Despite the perception that GA has low toxicity to humans and the environment [13], GA poisoning remains a significant health issue in our country due to the delayed onset of symptoms. Many patients with GA poisoning present to the emergency department without any apparent symptoms but later develop complications during diagnosis and treatment. Unfortunately, there are currently no reliable early indicators that can accurately predict the prognosis of patients with GA poisoning.
In this study, we provide a summary of the clinical features of acute oral GA poisoning for. Nausea and vomiting were the most common symptoms experienced by 80% of patients within 6 hours after ingesting the herbicide, additionally, herbicides can also cause gastrointestinal irritation. The majority of patients recovered from these symptoms within 1–2 days after hospitalization. However, neurological complications, such as coma, dizziness, lethargy, and seizure, occurred in 27 patients (40.3%), and were not apparent during the first few hours of hospitalization. The incidence of neurotoxicity was lower than the results of the research conducted by Lee DK [14]. In their research, the incidence of neurotoxicity was 64.4%, with only the latent periods of seizure was studied. The reason of the difference may be relevant to the fact that we collected more samples. We first reported that the different latent periods of different symptoms of neurotoxicity. The median time for consciousness and convulsion or seizure was 33.0 (26.0, 40.0) hours and 45.0 (37.5, 48.5) hours after ingesting GA, respectively. Inhibition of glutamine synthetase by glufosinate ammonium may lead to elevated blood ammonia levels that are related to neurotoxicity symptoms [15]. Glutamine synthetase is a crucial enzyme in the human body that plays a critical role in brain metabolism and the normal function of various organs[16]. Hyperammonemia caused by herbicides was difficult to decrease through lactulose, which is different from the elevated serum ammonia levels associated with hepatic encephalopathy[17]. It is important to monitor respiratory function within 24 hours of taking the herbicide, as 11 patients (16.4%) suffered from respiratory failure during hospitalization, with 80% of these cases occurring within 12 hours after admission. The mechanism of respiratory failure is not well understood, but it should be closely monitored in the early stages of hospitalization. The overall mortality rate was 13.4% (9 patients), with hyperammonemia and hemodynamic toxicity being the main mechanisms of GA poisoning in humans [18–19]. The mortality of GA poisoning patients was rarely reported in the literature. Neurotoxicity symptoms and central apnea requiring mechanical ventilation support were thought to be caused by hyperammonemia and hemodynamic toxicity [20]. Although previous study[21] have found significant correlations between ammonia levels in the serum and CSF and neurological complications, CSF ammonia detection was not available in our hospitals include our hospital. Age > 70 years and GCS score < 9 at admission were predictors of mortality in patients with GA poisoning, according to Hsiao JT et al [22]. Lee [23] also found that PCO2 level, mechanical ventilator application, and the use of vasopressors could be valuable prognostic information for evaluating the severity and mortality of patients with GA poisoning. However, there was no significant difference in age, PCO2 level in our research, which may be explained by the formulation of GA herbicides differing in different countries[14]. GCS score were difficulty to collect from the GA poisoning patients accurately which were differ from the previous research. The reason hidden behind this is that the cause of GA poisoning patients were suicide. Patients who commit suicide were accompanied by depression or mania. We hardly got a objective and real GCS score without the cooperation of patients.
In our study, the initial serum ammonia levels, the ingestion amount of GA and CK-MB levels had significant difference between unfavorable outcomes group and favorable outcomes group. Multiple logistic regression analyses indicated that initial serum ammonia levels (OR = 1.031, 95%CI, 1.069–1.197, P < 0.001), ingestion amount (OR = 1.017, 95%CI, 0.997–1.039, P = 0.013) and CK-MB (OR = 1.100, 95%CI, 1.017–1.189, P = 0.017) were independently associated with unfavorable outcomes. ROC curves were used to determine the optimal initial serum ammonia level (62.7mmol/L with sensitivity of 85.7% and specificity of 87.2%, and AUC = 0.873, 95%CI, 0.773–0.974, P < 0.001), CK-MB level (43.5U/L with sensitivity of 42.9% and specificity of 87.2%, and AUC = 0.680, 95%CI, 0.562–0.809, P = 0.012) and the ingestion amount(110ml with sensitivity of 32.1% and specificity of 92.3%, and AUC = 0.652, 95%CI, 0.518–0.786, P = 0.035) respectively. The initial serum ammonia had the highest sensitivity, with the highest specificity was the ingestion amount of GA. Toxicant intake is closely related to the severity and prognosis of the pesticide toxicity disease. The gold standard for the diagnosis of poisoning is poison detection, in the meaning time, the specificity of the amount of ingestion in our research was the highest. Unfortunately, most hospitals in China do not have the capability to perform poison detection alone, and the ingestion amount of GA were provided by patients or their guardian approximately. This is not an ideal predictor. The increase of CK-MB was associated with various reason, such as myocardial injury, muscle injury, craniocerebral damage, seizure and so on. The reason that GA poisoning patients with a increased CK-MB might be related to the myocardial damage. Kim [25] published a case report about a various clinical aspects associated with cardiotoxicity after GA poisoning. In our research, 3 patients died of Cardiovascular cause(two patients suffered cardiac arrest and one patient died of cardiogenic shock). This reminded us to pay attention to cardiotoxicity as well as neurotoxicity of GA poisoning. The intracellular accumulation of ammonia is a result of the inhibition of glutamine synthesizer. Hyperammonemia destroys cell membranes and inhibits protein synthesis. Previous studies[1, 24] have suggested that serum ammonia levels may be a potential indicator of severe symptoms, but these findings were based on case reports with limited statistical power. Our results were consistent with previous studies. Furthermore, the effective of the initial serum ammonia levels and CK-MB levels in predicting prognosis could widely applied and available in primary hospitals with its easy accessibility as well as high sensitivity and specificity.
In summary, our study found that GA poisoning patients had a range of symptoms, including some fatal symptoms of cardiovascular toxicity and neurotoxicity, but there is a certain latent period. This reminds us to focus on surveillance and prevention even in the asymptomatic phase. Initial serum ammonia levels and CK-MB levels were good predictors in evaluating the prognosis of GA poisoning.