Glyphosate poisoning - a case report.

Glyphosate is the most commonly used broad-spectrum, non-selective herbicide in the world. The toxicity is supposed to be due to uncoupling of oxidative phosphorylation and the surfactant polyoxyethylene amine (POEA)- mediated cardiotoxicity. Clinical features of this herbicide poisoning are varied, ranging from asymptomatic to even death. There is no antidote and aggressive supportive therapy is the mainstay of treatment for glyphosate poisoning. We present a 69-year-old female patient with suicidal consumption of around 500 ml of Glycel®. Initially, gastric lavage was done and intravenous fluids were given. Within two hours of presentation, the patient developed respiratory distress needing intubation, hypotension needing vasopressor support, and severe lactic acidosis. She also developed acute respiratory distress syndrome, hypokalemia, hypernatremia, and aspiration pneumonia. Our patient was critically ill with multiple poor prognostic factors, but with timely aggressive supportive management, the patient gradually recovered.

Serial measurement of glyphosate blood concentration in a glyphosate potassium herbicide-intoxicated patient: A case report.

INTRODUCTION: This report describes changes in blood and urine concentrations of glyphosate potassium over time and their correlations with clinical symptoms in a patient with acute glyphosate potassium poisoning. CASE REPORT: A 67-year-old man visited the emergency center after ingesting 250 mL of a glyphosate potassium-based herbicide 5 h before. He was alert but presented with nausea, vomiting, and bradyarrhythmia with atrial fibrillation (tall T waves). Laboratory findings revealed a serum potassium level of 6.52 mEq/L. After treatment with an injection of calcium gluconate, insulin with glucose, bicarbonate, and an enema with polystyrene sulfonate, the patient's serum potassium level normalized and the bradyarrhythmia converted to a normal sinus rhythm. During admission, the blood and urine concentration of glyphosate and urine aminomethylphosphonic acid (AMPA, a glyphosate metabolite) was measured at regular time intervals. The patient's glyphosate blood concentration on admission was 11.48 mg/L, and it had decreased rapidly by 16 h and maintained about 1mgl/L by 70 h after admission. Urine glyphosate and AMPA levels had also decreased rapidly by 6 h after admission. DISCUSSION: Glyphosate potassium poisoning causes hyperkalemia. Blood concentrations of glyphosate were decreased rapidly by 16 h after admission, and urine concentrations were also decreased by 6 h after admission.

Exploring the potential benefit of natural product extracts in paraquat toxicity.

Paraquat dichloride, a herbicide used for weed and grass control, is extremely toxic to humans and animals. The mechanisms of toxicity involve the redox cycling of paraquat resulting in the generation of reactive oxygen species and the depletion of the cellular NADPH. The major cause of death in paraquat poisoning is respiratory failure due to its specific uptake by and oxidative insult to the alveolar epithelial cells and inflammation with subsequent obliterating fibrosis. Paraquat also causes selective degeneration of dopaminergic neurons in the substantia nigra pars compacta, reproducing an important pathological feature of Parkinson disease. Currently, there are no antidotes for the treatment of paraquat poisoning and therapeutic management is mostly supportive and directed towards changing the disposition of the poison. The lack of effective treatments against paraquat poisoning has led to the exploration of novel compounds with antioxidant and/or anti-inflammatory properties. Recently, there is an interest in plant compounds, particularly those used in traditional medicine. Phytochemicals have been highlighted as a possible therapeutic modality for a variety of diseases due to their putative efficacies and safety. In this review, the status of plant extracts and traditional medicines in ameliorating the toxicity of paraquat is discussed.

Paraquat poisoning: Acute lung injury - a missed diagnosis.

Paraquat is a herbicide of great toxicological importance because it is associated with high mortality rates, mainly due to respiratory failure. We report the case of a 28-year-old man admitted to the casualty department at Ngwelezana Hospital, Empangeni, KwaZulu-Natal, South Africa, with a history of vomiting and abdominal pain after ingestion of ~100 mL of an unknown substance, later identified as paraquat, together with an unknown amount of alcohol, in a suicide attempt. He developed respiratory distress associated with lung parenchymal infiltrates that required ventilatory support and later a spontaneous pneumothorax, and died in the intensive care unit. We discuss the importance of a high index of suspicion of paraquat poisoning in rural areas, where paraquat is readily available as a herbicide on farms, in patients with a similar presentation. We further stress the importance of identifying the classic radiological progression after paraquat poisoning, to help avoid a delay in diagnosis if the culprit substance is not known (as happened in our case). Lastly, we look at the importance of avoiding oxygen supplementation, and early administration of immunosuppressive therapy, to improve outcome.

