Hyperammonemia After Lung Transplantation: Systematic Review and a Mini Case Series

Abstract

Graphical Abstract

Treatment of Hyperammonemia Syndrome in Lung Transplant Recipients

“…The majority of natural ammonia production in the human body occurs in the gut after protein metabolism. These nitrogenous waste products are eliminated by conversion to urea through the urea cycle in the liver and subsequently excreted by the kidneys, or by conversion to glutamine in the liver, skeletal muscle, and central nervous system [2,4,5]. Acute hyperammonemia, most commonly presenting as encephalopathy, can result when mechanisms of elimination are disrupted or when there is excessive production.…”

“…Kamel et al were unable to find cases of lung transplant patients with UCDs in their systematic review, but they did find evidence to support downregulation of hepatic glutamine synthetase in lung transplant patients. This may result in decreased ammonia elimination [5]. Malnutrition is rarely investigated in the context of hyperammonemia after lung transplant but has been linked with higher prevalence of non-hepatic hyperammonemia in other populations [7][8][9][10].…”

“…Blood ammonia levels, liver function tests, tests for urea cycle disorders, imaging, and antimicrobial cultures and molecular testing can help identify hyperammonemia syndrome and guide treatment. Kamel et al routinely check daily ammonia levels for the first week after lung transplant as well as after any change in mental status, and they found that their strategies allowed for earlier detection of hyperammonemia and potentially lowered mortality [5]. There is no universally accepted ammonia level threshold for the diagnosis of hyperammonemia syndrome, but some examples in the literature include ammonia greater than 50, 60, 90, or 200 µmoL/L [1,2,[4][5][6]15].…”

“…Kamel et al routinely check daily ammonia levels for the first week after lung transplant as well as after any change in mental status, and they found that their strategies allowed for earlier detection of hyperammonemia and potentially lowered mortality [5]. There is no universally accepted ammonia level threshold for the diagnosis of hyperammonemia syndrome, but some examples in the literature include ammonia greater than 50, 60, 90, or 200 µmoL/L [1,2,[4][5][6]15]. Reported peak levels also vary widely ranging from 143 to 5000 µmol/L [1,16].…”

Ammonia and nutritional therapy in the critically ill: when to worry, when to test and how to treat?

“…A thorough drug history and measurement of blood valproate concentration will readily identify drug-related hyperammonaemia in many instances. Several case reports identify that hyperammonaemia can occur following both solid organ and haematopoietic stem cell transplantation, with lung transplantation being the most recognized [10,11]. The specific underlying contributing factors to all urea cycle disorders are unclear, but likely include a combination of drugs affecting the urea cycle, steroidinduced catabolism, nutritional deficits and infections with urea-splitting organisms [12].…”