Management of Acute Cholecystitis in a Patient With Eisenmenger Syndrome and Abdominal Heterotaxy: A Case Report

Introduction

Complete atrioventricular septal defect (AVSD) is a complex congenital cardiac anomaly where i) a defect exists in the walls separating the atria and ventricles, and ii) there is a single atrioventricular valve instead of separate mitral and tricuspid valves [1]. Given there is increased systemic vascular resistance (SVR) compared with pulmonary vascular resistance (PVR), blood is shunted left to right, markedly increasing pulmonary flow [2]. Over time, this increased flow leads to increased PVR, reversal of flow (ie, right-to-left shunting), and chronic hypoxia, a state known by the eponymous name Eisenmenger syndrome [2]. Eisenmenger syndrome is estimated to occur in between 1 and 5.7% of adults with congenital cardiac disease, but the prevalence has decreased due to medical advances in the field of cardiology and cardiac surgery [3]. Secondary to the right-to-left shunt, any physiologic changes that increase PVR and/or decrease SVR can worsen hypoxia and progress to cardiovascular collapse [4].

Heterotaxy is a group of associated congenital malformations that result in abnormal arrangement of thoraco-abdominal organs across the left-to-right axis of the body [5]. Heterotaxy is further characterized depending on the degree of left-right asymmetry and is associated with congenital cardiac defects, intestinal rotational abnormalities, asplenia or polysplenia, ciliary dyskinesia [6], and the development of Eisenmenger syndrome. With an incidence of 1 in 10 000 live births [5], the management of these patients requires highly specialized care to address both disease-specific conditions and also routine pathologies.

Here, we report the management of a patient with complete AVSD, Eisenmenger syndrome, and abdominal heterotaxy who presented with acute, calculous cholecystitis. Early laparoscopic cholecystectomy is the recommended treatment strategy even in high-risk patients [7], but recent studies have reported 30-day mortality rates ranging from 2–18% for elective surgery and as high as 50% for emergency non-cardiac surgery in patients with pulmonary hypertension [8,9]. These complications are attributed to acute exacerbation of the maladaptive physiology described above leading to right ventricular failure. In this case report, we highlight difficulties in treating such complex patients including pre-operative optimization and risk stratification, anesthetic management, careful operative planning, including assessment of anatomical variants and bailout maneuvers, and comprehensive post-operative care to minimize complications associated with nontypical physiology. Our experience underscores the importance of multi-disciplinary care in the treatment of general surgery diseases in this population.

Case Report

The patient was a 35-year-old woman who presented with 2 days of constant, sharp epigastric and left upper quadrant abdominal pain. The pain did not radiate and was associated with subjective fevers, decreased appetite, nausea, and 6 episodes of non-bloody, non-bilious emesis. Her medical history was notable for abdominal heterotaxy, with transposition of her liver and biliary anatomy to the left in a mirror image, and an unrepaired complete AVSD complicated by Eisenmenger syndrome and pulmonary hypertension. Her vitals were remarkable for an oxygen saturation of 80%, and she was tender in the left upper quadrant. Laboratory evaluation revealed a white blood cell count of 19.4×103 cells/μL, hemoglobin 20.2 g/dL, alanine aminotransferase (ALT) 35 units/L, aspartate aminotransferase (AST) 32 units/L, alkaline phosphatase 48 units/L, lipase 9 U/L, and total bilirubin 1.3 mg/dL. At this time, the differential was broad, given her cardiac and anatomic anomalies, and included gastritis, peptic ulcer disease, diverticulitis, pancreatitis (although the lipase was normal), and cholecystitis. A computed tomography (CT) scan of the abdomen and pelvis was consistent with acute cholecystitis (Figure 1). Given an association between Eisenmenger syndrome, heterotaxy, and biliary anomalies [10,11, magnetic resonance cholangiopancreatography was conducted, which revealed a large, impacted, stone in a short cystic duct near the confluence of the common bile duct (Figure 2). Intravenous antibiotics were initiated, and she was admitted to our surgical intensive care unit (SICU).

Prior to admission, she had close monitoring and recent testing of her baseline cardiac and pulmonary function. At rest, her oxygen saturation was 80–85%, and she could tolerate walking on a treadmill at 2.8 mph and a 2–3% incline for 30 minutes. A 6 minute walk test showed a resting oxygen saturation of 84% on room air, a resting pulse of 75 beats per minute, and 1985 feet (>600 meters) walked over 6 minutes. Her most recent echocardiogram showed a dilated right ventricle with severe hypertrophy, but overall normal function. Estimated pulmonary pressure was 67 mmHg+right atrial pressure (10 mmHg+). Her cardiac defect consisted of a complete atrioventricular canal defect with inlet ventricular septal defect, large atrial septal defect with no interatrial septum, and common atrioventricular bridging valve with mild regurgitation and no attachment of the bridging anterior leaflet to the interventricular septum. She was medically managed with dual pulmonary artery vasodilator therapy (tadalafil 40 mg daily, ambrisentan 10 mg daily) and was without signs of pulmonary congestion. The only previous intervention for her congenital cardiac defect was embolization of aorto-pulmonary collaterals approximately 20 years prior, when she presented with hemoptysis. She lives with her husband, is independent in her activities of daily living, and is employed as a physician.

