Proposed Management Algorithm for Severe Hypoxemia After Liver Transplantation in the Hepatopulmonary Syndrome

Abstract

The hepatopulmonary syndrome (HPS) is defined as the triad of liver disease, intrapulmonary vascular dilatation, and abnormal gas exchange, and is found in 10–32% of patients with liver disease. Liver transplantation is the only known cure for HPS, but patients can develop severe posttransplant hypoxemia, defined as a need for 100% inspired oxygen to maintain a saturation of ≥85%. This complication is seen in 6–21% of patients and carries a 45% mortality. Its management requires the application of specific strategies targeting the underlying physiologic abnormalities in HPS, but awareness of these strategies and knowledge on their optimal use is limited. We reviewed existing literature to identify strategies that can be used for this complication, and developed a clinical management algorithm based on best evidence and expert opinion. Evidence was limited to case reports and case series, and we determined which treatments to include in the algorithm and their recommended sequence based on their relative likelihood of success, invasiveness, and risk. Recommended therapies include: Trendelenburg positioning, inhaled epoprostenol or nitric oxide, methylene blue, embolization of abnormal pulmonary vessels, and extracorporeal life support. Availability and use of this pragmatic algorithm may improve management of this complication, and will benefit from prospective validation.

Potential Clinical Targets in Hepatopulmonary Syndrome: Lessons From Experimental Models

“…Downstream, NO diffuses across the vascular smooth muscle cell membrane and activates the guanylate cyclase/cyclic guanosine monophosphate signaling pathway, leading to vascular relaxation. In this regard, intravenous methylene blue, which blocks stimulation of guanylate cyclase by NO, has been used anecdotally to treat severe posttransplant hypoxemia in HPS patients …”

Extracorporeal membrane oxygenation for post-transplant hypoxaemia following very severe hepatopulmonary syndrome

“…A single report in a non-transplant setting of seven patients showed improvement 13. The mechanism is vasoconstriction in the dilated pulmonary vessels in the lower lung zones and redirection of blood to the upper and middle lung zones 5. Although it has been suggested that methylene blue can be administered with the patient in head-up position and combined with a inhaled vasodilator, reports of its successful use are unavailable.…”

Molecular mechanisms of hepatopulmonary syndrome

“…This syndrome can be considered as a separate indication for a liver transplant [13][14][15][16], but at the same time the severe hypoxia in the case of HPS is associated with a high risk of liver transplant complications (30% during the first 90 days) and increased gap between the transplant surgery and improvement in arterial oxygenation [17]. This complication is seen in 6-21% of the patients and carries a 45% chance of mortality [18]. …”