pralidoxime and Poisoning

Acute organophosphorus pesticide poisoning causes tens of thousands of deaths each year across the developing world. Standard treatment involves administration of intravenous atropine and oxime to counter acetylcholinesterase inhibition at the synapse. The usefulness of oximes, such as pralidoxime and obidoxime, has been challenged over the past 20 years by physicians in many parts of the world, who have failed to see benefit in their clinical practice.. To find the clinical trial evidence for oximes producing clinical benefit in acute organophosphorus pesticide-poisoned patients.. We carried out a systematic search to find randomised clinical trials (RCTs) of oximes in acute organophosphorus pesticide poisoning, using MEDLINE, EMBASE and Cochrane databases. All articles with the text words 'organophosphate' or 'oxime' together with 'poisoning' or 'overdose' were examined. (Search last updated November 2003.). Articles that could possibly be randomised clinical trials were retrieved to determine if this was the case.. The published methodology of the possible RCTs located is not clear. One was found in abstract form only and two other published trials also had many gaps in the published methodology. We have attempted to contact the principal authors of all three trials but have been unable to obtain further information.. Two RCTs have been published, involving 182 patients treated with pralidoxime. These trials did not find benefit. However, the studies did not take into account a number of issues important for outcome and the methodology is unclear. Therefore, a generalised statement on effectiveness cannot be supported by the published results. In particular, characteristics at baseline were not evenly balanced, the dose of oxime was much lower than recommended in guidelines, there were substantial delays to treatment, and the type of organophosphate was not taken into account. The abstract of the third trial, a small possible RCT, is uninterpretable without further data.. Current evidence is insufficient to indicate whether oximes are harmful or beneficial in the management of acute organophosphorus pesticide poisoning. A much larger RCT is required to compare the World Health Organization recommended pralidoxime regimen (>30 mg/kg bolus followed by >8 mg/kg/hr infusion) with placebo. There are many theoretical and practical reasons why oximes may not be useful to patients with overwhelming self-poisoning. Such a study will need to be designed with pre-defined sub-group analysis to allow identification of patient sub-groups that may benefit from oximes.

Topics: Antidotes; Cholinesterase Reactivators; Humans; Organophosphate Poisoning; Oximes; Pesticides; Poisoning; Pralidoxime Compounds; Randomized Controlled Trials as Topic

Organophosphates may cause serious life-threatening conditions, such as an initial acute cholinergic crisis and intermediate syndrome. Each of these conditions has a potential for respiratory failure requiring ventilatory support. For this reason, it is very important to recognize them early, especially to institute appropriate management. The diagnosis of organophosphate poisoning is based essentially on a clinical assessment, followed by laboratory examinations. Sometimes the diagnosis may be difficult, as in case 1, identified initially as brainstem stroke. However, if neurological syndromes associated with organophosphate poisoning are well known, they can easily be distinguished from other conditions that resemble them. Two cases displayed the symptoms and signs of intermediate syndrome; however, one case (no. 2) did not have severe poisoning on admission but needed artificial ventilation. Each case recovered completely from organophosphate poisoning as a result of early diagnosis and appropriate therapy. Therefore, we would like to describe the clinical and laboratory features of these syndromes, observed in three interesting cases, and to emphasize the importance of early and accurate diagnosis for the appropriate management of acute organophosphate poisoning.

Topics: Acetylcholinesterase; Acute Disease; Adult; Aged; Antidotes; Atropine; Emergency Medicine; Female; Humans; Insecticides; Male; Organophosphorus Compounds; Poisoning; Pralidoxime Compounds; Treatment Outcome

Topics: Acetylcholinesterase; Adult; Cholinesterase Reactivators; Humans; Male; Nervous System; Organophosphate Poisoning; Organophosphorus Compounds; Peripheral Nervous System; Poisoning; Pralidoxime Compounds; Sarin

Aldicarb is the most potent of the commercially available carbamate pesticides and is an unusual source of acute human poisonings. We present the case of a 43-year-old man exposed to aldicarb who developed severe cholinergic symptoms and progressive weakness requiring intubation for 5 days. Both his red blood cell cholinesterase and plasma pseudocholinesterase levels were depressed for a minimum of 44 hours. He demonstrated neuromuscular improvement concurrent with pralidoxime administration. The pertinent medical literature on aldicarb poisoning is reviewed.

Topics: Adult; Aldicarb; Cholinesterase Reactivators; Cholinesterases; Humans; Male; Poisoning; Pralidoxime Compounds

Organophosphate toxicity can be fatal. It accounts for almost 40 percent of all insecticide- and pesticide-related illnesses reported by the American Association of Poison Control Centers. Skin contamination is the most important route of occupational exposure. Carbamate insecticides exhibit a similar mechanism of acute toxicity. Organophosphate pesticides act as irreversible acetylcholinesterase inhibitors, while carbamate pesticides produce reversible effects. The inhibition of acetylcholinesterase causes accumulation of acetylcholine at nerve endings, resulting in a cholinergic or hypersecretory syndrome. Persons who are exposed to organophosphates must be admitted to the hospital for careful observation. Symptoms should be treated with atropine, and most patients should also receive pralidoxime, a cholinesterase-regenerating drug.

