PURPOSE: Organophosphorus (OP) pesticides are differentiated into 3 groups according to their toxicity. The differences in chemical composition of each OP pesticide determines its toxicokinetic characteristics. There are few human studies that address the clinical results of poisoning according to the OP pesticide. In this study, we aimed to examine the differences in clinical features among self-poisoning from 4 highly toxic OP pesticides. METHODS: The 4 kinds of OP poisonings included 17 cases of Dichlorvos, 17 cases of EPN, 17 cases of methidathion, and 13 cases of phosphamidon. We set primary outcomes as GCS, atropine dose required, duration of patient need for atropine, proportion who required ventilation, duration on ventilation, and the interval from ingestion to ventilation. Secondary outcomes were the proportion of OP-induced delayed neuropathy, duration of ICU stay, and proportion who required additional infusion of pralidoxime chloride (PAM). RESULTS: The EPN group required the largest amount of atropine, the longest duration of atropine use, the longest duration for support of mechanical ventilation, and the longest ICU stay. Furthermore the proportion who required additional PAM and neuropathy were in the EPN group. However, the EPN group had the longest interval from ingestion to ventilatory support. Meanwhile, the Dichlorvos group exhibited comparatively mild clinical features. CONCLUSION: Throughout this study, we found different clinical features to each OP pesticide poisoning. It can be explained by differences in chemical composition, which determined the speed of aging, the reactivation rate of OPenzyme, the metabolism, the fat solubility, and other characteristics of the pesticides.
Aging ; Atropine ; Dichlorvos ; Eating ; Humans ; Organophosphorus Compounds ; Organothiophosphorus Compounds ; Pesticides ; Phosphamidon ; Pralidoxime Compounds ; Respiration, Artificial ; Solubility ; Ventilation

Organophosphate fungicides include edifenphos, iprobenfos and tolclofos-methyl. Edifenphos inhibits cell wall synthesis by reduction in chitin synthase activity and inhibits the action of acetylcholinesterase. Thus, exposure to this chemical results in excessive salivation, lacrimation, urination, defecation, gastrointestinal motility and emesis symptoms, just like other organophosphate insecticides. Although edifenphos is an organophosphate fungicide, it is the only agricultural chemical which inhibits the action of pralidoxime and atropine, an activity which in turn, inhibits treatment. Thus, we have to treat these cases as soon as possible with atropine and pralidoxime, using the same approach as used for exposure to other organophosphate insecticides. In this report we evaluate the results of treatment of 4 patients who were intoxicated by fungicides (3 cases with edifenphos and 1 case with iprobenfos).
Acetylcholinesterase ; Atropine ; Cell Wall ; Chitin Synthase ; Defecation ; Gastrointestinal Motility ; Humans ; Insecticides ; Organothiophosphorus Compounds ; Pralidoxime Compounds ; Salivation ; Urination ; Vomiting

OBJECTIVETo investigate the activity of ChE in rats poisoned by dimehypo and then treated with pralidoxime methylchloride or unithiol.

METHODRats were divided into control group (dimehypo); intervention groups [dimehypo plus pralidoxime methylchloride or dimehypo plus unithiol (sodium dimercaptopropanesulphonate)]. Rats were dosed with 4 different doses of dimehypo: 1/16, 1/8, 1/4 and 1/2 of LD50 respectively(the LD50 of dimehypo is 342 mg/kg). After being poisoned with dimehypo orally, rats were immediately injected intramuscularly with pralidoxime methylchloride or unithiol. The activity of ChE in blood was detected before and 1/2, 1, 2, 4 and 24 h after poisoning in dimehypo and intervention groups.

RESULTThe ChE activity of four dose subgroups at 1 h after poisoning were (1.04 +/- 0.21), (0.84 +/- 0.12), (0.71 +/- 0.12), (0.66 +/- 0.07) U/ml respectively; the ChE activity of pralidoxime methylchloride intervention groups were (1.01 +/- 0.18), (1.17 +/- 0.11), (1.01 +/- 0.04), (1.03 +/- 0.12) U/ml respectively; and the ChE activity of unithiol intervention groups were (1.15 +/- 0.15), (1.26 +/- 0.27), (1.08 +/- 0.08), (1.04 +/- 0.12) U/ml respectively. The inhibited ChE in blood was recovered by either treatment with pyraldoxime methylchloride or unithiol. These two drugs had similar effects of recovering the activity of ChE(P > 0.05), but at higher doses(1/4 and 1/2 of LD50) the effects of both were not so good.

