of pregnant patients with congenital heart defects develop ES. Maternal mortality in ES is very high ranging from 30 to 70 %, whereas the feto-neonatal mortality can be up to 8 %.² In background of the sinister outcome and minimal available supportive literature, the anesthetic management of an ES in pregnancy can be challenging. We present one such case which was successfully managed with coordinated multidisciplinary approach.

Case report

A 27-year-old G3P1L0A2 with bad obstetric history (BOH) and “no known” co-morbidities was incidentally found to have persistent polycythemia at 25 weeks period of gestation (POG). She had apparently been asymptomatic since childhood, was New York Heart Association Class II (NYHA-II) in present pregnancy with no other significant past/personal/family history, and had uneventful first and second trimesters. On evaluation, patient was found to have differential clubbing (Fig. 1), cyanosis, and desaturation of toes when compared to the fingers (Fig. 2a and b). Systemic examination disclosed left sided parasternal heave and loud P2 with variable wide split. Investigations revealed hemoglobin 18.8/17.5/15.6 gm% and raised hematocrit in first, second, and third trimesters, respectively. No other blood investigation was found abnormal for the ongoing physiological state. 2D-ECHO showed dilated right atrium and right ventricle with moderate tricuspid regurgitation and raised right ventricular (RV) systolic pressure (65 mmHg). Diagnosis was confirmed by magnetic resonance imaging (MRI) heart revealing large patent ductus arteriosus (PDA) with bidirectional shunting, RV hypertrophy, and dilated pulmonary artery. A provisional diagnosis of antenatal case with BOH and ES, chronic Cor Pulmonale, and severe pulmonary arterial hypertension (PAH) was made. Patient was planned for multi-specialty management and early viable termina-tion of pregnancy at 32 weeks.

Fig. 1.

Differential clubbing present between upper and lower limbs.

Fig. 2.

(a) Higher oxygen saturation of the right upper limb. (b) Lower oxygen saturation of the right lower limb on the multipara monitor.

Preoperatively, the counseling of patient and relatives was done in view of anticipated high feto-maternal mortality. She was started on supplemental oxygen therapy via nasal cannula (4 L/min), tab sildenafil 25 mg TDS, and Inj enoxaparin, a lower molecular weight heparin (LMWH) 40 mg subcutaneous OD. Preoperative preparation included high-risk consent, antenatal steroids. A thorough pre-anesthesia checkup (PAC) was done, and patient was accepted under the American Society of Anesthesiologist (ASA) physical status Grade-IV for elective lower segment cesarean section (LSCS) under combined spinal-epidural (CSE) anesthesia. Appropriate blood was demanded, LMWH prophylaxis withheld 24 h prior to surgery as per American Society of Regional Anesthesia (ASRA) guidelines, and patient was administered prophylactic antibiotic (Inj. Augmentin 1.2 gm I.V. stat) 60 min prior to surgery and was shifted to OT on inhaled oxygen.

Intraoperatively, standard monitoring was instituted, preoperative 2D-ECHO assessment on OT table was done, and manual defibrillator was kept standby. Central venous access was secured along with the commencement of invasive blood pressure monitoring (right radial artery) and cardiac (EV1000, Edward Lifesciences) output monitoring (targets: systemic vascular resistance (SVR) > 1000 dyn/s/cm⁻⁵, stroke volume variation (SVV) < 13 %, central venous pressure (CVP) < 8, and central venous oxygen saturation (ScvO2) >60–65 %). Intravenous fluid was restricted, prophylactic antibiotic administered, and infusions of injection sildenafil (0.03 mg/kg/hr) and nor-adrenaline (0.05 μg/kg/min) were initiated. In left lateral position, a 20 G epidural catheter was placed using 18G Tuohy's needle, and 0.5 ml levobupivacaine (heavy) 0.5 % and fentanyl 25 μg were administered intra-thecally with 27G Whitacre's spinal needle. This was followed by graded epidural using 12 ml bupivacaine 0.5 % in divided doses over 30 min. Elective LSCS was successfully performed with minimal blood loss, and a male baby was delivered. Intraoperative period was uneventful, and patient was shifted to ICU for postoperative monitoring.

Postoperatively in intensive care unit (ICU), patient's vitals and urine output along with cardiac output were diligently monitored. Supplemental oxygen was delivered, sildenafil and nor-adrenaline infusions were weaned off over two days, and oral sildenafil was started. Multi-specialty consults and management continued with point-of-care (POC) tests like 2D-ECHO, ultrasonography (USG) lungs, and serum lactate. Ambulation was commenced after postoperative day (POD) – two, with intermittent oxygen support. By sixth POD, the patient was shifted back to the obstetric ward. Informed consent was obtained from the patient/relatives for use of figures and data in the case report.

Discussion

Acyanotic CHD, such as ventricular septal defect, atrial septal defect, atrioventricular septal defect, and PDA, when left untreated, lead to irreversible pulmonary vascular injury, increased pulmonary vascular resistance (PVR), and severe PAH, culminating in reversal of shunt direction, over years.^1,3 This may present as hypoxemia and cyanosis with manifestations like clubbing (differential in PDA, as seen in our patient), erythrocytosis, increased hemorrhagic tendency, and symptoms of biventricular failure. Physiological changes like reduction in SVR and increased blood volume (in the absence of ability to reduce PVR) that occur during pregnancy may increase right to left shunt and hence hypoxemia and cyanosis in ES. The normal pulmonary circulation is a low-pressure high compliance system. In PAH, there is a reduction in compliance, leading to inability to adapt to the increased cardiac output and pulmonary blood flow. This results in an increase in RV afterload and end-diastolic volume and ultimately RV dysfunction.

