Hyperammonemia Post Lung Transplantation: A Review

Abstract

Hyperammonemia is the pathological accumulation of ammonia in the blood, which can occur in many different clinical settings. Most commonly in adults, hyperammonemia occurs secondary to hepatic dysfunction; however, it is also known to be associated with other pathologies, surgeries, and medications. Although less common, hyperammonemia has been described as a rare, but consistent complication of solid organ transplantation. Lung transplantation is increasingly recognized as a unique risk factor for the development of this condition, which can pose grave health risks-including long-term neurological sequelae and even death. Recent clinical findings have suggested that patients receiving lung transplantations may experience postoperative hyperammonemia at rates as high as 4.1%. A wide array of etiologies has been attributed to this condition. A growing number of case studies and investigations suggest disseminated opportunistic infection with Ureaplasma or Mycoplasma species may drive this metabolic disturbance in lung transplant recipients. Regardless of the etiology, hyperammonemia presents a severe clinical problem with reported mortality rates as high as 75%. Typical treatment regimens are multimodal and focus on 3 main avenues of management: (1) the reduction of impact on the brain through the use of neuroprotective medications and decreasing cerebral edema, (2) augmentation of mechanisms for the elimination of ammonia from the blood via hemodialysis, and (3) the diminishment of processes producing predominantly using antibiotics. The aim of this review is to detail the pathophysiology of hyperammonemia in the setting of orthotopic lung transplantation and discuss methods of identifying and managing patients with this condition.

Keywords: Hyperammonemia; Mycoplasma hominis; Ureaplasma; ammonia; critical care; dialysis; lung transplantation.

Figure 1.

The urea cycle. The figure depicts the key organs responsible for producing, metabolizing, and eliminating ammonia. (a) NH₃ can accumulate in the liver either when the production in the body exceeds its ability to metabolize it or when the liver’s metabolic functions are deranged such as in the case of cirrhosis. (b) Skeletal muscle functions to both produce and eliminate ammonia, it can contribute to hyperammonemia when there is severe sarcopenia such as in the setting of calcineurin inhibitors and corticosteroids. (c) The gastrointestinal system is the primary producer of ammonia under physiologic conditions. Its rate of consumption can be elevated in the setting of high dietary protein. (d) Urease positive bacteria are only responsible for ammonia production in pathological states and play no role in the normal urea cycle. (e) The kidneys are able to produce and eliminate NH₃ in the form of urea, they can shift their production to elimination ratio in times of excess.