[Clinical analysis of 15 cases of acute glufosinate poisoning].

The glufosinate poisoning can cause damage to the respiratory system and nervous system. In severe cases, respiratory failure and toxic encephalopathy are life-threatening. It should be paid attention to and supportive treatment.In this paper, 15 cases of acute oral glyphosate poisoning diagnosed by toxicant test in the Poisoning Treatment Center of the Army from March to August 2018 were analyzed, and the clinical characteristics and treatment effect of acute glyphosate poisoning were summarized, so as to improve the understanding, diagnosis and treatment level of the disease.

[One case successfully rescued acute poisoning caused by misadministration of large amount of glufosinate].

Objective: To report a case of acute glufosinate-ammonium poisoning cause respiratory cardiac arrest and grass amine poisoning cases of successful rescue. Methods: The clinical data of a case of acute glufosinate-ammonium poisoning admitted to a third-class a hospital in April 2018 were analyzed and summarized. Results: The patient was poisoned by oral administration of a large amount of glufosinate-ammonium. Respiratory and cardiac arrest occurred during treatment and resuscitation was successful Later, the nervous system showed impaired function, The patients were treated with complete gastrointestinal cleansing, hemoperfusion, and the protection of important organs. Conclusion: For a large number of patients with oral glufosinate-ammonium poisoning, we should pay close attention to the damage of nervous system while taking active and conventional detoxification treatment.

Application of probe electrospray ionization-tandem mass spectrometry to ultra-rapid determination of glufosinate and glyphosate in human serum.

Glufosinate and glyphosate, which are non-selective herbicides that include an amino acid moiety in their structures, are frequently used worldwide to control unwanted vegetation. Unfortunately, these readily available herbicides are also used by people to commit suicide, and thus represent important chemicals of interest in the fields of clinical medicine and forensics. Because of the high water solubility of these herbicides, most analytical methods for their detection require a derivatization step, which results in longer analysis times. Therefore, derivatization-based methods do not currently contribute to judgements on treatment decisions in emergency medicine. In this study, we addressed this limiting factor by developing an ultra-rapid and simple analytical technique using a combination of probe electrospray ionization (PESI) and tandem mass spectrometry (MS/MS), which gives quantitative results within 0.3 min. Herbicide standards were added to human serum that was then subjected to analysis (N = 5 per concentration). The analysis was repeated daily over eight consecutive days. The limit of detection (LOD) was 0.59 µg/mL for glufosinate and 0.20 µg/mL for glyphosate. The limit of quantitation (LOQ), i.e., the lowest point on the calibration curves, was 1.56 µg/mL for both the herbicides. The matrix effects were observed at three different concentrations (between 95.7%-104% for glufosinate, and between 90.7%-95.7% for glyphosate). When applied to samples taken from actual poisoning cases (six samples for each herbicide), the present method gave almost the same quantitative values as those obtained by conventional high-performance liquid chromatography with fluorescence detection. Thus, we believe that PESI-MS/MS could emerge as a rapid diagnosis method in the clinical emergency field.

Serum ammonia as an early predictor of in-hospital mortality in patients with glufosinate poisoning.

BACKGROUND: The mortality rate associated with human glufosinate poisoning is high. We evaluated the usefulness of serum ammonia and sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE II) scores for early prediction of in-hospital mortality in glufosinate ammonium poisoning. METHODS: A prospectively collected pesticide poisoning registry at a single academic medical center was retrospectively analyzed. Data were collected from consecutive patients diagnosed with glufosinate ammonium poisoning between May 2007 and February 2018. The initial serum ammonia level was defined as the highest serum ammonia level measured within 12 h after emergency department (ED) arrival. The SOFA and APACHE II scores were calculated using data obtained within the first 12 h after ED arrival. The patients were divided into survivor and nonsurvivor groups by in-hospital death status. RESULTS: In total, 110 patients were included. Ten patients (9.1%) died in the hospital despite treatment. Median initial serum ammonia level was significantly higher in the nonsurvivor group than in the survivor group (219 (range: 158-792) versus 100.5 (range: 25-317) µg/dL, p < 0.001). Median SOFA and APACHE II scores in the survivor and nonsurvivor groups were 2 (range: 0-10) versus 5 (range: 1-8) (p = 0.044) and 7 (range: 0-28) versus 16 (range: 8-22) (p = 0.001), respectively. In the multiple logistic regression analysis, the initial serum ammonia level was the only independent predictor (cutoff value: 151 µg/dL). CONCLUSION: An initial serum ammonia level >151 µg/dL was an independent early predictor of in-hospital mortality in glufosinate ammonium poisoning.