CONCLUSIONPralidoxime methylchloride and unithiol could partly recover the activity of ChE inhibited by dimehypo.

Animals ; Antidotes ; pharmacology ; Cholinesterase Inhibitors ; poisoning ; Cholinesterases ; blood ; Dose-Response Relationship, Drug ; Insecticides ; poisoning ; Pralidoxime Compounds ; pharmacology ; Rats ; Unithiol ; pharmacology

OBJECTIVETo observe the effect of sodium bicarbonate combined with ulinastatin on cholinesterase activity for patients with acute phoxim pesticide poisoning.

METHODSA total of 67 eligible patients with acute phoxim pesticide poisoning, Who were admitted to the emeryency department of hospital from March 2011 to February 2014, Acording to different treatments au patients were randomly divided into the conventional treatment group (n=34) and the sodium bicarbonate+ulinastatin group (n=35) . The conventional treatment group were given thorough gastric lavage with water, the sodium bicarbonate + ulinastatin group were given gastric lavage with 2% sodium bicarbonate solution. Both groups were given such treatments as catharsis, administration of oxygen, fluid infusion, diuresis, and antidotes such as atropine and pralidoxime methylchloride. On the basis of comprehensive treatment, people in the sodium bicarbonate+ulinastatin group were given 5% sodium bicarbonate injection and ulinastatin. The clinical effect of the two groups were compared.

RESULTSThe serum cholinesterase activity of the sodium bicarbonate+ulinastatin group was significantly higher than the conventional treatment group from the 5th day, and the difference was statistically significant (P<0.05) . The total atropine dosage, total pralidoxime methylchloride dosage and hospitalization days were better than the conventional treatment group, and the differences were statistically significant (P<0.05) . The difference in the time of atropinization between the two groups was not statistically significant (P>0.05) . The results of arterial blood pH, HCO3- of the sodium bicarbonate + ulinastatin group were higher than the conventional treatment group, and the difference of HCO3- at the 10th day was statistically significant (P<0.05) .

CONCLUSIONSSodium bicarbonate combined with ulinastatin can improve the therapeutic effect and reduce complications in the treatment of acute phoxim pesticide poisoning, and have beneficial effects on the recovery of cholinesterase activity.

Atropine ; therapeutic use ; Cholinesterases ; metabolism ; Glycoproteins ; therapeutic use ; Humans ; Organophosphate Poisoning ; drug therapy ; Organothiophosphorus Compounds ; poisoning ; Pesticides ; poisoning ; Pralidoxime Compounds ; therapeutic use ; Sodium Bicarbonate ; therapeutic use

Purpose: Dichlorvos has been in widespread use as an organophosphate (OP) insecticide compound. The purpose of this study was to access the epidemiology and clinical features of dichlorvos in Korea. Methods: This was a 38 multi-center prospective study of dichlorvos poisoning using surveys, a structural reporting system and review of hospital records from August 2005 to July 2006. A total of 54 patients with acute dichlorvos poisoning on a national basis were enrolled. We analyzed the epidemiologic characteristics and clinical manifestations of dichlorvos poisoning. In addition, the clinical features of dichlorvos poisoning were compared with others OP compounds. Results: During the study period, compounds involving pure OP poisoning were dichlorvos (22.7%), methidathion (8.4%), and phosphamidon (6.7%). In acute dichlorvos poisoning, all ingestion routes were oral. Intentional poisoning involved 74.1% of cases. The common initial complaints involved gastrointestinal (64.8%), systemic (61.1%), central or peripheral nervous system (53.7%), and respiratory symptoms (50.0%). The median arrival time to hospital after dichlorvos poisoning was 2.6 hours and mean hospitalization duration was 7.1 days. 2-PAM was administered in 35 patients in mean doses of 6.3 g/day intravenously. Atropine was administered in 30 patients with a mean dose of 62.8 mg/day (maximal 240 mg/day). Overall mortality rate for dichlorvos poisonings were 14.8% (8/54). Immediate causes for death included sudden cardiac arrest or ventricular dysrhythmias (50%), multi-organ failure (25%), acute renal failure (12.5%), and unknown causes (12.5%). Conclusion: When compared to previous reports, dichlorvos poisoning displayed relatively moderate severity. The presence of a lower GCS score, altered mental status, serious dysrhythmias, systemic shock, acute renal failure, and respiratory complications upon presentation were associated with a more serious and fatal poisoning.
Acute Kidney Injury ; Atropine ; Death, Sudden, Cardiac ; Dichlorvos ; Eating ; Hospital Records ; Hospitalization ; Humans ; Korea ; Organothiophosphorus Compounds ; Peripheral Nervous System ; Phosphamidon ; Pralidoxime Compounds ; Prospective Studies ; Shock

