Octreotide infusion as a treatment for hepatic hydrothorax in a hospital-at-home program: case report from Mayo Clinic

Background

Hepatic hydrothorax (HH), occurring in approximately 5%–10% of patients with cirrhosis, is a rare but potentially life-threatening complication of cirrhosis and portal hypertension, associated with significant morbidity and high mortality. ¹ It is defined as a pleural effusion exceeding 500 mL in a patient with cirrhosis in the absence of primary cardiac or pulmonary disease.^1,2 HH develops due to the passage of ascitic fluid into the pleural cavity through diaphragmatic defects, driven by increased intra-abdominal pressure and impaired lymphatic drainage. A technetium-99 sulfur colloid scan can be employed to confirm the diagnosis of HH by demonstrating transdiaphragmatic passage of peritoneal fluid into the pleural space. ³ Following intraperitoneal injection of the radiotracer, serial imaging is used to track the distribution of the tracer over time. The timing of tracer appearance in the pleural space can help elucidate the underlying mechanism of fluid migration. Tracer transit via the lymphatic system typically requires several hours; by contrast, detection of tracer activity in the pleural cavity within minutes suggests direct communication through a diaphragmatic defect. ³

HH is a transudative pleural effusion resulting from altered oncotic and hydrostatic pressures across the pleural membrane, leading to fluid accumulation that exceeds the capacity for pleural resorption. Transudative effusions are typically characterized by low protein and cell content, with a serum-to-pleural fluid albumin gradient greater than 1.1 g/dL. While HH is a recognized cause of transudative effusions in the setting of cirrhosis, other common etiologies include congestive heart failure and nephrotic syndrome.^4,5

The clinical presentation varies with the volume of pleural effusion. Among patients with large effusions, the most commonly reported symptoms are dyspnea at rest (34%), followed by cough (22%), nausea (11%), and pleuritic chest pain (8%). ⁶ A major complication of HH is spontaneous bacterial empyema (SBE), which occurs when the pleural effusion becomes infected.^1,2,5,7 SBE refers to the infection of a preexisting HH in cirrhotic patients, occurring in the absence of concomitant pneumonia on the affected side. The diagnosis is established when pleural fluid analysis reveals either a positive culture or a polymorphonuclear leukocyte count greater than 500 cells/μL, in the absence of radiographic or clinical evidence of pneumonia. SBE is distinct from parapneumonic effusion (PPE), which arises secondary to pulmonary infection. Although both conditions involve pleural space infection, SBE is typically managed with antimicrobial therapy alone, whereas PPE often requires both antimicrobial treatment and procedural drainage.^1,2,5,7

Treatment strategies typically include fluid and salt restriction, diuretic therapy, and repeated thoracentesis. While these measures provide symptomatic relief, they do not address the underlying pathophysiology. ⁸ More invasive interventions, such as indwelling tunneled pleural catheters (IPC), pleurodesis, and transjugular intrahepatic portosystemic shunt (TIPS) placement, may be considered in refractory cases. The American Association for the Study of Liver Disease advises against the usage of large-bore chest tubes in the management of HH, citing increased mortality and higher complications, including empyema, clinical deterioration, and fistula formation. ⁸

For refractory cases, IPCs are preferred over large-bore chest tubes, either for palliative management or as a bridge to liver transplant (LT), as they reduce the frequency of thoracentesis in this population. However, despite their relative advantage, IPCs are associated with risks such as infection, protein loss, malnutrition, and dehydration.^{9 –11} Ultimately, LT remains the only definitive treatment for HH.^1,8,12

Octreotide, a somatostatin analog, exerts its effects by inhibiting a broad range of peptide and regulatory hormones. It is used in the management of various endocrine and enteroendocrine conditions, including acromegaly, carcinoid syndrome, high-output fistulas, and refractory diarrhea associated with acute graft-versus-host disease, chemotherapy, or neuroendocrine tumors. ¹³ Octreotide also inhibits the renin–angiotensin–aldosterone axis, leading to improved renal plasma flow and enhanced natriuresis. It is widely used in the management of variceal bleeding due to its potent vasoconstrictive effects on the splanchnic circulation and, along with midodrine, is employed in the treatment of hepatorenal syndrome. Given its ability to decrease systemic and portal vascular resistance while reducing splanchnic vasodilation and stimulating renal sodium excretion, octreotide has been explored as a potential adjunct therapy for HH. Reduced blood flow to the abdominal organs alleviates portal vein pressure and has been theorized to decrease the fluid accumulation precipitating HH. Despite its therapeutic utility, octreotide is associated with a range of adverse effects. Common side effects include nausea, vomiting, diarrhea, and transient elevations in liver enzymes. Although there are no absolute contraindications aside from hypersensitivity reactions, serious but less common complications have been reported. These include gallbladder sludge and cholelithiasis, cardiovascular conduction disturbances ranging from sinus bradycardia to complete atrioventricular block, and various endocrine or exocrine disturbances related to hormone dysregulation. ¹³ In addition, the development of tachyphylaxis has been observed in patients receiving octreotide for cirrhosis and portal hypertension, particularly in the setting of esophageal varices. This phenomenon is thought to result from rapid downregulation of somatostatin receptors; once receptor saturation occurs, further octreotide administration may offer limited or no additional therapeutic benefit, even at escalated doses, thereby potentially limiting its long-term efficacy in these populations. ¹⁴ While its application in HH has been reported in case studies, no clinical trials have been conducted to evaluate its efficacy in this context.^{15 –18}