Topics: Antidotes; Atropine; Cholinesterase Inhibitors; Cholinesterases; Environmental Monitoring; Epidemiological Monitoring; Erythrocyte Count; Humans; Insecticides; Occupational Exposure; Poisoning; Pralidoxime Compounds; Risk Factors

Topics: Administration, Oral; Antidotes; Deferoxamine; Dimercaprol; Hot Temperature; Humans; Injections, Intramuscular; Kinetics; Naloxone; Penicillamine; Physical Exertion; Poisoning; Pralidoxime Compounds; Thiamine

In developing countries, including Sri Lanka, a high proportion of acute poisoning and other medical emergencies are initially treated in rural peripheral hospitals. Patients are then usually transferred to referral hospitals for further treatment. Guidelines are often used to promote better patient care in these emergencies. We conducted a cluster randomized controlled trial (ISRCTN73983810) which aimed to assess the effect of a brief educational outreach ('academic detailing') intervention to promote the utilization of treatment guidelines for acute poisoning.. This cluster RCT was conducted in the North Central Province of Sri Lanka. All peripheral hospitals in the province were randomized to either intervention or control. All hospitals received a copy of the guidelines. The intervention hospitals received a brief out-reach academic detailing workshop which explained poisoning treatment guidelines and guideline promotional items designed to be used in daily care. Data were collected on all patients admitted due to poisoning for 12 months post-intervention in all study hospitals. Information collected included type of poison exposure, initial investigations, treatments and hospital outcome. Patients transferred from peripheral hospitals to referral hospitals had their clinical outcomes recorded. There were 23 intervention and 23 control hospitals. There were no significant differences in the patient characteristics, such as age, gender and the poisons ingested. The intervention hospitals showed a significant improvement in administration of activated charcoal [OR 2.95 (95% CI 1.28-6.80)]. There was no difference between hospitals in use of other decontamination methods.. This study shows that an educational intervention consisting of brief out-reach academic detailing was effective in changing treatment behavior in rural Sri Lankan hospitals. The intervention was only effective for treatments with direct clinician involvement, such as administering activated charcoal. It was not successful for treatments usually administered by non-professional staff such as forced emesis for poisoning.. Controlled-Trials.com ISRCTN73983810 ISRCTN73983810.

Topics: Acute Disease; Antidotes; Charcoal; Cluster Analysis; Education, Continuing; Hospitalization; Hospitals, Rural; Humans; Outcome Assessment, Health Care; Personnel, Hospital; Poisoning; Practice Guidelines as Topic; Pralidoxime Compounds; Sri Lanka

Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit.. We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 [21.5%], placebo 24/114 [21.1%], adjusted HR 1.27 [95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit.. Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required.

Topics: Acetylcholinesterase; Adult; Antidotes; Atropine; Drug Therapy, Combination; Female; Humans; Insecticides; Intubation, Intratracheal; Male; Organoplatinum Compounds; Poisoning; Pralidoxime Compounds

Organophosphorus (OP) compounds are the most common suicidal poison in developing countries and mortality continues to be high.. A study was done to see butyryl cholinesterase (BuChE) profile after OP poisoning in pralidoxime (P2AM) and placebo treated cases. Highest recommended dose of P2AM was used to study the reactivation of cholinesterase. Clinical outcomes like, correlation of BuChE and severity of poisoning, mortality and complications like Type I and II paralysis, need for ventilation and ICU stay were also studied.. Twenty one cases of moderate and severe poisoning with OP compounds were included in the study. Mean BuChE levels came up gradually over 6-7 days, some taking up to two weeks. There was no. difference between the treatment and placebo groups. BuChE levels did not correlate with severity of poisoning nor did it correlate with Type I or II paralysis, need for ventilation, ICU stay or mortality.. Treatment with P2AM does not make any difference in BuChE reactivation or complications of moderate and severe OP poisoning. We have not been using P2AM for OP poisoning in our medical ICU with good patient outcomes.

Topics: Antidotes; Butyrylcholinesterase; Chemical Warfare Agents; Cholinesterase Reactivators; Developing Countries; Humans; Occupational Exposure; Organophosphate Poisoning; Pesticides; Poisoning; Pralidoxime Compounds; Suicide, Attempted; Treatment Outcome

To define the pharmacokinetics of continuous infusion pralidoxime in organophosphate-poisoned children.. Open-label study in 11 children and adolescents poisoned with organophosphates or carbamates. Serial blood samples were obtained during continuous pralidoxime infusion and after the drug was stopped.. Patients were treated for 12-43 hours. Steady-state concentrations were (mean +/- SD) 22.2 +/- 12.3 mg/L. Volume of distribution ranged from 1.7 to 13.8 L/kg and was significantly higher in the more severely poisoned subjects. Elimination half-life was 3.6 +/- 0.8 hours, and clearance was 0.88 +/- 0.55 L/h/kg. After initiation of continuous infusion pralidoxime, only 1 patient required any additional atropine to control recurrent muscarinic symptoms. All patients exhibited complete clinical recovery.. The pharmacokinetics of pralidoxime in poisoned children following continuous intravenous infusion are widely variable and differ from those previously reported in both healthy and poisoned adults. A loading dose of 25-50 mg/kg is recommended followed by a continuous infusion of 10-20 mg/kg/h. A loading dose of 50 mg/kg may be appropriate in more severely poisoned patients.

