Use of methylene blue to treat vasoplegia syndrome in cystic fibrosis patients undergoing lung transplantation: A case series.

Background: Several studies have demonstrated the utility of methylene blue (MB) to treat vasoplegic syndrome (VS), but some have cautioned against its routine use in lung transplantation with only two cases described in prominent literature. Cystic fibrosis patients commonly have chronic infections which predispose them to a systemic inflammatory syndrome-like vasoplegic response during lung transplantation. We present 13 cystic fibrosis patients who underwent lung transplantation and received MB for vasoplegic syndrome while on cardiopulmonary bypass, with or without inhaled pulmonary vasodilator therapy. Methods: Single-center, retrospective, case series analysis of cystic fibrosis patients who underwent lung transplant and received MB for vasoplegia. We defined the primary outcome as 30-day mortality, and secondary outcomes as primary graft failure, 1-year mortality, postoperative complications, and hemodynamic response to MB. Results: MB was associated with a significant increase in mean arterial pressure (MAP) (P < 0.001) in all patients, and 84.6% (11/13) of the patients had either a decrease or no change in vasopressor requirement. No patients developed acute primary graft dysfunction and there was 100% 30-day and 1-year survival. One patient required Extracorporeal membrane oxygenation (ECMO) for hypoxemia and 69% (9/13) of the patients had evidence of postoperative right ventricular dysfunction, but no patients required a right ventricular assist device. Conclusion: This case series demonstrates the effectiveness of MB in treating vasoplegia in cystic fibrosis patients during lung transplantation, without evidence of primary graft dysfunction, 30-day or 1-year mortality. The safety of MB regarding hypoxemia and increased pulmonary vascular resistance requires further investigation.

Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis.

Neonatal cholestasis is a potentially life-threatening condition requiring prompt diagnosis. Mutations in several different genes can cause progressive familial intrahepatic cholestasis, but known genes cannot account for all familial cases. Here we report four individuals from two unrelated families with neonatal cholestasis and mutations in NR1H4, which encodes the farnesoid X receptor (FXR), a bile acid-activated nuclear hormone receptor that regulates bile acid metabolism. Clinical features of severe, persistent NR1H4-related cholestasis include neonatal onset with rapid progression to end-stage liver disease, vitamin K-independent coagulopathy, low-to-normal serum gamma-glutamyl transferase activity, elevated serum alpha-fetoprotein and undetectable liver bile salt export pump (ABCB11) expression. Our findings demonstrate a pivotal function for FXR in bile acid homeostasis and liver protection.