Prognostic factor determination mortality of acute glufosinate-poisoned patients.

BACKGROUND:: Glufosinate-containing herbicide is increasingly used in agriculture. Its poisoning is a worldwide concern. More and more patients are poisoned by glufosinate. The aim of this study was to determine the factors associated with mortality of patients with acute poisoning of glufosinate. METHODS:: This was a retrospective cohort study conducted from January 1998 to October 2015. Using a multivariate logistic analysis, data for the total population were retrospectively analyzed to determine the factors associated with mortality. Various variables were compared in survivors and non-survivors. Significant predictive variables, Acute Physiology and Chronic Health Evaluation (APACHE) II scoring system, the Simplified Acute Physiology Score (SAPS) II, and Sequential Organ Failure Assessment (SOFA) score were compared by analyzing receiver operating characteristic (ROC) curves. RESULTS:: A total of 253 patients (mean age: 58 years) were enrolled. Of the 253 patients, 219 (86.6%) survived and 34 (13.4%) died. Decreased Glasgow Coma Scale (GCS) and bicarbonate (HCO3-), use of mechanical ventilator, and use of vasopressors (dopamine, dobutamine, norepinephrine) were associated with mortality. The areas under the curve in the ROC curve analysis for the predictive variables, SOFA score, APACHE II scoring system, and SAPS II were 0.952, 0.829, 0.927, and 0.944, respectively. CONCLUSION:: Four predictive variables (GCS < 9, HCO3- < 16.0 mmol/L, mechanical ventilator apply, and use of vasopressors) were associated with mortality in the total population of patients with acute poisoning of glufosinate. These predictive variables had good discriminative power for predicting mortality of patients with acute poisoning of glufosinate-containing herbicide compared to APACHE II, SOFA, and SAPS II.

Seizures in patients with acute pesticide intoxication, with a focus on glufosinate ammonium.

The incidence and clinical aspects of seizures remain to be elucidated in patients with acute pesticide intoxication. The present study included subjects who ingested pesticide with the intention of committing suicide and were treated at Soonchunhyang University Hospital (Cheonan, Korea) between January 2011 and December 2014. We analyzed the incidence and characterized the type and frequency of seizure, from the medical records of 464 patients with acute pesticide intoxication, according to the pesticide class. The effect of seizure on the clinical outcome was assessed. The incidence of seizure was 31.5% in patients who ingested glufosinate ammonium {2-amino-4-[hydroxyl (methyl) phosphinoyl] butyrate; ammonium DL-homoalanin-4-yl (methyl) phosphinate}, followed by those who ingested pyrethroid (5.9%) or glycine derivatives (5.4%). All of the seizures developed between 12 and 24 h of pesticide ingestion and had ceased by 72 h after seizure initiation, following treatment with antiseizure medication. Generalized tonic-clonic seizures were the most commonly observed (85.7% of the cases). Multivariable logistic regression analysis showed that the effect of seizure on mortality was not statistically significant. In conclusion, glufosinate ammonium herbicide is the most common seizurogenic pesticide class. Seizure itself was not a risk factor for mortality in patients with acute glufosinate ammonium intoxication.

The relationship between serum ammonia level and neurologic complications in patients with acute glufosinate ammonium poisoning: A prospective observational study.