Topics: Adolescent; Antidotes; Carbamates; Child; Child, Preschool; Cholinesterase Reactivators; Cholinesterases; Dose-Response Relationship, Drug; Female; Half-Life; Humans; Infant; Infusions, Intravenous; Insecticides; Male; Organophosphorus Compounds; Poisoning; Pralidoxime Compounds; Tissue Distribution; Treatment Outcome

Organophosphorus (OP) poisoning is most frequently encountered among our community. Treatment of poisoning is primarily aimed at reversing the effects of the compound by administration of atropine. Oximes have been shown to be efficacious in case reports. The dose of this drug in these reports varies from 1 gm which is a very low dose and physiologically no dose, to doses upto 16 gm. This is also a very expensive imported drug which causes the nation considerable loss of foreign exchange. We report our experience with the use of two treatment regimens of Pralidoxime (P2AM) in the management of patients with OP poisoning in a prospective trial. Seventy-two adult patients presenting to a large university affiliated teaching institution with a history of consumption of OP compounds and requiring intensive care were entered into the trial. Patients were randomized using a block randomisation to receive either a single bolus dose of 1 gm P2AM at admission (Low dose group) followed by placebo infusion over the next 4 days or a single placebo bolus at admission followed by P2AM 12 gm as a continuous infusion over the next 4 days. Outcome measures analyzed were mortality, duration of ICU stay, need for ventilation and duration of ventilation, time to recovery of consciousness, development of intermediate syndrome and infections. A higher prevalence of intermediate syndrome (p = 0.08) was observed in the high dose group. Ventilatory requirement was also more in the high dose group (p = 0.09). Since this was an equivalence study designed to show that the low dose was as effective as the high dose, these results attain greater significance as the low dose group fared better than the high dose group, even though the pre-test hypothesis was in the reverse direction. Subgroup analysis of patients who received at least 1 gm of P2AM within 12 hours of ingestion of the OP poison with those who received P2AM after 12 hours, showed that there was a significant reduction of intermediate syndrome (p = 0.05) but no significant difference was noted in number ventilated. High dose P2AM infusion has no role in the routine management of patients with OP poisoning. These results also suggest that the time of administration of P2AM after the ingestion of the poison mabe a crucial factor which determines response to therapy. A prospective double blind placebo controlled trial is now justified in the light of the above findings.

Topics: Adult; Antidotes; Cholinesterase Reactivators; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Male; Organophosphate Poisoning; Poisoning; Pralidoxime Compounds

Acute organophosphorus (OP) poisoning is usually treated with atropine plus cholinesterase reactivators such as oximes, but controlled trials to assess the efficacy of oximes in OP poisoning have not been done. A period when the acetyl cholinesterase reactivator pralidoxime chloride was not available in Sri Lanka gave us the opportunity to compare atropine alone for treatment of moderate to severe OP poisoning (21 patients) with atropine plus pralixodime (24 patients). Outcome, as assessed clinically, was similar in the two groups. These results cast doubt on the necessity of cholinesterase reactivators for treatment of acute OP poisoning.

Topics: Adolescent; Adult; Aged; Atropine; Cholinesterase Reactivators; Critical Care; Drug Therapy, Combination; Female; Humans; Length of Stay; Male; Middle Aged; Organophosphate Poisoning; Poisoning; Pralidoxime Compounds; Sri Lanka; Treatment Outcome; Ventilators, Mechanical

It is very important to establish a sustained-release pralidoxime chloride (2-PAM) drug system with brain targeting function for the treatment of neurotoxicant poisoning. Herein, Vitamin B1 (VB1), also known as thiamine, which can specifically bind to the thiamine transporter on the surface of the blood-brain barrier, was incorporated onto the surface of MIL-101-NH

Topics: Acetylcholinesterase; Animals; Blood-Brain Barrier; Cholinesterase Inhibitors; Cholinesterase Reactivators; Iron; Mice; Nerve Agents; Oximes; Poisoning; Zebrafish

Organophosphorus (OP) insecticide poisoning causes respiratory failure due to acetylcholinesterase (AChE) inhibition. The AChE reactivating antidote pralidoxime was developed in the 1950s and was soon noted to benefit patients occupationally poisoned with the highly potent OP insecticide parathion. Routine use of pralidoxime and other oximes such as obidoxime then became widely recommended. However, nearly all severe cases of OP poisoning now result from self-poisoning with large volumes of less potent (WHO hazard class Ib and II) insecticides and co-formulated solvents. Unfortunately, oxime clinical trials have never shown benefit from their use for these patients, and some have shown that pralidoxime may be associated with harm, including increased mortality. Oximes should not be used routinely for the care of OP insecticide-poisoned patients until translational and clinical studies have identified a safe and effective oxime regimen and identified the patients who benefit.

