Hyperammonemia Refractory to Continuous Renal Replacement Therapy, a Fatal Complication Post-Lung Transplant

Abstract

<h3>Introduction</h3> Post-lung transplant hyperammonemia is a rare complication associated with high mortality. Incidence is about 1-4% usually presenting within 2 weeks post-lung transplant. We describe a rare case of delayed-onset hyperammonemia post-lung transplant refractory to Continuous Renal Replacement Therapy (CRRT). <h3>Case Report</h3> A 30-year-old female underwent re-do bilateral lung transplantation for bronchiolitis obliterans syndrome. Her initial lung transplant was done for interstitial lung disease secondary to radiation-induced lung injury following treatment for childhood acute lymphocytic leukemia. Her first-week Bronchoalveolar lavage was positive for MRSA, <i>Pseudomonas</i> & <i>Ureaplasma</i> which were treated with antibiotics. Her postoperative course was complicated by prolonged hospitalization and need for ventilator support. She required Veno-venous Extra Corporeal Membrane Oxygenation support and CRRT. On POD 140, she was found to have decreased responsiveness. Workup revealed ammonia levels 353mmol/l. Her liver function was normal and repeat BAL cultures were negative for Ureaplasma & Mycoplasma. She was treated with lactulose, polyethylene glycol, levocarnitine, rifaximin, acarbose & sodium benzoate. Despite being on CRRT & this regimen, her ammonia levels continued to rise and peaked at 493 mmol/l. On continuous EEG, seizure-like activity was seen with features suggestive of metabolic encephalopathy. MRI revealed cerebral edema and findings consistent with hyperammonemic encephalopathy. MARS therapy (Molecular Adsorbent Recirculating System) was started, which resulted in a rapid decline in ammonia levels and some improvement in her mental status. In spite of improved ammonia levels, given her poor overall prognosis, the patient & family chose to transition to comfort measures and she subsequently passed away. <h3>Summary</h3> Post-lung transplant hyperammonemia is a poorly understood relatively uncommon condition associated with poor outcomes. Ammonia is a small molecule that does not bind to proteins & is amenable to removal by dialysis. Therefore, significantly elevated ammonia levels despite being on CRRT & medical management, so late following the lung transplant in the absence of any definitive etiology makes this rare. MARS has been proven to successfully treat refractory hyperammonemia post lung transplantation.