Extracorporeal Liver Support for the Treatment of Hyperammonemia After Lung Transplantation.

Abstract

Acute hyperammonemic encephalopathy after lung transplant can result in significant morbidity, and fatal outcomes have been reported.1 We describe 2 cases where the extracorporeal liver support system (ELS), Molecular Adsorbent Recirculating System (MARS Monitor; Teraklin AG, Rostock, Germany), was used to treat refractory hyperammonemia post-lung transplant. CASE 1 A 63-year-old woman with chronic obstructive pulmonary disease received bilateral lung transplant on cardiopulmonary bypass. The patient had no prior history of liver disease or alcohol use. Pseudomonas aeruginosa was isolated from the donor lung, and she received prophylactic cefepime, metronidazole, and levofloxacin. Two days after transplant, as sedation was weaned, she was noted to have West Haven criteria grade 3 encephalopathy with bilateral clonus and hyperreflexia. Laboratory tests revealed an elevated ammonia level of 144 µmol/L. Hyperammonemia was aggressively treated medically with lactulose, rifaximin, zinc, levocarnitine, sodium benzoate, and empirical azithromycin to cover for potential ureaplasma infection. Hyperammonemia remained refractory to medical therapy. After 48 hours, ELS was initiated. With one session of ELS, her ammonia level dramatically decreased to 56 µmol/L (Figure 1), with associated improvement in alertness. Results of Ureaplasma polymerase chain reaction in bronchoalveolar lavage fluid remained negative. Over the ensuing days, the patient recovered to full wakefulness and was discharged home on posttransplant day 24.FIGURE 1.: Serum ammonia level in association with extracorporeal liver support system (ELS) application.CASE 2 A 60-year-old woman with pulmonary fibrosis underwent bilateral lung transplant on venoarterial extracorporeal membrane oxygenation (ECMO) support. Postoperative course was complicated by hypoxemic respiratory failure attributed to severe primary graft dysfunction. This necessitated ongoing ECMO support (converted to venovenous), coupled with plasmapheresis, augmentation of immunosuppression, and continuous renal replacement therapy. Acinetobacter pittii was isolated from the donor lung. The patient received piperacillin-tazobactam, vancomycin, and metronidazole. Despite discontinuation of sedation and optimization of gas exchange and pulmonary mechanics over the ensuing days, the patient developed West Haven criteria grade 3 encephalopathy with anisocoria and obtundation. Her ammonia level was elevated at 95 µmol/L and remained refractory to medical therapy, including lactulose, rifaximin, zinc, empirical azithromycin, and ongoing continuous renal replacement therapy. Ureaplasma polymerase chain reaction in bronchoalveolar lavage fluid was negative. Twenty-four hours later, ELS therapy via the existing ECMO circuit (Figure 2) was initiated and applied for 2 sessions. Her ammonia level rapidly normalized (Figure 1), her mental status improved, and she was following commands by day 4 after initiation of ELS. The patient was successfully weaned off ECMO support 2 weeks after transplant. She had a prolonged hospital course due to multiple complications, including renal failure, atrial fibrillation, and deconditioning. She recovered sufficiently to be discharged to a rehabilitation facility 2.5 months posttransplant. She continues to do well >6 months posttransplant.FIGURE 2.: Diagram depicting concomitant application of extracorporeal liver assist system (albumin and dialyzer circuit) and extracorporeal membrane oxygenation system (ECMO). Cardiac image from Smart Servier Medical Heart, https://smart.servier.com/smart_image/heart-11/. IVC, inferior vena cava; RA, right atrium; SVC, superior vena cava.SUMMARY To our knowledge, this is the first report of successful use of ELS for treatment of idiopathic hyperammonemia after lung transplant. Hyperammonemia after solid organ transplant can result from diverse etiologies, including medications, inborn errors of metabolism, and infection with urease-producing pathogens. ELS provides an effective strategy for ammonia removal by dialyzing blood across a hybrid membrane and circulating albumin countercurrent to it.2,3 While the etiology of hyperammonemia after lung transplant is not always obvious, this report highlights the feasibility of using ELS to treat this potentially lethal entity.