Topics: Acetylcholinesterase; Cholinesterase Inhibitors; Humans; Insecticides; Organophosphate Poisoning; Organophosphorus Compounds; Oximes; Poisoning

This study reports efficacy of three bis pyridinium derivatives of 2-(hydroxyimino)- N-(pyridine-3-yl) acetamide in terms of survival, reactivation of brain and serum acetylcholinesterase (AChE) activity in diisopropylphosphorofluoridate (DFP) intoxicated Swiss albino male mice. LD50 of DFP (3.9 mg/kg, s.c.) and new oximes, HNK-102, HNK-106, HNK-111, (282.8, 35.0 and 35.0 mg/kg respectively, i.m.) was determined. Various doses of DFP and oximes as treatment doses with atropine (10 mg/kg, i.p.) were used to determine protection index (PI). For time dependent maximum AChE inhibition, two doses of DFP (0.20 and 2.0 LD50) were chosen. At optimized time i.e. Sixty minutes, IC50 value was calculated as 0.249 and 0.017 LD50 of brain and serum AChE, respectively. Shift of DFP induced brain AChE IC50 curves to right was observed at 0.20 LD50 treatment dose of oximes with respect to 2-PAM. These findings propose that new HNK series of oximes are effective antidote, compared to that of 2-PAM in vivo.

Topics: Acetylcholinesterase; Animals; Atropine; Cholinesterase Inhibitors; Cholinesterase Reactivators; Isoflurophate; Male; Mice; Oximes; Poisoning; Pralidoxime Compounds

Improper use of pesticides on food plants can result in significant toxicity. In spite of regulations, enforcement, and prior episodes of poisonings, poisonings from misapplication of pesticides continues to occur. The objective of this study was to present a case series of toxicity resulting from ingestion of watermelon inappropriately treated with the carbamate insecticide aldicarb. A restrospective review of medical records, impounding the suspected watermelons, and chemical analysis of the watermelon samples using liquid chromatography and mass spectroscopy were carried out. Seven farm workers shared a watermelon and presented to a rural emergency department with symptoms of cholinergic poisoning. They were treated empirically with atropine and pralidoxime. The farmer denied use of insecticides other than rat poison on the watermelon patch. Chemical analyst verified aldicarb in the watermelon samples from the field, but none in control samples. Despite government regulations, application of restricted pesticides such as aldicarb continues to occur and cause significant poisonings.

Topics: Administration, Oral; Adult; Aldicarb; Atropine; Citrullus; Food Contamination; Humans; Insecticides; Male; Middle Aged; Poisoning; Pralidoxime Compounds; Retrospective Studies; Young Adult

Topics: Adult; Atropine; Charcoal; Diazepam; Drug Combinations; Gastric Lavage; Humans; Insecticides; Intubation, Gastrointestinal; Male; Midazolam; Poisoning; Poisons; Pralidoxime Compounds; Propoxur; Spasm; Strychnine; Suicide, Attempted

Topics: Acetylcholinesterase; Adult; APACHE; Atropine; Cholinesterases; Erythrocytes; Female; Humans; Male; Multiple Organ Failure; Muscarinic Antagonists; Parathion; Poisoning; Pralidoxime Compounds; Receptors, Muscarinic; Receptors, Nicotinic; Respiratory Distress Syndrome; Retrospective Studies; Severity of Illness Index; Spain; Suicide, Attempted; Young Adult

Organophosphate poisoning by oral or inhalation routes is characterized by a typical time-course of clinical features.. We report a case of subcutaneous chlorpyrifos self-injection leading to a delayed cholinergic phase, prolonged coma, and severe permanent neurologic injury with electrophysiological patterns suggestive of overlapping intermediate syndrome and distal peripheral neuropathy. Time-course and severity of clinical features were not altered by either atropine or pralidoxime administration. Due to prolonged and severe alteration in consciousness, we used brain multimodal nuclear magnetic imaging and auditory cognitive event-related potentials to assess the patient's potential for awakening. Electrophysiological testing used to monitor muscle weakness showed the coexistence of 20 Hz-decremental responses in proximal muscles and severe denervation in distal muscles. Red blood cell acetylcholinesterase activity progressively normalized on day 60, while plasma butyrylcholinesterase activity remained low until day 100. Chlorpyrifos was detectable in serum until day 30 and urine metabolites for up to three months, supporting the hypothesis of a continuous chlorpyrifos release despite repeated surgical debridement. We suggest that adipose and muscle tissues acted as a chlorpyrifos reservoir. At one-year follow-up, the patient exhibited significant neuromuscular sequelae.. Subcutaneous chlorpyrifos self-injection may result in severe toxicity with prolonged neurologic injury, atypical overlapping electrophysiological patterns, and a poor final outcome.

