Hyperammonemia in lung transplant patients and its management: a review

Objective: To synthesize the evidence for incidence, pathophysiology, etiology, and protocol-based management of hyperammonemia in lung transplant patients. Background: Elevated ammonia levels are toxic to the brain, and hyperammonemia results in a potentially fatal complication for lung transplant recipients. The hallmark of this condition is ammonia production being way out of proportion to the degree of liver derangement. While there are many hypotheses, the cause remains obscure. Methods: A retrospective review of patients with hyperammonemia following lung transplantation was done to understand the pathophysiology, various treatment modalities, and its impact on patient mortality and morbidity. Studies in the English literature were identified through an electronic database search from PubMed/MEDLINE, Ovid Embase, Google Scholar, Cochrane Database of Systematic Reviews (CDSR), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Web of Science, and ClinicalTrials.gov until June 2020. No restriction of dates were used, and the search was up until June 2020. Discussion: Mortality among patients with hyperammonemia following lung transplantation is high. Multi-modal treatment approaches include avoiding nephrotoxic drugs, use of bowel decontamination, nitrogen scavengers, branched-chain amino acids, adjustment of immunosuppression, antibiotics like fluoroquinolones or azithromycin, and renal replacement therapy. However, there remains a scarcity of preoperative screening protocol for patients at risk of hyperammonemia as well evidence-based post-operative management guidelines. Intermittent hemodialysis, compared to continuous venovenous hemodialysis, provides better patient outcomes. Conclusion: Early detection of patients at risk by appropriate screening, along with maintaining a high degree of suspicion for hyperammonemia and multi-modal treatment approach, is the key to successful patient outcomes. Further prospective observational studies would facilitate development of protocol-based treatment of this potentially fatal condition.