Intraperitoneal Corticosteroid Injection for Refractory Ascites in a Patient with Fontan Circulation

Abbreviations

PLE, Protein-losing enteropathy

SAAG, Serum-ascites albumin gradient

INTRODUCTION

The Fontan circulation, a surgical procedure, redirects systemic venous inflow to the pulmonary circulation without a pumping ventricle. This technique has significantly improved the prognosis for individuals with single ventricular congenital heart disease. Protein-losing enteropathy (PLE) is one of the long-term complications of Fontan circulation. It is associated with high morbidity and mortality and is often characterized by generalized edema and massive ascites. While there are various strategies to manage PLE, their effectiveness varies among patients.¹ Ascites often requires repeated drainage to alleviate symptoms. We report a case of an 18-year-old girl with hypoplastic left heart syndrome who had undergone the Fontan operation and was experiencing massive ascites. The patient’s condition improved following intraperitoneal corticosteroid injections.

CASE REPORT

An 18-year-old female patient, previously diagnosed with hypoplastic left heart syndrome, underwent a fenestrated extracardiac conduit Fontan operation at the age of 3. By the time she reached 12, she developed PLE.

A hemodynamic study conducted when she was 15 revealed elevated pulmonary pressure (25-27 mmHg) and high systemic ventricular end-diastolic pressure (23 mmHg).² In response to these findings, a comprehensive and multidisciplinary medical approach was adopted. This approach, which included intermittent intravenous immunoglobulin, diuretics, pulmonary vasodilators, and peripheral vasopressors, was tailored to her clinical status. As a result, a stable condition was maintained, characterized by normal serum albumin, cardiac output, and only mild peripheral edema.

Despite the overall clinical stability, the patient continued to suffer from refractory massive ascites (Figure 1A, 1B, 1C, and 1D). To alleviate symptoms, paracentesis was performed every 2 to 4 months, each time yielding 2 to 5 liters of ascites. The fluid was light-yellow in color, with a serum-ascites albumin gradient (SAAG) of 1.0 and a total protein of 4404 mg/dL, suggesting a possible inflammatory reaction. Cytology revealed no malignant cells and bacterial culture yielded no bacteria. Consequently, after a thorough discussion with the patient and her family, we decided to try intraperitoneal corticosteroid injections.

Figure 1.

This figure presents abdominal ultrasound images depicting the accumulation of ascites (*). The images are categorized into three stages: prior to the initial intraperitoneal injection of triamcinolone acetonide (A, B, C, and D), 3 months post the initial treatment and prior to the second intraperitoneal injection of triamcinolone acetonide (E, F, G, and H), and 6 months following the initial triamcinolone acetonide injection (I, J, K, and L). The images in (A), (E), and (I) display a transverse section at the subcostal region. (B), (F), and (J) depict the Morison’s pouch. (C), (G), and (K) illustrate the splenorenal recess, while (D), (H), and (L) show the Douglas pouch. The labels represent the following: L for liver, K for kidney, S for spleen, and U for uterus.

Prior to the initial trial of intraperitoneal steroids, a comprehensive evaluation revealed normal renal function (creatinine 0.7 mg/dL) and liver function (aspartate aminotransferase 21 U/L). The N-terminal pro-brain natriuretic peptide was 145.8 pg/mL. There were no ongoing infectious events. After the removal of 5074 ml of ascites, 400 mg of triamcinolone acetonide was injected into the peritoneal cavity. The procedure was well-tolerated, and the patient exhibited no post-procedural complications, including infection, electrolyte imbalance, hypertension, or hyperglycemia.

Three months after the initial treatment, the patient reported a decrease in abdominal distention. However, an abdominal ultrasound showed a reduction, but still a significant volume, of ascites (Figure 1E, 1F, 1G, and 1H). Following a therapeutic paracentesis, a second intraperitoneal administration of 520 mg of triamcinolone acetonide was performed, during which 5200 mL of ascites were removed. The patient experienced no complications, similar to the initial treatment. Notably, she demonstrated a marked reduction in ascitic fluid accumulation 6 months post the initial treatment (Figure 1I, 1J, 1K, and 1L). Furthermore, she required no additional paracentesis for at least 6 months following the second intraperitoneal administration of triamcinolone acetonide.

DISCUSSION

Protein-losing enteropathy in Fontan circulation

Patients with Fontan circulation, in the absence of a subpulmonary ventricle, consistently exhibit elevated central venous pressure, leading to numerous long-term complications. PLE, characterized by the nonselective depletion of all plasma proteins into the intestinal lumen, occurs in 5% to 12% of individuals undergoing Fontan palliation.¹ PLE is defined as elevated α-1 antitrypsin levels in stool samples and serum hypoalbuminemia.³ Common symptoms include hypercoagulability, immunodeficiency, chronic diarrhea, abdominal cramps, vomiting, pleural effusions, ascites, and malnutrition.

