Guideline sources The following summarized guidelines for the evaluation and management of hepatopulmonary syndrome (HPS) are prepared by our editorial team based on guidelines from the Society of Critical Care Medicine (SCCM 2020), the European Association for the Study of the Liver (EASL 2018), and the International Liver Transplantation Society (ILTS 2016). 1 2 3 Guidelines 1. Screening and diagnosis Indications for testing: As per EASL 2018 guidelines, evaluate patients with the hallmarks of chronic liver disease for HPS in the presence of tachypnea and polypnea, digital clubbing, and/or cyanosis. B As per ILTS 2016 guidelines, obtain screening for HPS, especially in liver transplant candidates, since its clinical presentation may be variable, adversely influencing the quality of life and https://web.pathway.md/diseases/rectEmLOKI8HSRbNu 1/5 6/24/23, 12:41 PM Hepatopulmonary syndrome Pathway survival. B Diagnostic criteria: use the ERS diagnostic criteria for the diagnosis of HPS in research and clinical settings. B 2. Classification and risk stratification Severity assessment: consider using the ERS severity classification of HPS in research and clinical settings. C 3. Diagnostic investigations Pulse oximetry: As per EASL 2018 guidelines, obtain pulse oximetry to screen for HPS in adult patients. B As per ILTS 2016 guidelines, consider obtaining pulse oximetry (O2 saturation < 96%) as a reasonable screening test to detect hypoxemia in adult patients otherwise suitable for liver transplantation. Obtain sequential pulse oximetry for oxygenation monitoring. B Blood gas analysis: As per EASL 2018 guidelines, obtain arterial blood gas analysis in patients with SpO < 96%. Obtain further investigations in patients with a PaO < 80 mmHg and/or an alveolar-arterial oxygen gradient 15 mmHg in ambient air ( 20 mmHg in 65 years old patients). B As per ILTS 2016 guidelines, obtain arterial blood gas analysis for the diagnosis of HPS. B Contrast echocardiography: As per EASL 2018 guidelines: Obtain contrast (microbubble) echocardiography to characterize HPS. B Consider obtaining a contrast-enhanced TEE to definitively exclude intracardiac shunts. C As per ILTS 2016 guidelines, consider obtaining a contrast-enhanced TTE as an optimal screening test and criterion for detection of intrapulmonary vascular dilatation. B Macroaggregated albumin lung perfusion scan: As per EASL 2018 guidelines: Obtain macroaggregated albumin scan as a complementary tool to quantify the degree of shunting in patients with severe hypoxemia and coexistent intrinsic lung disease or to assess the prognosis in patients with HPS and very severe hypoxemia (PaO < 50 mmHg). B Recognize that neither contrast echocardiography nor macroaggregated albumin scan can definitively differentiate discrete arteriovenous communications from diffuse precapillary and capillary dilatations or cardiac shunts. B As per ILTS 2016 guidelines, consider obtaining a macroaggregated albumin scan to clarify the contribution of HPS-related hypoxemia in coexistent intrinsic cardiopulmonary disease. B https://web.pathway.md/diseases/rectEmLOKI8HSRbNu 2/5 6/24/23, 12:41 PM Hepatopulmonary syndrome Pathway Pulmonary angiography: perform pulmonary angiography only in patients with the severe hypoxemia (PaO < 60 mmHg), poorly responsive to administration of 100% oxygen, and if there is a strong suspicion of arteriovenous communications amenable to embolization. B 4. Respiratory support Oxygen therapy: As per SCCM 2020 guidelines, provide supportive care with supplemental oxygen in the management of patients with HPS, pending possible liver transplantation. E As per EASL 2018 guidelines, initiate long-term oxygen therapy in patients with HPS and severe hypoxemia, recognizing that there is insufficient evidence regarding its effectiveness, tolerance, cost-effectiveness, compliance, and effects on survival rates. B 5. Medical management Pharmacotherapy: As per EASL 2018 guidelines, insufficient evidence regarding the use of medical therapy for the treatment of patients with HPS. I As per ILTS 2016 guidelines, recognize that aside from supplemental oxygen (rest, exercise, and sleep) no medical therapies are definitively established or FDA approved for HPS. B 6. Therapeutic procedures Transjugular intrahepatic portosystemic shunt: As per EASL 2018 guidelines, insufficient evidence to recommend TIPS placement for the treatment of patients with HPS. I As per ILTS 2016 guidelines, insufficient evidence to recommend portal decompression with TIPS in adult patients with HPS. I Coil embolization: consider performing coil embolization in rare cases to improve oxygenation in selected patients with HPS. C Extracorporeal membrane oxygenation: consider performing ECMO as a bridge to liver transplantation and to reduce the need for mechanical ventilation in patients with severe HPS. C 7. Perioperative care Introperative oxygen monitoring: Obtain continuous monitoring of mixed venous oxygen saturation. Consider performing venovenous bypass if the mixed venous oxygen saturation falls < 65% on vascular exclusion of the liver. B https://web.pathway.md/diseases/rectEmLOKI8HSRbNu 3/5 6/24/23, 12:41 PM Hepatopulmonary syndrome Pathway Recognize that intraoperative oxygenation is not adversely affected by different anesthetic deliveries. B Postoperative oxygen therapy: perform early extubation to prevent ventilator-associated pneumonia. B Show 5 more Postoperative fluid management: initiate goal-directed fluid therapy to avoid fluid overload and pulmonary congestion. B Postoperative imaging: do not obtain routine post-transplantation contrast-enhanced TTE unless clinically indicated. D 8. Surgical interventions Liver transplantation: As per EASL 2018 guidelines: Evaluate patients with HPS and PaO < 60 mmHg for liver transplantation since it is the only effective treatment for HPS. B Obtain arterial blood gas analysis every 6 months to facilitate prioritization of liver transplantation since severe hypoxemia (PaO < 45-50 mmHg) is associated with increased post-liver transplantation mortality. B As per ILTS 2016 guidelines: Consider performing liver transplantation in patients with severe hypoxemia due to HPS (PaO < 60 mmHg). B Use standard model for end-stage liver disease exception scores if PaO is < 60 mmHg due to HPS. Consider using increased model for end-stage liver disease exception scores (higher model for end-stage liver disease points) if PaO is < 50 mmHg. B 9. Specific circumstances Pediatric patients: consider correcting congenital portosystemic shunts in pediatric patients. C References 1. European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018 Aug;69 2 406 460. Open 2. Michael J Krowka, Michael B Fallon, Steven M Kawut et al. International Liver Transplant Society Practice Guidelines: Diagnosis and Management of Hepatopulmonary Syndrome and Portopulmonary Hypertension. Transplantation. 2016 Jul;100 7 1440 52. Open 3. Rahul Nanchal, Ram Subramanian, Constantine J Karvellas et al. Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU Cardiovascular, Endocrine, Hematologic, Pulmonary https://web.pathway.md/diseases/rectEmLOKI8HSRbNu 4/5 6/24/23, 12:41 PM Hepatopulmonary syndrome Pathway and Renal Considerations: Executive Summary. Crit Care Med. 2020 Mar;48 3 415 419. 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