Pearls & Oy-sters: Status epilepticus from hyperammonemia after lung transplant

Abstract

PEARLS• Even when the cause of metabolic coma seems clear, consider an arterial ammonia level.• Refractory status epilepticus may be due to acute hyperammonemia, and not the more commonly seen calcineurin inhibitor neurotoxicity.• Hyperammonemia causes brain edema and requires multiple measures to lower it quickly.CASE REPORT A 64-year-old woman with familial pulmonary fibrosis underwent bilateral lung transplantation under general anesthesia with midazolam, propofol, and fentanyl. Her post-transplant immunosuppression regimen consisted of prednisone, azathioprine, and tacrolimus. She was initially alert and following commands but on postoperative day 3 became increasingly somnolent, necessitating reintubation. Sodium, renal and liver function tests, and CSF analysis (including opening pressure) were normal. Noncontrast CT scan of the head was unrevealing with no early evidence of cerebral edema. EEG showed diffuse delta with frequent 1-to 2-Hz triphasic waves. Her somnolence was attributed to her tacrolimus level (66.8 ng/mL) and the medication was held with normalization of the level by postoperative day 4. On postoperative day 5, she had persistent arrhythmic twitching of her left arm that within a minute generalized to a full-blown convulsive status epilepticus. Multiple doses of Ativan, totaling 10 mg, and 20 mg/kg PE of fosphenytoin were administered, with cessation of seizures. An ammonia level was obtained and was unreadable at greater than 1,200 g/dL. AST was 36 U/L. Lactulose, rifaximin, and continuous venous-venous hemofiltration (CVVH) were initiated to normalize the ammonia level and continuous EEG monitoring was initiated.An intraparenchymal intracranial pressure (ICP) monitor was placed but the initial intracranial pressure was 4 mm Hg. Two hours after initial cessation of seizures, she had recurrent left arm twitching, which quickly generalized and was refractory to additional 4 mg/kg PE of fosphenytoin, maximal infusion rates of midazolam and propofol, and ultimately was controlled with pentobarbital infusion at a rate of 5 mg/kg/h, at which point the background changed from a pattern of generalized spike and waves to a completely suppressed background in the 1-to 2-Hz range without reactivity. Clinical seizures became under control within 1 hour after onset. Full resolution of electrographic status epilepticus took 6 hours longer. At that time, propofol and midazolam were stopped. Lactulose, rifaximin, and CVVH were continued and arterial ammonia declined gradually. After arterial ammonia had normalized, pentobarbital was slowly weaned. Her ICP remained below 10 mm Hg with the exception of 2 isolated spikes to 19 mm Hg lasting several minutes each on postoperative days 8 and 9. A repeat CT scan of the head on postoperative day 11 showed lack of gray-white matter differentiation and absence of sulci (figure). When the pentobarbital was no longer detectable in her blood, the patient was declared brain dead.DISCUSSION Idiopathic hyperammonemic encephalopathy (IHE) is an uncommon complication of so...

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

“…Ultimately, the cause of HA may be related to excess production, decreased clearance of ammonia, or both. Disorders of glutamine synthetase (GS) have been described in patients with HALT ( 1 , 13 , 14 ). More recently, infection with urea-splitting microorganisms has been reported in patients with HA after organ transplantation ( 11 , 12 , 15 – 17 ).…”

Hyperammonemia Presenting as Refractory Status Epilepticus after Lung Transplant in a Patient Positive for Ureaplasma parvum

“…In our case, hyperammonemia presented as seizures and progressed to cerebral edema, coma, and death, likely due to glutamine production in the brain from ammonia metabolism, which creates an osmotic effect and leads to cerebral edema. [ 8 ] This phenomenon was reported in two cases where cerebral spinal fluid glutamine levels were measured and increased with dissociation between plasma glutamine levels, which were decreased. [ 5 7 ] The etiology of this disease after lung transplant is not known.…”

“…Some have hypothesized that hyperammonemia is triggered by major medical stressors, particularly gastrointestinal stress, hepatic glutamine synthetase deficiency, or a partial urea cycle deficiency unmasked by the stress of surgery. [ 2 8 ] In our patient, medications such as VPA may have contributed to hyperammonemia by inhibition of the first stage of the urea cycle as a result of inhibition of carbamoyl phosphate synthetase I activation and resultant decrease of N-acetylglutamate availability. [ 10 ]…”

“…[ 2 4 5 6 ] When diagnosed late, hyperammonemia is often accompanied by seizures, severe cerebral edema, and increased intracranial pressure and frequently leads to death. [ 1 2 7 8 ]…”

Non-cirrhotic Hyperammonemia—When High Ammonia Is not Always from Cirrhosis

“…Encephalopathy is associated with development of advanced disease (e.g., myeloma cells in the peripheral blood) and an increased risk of mortality, especially at a level of >114 μmol/L [53,54]. Patients receiving bone marrow transplantation for hematological malignancies [55] and rarely those with lung transplants [56] are also at risk of developing elevated ammonia with encephalopathy due to unclear reasons. Intensive cytoreductive chemotherapy for acute leukemia has also been linked to hyperammonemia and encephalopathy [57,58].…”