Patients with HH frequently require hospitalization to manage acute complications. However, traditional hospital stays can be uncomfortable, expensive, and associated with risks such as hospital-acquired infections and delirium. ¹⁹ Hospital-at-home (HaH) is an emerging alternative that provides hospital-level care to acutely ill patients within their home environment, offering comparable or superior outcomes to conventional inpatient care while improving patient comfort.^19,20 In the United States, HaH programs have been primarily implemented for common conditions such as cellulitis, pneumonia, and heart failure; however, some programs have expanded to include complex conditions such as cancer, organ transplantation, and post-surgical care.^19,20 This evolution, shifting the focus from specific diagnoses to tailored interventions on patient needs, highlights the growing capabilities and potential of HaH as a viable care model.^21,22 HaH is considered an inpatient unit of the hospital, and as such, requires the same level of shared decision-making and informed consent as traditional hospitalization. A thorough discussion of the risks, benefits, and alternatives is essential prior to enrollment. At Mayo Clinic, these conversations are conducted by physicians or advanced practice providers familiar with the program, and all patients are required to provide written consent before initiation of home-based care. ²⁰

Case presentation

We present a case of a 75-year-old White woman admitted for cough and dyspnea. The cough was non-productive and not associated with fever or chest pain. Her dyspnea was constant, worsening with activity and when lying supine. Both symptoms were present for 2 months, with significant exacerbation 48 h prior to admission.

Her medical history was significant for class I obesity, insulin-dependent type II diabetes mellitus, hypertension, dyslipidemia, and cirrhosis secondary to Metabolic Dysfunction-Associated Steatotic Liver Disease, with a Model for End-Stage Liver Disease (MELD) sodium score of 25 (14%–15% estimated 90-day mortality). She was a lifelong non-smoker and reported no alcohol or illicit drug use. Her prescribed medications included atorvastatin, carvedilol, rifaximin, lactulose, and both short- and long-acting insulin. The patient had multiple cirrhosis-related complications, including hepatic encephalopathy, esophageal varices with prior bleeding, thrombocytopenia, ascites, portal hypertensive gastropathy, and portal vein thrombosis. She had a history of intolerance to anticoagulation with enoxaparin due to recurrent gastrointestinal bleeding. Diuretics had been discontinued due to recurrent hyponatremia and associated acute kidney injury. Although her ascites was effectively managed through serial paracentesis, this did not result in a corresponding improvement in her HH.

Six months prior to this admission, the patient was diagnosed with recurrent HH, confirmed by a transudative right-sided pleural effusion and technetium-99 sulfur colloid imaging. She underwent multiple therapeutic interventions, including repeated thoracentesis, IPC placement (PleurX—Becton; Dickinson and Company, Franklin Lakes, NJ, USA), and ultimately chemical talc pleurodesis. However, these measures failed to achieve long-term control of her large, recurrent right-sided HH. Consideration was given to TIPS placement and referral for LT; however, the patient declined both options, expressing a desire to focus on palliative medical management. Prior to admission, she continued to experience excessive fluid output through the persistent fistula in the right chest wall, which had failed to heal following IPC removal done prior to the talc pleurodesis. This fluid was normally collected and volume monitored by an external ostomy bag attached to the thoracic defect site.