OBJECTIVETo study the effects of improving the neuromuscular transmission (NMT), "non-AChE-reactivating effects", by oximes in treating acute isocarbophos poisoning.

METHODSThe effect of pralidoxime chloride(PAM-Cl) on the neuromuscular transmission(NMT) in rats exposed to isocarbophos was studied by using the stimulation single fiber electromyography (SSFEMG) to determine the single fiber action potential.

RESULTSAfter the rats exposed to isocarbophos were treated by PAM-Cl, the mean consecutive difference(MCD) value [(25.99 +/- 5.84) microsecond] of single fiber action potential was significantly lower than that before PAM-Cl treatment [(33.21 +/- 4.09) microsecond, (P < 0.01)], but no AChE reactivation in blood and gastrocnemius was observed.

CONCLUSIONPAM-Cl has "non-AChE-reactivating effects", it could markedly improve isocarbophos-induced NMT block of gastrocnemius.

Acute Disease ; Animals ; Antidotes ; pharmacology ; Cholinesterase Inhibitors ; poisoning ; Insecticides ; poisoning ; Malathion ; poisoning ; Neuromuscular Junction ; drug effects ; physiology ; Pralidoxime Compounds ; pharmacology ; Rats ; Synaptic Transmission ; drug effects

Adult ; Antidotes ; administration & dosage ; therapeutic use ; Female ; Humans ; Insecticides ; poisoning ; Parathion ; poisoning ; Poisoning ; drug therapy ; Pralidoxime Compounds ; administration & dosage ; therapeutic use ; Treatment Outcome

PURPOSE: The optimal dose of oximes for use in the treatment of organophosphorus pesticide poisoning has not been conclusively established. In this retrospective study, we assessed the effectiveness of the use of high-dose pralidoxime infusion in treating organophosphorus pesticide poisoning. METHODS: From January 1998 to December 2009, 71 patients visited the hospital Emergency Department (ED) as a result of organophosphate pesticide intoxication. All of these patients received an initial bolus of 2 g of pralidoxime as the first step of treatment. Patients who then received continuous infusion of pralidoxime at a dose of 500 mg/hr were entered into study group 1 (low dose), and those treated by continuous infusion of pralidoxime at a dose of 1000 mg/hr were entered into study group 2 (high-dose). Plasma cholinesterase activities for each patient were evaluated at ED arrival and re-evaluated 24 hours after pralidoxime infusion. The effectiveness of the two treatment modalities was gauged by comparing the required duration of mechanical ventilation, time spent in the intensive care unit (ICU) and total time spent in the hospital. RESULTS: The mean duration of mechanical ventilation was 9.98+/-6.47 days for group 1 and 4.39+/-6.44 days for group 2. The respective mean duration of time spent in ICU and the total number of days in the hospital were 16.38+/-18.84 days and 21.87+/-20.16 days for group 1, and 7.83+/-9.99 days and 11.71+/-13.53 days for group 2. High-dose pralidoxime treatment was associated with shorter required durations for mechanical ventilation, ICU and hospital stay. In addition, plasma cholinesterase reactivation rates were higher for those patients receiving high-dose pralidoxime treatment. CONCLUSION: The results suggest that high-dose pralidoxime treatment has greater efficacy for patients suffering from organophosphorus pesticide poisoning.
Cholinesterases ; Emergencies ; Humans ; Intensive Care Units ; Length of Stay ; Organophosphates ; Oximes ; Plasma ; Pralidoxime Compounds ; Resin Cements ; Respiration, Artificial ; Retrospective Studies ; Stress, Psychological

