Tuchman and colleagues recently reported the association of hepatic glutamine synthetase deficiency and fatal hyperammonemia after lung transplantation in two patients [1, 2]. To date, no reports have described successful treatment of this syndrome in lung transplant recipients.

We report the successful treatment of hyperammonemia in a 46-year-old man who developed severe emphysema secondary to ₁-antitrypsin and underwent bilateral orthotopic lung transplantation. Immunosuppressive therapy included azathioprine, cyclosporine, antithymocyte globulin, and methylprednisolone. Nine days after surgery, the patient became agitated and restless; he progressed to coma with decerebrate posturing within 12 hours. The patient was febrile (temperature, 38.5°C), and his leukocyte count was 25.2 x 10 (⁶)/mm³. Broad-spectrum antibiotic therapy with vancomycin and ceftazidime began; therapy was discontinued when all blood cultures remained negative. Although initial computed tomography of the head showed no signs of increased intracranial pressure, an intracranial pressure monitor placed the following day revealed a pressure of 26 mm Hg (normal, 0 to 20 mm Hg). The ammonia level was 269 µmol/L (normal, 9 to 33 µmol/L). The serum alanine aminotransferase level was 32 IU/L (normal, 11 to 47 IU/L), alkaline phosphatase level was 78 IU/L (normal, 38 to 126 IU/L), total bilirubin level was 1.3 mg/dL (normal, 0.3 to 1.0 mg/dL), conjugated bilirubin level was less than 0.1 mg/dL, serum creatinine level was 1.0 mg/dL (normal, 0.7 to 1.5 mg/dL), and cyclosporine 12-hour trough level was 363 ng/mL.

Quantification of plasma amino acids revealed normal levels of arginine, citrulline, glutamine, glycine, asparagine, and ornithine. Alanine levels were low at 139 µmol/L (normal, 158 to 393 µmol/L). Urinary lysine level was normal, indicating an intact urea cycle. Hemoperfusion with charcoal was done once but was discontinued because of thrombocytopenia. Hemodialysis was performed daily for 6 days (3.5 hours daily). Because the patient had a persistent ileus and the possibility of bowel bacterial overgrowth with urease-splitting bacteria that could increase ammonia levels [3], bowel decontamination was attempted with neomycin and lactulose (given orally and as an enema). Arginine, sodium benzoate, and sodium phenylacetate were administered intravenously to stimulate alternative pathways of nitrogen excretion; acetohydroxamic acid was administered orally to inhibit urease (Figure 1) [3].

View larger version (15K): [in this window] [in a new window]   Figure 1. Plasma ammonia levels and treatment given. *Arginine hydrochloride, sodium benzoate, and intravenous sodium phenylacetate.

Despite these treatments, the patient's ammonia level did not return to normal until after the sixth dialysis treatment. His intracranial pressure decreased, and his mental status returned to baseline.

The cause of our patient's hyperammonemia remains elusive, but we believe that the multifaceted therapeutic strategy we used contributed to the successful outcome. We suggest that a similar approach be considered for other lung transplant recipients with post-transplantation hyperammonemia.