Upon this admission, the patient’s vital signs were notable for a blood pressure of 90/40 mmHg, a heart rate of 60 beats/min, and a respiratory rate of 18 breaths/min. The patient’s oxygen saturation was within normal limits on ambient air. She appeared chronically ill but was in no acute distress. The patient was alert and oriented, with no clinical evidence of hepatic encephalopathy. Her BMI was 32, and there was no evidence of cachexia. Physical examination revealed an obese woman without icterus or jugular venous distention. Her mucous membranes were dry. Lung auscultation demonstrated absent breath sounds on the right side and normal breath sounds on the left. Cardiac examination revealed regular heart sounds without murmurs. Notably, on the right side of her chest, there was an opening at the site of a prior chest tube, with serous fluid draining into her ostomy bag. Her abdomen was mildly distended, non-tender, and demonstrated a positive fluid shift. Bilateral trace pitting edema was present in the lower extremities.

Initial hospital workup revealed that with her daily hydrothorax output exceeding 4 L, she had developed recurrent intravascular volume depletion resulting in hypotension, hyponatremia, hypokalemia, and acute kidney injury. The patient’s serum sodium levels fluctuated between 118 and 124 mmol/L (normal: 135–145 mmol/L), potassium levels ranged from 2.8 to 3.3 mmol/L (normal: 3.5–5.0 mmol/L), and serum creatinine levels varied between 1.2 and 1.6 mg/dL (normal: 0.6–1.2 mg/dL), with an estimated glomerular filtration rate ranging from 35 to 44 mL/min/1.73 m² (normal: ⩾90 mL/min/1.73 m²). As such, she was admitted to the hospital in inpatient status for management of these electrolyte imbalances and acute kidney injury. A computed tomography scan of the chest ruled out pulmonary infiltrations, and an echocardiogram demonstrated a preserved ejection fraction, no regional wall motion abnormalities, no valvular disease, and no significant pericardial effusion. Her symptoms of cough and dyspnea were attributed to recurrent HH. After determination of the patient’s clinical stability and future hospital treatment plan, HaH was discussed with the patient as an alternative option for her inpatient care. She agreed with this plan of care and was transferred to our HaH program on hospital day 2 for ongoing intravenous fluid administration and electrolyte replacement.

After several days of supportive care with intravenous fluids and electrolyte replacement, the patient’s chest fluid output remained significantly elevated. A multidisciplinary team, including Thoracic Surgery, Nephrology, Hepatology, and Hospital Medicine, was consulted to explore potential treatment strategies for persistent high-output HH. The patient refused the option of TIPS or referral to a liver transplant center (Mayo Clinic in Rochester) due to a desire to avoid any further aggressive intervention and to pursue medical management alone. Following multidisciplinary discussion, an octreotide infusion was deemed the best treatment. Because intravenous octreotide infusions are typically reserved for the institutional setting, the pharmacy was consulted to assess the feasibility of home administration. Based on stability data and internal compounding guidelines, octreotide was prepared at a concentration of 2 mcg/mL, protected from light to maintain product integrity, and infused at a rate of 25 mcg/h intravenously via a computerized ambulatory drug delivery pump with bag changes every 20 h. This intervention resulted in a reduction in daily pleural fluid output from 4000 to 2200 mL. After 48 h, the infusion rate was increased to 50 mcg/h; however, the patient developed nausea, vomiting, and abdominal pain, necessitating a dose reduction back to 25 mcg/h. Within the subsequent 48 h, pleural output further decreased to 100 mL/day. Following this response, the octreotide infusion was switched to subcutaneous dosing of 200 mcg every 8 h for 1 week, then reduced to 200 mcg twice daily for the next week. After another week, the dose was further reduced to 200 mcg once daily. However, the dose was increased back to twice daily due to an increase in HH and remained at that level.

The patient was subsequently discharged from HaH and was scheduled for follow-up with the hepatology team. Due to the substantial cost of octreotide, prior authorization was required; however, the insurance provider ultimately approved coverage for the medication. Over the ensuing 6 months, the patient experienced sustained clinical improvement while on a regimen of 200 mcg twice daily, with a marked reduction in HH, now effectively managed in the outpatient setting.

Discussion

HH is a rare but significant complication of cirrhosis, affecting approximately 10% of patients, with over 80% of cases occurring on the right side. When HH is presented on the left or bilaterally, diagnosis can be particularly challenging. Approximately 25% of cases are refractory to conventional management, making HH an independent predictor of both overall and pre-liver transplant mortality.^8,12 Liver transplantation has been shown to confer a survival benefit to these patients compared to those without HH. ¹² The precise pathophysiology of HH remains an area of active investigation, with several mechanisms proposed to explain its development. These include hypoalbuminemia, azygos vein hypertension, thoracic duct leakage, transdiaphragmatic lymphatic migration, and pressure-gradient-driven flow through small physiological defects in the diaphragm.^5,6 However, the most widely accepted theory suggests that HH results from the direct translocation of fluid from the peritoneal cavity into the pleural space via small diaphragmatic defects.^1,2,12,23