Traditional chinese medicine Xuebijing treatment is associated with decreased mortality risk of patients with moderate paraquat poisoning.

Paraquat poisoning causes multiple organ injury and high mortality due to severe toxicity and lack of effective treatment. Xuebijing (XBJ) injection, a traditional Chinese medicine preparation of five Chinese herbs (Radix Salviae Miltiorrhiae, Rhizoma Chuanxiong, Flos Carthami, Angelica Sinensis and Radix Paeoniae Rubra), has an anti-inflammatory effect and is widely used in the treatment of sepsis. This retrospective study was designed to evaluate the effects of XBJ combined with conventional therapy on mortality risk of patients with acute paraquat poisoning. Out of 68 patients, 27 were treated with conventional therapy (control group) and 41 were treated with intravenous administration of XBJ (100 ml, twice a day, up to 7 days) plus conventional therapy (XBJ group). Vital organ function, survival time within 28 days and adverse events during the treatment were reviewed. Results indicated that XBJ treatment significantly increased median survival time among patients ingesting 10-30 ml of paraquat (P=0.02) compared with the control group. After adjustment for covariates, XBJ treatment was associated significantly with a lower mortality risk (adjusted HR 0.242, 95% CI 0.113 to 0.516, P=0.001) compared with the control group. Additionally, compared with Day 1, on Day 3 the value of PaO2/FiO2 was significantly decreased, and the values of serum alanine aminotransferase, creatinine and troponin T were significantly increased in the control group (all P<0.05), but these values were significant improved in the XBJ group (all P<0.05). Only one patient had skin rash with itch within 30 minutes after injection and no severe adverse events were found in the XBJ group. In conclusion, XBJ treatment is associated with decreased mortality risk of patients with moderate paraquat poisoning, which may be attributed to improved function of vital organs with no severe adverse events.

Effect of intravenous lipid emulsion in patients with acute glyphosate intoxication.

BACKGROUND: Although glyphosate intoxication has been considered minimally toxic in animals, severe toxicity has been observed in humans due to surfactant. We aimed to examine the potential therapeutic effects of intravenous lipid emulsion (ILE) on the patients with acute glyphosate intoxication. METHODS: This study enrolled 64 glyphosate-intoxicated patients with allocation to two groups: those treated with ILE (ILE group, n = 22), and control patients treated with only supportive (conservative) care. Control patients were selected by matching for the amount ingested and time since ingestion. Twenty-two control patients were separately selected from the 42 patients receiving supportive care only. In ILE group, 20% lipid emulsion product was injected intravenously at the rate of 20 mL/h for the patients who ingested less than 100 ml of glyphosate. In the patients who ingested more than 100 ml of glyphosate, the loading dose was 500 ml for 2-3 h according to the status of the patients, followed by a maintenance dose of 1000 ml for the next 24 h. RESULTS: Thirteen patients received high dose of ILE because the ingestion amount was more than 100 ml. None of the ILE group suffered from the complication of hypotension, while approximately 41% of the control group developed the complication. Additionally, arrhythmia was not observed in the ILE group. The incidence of mental change, respiratory failure, and acute kidney injury was similar between the two groups. CONCLUSIONS: ILE administration was associated with lower incidence of hypotension and arrhythmia in patients with acute glyphosate intoxication. ILE administration seems to be an effective treatment modality in patients who ingested sufficient amount of glyphosate herbicide that is expected to bring about significant toxicity.

Xuebijing for paraquat poisoning.