The common causes of mortality in pregnant patient with ES include hypovolemia, thromboembolism, pre-eclampsia, hemoptysis, arrhythmias, heart failure, and sudden cardiac death which manifest as sequel of PAH and pulmonary vascular disease.¹ The poor prognostic signs in these patients are hematocrit >60 %, arterial oxygen saturation (SaO2) < 80 %, RV hypertension, PAH, and recurrent syncopal attacks.⁴ Our patient had all the features mentioned above except syncopal attacks.

Females with ES should ideally avoid pregnancy, but in case of extreme will to conceive, a multidisciplinary consultation is warranted. Supportive management incorporates oxygen therapy, antiarrhythmics, diuretics, anticoagulants, and PAH-specific vasodilator therapy using prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors. Pulmonary vasodilator therapy in the setting of PAH has shown to be of symptomatic as well as of mortality benefits in a four years follow-up period.¹ The Bosentan Randomized Trial of Endothelin Antagonist Therapy-5 (BREATHE-5) showed improvement in exercise tolerance as well as good symptomatic relief with Bosentan in patients of ES with acyanotic CHD and further studies showed mortality benefits with sildenafil as well.⁵ Use of anticoagulants in these patients is controversial. Considering the risk-to-benefit ratio in this patient with no bleeding diathesis and increased risk of thrombotic events, prophylactic anticoagulant was used in the peripartum period, though there are studies warranting caution while using anticoagulants in patients with high risk of hemorrhage.⁶

Perioperative goals include counseling, hemodynamic optimization prior to surgery, early viable termination of pregnancy, and conduct of short effortless labor and atraumatic delivery.² During peripartum period, when the cardiac output is physiologically accentuated, prolonged labor (increases RV pressure) and autotransfusion post-delivery can cause a further increase in cardiac output (50–80 %) possibly precipitating heart failure in women with cardiovascular compromise. To add, surgery and anesthesia in pregnant ES patient itself pose a risk by decreasing SVR, possibly inducing a circulatory collapse and additional problems of excessive bleeding, perioperative arrhythmias, and venous thromboembolism or paradoxical embolus.⁷ All this mandates diligent invasive monitoring. We instituted continuous cardiac output monitoring (EV1000, Edward Lifesciences) along with real-time blood pressure assessment. The central venous access taken for multiple drug infusions also facilitated ScvO₂ measurements and management of paradoxical embolisms.

Anesthetic goals incorporate, maintaining hemodynamic variables in pre-optimized ranges by preventing hypoxemia (targeting PaO2 above 60 mmHg), maintaining a delicate balance between PVR and SVR to minimize right to left shunt, and precluding the chances of heart failure due to worsening PAH by avoiding hypoxemia, hypercarbia, and acidosis by choosing the optimum method of anesthesia to achieve such goals. The oxygen supplementation via nasal cannula prevented hypoxia, thereby avoiding acute pulmonary hypertensive crisis. General anesthesia remarkably reduces SVR, decreases venous return and cardiac output, and worsens shunting with oxygen desaturation, causing further misbalance between SVR and PVR along with unpredictable hemodynamic response to intubation/extubation. Epidural anesthesia in normal labor or LSCS has the advantage of minimal risks, excellent perioperative analgesia, and reduction of PVR and SVR (lesser extent as compared to SAB). Epidural or intrathecal opioids are devoid of hemodynamic effects signifying their essential role as an adjuvant to local anesthetics.⁸ Cole et al. used incremental graded spinal anesthesia using spinal catheters in cesarean section of ES patient and achieved quick block and a satisfactory anesthetic effect without any declared risks.⁹ We used the combination of CSE anesthesia with initial, low dose subarachnoid levobupivacaine and opioids to achieve immediate sensory blockade followed by graded epidural analgesia, providing optimum conditions for LSCS with excellent perioperative analgesia. Prophylactically injection sildenafil and noradrenaline were started to reduce PVR and increase SVR respectively as patient was already in severe PAH and also in anticipation of peripheral vasodilatation due to neuraxial techniques.

The majority of maternal deaths occur during or within the first week after delivery.¹⁰ Hence, the patient was shifted to ICU for postoperative management with multidisciplinary approach and POC tests facilitating the favorable outcome of the case.

This case report is unique in a way to have employed CSE technique for which not much literature is available and description of various physiological changes during pregnancy with its implications and considerations for this entity.

To conclude, the management of a case of ES in pregnancy is challenging, requiring a multidisciplinary team approach with closed-loop functioning, meticulous planning, intensive monitoring, and extensive perioperative care for a favorable outcome.

Patients/ Guardians/ Participants consent

Patients informed consent was obtained.

Ethical clearance

Not Applicable.

Source of support

Nil.

Disclosure of competing interest

The authors have none to declare.