During her hospitalization, a series of multi-disciplinary meetings were held, and it was determined that a percutaneous cholecystostomy tube (PCT) should be pursued, given her risk of cardiovascular collapse with anesthesia, and to allow for appropriate multi-disciplinary planning. On hospital day 3, a PCT was placed by interventional radiology. Post-procedurally, she developed atrial fibrillation with rapid ventricular response that resolved with diltiazem (5 mg/h) and phenylephrine (maximum dose 75 mcg/min). Even though diltiazem can decrease SVR, it was chosen for primary treatment of atrial fibrillation after she did not respond to low dose beta blockade. Phenylephrine was tapered off within 2 hours and diltiazem within 4 hours. The episode of atrial fibrillation lasted less than 4 hours and did not recur; however, she remained on continuous telemetry for the remainder of her hospitalization. After consulting with her heart failure team, if atrial fibrillation were to recur, we would plan for digoxin and/or amiodarone for primary treatment to minimize risk of decreasing SVR with other treatment modalities. During her post-procedure course, she also sustained an acute cerebrovascular accident (CVA) due to air embolism. At the onset of her neurologic symptoms, her score on the NIH Stroke Scale was 1, and she was noted to have mildly decreased finger abduction and wrist extension along with sensory deficits in the left hand. CT of the head showed a curvilinear lucency in the right frontal sulcus that was confirmed to be an area of diffusion restriction consistent with an acute infarct on magnetic resonance imaging (MRI). Over the following days, her neurologic symptoms improved and at the time of discharge on hospital day 6, they had largely resolved with only minor left hand fine motor deficits.

She presented 3 months later for an interval open cholecystectomy. A pre-operative epidural was placed to provide slowly titratable analgesia to avoid abrupt changes in hemodynamics that had the potential to worsen the shunt, an approach that has been successfully employed in women with Eisenmenger syndrome undergoing caesarean section [12]. The patient was taken to the operating room and placed supine. A pre-induction, radial arterial line was secured and intubation proceeded without difficulty. Etomidate and rocuronium were used for induction to minimize any decrease in SVR. General anesthesia and hemodynamics were then maintained with low dose sevoflurane and phenylephrine. Pre-operative hemoglobin was 17.0 g/dL, hematocrit 51.3%, and international normalized ratio (INR) 1.1. Given that she had no hyperviscosity symptoms, hematocrit was less than 65%, and she was euvolemic on exam, there was no plan for pre-operative phlebotomy and her euvolemic status would be maintained with intravenous (IV) crystalloids. Due to the increased risk of bleeding in patients with Eisenmenger syndrome despite normal laboratory evaluation, several units of packed red blood cells and fresh frozen plasma were crossed prior to surgery.

The operation began with a left-sided subcostal incision which was carried down until the abdomen was entered sharply. There was significant inflammation in the left upper quadrant, but after dissection, the PCT was visible entering the gallbladder wall (Figure 3). A combination of sharp and electrocautery dissection was used to mobilize the gallbladder off the underlying portal vein and duodenum. Given the extensive chronic inflammation and scarring, the gallbladder was mobilized in top-down fashion. The gallbladder was separated from the cystic plate down to the region of the impacted stone, at which point it was opened and the stone removed with free flow of bile (Figure 4). The remaining gallbladder was removed and the cystic duct was over-sewn with a permanent running suture. The cystic artery was secured with a suture ligature. A 19 Fr drain was placed in the resection bed, and the incision was closed. The patient was extubated successfully and transferred to the SICU for hemodynamic monitoring. The patient’s post-operative course was uncomplicated. The drain was removed on post-operative day (POD) 4, and the patient was discharged on POD5. On POD7, she developed a superficial surgical site infection that was managed with incision and drainage and a 7-day course of cephalexin. Approximately 1-month post-operatively, she was seen in the clinic with a well-healed incision and no other concerns.

Discussion

We present the case of a 35-year-old woman with a history of complete AVSD, Eisenmenger syndrome, and abdominal heterotaxy who presented with acute calculous cholecystitis. She underwent PCT placement followed by an interval open cholecystectomy. Her initial course was complicated by atrial fibrillation and an acute CVA with minor left hand deficits that subsequently resolved. Her interval operative course was only complicated by a superficial surgical site infection. Although there is a lack of robust data, it has been reported that Eisenmenger syndrome can result in death in ~3–30% of individuals undergoing non-cardiac surgery [13,14]. A variety of factors inherent to the surgical pathology and underlying cardiopulmonary dysfunction related to Eisenmenger syndrome contribute to this rate, including disease severity, urgency of surgery, anesthesia type, and baseline degree of right-to-left shunting.