Our patient had a MELD sodium score of 25, a widely used metric for estimating mortality risk in patients with advanced liver disease and a key determinant in LT prioritization.^24,25 Despite this elevated score, she declined both TIPS and referral to the LT center, opting instead for palliative medical management. The standard management strategies for HH, including fluid and sodium restriction, were ineffective in controlling her condition. In addition, diuretic therapy was complicated by recurrent acute kidney injury and hyponatremia. She underwent multiple thoracenteses and eventually underwent IPC placement, which was removed prior to talc pleurodesis. Although talc pleurodesis is recommended as a palliative option for managing HH, it is not considered a first-line therapy. In our patient’s case, talc pleurodesis was pursued only after standard management failed to adequately control her symptoms. A systematic review and meta-analysis reported a complete response rate of approximately 72% with talc pleurodesis; however, complications are frequent, occurring in up to 80% of cases. These may include rapid re-accumulation of the effusion, development of empyema, and formation of percutaneous fistulas.^26–28

Unfortunately, in this case, pleurodesis failed to alleviate her symptoms. Notably, the site of her prior pleural catheter did not heal, leading to persistent fluid loss of up to 4000 mL/day through the chest wall fistula. This excessive fluid loss resulted in hypotension, acute kidney injury, and electrolyte disturbances.

This case is unique in several aspects. First, to our knowledge, it is the first report to describe the use of a continuous octreotide infusion in a home-based hospital setting. Traditionally, treatments for complex cirrhosis-related complications, such as octreotide infusion, are administered to patients in a conventional hospital inpatient ward. In this case, the ability to provide inpatient care at patient’s home and multidisciplinary collaboration were essential to ensuring patient safety and equipping the HaH care team with the necessary expertise to manage her condition while respecting her goals of care.

Mayo Clinic’s HaH program provides hospital-level care to eligible patients in the comfort of their homes. Care plans are personalized based on clinical needs and adhere to Centers for Medicare and Medicaid Services requirements, including a minimum of two in-person visits per day. Eligibility criteria include residence within a 30-mile radius of a Mayo Clinic hospital, verified insurance coverage, and access to reliable high-speed internet to facilitate continuous communication with the care team. A tele-hospitalist (virtualist) serving as the attending physician remotely oversees care from a central command center and manages multiple patients concurrently. In-home care is delivered by a multidisciplinary team comprising advanced practice providers, registered nurses, paramedics, respiratory therapists, physical therapists, pharmacists, subspecialists, and other healthcare professionals. This model emphasizes collaborative care coordination, incorporating input from the patient, caregivers, and various clinical team members to ensure safe, effective, and patient-centered treatment at home. ²⁰

Pairing Mayo Clinic’s previously described robust HaH operational infrastructure with in-home and cloud-based technology to monitor clinical status, particularly for early signs of deterioration, establishes a sturdy foundation of trust for managing complex acute issues in the home setting. While the majority of HaH admissions currently involve common inpatient diagnoses such as pneumonia and cellulitis, expanding the scope to include more complex conditions is essential to extend the well-documented benefits of HaH, including reduced mortality, lower rates of hospital-acquired infections, and improved patient satisfaction. As HaH teams evaluate patient eligibility, two central questions guide decision-making: (1) “What does the patient need?” and (2) “Can this be delivered safely in HaH?” In this patient’s case, multidisciplinary collaboration led the team to identify continuous octreotide infusion as the most appropriate next therapeutic option. To assess feasibility within the HaH model, existing guidelines for intravenous octreotide administration were reviewed, and operational logistics were thoroughly addressed to ensure that the patient’s needs could be safely and effectively met with HaH. ²⁰ Once HaH was deemed a viable option, engaging the patient and caregivers in shared decision-making was essential to successfully navigate the challenges of a complex home-based hospitalization. Notably, the patient reported an improved quality of life while receiving hospital-level care at home. This HaH episode coincided with a religious holiday significant to the patient, allowing her to receive hospital-level care while surrounded by family and friends.

Second, this case highlights the long-term use of long-acting subcutaneous octreotide for the management of HH. Although tachyphylaxis is a known concern with prolonged octreotide therapy, our patient has not exhibited diminished responsiveness. This suggests that a select group of patients with HH may benefit from sustained subcutaneous octreotide therapy. Six months after initiating octreotide treatment, our patient has remained free of recurrent HH. To the best of our knowledge, this is the first documented case demonstrating the successful and prolonged use of octreotide for HH beyond 2 weeks.

