Hyperammonemia in lung transplant patients and its management: a review

Abstract

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.

Keywords: Hyperammonemia; Lung transplantation; Renal replacement therapy.

Fig. 1

Human ammonia physiology. The complete urea cycle resides exclusively in the liver. The intestine is the source of both ammonia and citrulline (CPS, carbamoyl phosphate synthase; OTC, ornithine transcarbamoylase)

Fig. 2

The urea cycle metabolism analysis (CPSI, carbamoyl phosphate synthase I; OTC, ornithine transcarbamoylase; ARG, arginase; ASS, arginosuccinate synthetase; ASL, arginosuccinase)

Fig. 3

MRI scan with DWI (A, B) and FLAIR images (C, D) shows symmetric abnormal signal intensity in the insular (arrows) and cingulate (arrowheads) bilaterally. Extensive signal-intensity change involving both the cortex and subcortical white matter is also seen in right temporo-parietal and left occipital lobes