Topics: Antidotes; Atropine; Brain; Chlorpyrifos; Humans; Injections, Subcutaneous; Insecticides; Magnetic Resonance Imaging; Male; Muscarinic Antagonists; Nervous System Diseases; Poisoning; Pralidoxime Compounds; Suicide, Attempted; Treatment Outcome; Young Adult

Topics: Antidotes; Dichlorvos; Emergency Service, Hospital; Follow-Up Studies; Glasgow Coma Scale; Humans; Infusions, Intravenous; Male; Organophosphate Poisoning; Organophosphorus Compounds; Poisoning; Pralidoxime Compounds; Risk Assessment; Severity of Illness Index; Time Factors; Treatment Outcome; Young Adult

The organophosphorus (OP) pesticide malathion is a highly neurotoxic compound and its toxicity is primarily caused by the inhibition of acetylcholinesterase (AChE), leading to cholinergic syndrome. Although oximes have been used as potential antidotal treatments in malathion poisoning because of their potential capability to reactivate the inhibited enzyme, the clinical experience with the clinically available oximes (e.g. pralidoxime) is disappointing and their routine use has been questioned. In the present study, we investigated the potency of pralidoxime and K074 in reactivating AChE after acute exposure to malathion, as well as in preventing malathion-induced changes in oxidative-stress related parameters in mice. Malathion (1.25 g/kg, s.c.) induced a significant decrease in cortico-cerebral, hippocampal and blood AChE activities at 24h after exposure. Oxime treatments (1/4 of LD(50), i.m., 6h after malathion poisoning) showed that pralidoxime significantly reversed malathion-induced blood AChE inhibition, although no significant effects were observed after K074 treatment. Interestingly, both oximes tested were unable to reactivate the cortico-cerebral and hippocampal enzymes after intramuscular or intracerebroventricular injection (1/4 of LD(50), 6h after malathion poisoning). Biochemical parameters related to oxidative stress (cerebro-cortical and hippocampal glutathione peroxidase, glutathione reductase and catalase activities, as well as lipid peroxidation) were not affected in animals treated with malathion, oximes or atropine alone. However, pralidoxime and K074, administered intramuscularly 6h after malathion poisoning, were able to increase the endogenous activities of these antioxidant enzymes in the prefrontal cortex and hippocampus. Taken together, the results presented herein showed that pralidoxime (the most common clinically used oxime) and the recently developed oxime K074, administered 6h after malathion poisoning, were unable to reactivate the inhibited AChE in mouse prefrontal cortex and hippocampus. However, only pralidoxime significantly reversed the blood AChE inhibition induced by malathion poisoning. This indicates that peripheral and central AChE activities are not necessarily correlated after the treatment of OP compounds and/or oximes, which should be taken into account in the diagnosis and management of OP-exposed humans. In addition, considering that the available treatments to malathion poisoning appear to be ineffective,

Topics: Acetylcholinesterase; Animals; Antidotes; Antioxidants; Brain; Butanes; Catalase; Cholinesterase Inhibitors; Cholinesterase Reactivators; Glutathione Peroxidase; Glutathione Reductase; GPI-Linked Proteins; Insecticides; Lethal Dose 50; Lipid Peroxidation; Malathion; Male; Mice; Oxidative Stress; Oximes; Poisoning; Pralidoxime Compounds; Pyridinium Compounds; Time Factors

Anticholinesterase poisoning is an important health problem in our country, and a complete understanding of its underlying mechanisms is essential for the emergency physician. So, this study focused on two purposes. First one was aimed to investigate the biochemical analysis to determine the tissue levels of malondialdehyde (MDA), glutathione and nitric oxide (NO). Secondly, it was planned to model and formulate the effects of some drugs on cardiac tissues levels of NO, MDA and glutathione in acute organophosphate poisoning in rats by the application of neural network based on experimental results. It has been planned to determine whether artificial neural network (ANN) is appropriate tool to analyze and formulate it. As a result, it has been considered that ANN can be effectively used to model NO, MDA and glutathione level. The performances of ANN formulation versus target experimental values are found to be quite high. It is concluded that, proposed NN models are also presented as simple explicit mathematical functions for further use by researchers.

Topics: Animals; Anti-Arrhythmia Agents; Antidotes; Atropine; Dichlorvos; Glutathione; Insecticides; Magnesium Sulfate; Male; Malondialdehyde; Muscarinic Antagonists; Myocardium; Neural Networks, Computer; Nitric Oxide; Poisoning; Pralidoxime Compounds; Random Allocation; Rats; Rats, Wistar

Topics: Aged; Bradycardia; Cholinesterase Inhibitors; Cholinesterase Reactivators; Cholinesterases; Combined Modality Therapy; Diagnosis, Differential; Diagnostic Errors; Fatal Outcome; Humans; Hypertension; Male; Organophosphate Poisoning; Poisoning; Pralidoxime Compounds; Pulmonary Edema; Respiration, Artificial; Respiratory Paralysis; Syndrome

A term neonate was born to a mother who had consumed an organophosphorus compound with suicidal intent 50 hours before delivery. At birth, the infant showed signs and symptoms of organophosphorus poisoning and was treated with atropine and pralidoxime to which she responded well. Unfortunately, the mother died despite appropriate treatment. This is only the second report documenting transplacental organophosphate poisoning.