Glufosinate ammonium poisoning can cause neurological complications even after a symptom-free period. We prospectively investigated the predictors of neurologic complications in acute glufosinate ammonium poisoning and the change of serum ammonia level as a predictor of patient's presence and recovery of neurologic complication. This prospective observational study collected data from consecutive patients diagnosed with acute glufosinate ammonium poisoning between September 2014 and June 2016. Serum ammonia was serially measured. The patients were divided into two groups: the neurologic complication group and the nonneurologic complication group. We also defined 25 other insecticide- or herbicide-poisoned patients as controls. The neurologic complication group included 18 patients (72.0%). The latency period for neurologic complications was within 48-h postingestion. The peak ammonia level was statistically higher in the neurologic complication group than in the control group ( p < 0.001) and the nonneurologic complication groups ( p = 0.001). There was a statistical difference between the nonneurologic complication group and the neurologic complication group ( p = 0.0085) in terms of ingested amount. The peak ammonia was the only predictor for the development of neurologic complications (the optimal cutoff: 90 µg/dL). In patients with mental changes, the mean serum ammonia levels before and after recovery of the mental changes were statistically different ( p = 0.0019). In acute glufosinate ammonium poisoning, serial serum ammonia level measurements are needed and a serum peak ammonia level greater than 90 µg/dL is a predictor of neurologic complications. Also, it is important to treat the hyperammonemia in acute glufosinate ammonium poisoning.

Serum S100 protein could predict altered consciousness in glyphosate or glufosinate poisoning patients.

BACKGROUND: Central nervous system (CNS) complications such as seizures and reduced consciousness are important in glufosinate and may occur in severe glyphosate poisoning. The aim of this study was to assess the possible role of serum S100B protein as a biochemical marker of CNS complications associated with glyphosate or glufosinate poisoning. METHODS: The study enrolled 40 patients (23 glyphosate poisoning and 17 glufosinate poisoning). Altered consciousness and seizure were observed during hospitalization. S100B level was measured with fully automated modular analytic E170 system using electrochemoluminometric immunoassay. RESULTS: Among 40 patients, neurologic features were observed in 12 patients with a median time to onset of 21.5 (IQR 8.25-24.75) h. Serum S100B concentrations measured on admission were higher in the group with neurologic features than in the group without neurologic features [0.148 µg/L (IQR 0.128-0.248) vs. 0.072 µg/L (IQR 0.047-0.084), p < .001]. Univariate analysis of measured patient raw parameters using a ROC curve showed that S100B was a significant predictor of neurologic features in glyphosate and glufosinate poisoning. The area under the ROC curve was 0.894 (95% confidential interval 0.791-0.998). When S100B was set at 0.0965, its sensitivity and specificity for predicting neurologic features in glyphosate and glufosinate poisoning were 92% and 82%, respectively. CONCLUSIONS: In our pilot study, S100B was a significant predictor of neurologic complications in patients with glyphosate and glufosinate poisoning. Large prospective cohorts are needed to confirm this finding.

Initial Serum Ammonia as a Predictor of Neurologic Complications in Patients with Acute Glufosinate Poisoning.

PURPOSE: Glufosinate poisoning can cause neurologic complications that may be difficult to treat due to delayed manifestation. Studies assessing possible predictors of complications are lacking. Although serum ammonia level is a potential predictor of severe neurotoxicity, it has only been assessed via case reports. Therefore, we investigated factors that predict neurologic complications in acute glufosinate-poisoned patients. MATERIALS AND METHODS: We conducted a retrospective review of 45 consecutive glufosinate-poisoning cases that were diagnosed in the emergency department (ED) of Wonju Severance Christian Hospital between May 2007 and July 2014. Patients with a Glasgow Coma Scale (GCS) score of <8, seizure, and/or amnesia were defined to a neurologic complication group. RESULTS: The neurologic complication group (29 patients, 64.4%) comprised patients with GCS<8 (27 patients, 60.0%), seizure (23 patients, 51.1%), and amnesia (5 patients, 11.1%). Non-neurologic complications included respiratory failure (14 patients, 31.1%), intubation and ventilator care (23 patients, 51.1%), shock (2 patients, 4.4%), pneumonia (16 patients, 35.6%), acute kidney injury (10 patients, 22.2%), and death (4 patients, 8.9%). Complications of GCS<8, seizure, respiratory failure, and intubation and ventilator care appeared during latent periods within 11 hrs, 34 hrs, 14 hrs, and 48 hrs, respectively. Initial serum ammonia was a predictor of neurologic complications [odds ratio 1.039, 95% confidence interval (1.001-1.078), p=0.046 and area under the curve 0.742]. CONCLUSION: Neurologic complications developed in 64.4% of patients with acute glufosinate poisoning. The most common complication was GCS<8. Initial serum ammonia level, which can be readily assessed in the ED, was a predictor of neurologic complications.

Serial ammonia measurement in patients poisoned with glufosinate ammonium herbicide.