In our patient, these factors influenced our decision to proceed with PCT placement during the index hospitalization with plans for interval cholecystectomy. At our patient’s initial presentation, she was hemodynamically stable with leukocytosis, largely normal liver enzyme evaluation, and evidence of acute cholecystitis without signs of emphysematous cholecystitis, abscess, or perforation. Although cholecystectomy is recommended in surgically fit patients [15,16] and early cholecystectomy has been shown to be the preferred approach over PCT and PCT with delayed cholecystectomy [17–19], PCT placement is an alternative in patients with comorbidities that may prohibit laparoscopic and/or open surgery [20,21]. Although some suggest that delayed operative management with a PCT can lead to challenging operations with significant fibrosis, it has also been suggested that PCT placement can decompress the gallbladder, allow for resolution of inflammation, and afford a more straightforward operation [21]. We preferred this initial treatment modality as it would treat the acute cholecystitis and provide adequate time to prepare for her perioperative hemodynamic management with appropriate bailout maneuvers in the event of cardiovascular collapse. These factors also influenced our decision to use an open rather than a laparoscopic approach. Laparoscopic surgery increases intra-abdominal pressure, decreasing venous return to the heart and leading to hypercapnia, both of which increase PVR, shunting, and potential for sudden cardiovascular collapse [22]. Some centers have successfully completed laparoscopic cholecystectomy in patients with Eisenmenger syndrome utilizing xenon anesthesia [23] and low-pressure insufflation [24]. In light of these previous successes, we felt the anomalous anatomy associated with the patient’s abdominal heterotaxy would be better ascertained with an open approach, thereby decreasing the potential for iatrogenic injury. As shown in Figures 1 and 2, the patient’s anatomy was not only complicated by her heterotaxy, but also by an extremely short cystic duct with an impacted stone and closely associated portal vein and duodenum.

Although our patient was well compensated from a cardiac and pulmonary standpoint, all efforts should be made to optimize cardiopulmonary function prior to operative intervention in patients with Eisenmenger syndrome, including use of diagnostics (ie, echocardiogram, pulmonary function tests), medical therapies (ie, inotropes, pulmonary vasodilators), and avoidance of related complications (ie, thrombosis, bleeding diatheses). Anesthetic management should be carefully designed to maintain SVR and minimize the risk of cardiovascular collapse [14,25,26]. We utilized induction agents with few negative cardiac effects and minimized use of inhaled agents that can decrease SVR. There were no significant hemodynamic changes during the operation, and she was extubated without difficulty. Clinical practice guidelines support that patients with congenital cardiac disease and severe pulmonary hypertension require appropriate pre-operative optimization and risk stratification prior to undergoing non-cardiac surgery with meticulous attention paid towards perioperative management of volume status, hemodynamics, and acid/base status [27]. Furthermore, as stated in those same guidelines and highlighted by the case presented here, all of these considerations further underscore the need for collaboration amongst cardiac anesthesiologists, congenital cardiologists, pulmonologists, and surgical care teams at centers familiar with the care of these complex patients.

This report also illustrates other key aspects in the management of patients with Eisenmenger syndrome. Our patient experienced an air embolism that resulted in a CVA and left hand fine motor deficits at the time of discharge. This was a direct result of air introduction into a peripheral IV with passage of air across the right-to-left shunt leading to the embolic event. At present, she has only minor finger abduction and wrist extension weakness in the left hand and continues to work with physical therapy. This complication highlights the need for vigilant IV filter use in these patients given the large shunt present. Consideration should also be given to pre-operative cardiac surgery evaluation in the event of cardiovascular collapse requiring the initiation of advanced life support measures such as extracorporeal membrane oxygenation (ECMO). Pre-operative imaging should be obtained in patients with Eisenmenger syndrome as there is an association of Eisenmenger syndrome with altered venous drainage. In our patient, a CT venogram showed an interrupted left-sided inferior vena cava (IVC) with azygous continuation and bilateral superior vena cava (Figures 5, 6). Given her limited venous drainage options, we consulted with cardiac surgery and planned for axillary arterial and right internal jugular vein cannulation in the event she required emergent ECMO support. As shown in Figure 6, the downside of femoral vein cannulation was a direct result of her interrupted IVC. Although the IVC had azygous continuation and there are case reports of successful cannulation in neonates [28], we planned for a right IJ venous cannulation to ensure proper positioning of the venous cannula for adequate drainage. Use of the left IJ would additionally result in inadequate drainage given the left-sided superior vena cava drained into a dilated coronary sinus. Regarding arterial cannulation, the plan was for axillary artery cannulation in order to establish antegrade flow, decreasing the potential afterload effects on the left ventricle and resultant pulmonary edema. Additionally, axillary cannulation can minimize the risk of worsened oxygenation to the upper body, which can be observed with femoral artery cannulation [29].

Conclusions

Non-cardiac surgery in patients with Eisenmenger syndrome requires meticulous pre-operative planning and multidisciplinary perioperative care. This should include collaboration amongst intensivists, experts in congenital cardiopulmonary disorders, anesthesia providers, and surgeons to optimize and execute the proposed surgical intervention with an acceptable perioperative risk profile.