Topics: Antitoxins; Atropine; Female; Humans; Infant, Newborn; Organophosphates; Poisoning; Pralidoxime Compounds; Pregnancy; Pregnancy Complications; Suicide, Attempted

Acephate (AP) is a widely available organophosphorus (OP) insecticide considered to have low mammalian toxicity. In plants and insects, AP is metabolized extensively to methamidophos (MP), a more potent OP insecticide. The limited mammalian metabolism of AP to MP has been studied in laboratory rat models and suggests that initial formation of MP from AP may inhibit further formation. No case reports of human ingestion with urine AP and MP levels have been previously published.. A 4-year-old male being evaluated for altered mental status and head trauma was noted to have muscarinic and nicotinic cholinergic signs. Further history suggested possible ingestion of a commercial AP product at an unknown time. Ingestion of AP was confirmed by the presence of urinary AP and MP and severely depressed red blood cell (RBC) cholinesterase and pseudocholinesterase activity levels. The patient initially received atropine in two 0.02 mg/kg IV boluses, then was started on 0.05 mg/kg IV per hour and titrated accordingly to clinical signs of cholinergic toxicity. Pralidoxime was also given at 20 mg/kg IV bolus, followed by an infusion of 10 mg/kg per hour. The patient required mechanical ventilation for 18 days and atropine infusion for 20 days. After a complicated intensive care unit course, he recovered and was discharged after a total of 32 days of hospitalization.. Four urine samples collected at different times were analyzed for AP and MP by using high-performance liquid chromatography-atmospheric pressure chemical ionization tandem mass spectrometry. Kinetic calculations were performed by using standard equations.. Suspected ingestion was confirmed by the presence of AP and MP in urine. The amount of MP found in urine suggests some limited human metabolism to this more toxic compound.. Urinary elimination kinetics of AP demonstrates low metabolic conversion of AP to MP in humans.

Topics: Antidotes; Atmospheric Pressure; Atropine; Butyrylcholinesterase; Child, Preschool; Chromatography, High Pressure Liquid; Drug Therapy, Combination; Erythrocytes; Humans; Insecticides; Male; Muscarinic Antagonists; Organothiophosphorus Compounds; Phosphoramides; Poisoning; Pralidoxime Compounds; Respiration, Artificial; Tandem Mass Spectrometry; Treatment Outcome

Organophosphate (OP) poisoning is a worldwide concern. Several factors have been identified to predict outcomes of OP poisoned patients. This study focuses on the relationship between the trend in Serum cholinesterase (SChE) activity and its clinical outcome in acute OP poisoned patients.. We retrospectively reviewed the medical records of all adult acute OP poisoned patients that visited the Emergency Department from 2000 to 2006. These patients were divided into two groups: the deceased patients as the sample group and all others as the control group. We collected data on the following: demographical factors, poisoning history, clinical manifestation, Glasgow Coma Scale (GCS), APACHE II score, all SChE data within 48 hours, hourly 2-PAM dosage, intubation, and mortality. Chi-Square test then examined the relationship between the trend of SChE activity and mortality.. 86 patients were enrolled. Follow-up measurements of SChE activity within 48 hours of poisoning were available in 50 cases. Among these, eight patients died. We found no significant difference between the sample and control groups on initial SChE activity, time interval to initial SChE data, and hourly 2-PAM dosage. The sampled group possessed a worse GCS score, lower systolic blood pressure, and a higher APACH II score. Increase patient mortality rates associated with the absence of elevating SChE activity within 48 hours of poisoning. (P = .006, odds ratio:11).. We propose that the absence of elevating SChE activity level within 48 hours of poisoning appears to associate with higher mortality in acute OP poisoned patients.

Topics: Adult; Aged; Antidotes; Cholinesterases; Cohort Studies; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Organophosphate Poisoning; Pesticides; Poisoning; Pralidoxime Compounds; Predictive Value of Tests; Retrospective Studies; Survival Rate; Treatment Outcome

The nationwide epidemiology of organophosphate pesticide (OP) poisoning has never been reported in detail for Taiwan.. This study retrospectively reviewed all human OP exposures reported to Taiwan's Poison Control Centers (PCCs) from July 1985 through December 2006.. There were 4799 OP exposures. Most OP exposures were acute (98.37%) ingestions (74.50%) of a single OP (80.37%) to attempt suicide (64.72%) in adults (93.25%). Males were the most common gender (64.95%). Most patients (61.97%) received atropine and/or pralidoxime. The mortality rate for all 4799 OP exposures was 12.71%. Exposures to single OPs without co-intoxicants caused 524 deaths; of these, 63.36% were due to dimethyl OPs.. Dimethyl OPs cause the majority of deaths in Taiwan.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidotes; Atropine; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Organophosphate Poisoning; Pesticides; Poison Control Centers; Poisoning; Pralidoxime Compounds; Retrospective Studies; Suicide, Attempted; Taiwan

The direct reaction of seven pyridinium oximes with the organophosphorus compounds (OPCs) crotylsarin, cyclosarin, and VX was studied by spectrophotometry. This method allows to quantify different parameters: (a) the half-life times (t (1/2)) of the oxime-OPC reactions on the basis of the changes in the absorption at the zwitterion (betaine) peak maximum, (b) the first- and second-order rate constants (k (1), k (2)), and (c) the maximum reaction velocities (v (max)). The results of the study show that the reaction velocity of the nerve agents with any of the oximes investigated decreased in the order crotylsarin > cyclosarin > VX. The comparison of the reaction rates of the three therapeutically used oximes (2-PAM, obidoxime, HI 6) with the respective OPC gave the highest rate for crotylsarin and cyclosarin with obidoxime and to a similar degree with HI 6, while in the case of VX the most reactive oxime was HI 6. The reaction velocity of the nerve agents with the monopyridinium oxime 2-PAM was lower as compared to the bispyridinium oximes (obidoxime, HI 6). The results obtained with the two sarin analogues indicate that the direct reaction with 2-PAM, obidoxime, or HI 6 could be used for non-corrosive decontamination purposes, especially, if sensitive biological surfaces like skin, mucous membranes, or wounds are considered. However, in view of the concentrations of nerve agents and oximes, which could be expected during OPC poisoning in man, the maximum reaction velocities would not be high enough to contribute markedly to the detoxication of nerve agents in vivo.

