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PloS One 2018Deliberate self-poisoning (DSP) using organophosphorus (OP) insecticides are a common clinical problem in Asia. OPs inhibit acetylcholine esterase (AChE), leading to...
BACKGROUND
Deliberate self-poisoning (DSP) using organophosphorus (OP) insecticides are a common clinical problem in Asia. OPs inhibit acetylcholine esterase (AChE), leading to over-activity of muscarinic and nicotinic cholinergic circuits. Intermediate syndrome (IMS) is mediated via prolonged nicotinic receptor stimulation at the neuromuscular junction and its onset is between 24-96 hours post ingestion. The aims of the present study were 1) to investigate whether neuromuscular junction dysfunction within the first 24 hours following exposure, quantified by jitter in single fibre electromyography (SfEMG), can predict IMS, and 2) to compare the changes in SfEMG jitter over the course of the illness among patients who developed IMS (IMS+) and those who did not (IMS-).
METHODS AND FINDINGS
We conducted a prospective cohort study in a tertiary care hospital in Sri Lanka on 120 patients admitted between September 2014 and August 2016 following DSP by OP insecticides viz., profenofos 53, phenthoate 17, diazinon 13, chlorpyrifos 5, others 12, unknown 20. SfEMG was performed every second day during hospitalization. Exposure was confirmed based on the history and red blood cell AChE assays. IMS was diagnosed in patients who demonstrated at least three out of four of the standard IMS criteria: proximal muscle weakness, bulbar muscle weakness, neck muscle weakness, respiratory paralysis between 24-96 hours post ingestion. Respiratory failure requiring intubation occurred in 73 out of 120 patients; 64 of these were clinically diagnosed with IMS. Of the 120 patients, 96 had repeated SfEMG testing, 67 of them being tested within the first 24 hours. Prolonged jitter (>33.4μs) within the first 24 hours was associated with greatly increased risk of IMS (odds ratio = 8.9, 95% confidence intervals = 2.4-29.6, p = 0.0003; sensitivity 86%, specificity 58%). The differences in jitter between IMS+ and IMS- patients remained significant for 72 hours and increased jitter was observed in some patients for up to 216 hours. For intubated patients, the median time for jitter to normalize and median time to extubate were similar, and the two variables had a moderate positive correlation (r = 0.49, P = 0.001).
CONCLUSIONS
Prolonged jitter recorded with SfEMG <24 hours of ingestion of an OP strongly correlates with subsequent occurrence of IMS. The time course of electrophysiological recovery of the NMJ was similar to the time course of respiratory recovery in IMS patients.
Topics: Acetylcholinesterase; Electromyography; Erythrocytes; Humans; Insecticides; Male; Neuromuscular Junction Diseases; Organophosphate Poisoning; Organophosphorus Compounds; Prospective Studies
PubMed: 30261032
DOI: 10.1371/journal.pone.0203596 -
Clinical Toxicology (Philadelphia, Pa.) May 2020Current therapeutic options for organophosphorus (OP) insecticide self-poisoning including atropine and oximes are inadequate and case fatality may exceed 20%. An OP...
Current therapeutic options for organophosphorus (OP) insecticide self-poisoning including atropine and oximes are inadequate and case fatality may exceed 20%. An OP hydrolase enzyme, OpdA, has been used for environmental cleansing of OP insecticides and prevented death in rat and non-human primate models of OP insecticide poisoning if given very quickly after exposure. We here tested OpdA's ability to break down OP insecticides in human serum and in clinically relevant minipig models of OP insecticide poisoning. Human serum was spiked with seven diverse WHO Class II OP insecticides (chlorpyrifos, quinalphos, diazinon, dimethoate, fenthion, phenthoate, and profenofos) and the effect of OpdA on degradation measured. The pharmacodynamic and clinical effects of OpdA treatment were studied in Gottingen minipigs orally poisoned with agricultural formulations of dimethoate EC40 or methyl parathion EC60; pharmacodynamic effects were also assessed in profenofos EC50-poisoned pigs. OpdA effectively hydrolysed OP insecticides in human serum, with rates varying from 856 (SD 44) down to 0.107 (SD 0.01) moles of substrate hydrolysed/mole of enzyme/sec (k) for quinalphos and phenthoate, respectively, although at rates 2-3 log orders less than found in buffered solution. It showed clinical benefit in minipig models, reducing the dose of noradrenaline required to sustain an adequate mean arterial pressure after dimethoate (mean 0.149 [SD 0.10] μg/kg/h vs. 1.07 [SD 0.77] μg/kg/h, < .0001) and methyl parathion (mean 0.077 [SD 0.08] μg/kg/h vs. 0.707 [SD 0.49] μg/kg/h, < .0001) poisoning. OpdA reduced blood OP insecticide concentration and acetylcholinesterase inhibition after poisoning by dimethoate, methyl parathion, and profenofos insecticides. incubation of OpdA in human serum showed hydrolysis of diverse OP insecticides, although at lower rates than found in buffer solutions. This activity results in clinical and pharmacodynamic efficacy against several OP insecticides. These results support the testing of OpdA in further animal models before considering human trials to determine whether it may become an urgently required novel therapeutic agent for OP insecticide self-poisoning.
