The Successful Use of Inhaled Nitric Oxide in the Management of Severe Hepatopulmonary Syndrome after Orthotopic Liver Transplantation

Abstract

Hepatopulmonary syndrome (HPS) is characterized by pulmonary vasodilation and subsequent hypoxemia in the setting of hepatic dysfunction. There is currently no pharmacologic intervention that has been shown to significantly affect outcomes and liver transplantation remains the mainstay of therapy. Unfortunately, patients undergoing liver transplantation are at high risk of significant hypoxemia and mortality in the early postoperative period. In the following case series, we present two cases of patients with severe HPS who underwent liver transplantation and experienced marked hypoxemia in the early postoperative period. In both cases, we successfully treated the patients with inhaled nitric oxide for their severe refractory life-threatening hypoxemia which led to immediate and dramatic improvements in their oxygenation. Although the use of inhaled nitric oxide in patients with HPS has been sporadically reported in pediatric literature and in animal studies, to our knowledge, our cases are the first recorded in adult patients.

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

“…Infection of the chest appeared to have contributed to the desaturation in addition to postoperative pulmonary vasoconstriction of normal vessels. Nitric oxide is useful in the management of hypoxaemia associated with HPS 12. A proposed mechanism is the abrupt alteration of substances mediating pulmonary vasodilatation following liver transplant and benefit of vasodilatation induced by nitric oxide 3.…”

Perioperative Considerations in Liver Transplantation

“…These strategies include NIPPV, Trendelenburg positioning, 160 and administration of methylene blue and/or iNO. [161][162][163][164] Recently, a management algorithm for severe hypoxia after LT in the setting of HPS was proposed and includes the use of iNO, inhaled epoprostenol, Trendelenburg positioning, inhaled iloprost, methylene blue, embolotherapy, and ECMO. 159 Examination of primary data for these strategies reveals case reports showing improvement of oxygenation in the setting of HPS after LT with positioning strategies and the use of methylene blue which inhibits nitric oxide-induced vasodilation.…”

“…Interestingly, nitric oxide has also been reported in case series to improve oxygenation in HPS after LT, presumably related to more uniform vasodilation of the pulmonary vasculature with redistribution of blood flow to the apical and mid-lung fields resulting in improved V/Q mismatch. 164 Long-term use of nitric oxide has been associated with renal failure in the setting of ARDS 165 and methemoglobinemia can also develop. Methylene blue is relatively safe to use for short periods of time, although its long-term use is limited by its coloration properties (coloration of urine, lacrimal fluid, mucus membranes, and skin).…”

“…166 Although embolization therapy may be an appealing option, rarely are arteriovenous malformations large enough to be amenable to embolization. 164 ECMO has been reported in case reports to successfully bridge both pediatric and adult LT patients with severe HPS and hypoxemia to recovery. This remains an option for refractory hypoxia but is invasive and should be avoided if possible.…”

Bubble Trouble in COVID-19

“…In HPS, medications that target hypoxic pulmonary vasoconstriction, such as almitrine, have been studied without consistent benefit ( 9 , 10 ). Other therapies, such as methylene blue, garlic, and inhaled pulmonary vasodilators, such as inhaled nitric oxide, have been associated with improved oxygenation in small studies or case series of patients with HPS ( 10 , 11 ). Inhaled nitric oxide is postulated to improve oxygenation in HPS by redistribution of pulmonary blood flow and improved /Q matching and is actively being studied as a treatment for COVID-19.…”