Topics: Cholinesterase Inhibitors; Cholinesterase Reactivators; Decontamination; Half-Life; Kinetics; Models, Chemical; Obidoxime Chloride; Organophosphorus Compounds; Organothiophosphorus Compounds; Oximes; Poisoning; Pralidoxime Compounds; Pyridinium Compounds; Sarin; Spectrophotometry, Ultraviolet

Poisoning from organophosphates and carbamates is a significant cause of morbidity and mortality worldwide. Concerns have been expressed over the safety and efficacy of the use of oximes such as pralidoxime (2-PAM) in patients with carbamate poisoning in general, and more so with carbaryl poisoning specifically. The goal of the present study was to evaluate the role of 2-PAM in a mouse model of lethal carbaryl poisoning.. Female ICR Swiss Albino mice weighing 25-30 g were acclimated to the laboratory and housed in standard conditions. One hundred and ten mice received an LD50 dose of carbaryl subcutaneously. Ten minutes later, they were randomized by block randomization to one of eight treatment groups: normal saline control, atropine alone, 100 mg/kg 2-PAM with and without atropine, 50 mg/kg 2-PAM with and without atropine, and 25 mg/kg 2-PAM with and without atropine. All medications were given intraperitoneally and the atropine dose was constant at 4 mg/kg. The single objective endpoint was defined as survival to 24 hours. Fatalities were compared using a Chi squared or Fisher's exact test.. Following an LD50 of carbaryl, 60% of the animals died. Atropine alone statistically improved survival (15% lethality). High dose 2-PAM with and without atropine was numerically worse, but not statistically different from control. While the middle dose of 2-PAM was no different than control, the addition of atropine improved survival (10% fatality). Low-dose 2-PAM statistically improved survival (25% lethality). Atropine further reduced lethality to 10%.. When appropriately dosed, 2-PAM alone protects against carbaryl poisoning in mice. Failure to demonstrate this benefit in other models may be the result of oxime overdose.

Topics: Animals; Antidotes; Atropine; Carbaryl; Cholinesterase Inhibitors; Cholinesterase Reactivators; Drug Therapy, Combination; Female; Insecticides; Mice; Mice, Inbred ICR; Poisoning; Pralidoxime Compounds

In this prospective case series study, we consider the different factors between death and survival groups of organophosphate poisoning. Patients in tertiary-care medical center who had been exposed to organophosphate were included in the study. Pralidoxime (PAM) was discontinued after atropine had controlled the clinical situation. We recorded the demographic data, amount of organophosphate consumption, duration of coma, duration of ventilator use, duration of hospitalization, findings of chest X-ray, white blood cell count, acetylcholinesterase concentration, plasma cholinesterase concentration, total atropine amount, duration of atropine use, total PAM amount, duration of PAM use, urine organophosphate peak concentration, duration of urine organophosphate and mortality rate. Urine was collected every 8 hours and was analyzed by gas chromatography equipped with a flame photometric detector and gas chromatography with mass spectrometer detector for organophosphate determination. The urine organophosphate peak concentration was recorded. Wilcoxon rank sum test was used to compare the factors between death and survival groups. Fisher's exact test was used to compare the different findings of chest X-ray between the death and survival groups. Evidently, the death group had a higher amount of organophosphate consumption, duration of coma, and higher white blood cell count than those in the survival group. Also, the death group had lower duration of hospitalization, and decreased concentrations of acetylcholinesterase and plasma cholinesterase. Total PAM amount use and duration of PAM use were lower. However, the duration of ventilator use, findings of chest X-ray, total atropine amount, duration of atropine, urine organophosphate peak concentration and duration of urine organophosphate were similar in both groups. The mortality rate of our 50 cases was 20%. As stated earlier, the cases of the death group had insufficient PAM therapy. The maximum duration of PAM use was shorter than the maximum duration of urine organophosphate, although the medians of duration of PAM use were more than the medians of duration of urine organophosphate in both the survival and death groups. Prolonged coma duration, lower level of acetylcholinesterase and lower level of plasma cholinesterase were related to the poor prognosis of the patients.