PLE is associated with heightened mortality rates and an increased demand for heart transplantation.⁴ The precise pathophysiological mechanisms underlying PLE development remain under investigation, potentially influenced by factors such as altered mesenteric blood flow, systemic inflammation, neurohormonal activation, and protein glycosylation.⁵ Potential risk factors for developing PLE in Fontan circulation include bradyarrhythmia, phrenic palsy, stenosis of the circulatory pathway, and absence of a fenestration.⁴ Initial medical management generally involves pulmonary vasodilators, diuretics, immunoglobulin, or albumin infusion. If symptoms persist, invasive procedures such as surgical valve reconstruction, diaphragm plication, transcatheter stent insertion may be considered.⁴ However, despite various evaluated management approaches, none have demonstrated consistently excellent efficacy.

Due to protein loss, PLE patients easily develop ascites. Ascites is prevalent in approximately 80% of patients undergoing Fontan circulation with PLE.⁴ The severity varies from mild, detectable only by sonography, to severe cases resistant to conventional diuretic therapy, necessitating repeated paracentesis. Though infrequent, paracentesis poses potential risks, including hemodynamic instability, protein depletion, electrolyte imbalances, hypovolemia, infection, perforation, hemoperitoneum, and bleeding.

While PLE is a primary contributor to ascites, concurrent factors such as cirrhosis, renal dysfunction, heart failure, lymphatic duct anomalies, malignancy, or inflammation can also contribute. The SAAG serves as a crucial marker for ascites diagnosis. An SAAG value of ≥ 1.1 g/dL indicates ascites associated with portal hypertension or hepatic congestion, while < 1.1 g/dL suggests alternative etiologies such as infection, malignancy, or inflammation.⁶ Ascitic total protein concentration more than 2500 mg/dL may also provide clues about possible exudate effects other than portal hypertension if elevated.⁷ In our case, the patient’s initial SAAG value was below 1.1 g/dL and the high ascites total protein level, suggesting the nature of inflammation alongside heart failure. Consequently, we considered anti-inflammatory agents as a potential relief for the patient’s intractable ascites.

Inflammation and protein-losing enteropathy

Reviewing prior researches, diverse anti-inflammatory agents, such as prednisone, heparin, infliximab, octreotide, and budesonide, have been investigated for mitigating symptoms of PLE associated with the Fontan operation.¹ However, their effects lack sustainability, and potential complications, including Cushingoid features, osteoporosis and infection, may arise. To minimize systemic side effects, emphasis has been placed on reducing local inflammation within the bowel lumens. Intraperitoneal triamcinolone, an insoluble glucocorticoid, injections have been employed in managing ascites caused by systemic lupus erythematosus, cancerous peritonitis and hemodialysis related aseptic peritonitis with successful remission of ascites.^8,9 Considering the local anti-inflammatory mechanism and previous successful experiences in inflammatory diseases, we believe that this therapy may benefit Fontan palliation.

Only a single case report outlines three patients with Fontan circulation who presented significant ascites and underwent administration of triamcinolone hexacetonide into the peritoneum. All exhibited a reduction in ascites accumulation, with two requiring multiple therapy sessions. Unfortunately, one patient experienced a severe adverse effect, specifically hyperglycemia and adrenal insufficiency.¹⁰ Hence, meticulous patient selection before initiating corticosteroid treatment is imperative. Higher-risk groups may encompass individuals with diabetes mellitus, hypopituitarism, adrenal insufficiency, hypertension, active infection, and inborn errors of immunity. Without the aforementioned underlying medical issues, our patient tolerated the procedure well, with no recorded adverse events, such as peritoneal perforation, hyperglycemia, or adrenal insufficiency. However, persistent fluid retention in the abdomen after the initial treatment necessitated a second intervention.

The positive outcome of our case suggests a potential therapeutic benefit of intraperitoneal corticosteroids in managing refractory ascites in the context of Fontan circulation. However, given the limitation of experience, more studies are needed to clarify the adequacy, dosage, frequency, and procedural details.

LEARNING POINTS

PLE, resulting from abnormal protein leakage from the bowel lumen, stands as a prominent complication of Fontan failure. As many as 80% of Fontan palliation patients with PLE experience varying degrees of ascites, with some relying on repeated paracentesis for symptom relief. Recognizing the potential role of inflammation in ascites formation among individuals with Fontan circulation, intraperitoneal triamcinolone injection emerges as a viable treatment option for such patients. Ensuring appropriate patient selection is paramount to mitigate potential side effects. Continued surveillance and further studies will contribute to a comprehensive understanding of the long-term efficacy and safety of this intervention in similar cases.

DECLARATION OF CONFLICT OF INTEREST

All the authors declare no conflict of interest.

FUNDING

None.