Acute organophosphate (OP) poisoning produces cholinergic symptoms resulting from the inhibition of cholinesterase, and the overstimulation of muscarinic and nicotinic receptors in the synapses. The dominant clinical features of acute cholinergic toxicity include bradycardia, miosis, lacrimation, salivation, bronchorrhea, and bronchospasm. All symptomatic patients should receive therapy with oxygen, atropine, and pralidoxime. Atropine works as a physiologic antidote by competitively occupying muscarinic receptor sites, reducing the effects of excessive acetylcholine. Atropine should be immediately administered, and the dose can be titrated according to the severity of OP poisoning. A large dose may be necessary to overcome the excessive cholinergic state in case of severe poisoning. Pralidoxime is a biochemical antidote that reactivates acetylcholinesterase by removing OP from it. It is effective in treating both muscarinic and nicotinic symptoms. After some period of time, the acetylcholinesterase-OP compound undergoes a conformational change, known as aging, which renders the enzyme irreversibly resistant to reactivation by a pralidoxime. There has been a great deal of controversy over the effectiveness of pralidoxime in acute OP poisoning. However, it may be beneficial to administer pralidoxime for a sufficient period in case of severe poisoning with a large quantity of OP, which is common in Korea.
Acetylcholine ; Acetylcholinesterase ; Aging ; Atropine* ; Bradycardia ; Bronchial Spasm ; Cholinesterases ; Humans ; Korea ; Miosis ; Oxygen ; Poisoning* ; Pralidoxime Compounds ; Receptors, Muscarinic ; Receptors, Nicotinic ; Salivation ; Synapses

OBJECTIVEInhibition of acetylcholinesterase (AChE) in human brain caused by phoxim or phoxim oxon, their reactivation with oxime and aging of phosphorylated AChE were studied and compared in vitro.

METHODSMicro-colorispectrophotometric assay was used to determine the activity of AChE.

RESULTSThe pI(50) of inhibition of AChE in human brain by phoxim and phoxim oxon were 5.39 and 5.77, respectively, whereas the pI(90) were 4.60 and 5.00, respectively. The reactivation rate of 0.1 mmol/L of pralidoxime (2-PAM), obidoxime (LüH(6)), trimedoxime (TMB-4) and pyramidoxime (HI-6) for phoxim-inhibited AChE in human brain was 65%, 97%, 91% and 56%, respectively, and their reactivation rate for phoxim oxon-inhibited AChE in human brain was 97%, 87%, 99% and 89%, respectively. The optimal reactivator for phoxim and phoxim oxon-inhibited AChEs was LüH(6) and TMB-4, respectively. The half aging time of phoxim and phoxim oxon inhibited phosphorylated AChEs were 39 and 28 hours, respectively, and the 99% aging time were 256 and 186 hours, respectively.

CONCLUSIONSLüH(6) or TMB-4 should be used at the earlier as possible after poisoning with phoxim and phoxim oxon, and the reactivator should be consecutively used for more than seven days, even after their acute symptoms have been well controlled.

Acetylcholinesterase ; metabolism ; Brain ; drug effects ; enzymology ; Cholinesterase Inhibitors ; pharmacology ; Cholinesterase Reactivators ; pharmacology ; Enzyme Stability ; Humans ; In Vitro Techniques ; Obidoxime Chloride ; pharmacology ; Organothiophosphorus Compounds ; pharmacology ; Oximes ; pharmacology ; Paraoxon ; pharmacology ; Pralidoxime Compounds ; pharmacology ; Time Factors ; Trimedoxime ; pharmacology