This study investigated whether ammonia concentrations can predict delayed neurotoxicity development and neurotoxicity latency in glufosinate ammonium (GLA) herbicide-poisoned patients presenting with an alert mental state and stable hemodynamics. This retrospective observational case study included 26 patients divided into 2 groups: neurotoxicity during hospitalization (complicated group) and without neurotoxicity (noncomplicated group). Thirteen patients (50.0%) experienced neurotoxicity at 16 h post-ingestion. Although ammonia concentrations at presentation did not differ significantly between the two groups, the ammonia level in the complicated group increased significantly at the next measurement and remained significantly higher than that in the noncomplicated group until 48 h after ingestion. The peak ammonia concentration before neurotoxicity development was an independent predictor of neurotoxicity (odds ratio: 1.047, 95% confidence interval: 1.010-1.087, p value = 0.014), and the optimal cutoff value of peak ammonia concentration for predicting neurotoxicity was 101.5 µg/dL. The rate of ammonia increase was not associated with the time latency from ingestion to neurotoxicity development. This study showed that serial ammonia measurements in GLA-poisoned patients may identify those who are at high risk of developing neurotoxicity. However, as this study enrolled few patients, further qualified trials are required to confirm our results and to reveal the etiology of hyperammonemia and its causality in neurotoxicity.

Reversible Splenial Lesion Syndrome (RESLES) Following Glufosinate Ammonium Poisoning.

Isolated and reversible lesion restricted to the splenium of the corpus callosum, known as reversible splenial lesion syndrome, have been reported in patients with infection, high-altitude cerebral edema, seizures, antiepileptic drug withdrawal, or metabolic disturbances. Here, we report a 39-year-old female patient with glufosinate ammonium (GLA) poisoning who presented with confusion and amnesia. Diffusion-weighted magnetic resonance imaging of the brain revealed cytotoxic edema of the splenium of the corpus callosum. The lesion was not present on follow-up MR imaging performed 9 months later. We postulate that a GLA-induced excitotoxic mechanism was the cause of this reversible splenial lesion.

Continuous renal replacement therapy circuit failure after antidote administration.

A 73-year-old man was transferred to the emergency department (ED). He was found unconscious in his house along with an empty 200-mL bottle of Basta(™), a herbicide containing 18% glufosinate. He was comatose with a Glasgow Coma Scale score of 3. As his blood pressure dropped to 60/30 mmHg despite fluids and norepinephrine, 20% intravenous fat emulsion product was injected. He experienced repeated cardiopulmonary arrests during his first 4 h in the ED. When the arrests occurred, standard cardiopulmonary resuscitation was performed, and boluses of fat emulsion were given. He was given a total of 1500 mL of 20% fat emulsion. In an attempt to correct the acidosis, continuous renal replacement therapy (CRRT) was started. Within 5 min of starting CRRT, the transmembrane pressure increased sharply and the machine stopped.

Glufosinate herbicide intoxication causing unconsciousness, convulsion, and 6th cranial nerve palsy.

Although glufosinate ammonium herbicides are considered safe when used properly, ingestion of the undiluted form can cause grave outcomes. Recently, we treated a 34-yr-old man who ingested glufosinate ammonium herbicide. In the course of treatment, the patient developed apnea, mental deterioration, and sixth cranial nerve palsy; he has since been discharged with full recovery after intensive care. This case report describes the clinical features of glufosinate intoxication with a focus on sixth cranial nerve palsy. Our observation suggests that neurologic manifestations after ingestion of a "low-grade toxicity herbicide" are variable and more complex than that was previously considered.

Glufosinate Herbicide Intoxication Causing Unconsciousness, Convulsion, and 6th Cranial Nerve Palsy

Although glufosinate ammonium herbicides are considered safe when used properly, ingestion of the undiluted form can cause grave outcomes. Recently, we treated a 34-yr-old man who ingested glufosinate ammonium herbicide. In the course of treatment, the patient developed apnea, mental deterioration, and sixth cranial nerve palsy; he has since been discharged with full recovery after intensive care. This case report describes the clinical features of glufosinate intoxication with a focus on sixth cranial nerve palsy. Our observation suggests that neurologic manifestations after ingestion of a "low-grade toxicity herbicide" are variable and more complex than that was previously considered.

Acute human glufosinate-containing herbicide poisoning.