BACKGROUND: At present, there is a lack of effective treatments for paraquat poisoning. Xuebijing injection is a complex traditional Chinese prescription consisting of Flos Carthami, Radix Paeoniae Rubra, Rhizoma Chuanxiong, Radix Salviae Miltiorrhizae and Radix Angelicae Sinensis. Although clinical experience suggests that Xuebijing injection might have potential in the management of paraquat poisoning, there is no conclusion on the effectiveness of this treatment. OBJECTIVES: To assess the effects of Xuebijing injection in patients with paraquat poisoning. SEARCH METHODS: We searched the Cochrane Injuries Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL (EBSCO), ISI Web of Science: Science Citation Index Expanded, ISI Web of Science: Conference Proceedings Citation Index-Science, Chinese bio-medical literature and retrieval system (CBM), China National Knowledge Infrastructure Database (CNKI), and the Traditional Chinese Medicine Database. The search was run on the 29th May 2013. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing Xuebijing injection combined with conventional care against conventional care alone. DATA COLLECTION AND ANALYSIS: Two or three authors independently selected studies, assessed study quality and extracted data. We calculated the mortality risk ratio (RR) and 95% confidence interval (CI). Data on all-cause mortality at the end of follow-up were summarised in a meta-analysis. MAIN RESULTS: We identified two trials including 84 people. Although there were fewer deaths in people treated with Xuebijing injection, meta-analysis showed that it did not provide a statistically significant benefit in reducing all-cause mortality in people with paraquat poisoning as compared to control (RR 0.71; 95% CI 0.48 to 1.04; P = 0.08). AUTHORS' CONCLUSIONS: Based on the findings of two small RCTs, Xuebijing injection did not have a statistically significant benefit on reducing all-cause mortality in people with paraquat poisoning. However, both included studies involved small numbers of participants and were considered to be of poor methodological quality. The results are imprecise and easily compatible with the play of chance. Xuebijing injection may be effective for people with paraquat poisoning; however, this needs to be proven by further high-quality evidence.

Antioxidant effects of selenium on lung injury in paraquat intoxicated rats.

CONTEXT: Paraquat (PQ) causes lethal intoxication by inducing oxidant injury to the lung. Selenium is a cofactor for glutathione peroxidase (GPx), which is one of the major endogenous antioxidant enzymes. OBJECTIVE: To determine whether selenium post-treatment activates GPx, decreases lung injury, and improves survival in PQ intoxicated rats. MATERIALS AND METHODS: Male Spraque-Dawley rats were categorized into three groups: sham (n = 6), PQ (n = 12), and PQ + Se (n = 12). In the PQ and PQ + Se groups, 50 mg/kg of PQ was administered intraperitoneally. After 10 minutes, 60 µg/kg of Se (PQ + Se) or saline (PQ) was administered via the tail vein. Six rats per group were euthanized 6 hours or 24 hours later. Lung tissues were harvested for the measurement of GPx activity, reduced glutathione (GSH), glutathione disulfide (GSSG) and malondialdehyde (MDA) and for histological analysis. Using separated set of rats, survival of PQ (n = 10) and PQ + Se (n = 10) were observed for 72 hours. RESULTS: GPx activity in the PQ group at the 6-hour and 24-hour time points was lower than in the sham group (p < 0.006). GPx activity in the PQ + Se group at the 6-hour and 24-hour time points was higher than in the PQ group at the same time (p < 0.006). GPx activity in the PQ + Se group at 24 hours was higher than at 6-hour time point and also higher than in the sham group (p < 0.006). The GSH/GSSG ratio in the PQ + Se group at 24 hours was lower than that in the sham group (p < 0.006). MDA levels in the PQ group at 6 hours and 24 hours were higher than in the sham group (p < 0.006). MDA levels at 24 hours in the PQ + Se group was lower than in the PQ group (p < 0.006). Acute lung injury (ALI) scores in the PQ group at 6 hours and 24 hours were higher than in the sham group (p < 0.006). ALI scores at 24 hours in the PQ + Se group were lower than in the PQ group. Survival rates did not differ between PQ and PQ + Se (p = 0.869). CONCLUSION: Single dose of selenium post-treatment activates GPx and attenuates lipid peroxidation and lung injury early after paraquat intoxication, but does not improve 72 hours of survival.

Successful treatment of paraquat poisoning by Xuebijing, an injection concocted from multiple Chinese medicinal herbs: a case report.

