Since
glufosinate irreversibly inhibits
glutamine synthetase, leading to intracellular accumulation of
ammonia,
hyperammonemia is considered one of the main mechanisms of
glufosinate ammonium toxicity in humans. However, whether
hyperammonemia causes neurotoxicity has not yet been studied. Therefore, the purpose of this study was to determine whether the serum
ammonia level is elevated before the development of neurotoxicity. In this retrospective observational study, we analyzed data from consecutive patients diagnosed with acute
glufosinate ammonium poisoning. The primary outcome was the development of neurotoxicity following the
poisoning. Patients who developed neurotoxicity were characterized by higher initial
ammonia levels compared to patients without neurotoxicity (121.0 µg/dL [87.0; 141.0] vs 83.0 µg/dL [65.0; 119.0], p < 0.01). However, there was no increase in
ammonia levels over time in both the asymptomatic and neurotoxicity groups when serial serum
ammonia levels were examined from emergency department admission to hospital discharge. In addition, there was no statistically significant difference between the peak
ammonia levels in the asymptomatic group and the peak
ammonia levels before symptom onset in the neurotoxicity group (135.0 µg/dL [109.0; 158.0] vs 144.0 µg/dL [120.0; 189.0], p = 0.15). Following the onset of neurotoxicity, the serum
ammonia level increased significantly (125.0 [111.0; 151.0] µg/dL to 148.0 [118.0; 183.0] µg/dL, p < 0.01). In conclusion,
hyperammonemia cannot be assumed as the cause of neurotoxicity in
glufosinate ammonium poisoning and further research is needed to examine the exact mechanism of GA
poisoning.