BACKGROUND: Glufosinate-containing herbicides are commonly used worldwide. Data on acute human glufosinate poisoning however remain scarce. METHODS: We retrospectively reviewed the medical records of all glufosinate poisoned cases reported to the Taiwan National Poison Control Center and two medical centers in Taiwan from August 1993 through February 2010. Their demographic and clinical data were then analyzed to identify potential predictors of severe effects following acute glufosinate poisoning. RESULTS: One hundred and thirty-one patients, including 115 oral and 16 non-oral exposures, were eligible for final analysis. Among patients with oral exposure, 25 were asymptomatic, while the others developed gastrointestinal, neurological, cardiovascular, and/or respiratory manifestations. Seven patients (6.1%) died following deliberate glufosinate ingestion. The median dose of glufosinate ingestion was 30.4 grams (interquartile range 18.5-45.6 grams) in the severe/fatal group compared to 6.8 grams (interquartile range 3.7-16.2 grams) in the non-severe group (p <0.001). Older age (≥ 61 years; adjusted OR 4.9, 95% CI 1.3-17.9) and larger amount of glufosinate ingestion (≥ 13.9 grams; adjusted OR 25.2, 95% CI 4.8-132.5) were positively associated with the development of severe toxicity, whereas ethanol consumption (adjusted OR 0.1, 95% CI <0.1-0.5) was inversely associated with the risk of severe toxicity. CONCLUSION: Although glufosinate is generally thought to be of low toxicity to humans, severe effects can occur and may be associated with older age, larger amount of ingestion and absence of concomitant ethanol consumption.

Hyperammonemia following glufosinate-containing herbicide poisoning: a potential marker of severe neurotoxicity.

Glufosinate-ammonium (GLA) is the active ingredient of certain widely used non-selective contact herbicides ("e.g.," Basta). Although it is thought to be much less toxic to humans than to plants, deliberate ingestion of GLA could still lead to serious effects ("e.g.," neurotoxicity) or even death. Three cases presented with delayed-onset neurotoxicity including stupor, delirium, seizures, coma, and amnesia after ingesting large amount of Basta. Considering that GLA could irreversibly inhibit glutamine synthetase (GS) in plants, we performed serial measurements of serum ammonia in those patients and revealed marked hyperammonemia in all of them. All patients recovered with the sequelae of persistent amnesia after receiving intensive care and hemodialysis. We speculated that the occurrence of hyperammonemia might at least be partially related to GS inhibition in humans. Moreover, hyperammonemia could serve as a potential marker of severe neurotoxicity, especially prolonged amnesia, following massive ingestion of GLA-containing herbicides. The possible dose-response relation between GLA exposure and serum ammonia level, however, needs more investigations.

Vasogenic edema in striatum following ingestion of glufosinate-containing herbicide.

Glufosinate-ammonium (GLA) is a broad-spectrum herbicide used worldwide. We report a patient who attempted suicide by ingesting a liquid herbicide containing GLA. A diffusion-weighted MRI showed cytotoxic edema in the hippocampus as well as vasogenic edema in the striata. To our knowledge, vasogenic edema caused by GLA-containing herbicide involving the striatum has not been reported in association with cytotoxic edema in the hippocampus. We assume that this herbicide affected the central nervous system via different mechanisms to produce both cytotoxic and vasogenic edema in the same patient.

Determination of glyphosate, glyphosate metabolites, and glufosinate in human serum by gas chromatography-mass spectrometry.

This paper describes an assay for the determination of glyphosate (GLYP), glyphosate metabolites [(aminomethyl) phosphonic acid] (AMPA), and glufosinate (GLUF) in human serum. After protein precipitation using acetonitrile and solid-phase extraction, serum samples were derivatized and analyzed by gas chromatography-mass spectrometry (GC-MS). The assay was linear over a concentration range of 3-100.0 microg/ml for GLYP, AMPA, and GLUF. The overall recoveries for the three compounds were >73%. The intra- and inter-day variations were <15%. Precision and accuracy were 6.4-10.6% and 88.2-103.7%, respectively. The validated method was applied to quantify the GLYP and AMPA content in the serum of a GLYP-poisoned patient. In conclusion, the method was successfully applied for the determination of GLYP and its metabolite AMPA in serum obtained from patient of GLYP-poisoning.