BACKGROUND AND OBJECTIVES: 1,1'-Dimethyl-4,4'-bipyridinium dichloride (Paraquat) poisoning remains a significant global health problem. Despite noteworthy research and clinical efforts worldwide in the last few decades, little improvement has been made in reducing fatality from Paraquat poisoning with conventional treatment strategies. We herein report a case of successful management of Paraquat poisoning by Xuebijing, a newly developed injection concocted from multiple traditional Chinese medicinal herbs. SETTINGS/LOCATION, SUBJECTS, AND INTERVENTIONS: A 25-year-old male patient was brought to the Emergency Department at the First Affiliated Hospital of Jilin University in Changchun, China approximately 23 hours after ingestion of approximately 50 mL of 20% (w/v) Paraquat in a suicide attempt. On admission, the patient presented with clinical symptoms as well as significantly abnormal results in the liver and kidney function tests that were typical of severe Paraquat poisoning. Following the routine emergency procedures for pesticide poisoning to minimize the poison exposure and relieve the poisoning symptoms, an intravenous drip of Xuebijing together with dexamethasone was given daily to the patient until discharge 10 days after admission. The patient was followed up for 15 months after discharge, during which monthly chest radiography was performed. Treatment outcomes: At the time of discharge, the patient had recovered well: His symptoms of poisoning in the mouth and gastrointestinal tract were all diminishing; his liver and kidney functions were recovering with the major test parameters improving; his chest radiograph was clear, showing no signs of pulmonary fibrosis. During the postdischarge follow-up period, the monthly chest radiographs were all normal. CONCLUSIONS: This case report suggests that Xuebijing has great potential as a novel effective alternative to the conventional management of Paraquat poisoning. This potential needs to be further evaluated in a substantially larger number of clinical cases in the future.

Acute arsenic poisoning in two siblings.

We report a case series of acute arsenic poisoning of 2 siblings, a 4-month-old male infant and his 2-year-old sister. Each child ingested solubilized inorganic arsenic from an outdated pesticide that was misidentified as spring water. The 4-month-old child ingested a dose of arsenic that was lethal despite extraordinary attempts at arsenic removal, including chelation therapy, extracorporeal membrane oxygenation, exchange transfusion, and hemodialysis. The 2-year-old fared well with conventional therapy.

Pulmonary function and exercise-associated changes with chronic low-level paraquat exposure.

The present study was undertaken to test the hypothesis that chronic, low-level paraquat exposure causes restrictive lung function with gas transfer impairment. Three hundred thirty-eight Costa Rican farm workers from banana, coffee, and palm oil farms completed a questionnaire, spirometry, and a test of single-breath carbon monoxide diffusing capacity. Subjects 40 years of age or older, without other medical risk factors, completed maximal cardiopulmonary exercise tests. Most (66.6%) were paraquat handlers; 24.8% of handlers and 27.3% of nonhandlers reported current cigarette smoking. In linear regression models, cumulative paraquat exposure was not an independent predictor of VA, carbon monoxide diffusing capacity, peak oxygen uptake, FVC, or oxygen pulse peak. However, the ventilatory equivalent for CO(2), although within normal range, was significantly higher with increased cumulative paraquat exposure. Oxygen desaturation greater than 5% from rest to peak exercise had an odds ratio of 1.7 (95% confidence interval = 0.9-3.0) with the cumulative paraquat exposure index in models adjusted for age, weight, and smoking status. The association of paraquat exposure with ventilatory equivalent and oxygen desaturation suggests that paraquat may be associated with subclinical gas exchange abnormalities, but overall these findings are consistent with no clinically significant increases in interstitial thickening or restrictive lung disease among this population.

Determination of glyphosate in biological fluids by 1H and 31P NMR spectroscopy.

Identification of glyphosate in four cases of poisoning, using nuclear magnetic resonance spectroscopy of biological fluids is reported. It has been performed by using a combination of 1H and 31P NMR analyses. Characterization of the N-(phosphonomethyl) glycine herbicide was achieved by chemical shift considerations and coupling constant patterns: CH2-(P) presents specific resonance at 3.12 ppm and appears as a doublet with a H-P characteristic coupling constant of 12.3 Hz. Moreover, resonances due to isopropylamine were present, confirming the ingestion of the considered trade formulation. After a calibration step, quantitation was performed by 1H and 31P NMR spectroscopy. The benefit and reliability of NMR investigations of biological fluids are discussed, particularly when the clinical picture is quite confusing.

The chelating treatment is not useful in human's intoxication with acute herbicidal organic arsenic.

The clinical manifestations of acute organic arsenic intoxication in humans have seldom been described and the associated treatment has been thought to be the same as that of acute inorganic arsenic intoxication. We have studied a collection of patients from 1996 to 2001 who called the Poison Control Center of Kaohsiung Medical University Hospital asking for information regarding acute organic arsenic intoxication. The 17 patients ranged in age from 23 to 64 years old, with 5 females and 12 males. The cause of arsenic ingestion was attempted suicide. Abdominal pain and vomiting were the main symptoms. There were no differences in results between patients treated with and those treated without chelating agents. We therefore believe that the results of acute organic intoxication are not same as acute inorganic intoxication and it is unnecessary to use chelating agents in such conditions.

Suspected herbicide toxicosis in a dog.