A PubMed search using keywords hepatic hydrothorax, recurrent, and medical management yielded several articles that described the successful use of octreotide for HH.^15–18 The selected cases and key patient characteristics are summarized in Table 1. As shown in Table 1, most of the patients were female, and in all reported cases, treatment was initiated with an intravenous octreotide infusion, which was subsequently transitioned to an equivalent 24-h subcutaneous dose after a few days of intravenous treatment. The tapering protocols and duration of therapy varied among cases, reflecting the need for individualized treatment approaches.^15–18

OPEN IN VIEWER

Table 1.

Summarizes selected case reports and key patient characteristics related to octreotide treatment for hepatic hydrothorax.

Reference	Age	Sex	Etiology of LC	HH location	Chest tube output (mL/day)	Complication	Octreotide dose and duration of treatment	Octreotide side effects	Outcome
Dumortier et al. 15	52	F	Alcoholism	Right	900–1500	HRS	600 mcg/day, IV for 5 days	None	Improved
Pfammatter et al. 16	58	F	Autoimmune hepatitis	Right	4650	None	50–100 mcg/h IV for 5 days	None	Improved
Barreales et al. 17	66	F	Alcoholism	Right	2000–2500	AKI dehydration	Day 1: 25 mcg/h IV Day 2: 50 mcg/h IV Day 3–7: 100 mcg/h IV Day 8–14: 100 mcg SQ	None	Improved
Calixto-Aguilar et al., 18 Case 1	56	M		Right	2300	ACLF	Day 1–25 mcg/h IV Day 2–50 mcg/h IV Days 3–14–100 mcg/h	None	Died after LT due to HA thrombosis
Calixto-Aguilar et al., 18 Case 2	66	F		Left	1500	HA thrombosis after LT	25mcg/h IV for 5 days 200 mcg SQ TID for 1 week 200 mcg SQ BID for 3 months	None	Died

ACLF, Acute-on-chronic liver failure; AKI, Acute kidney injury; HA, Hepatic artery thrombosis; HH, hepatic hydrothorax; HRS, Hepatorenal syndrome; IV, Intravenous; LC, Liver cirrhosis; LT, Liver transplantation; SQ, Subcutaneous.

Medications such as midodrine and terlipressin should be considered in the treatment of HH due to their ability to counteract splanchnic arterial vasodilation, a key mechanism contributing to fluid retention in cirrhosis. Midodrine, an oral α-adrenergic agonist, is a viable option for long-term use; however, the optimal dose and duration of therapy remain uncertain. An ongoing clinical trial (NCT03645642) is evaluating the efficacy of midodrine therapy in the treatment of HH, which may provide further insights into its role in disease management. ²⁹

Terlipressin is another potential treatment for HH, particularly in refractory cases when other therapies have failed. It is often administered in conjunction with albumin to optimize its hemodynamic effects. ³⁰ One case report has documented its successful use in a patient with hepatic hydropericardium, suggesting its potential utility beyond hydrothorax alone. ³¹ In addition, a novel approach was described by clinicians in Canada, who utilized an automatic low-flow ascites pump (Alfapump) to manage nonmalignant pleural effusion in an elderly cirrhotic patient, offering an alternative strategy for fluid management in select patients. ³²

Patients with recurrent HH who are not candidates for TIPS or LT have limited therapeutic options and extremely high mortality. A retrospective study evaluated 77 patients with HH with a mean MELD score of 16 at the time of presentation and a mean follow-up period of 12 months, demonstrating the mortality of 57%. This high mortality rate underscores the poor prognosis associated with HH in the context of advanced liver disease. ⁶ Consequently, further research is urgently needed to identify pharmacological treatments for this complication of liver cirrhosis. Octreotide has emerged as a potential therapeutic option for select patients; however, its role in HH management remains inadequately studied. Furthermore, octreotide therapy could be prohibitively expensive for some patients, and prior authorization may be required. Large-scale, rigorous clinical trials are essential to thoroughly assess its effectiveness and safety in managing refractory HH.

While this case report highlights the potential of HaH to support complex acute care in the home setting, further advancements in care delivery are essential to strengthen existing HaH programs and extend their benefits to underserved areas. Technological solutions are especially important to overcome challenges such as long travel distances from brick-and-mortar hospitals and the need for frequent adjustments to inpatient orders, which can lead to complex and inefficient coordination of home-based services. Finally, although this care model may result in cost savings in developed countries, it may still be cost-prohibitive to implement in under-resourced regions. Moreover, there is a lack of research on the implementation and effectiveness of such models of care in developing countries.

Supplemental Material