Topics: Animals; Aryldialkylphosphatase; Disease Models, Animal; Humans; Insecticides; Methyl Parathion; Organophosphate Poisoning; Swine; Swine, Miniature
PubMed: 31452424
DOI: 10.1080/15563650.2019.1655149 -
Basic & Clinical Pharmacology &... Feb 2022Self-poisoning with organophosphorus (OP) insecticides is an important means of global self-harm. The insecticides are formulated with solvents that may also contribute...
Self-poisoning with organophosphorus (OP) insecticides is an important means of global self-harm. The insecticides are formulated with solvents that may also contribute to toxicity. We set up a study to detect changes in osmolal and anion gaps following ingestion of OP insecticides. We recruited consecutive patients admitted to a Teaching Hospital, Sri Lanka, with a history of OP self-poisoning. The osmolal and anion gaps were calculated on admission and at 4, 24 and 72 h post-ingestion together with ethanol concentration. Forty-nine patients were recruited (28 profenofos, 10 diazinon, one coumaphos, one chlorpyrifos, one phenthoate and eight unknown OP). Only modest increases in osmolal and anion gaps were noted. Small rises in osmolal gap above the upper limit of normal were noted in 16/49 (32.7%) of all cases, 9/28 (32.1%) profenofos cases and 4/10 (40.0%) diazinon cases. The anion gap was raised in 24/49 (49.0%) of all cases, 15/28 (53.6%) profenofos cases and 5/10 (50.0%) diazinon cases. We observed a trend for a fall in osmolal gap during the first 24 h, followed by an increase up to 72 h. There was no correlation between the anion gap and serum lactate concentration, indicating that a lactic acidosis was not responsible for the anion gap. Formate, which could have explained the increased gap, was not detected in any of the samples; ketoacids (beta-hydroxybutyrate and acetoacetate) were not measured. This pilot study found that profenofos and diazinon poisoning caused only modest increases in the osmolal and anion gaps in a minority of cases.
Topics: Acid-Base Equilibrium; Adult; Diazinon; Female; Hospitals, Teaching; Humans; Insecticides; Male; Middle Aged; Organophosphate Poisoning; Organothiophosphates; Osmolar Concentration; Pilot Projects; Self-Injurious Behavior; Solvents; Sri Lanka
PubMed: 34796663
DOI: 10.1111/bcpt.13686 -
Environmental Health and Preventive... Jun 2018Acetylcholinesterase inhibitor insecticides (AChEIIs) were used extensively in the agrarian region of Anuradhapura for the past few decades. As a result, the region...
BACKGROUND
Acetylcholinesterase inhibitor insecticides (AChEIIs) were used extensively in the agrarian region of Anuradhapura for the past few decades. As a result, the region faced a heightened risk of toxicity. Carbaryl, carbofuran, chlorpyrifos, dimethoate, and fenthion were the five hazardous AChEIIs banned from Anuradhapura in 2014. Assessment of post-ban trends in acute poisoning will reveal the impact of the ban. Data on availability and sales of remaining AChEIIs will guide towards preventive measures against related toxicities.
METHODS
Cross-sectional surveys were conducted at Anuradhapura district of Sri Lanka. Details related to acute AChEII poisoning were sorted from the Teaching Hospital Anuradhapura. Main insecticide vendors in Anuradhapura were surveyed to find information on availability and sales of AChEIIs. Chi-square for goodness of fit was performed for trends in acute poisoning and sales.
RESULTS
Hospital admissions related to acute AChEII poisoning have declined from 554 in 2013 to 272 in 2017. Deaths related to acute AChEII poisoning have declined from 27 in 2013 to 13 in 2017. Sales of all five banned AChEIIs had reduced by 100%. Sales of the remaining AChEIIs were declining, except for acephate, phenthoate, and profenofos. However, one of the top selling, most frequently abused carbosulfan, had the highest risk of toxicity. Chi-square for goodness of fit showed a significance (P < 0.001) between the trends of hospital admissions for acute AChEII poisoning and the sales related to AChEIIs.
CONCLUSIONS
Hospital admissions related to acute poisoning was declining along with the overall sales of remaining AChEIIs, during the post-AChEII ban period. Nevertheless, future vigilance is needed on the remaining AChEIIs to predict and prevent related toxicities.
Topics: Agriculture; Cholinesterase Inhibitors; Commerce; Cross-Sectional Studies; Developing Countries; Female; Government Regulation; Health Policy; Hospitalization; Humans; Incidence; Insecticides; Male; Poisoning; Risk Factors; Sri Lanka
PubMed: 29945568
DOI: 10.1186/s12199-018-0716-1