An 8-year-old 38-kg spayed female Golden Retriever was admitted for vomiting, signs of abdominal pain on palpation, ataxia, anorexia, and generalized weakness of 2 days' duration. Ten hours prior to onset of clinical signs, the dog was found standing in and drinking from large pools of an accidentally spilled herbicide that contained an octanoic acid ester of bromoxynil (3,5-dibromo-4-hydroxybenzonitrile) and an isooctyl ester of (2-methyl-4-chloro) phenoxyacetic acid (MCPA). Appendicular muscles were firm on palpation and persistent muscle contraction (myotonia > 1 minute duration) was found on muscle percussion, using a reflex hammer. Electrical activity indicative of myotonia was identified on electromyographic evaluation. With supportive treatment, the dog eventually recovered from suspected MCPA toxicosis. Although rare, MCPA toxicosis should be considered as a cause of acquired myotonia in dogs.

Bialaphos poisoning with apnea and metabolic acidosis.

A 64-year-old man with ethanol intoxication, ingested a bottle of Herbiace (100 ml, 32 w/v% of bialaphos, CAS #35597-43-4, Meiji Seika Kaisha, Tokyo, Japan). He had severe metabolic acidosis and was treated with infusions of sodium bicarbonate and furosemide, plus gastric lavage and enema. The metabolic acidosis improved 15 hours after treatment but nystagmus, apnea and convulsions were progressive. Although his sensorium was clear, spontaneous respirations were not observed for 64 hours. The electroencephalographic findings of atypical triphasic waves and slow waves suggest a unique response to bialaphos poisoning. His clinical course indicates that the management of apnea is critically important to recovery from bialaphos poisoning.

Mortality study of Canadian male farm operators: non-Hodgkin's lymphoma mortality and agricultural practices in Saskatchewan.

A cohort study of the mortality experience (1971-1985) of male Saskatchewan farmers has been conducted. This study involved linkage of records of the almost 70,000 male farmers identified on the 1971 Census of Agriculture and the corresponding Census of Population to mortality records. Pesticide exposure indices for individual farm operators for the year 1970 were derived from the 1971 Census of Agriculture records. Although the cohort as a whole had no excess mortality for any specific causes of death, including non-Hodgkin's lymphoma, significant dose-response relationships were noted between risk of non-Hodgkin's lymphoma and acres sprayed in 1970 with herbicides, as well as with dollars spent on fuel and oil for farm purposes in 1970. Using Poisson regression modeling, we found that relative risks for the highest level of herbicide use (greater than or equal to 250 acres sprayed) and fuel purchased in 1970 (greater than or equal to $900) on farms less than 1,000 acres total area were 2.2 (95% confidence interval = 1.0-4.6) and 2.3 (95% confidence interval = 1.1-4.7), respectively.

[Anabolic effects of sodium selenite, vitamin E and retabolil in experimental hypotrophy induced by a pesticide]. / Anabolicheskii éffekt selenita natriia, vitamina E, retabolila na fone éksperimental'noi gipotrofii, vyzvannoi pestitsidom.

Forty Chinchilla rabbits of both sexes were examined for changes in some parameters of protein, lipid and trace elements metabolism (total protein, protein fractions, urea, residual nitrogen in blood serum, lipids, total cholesterol, free cholesterol, diglycerides, phospholipids, triglycerides, free fatty acids and the trace elements selenium, iron, zinc and so forth in the liver) during the animals' poisoning with the defoliant magnesium chlorate. A study was made of the effect on these changes of the administration for 3 weeks of sodium selenite (15 micrograms/kg), vitamin E (25 mg/kg) and retabolil (2 mg/kg once a week). It has been established that the combined administration of these agents removes and prevents the changes in protein, lipid and trace elements (hypoproteinemia, dysproteinemia and impairment of the nitrous balance) and lipid metabolism because of the animals' poisoning with magnesium chlorate.

Rapid determination of glyphosate in postmortem specimens using 31P NMR.

Glyphosate was quantified, using 31P NMR, in postmortem blood, liver, and urine specimens taken from two suicide victims. Apart from addition of D2O to give an NMR lock signal, the only pretreatment required of any of the specimens was an enzymic digestion of the liver. Glyphosate was confirmed by its characteristic 31P chemical shift and proton spin coupling and by a downfield shift on addition of NH4OH. Quantitation can be achieved either by comparison with an external standard or by spiking the specimen with glyphosate. Levels of 1 mg/mL could be detected in less than a minute.