Topics: Acetylcholinesterase; Adolescent; Adult; Aged; Female; Humans; Male; Middle Aged; Organophosphate Poisoning; Poisoning; Pralidoxime Compounds; Prognosis; Prospective Studies

Poisoning is one of the most important causes of morbidity and mortality in developing countries like India. Anticholinesterase compounds like organophosphates (OP) and carbamates account for the majority of these poisoning cases because of their easy availability and agricultural use. Carbamates are as popular as OPs as insecticides that often go undiagnosed. A fatal case of carbofuran poisoning is presented where serial cholinesterase estimation played a major role in the diagnosis of the same. The pertinent medical literature on carbofuran poisoning is reviewed. The establishment of poison information center in each state is needed for proper diagnosis and management of poisoning cases.

Topics: Carbofuran; Cholinesterase Inhibitors; Cholinesterase Reactivators; Cholinesterases; Forensic Medicine; Humans; Male; Middle Aged; Poisoning; Pralidoxime Compounds

Pralidoxime is indicated to treat patients poisoned with nerve agents. It is available in intravenous formulation for more seriously ill hospitalized patients and intramuscular formulation for field treatment and less seriously ill patients. Our study describes a method to convert the intramuscular formulation for intravenous use and determines the stability and sterility of the resulting formulation over time and under various environmental conditions.. An inventory was taken of all intravenous (Protopam) and intramuscular (Mark I Autoinjector kits) pralidoxime available in Franklin County, Ohio hospitals, and out-of-hospital stockpiles. A method was devised to safely convert the intramuscular pralidoxime to an intravenous formulation, which was then tested for stability and sterility under a variety of environmental temperatures over time.. In Franklin County, Ohio (population 1.1 million), the 10 acute care hospitals and out-of-hospital community have 36 g of intravenous pralidoxime and 4,398 g (7,270 Mark I kits) of intramuscular pralidoxime. The reformulated pralidoxime retained greater than 90% stability and remained sterile at all environmental temperatures through day 28.. Available pralidoxime in Franklin County is predominantly in the intramuscular preparation. Conversion of intramuscular to intravenous pralidoxime results in a stable and sterile solution for up to 28 days under a variety of environmental conditions and should be considered in a mass casualty situation in which additional intravenous supplies are needed.

Topics: Antidotes; Chemical Terrorism; Chemical Warfare Agents; Drug Compounding; Drug Contamination; Drug Stability; Humans; Infusions, Intravenous; Injections, Intramuscular; Peripheral Nervous System Agents; Poisoning; Pralidoxime Compounds

To evaluate the benefits of using serial measurements of plasma cholinesterase (butyrylcholinesterase, BuChE) activity in the management of cholinesterase inhibitor insecticidal poisoning.. After establishing and validating BuChE activity test, and making it available for clinical service in the toxicology laboratory at Jordan University Hospital. Serial measurements of BuChE were performed on samples taken from 10 symptomatic patients presented with the manifestations of poisoning due to acetylcholinesterase inhibitor insecticides during the year 2001. The number of serial repeats of BuChE activity tests ranged from 2 to 4 and from 8 to 11 for patients with carbamates and organophosphates (OPs) poisoning, respectively. The results of serial measurement of BuChE obtained from each patient's samples were used to draw a curve; three different types of curves were obtained from all patients samples.. The obtained curves were found to follow our three proposed curves, which support our point view regarding the importance of the proposed curves in the differential diagnosis and treatment of cholinesterase inhibitor pesticides poisoning.. This study pointed out the importance of utilizing serial measurements of BuChE activity in the diagnosis and the management of organophosphates and carbamates poisoning. The BuChE activity results were used to support diagnostic and prognostic criteria that guided patient management and follow up. Applying those curves to large number of patients' samples will enhance its credibility. The study also demonstrated the importance of direct contract between toxicologist and physician in treatment of the pesticides poisoned patients.

Topics: Adolescent; Adult; Antidotes; Atropine; Butyrylcholinesterase; Carbamates; Child, Preschool; Cholinesterase Reactivators; Female; Forensic Medicine; Humans; Male; Middle Aged; Muscarinic Antagonists; Poisoning; Pralidoxime Compounds

A 42-year-old pregnant woman (26 weeks of gestation, G(4)P(0+3)) presented at the emergency department with a two-hour history of dizziness, blurred vision and repeated vomiting. These symptoms started during the use of an undiluted insecticide liquid (diazinon 60 EC) while cleaning a small non-aired bathroom. After clinical and laboratory confirmation for organophosphate poisoning (plasma pseudocholinesterase levels 161 U/l), treatment with atropine and pralidoxime was started. She recovered within 7 days and delivered a healthy baby 12 weeks later (Apgar score 9 and 10) by elective cesarean section. The child showed no signs or symptoms of organophospate, atropine or pralidoxime exposure.

Topics: Adult; Antidotes; Apgar Score; Atropine; Diazinon; Female; Gestational Age; Humans; Infant, Newborn; Poisoning; Pralidoxime Compounds; Pregnancy; Pregnancy Complications; Pregnancy Outcome

Warangal district in Andhra Pradesh, southern India, records >1000 pesticide poisoning cases each year and hundreds of deaths. We aimed to describe their frequency and distribution, and to assess quality of management and subsequent outcomes from pesticide poisoning in one large hospital in the district.. We reviewed data on all patients admitted with pesticide poisoning to a district government hospital for the years 1997 to 2002. For 2002, details of the particular pesticide ingested and management were abstracted from the medical files.. During these 6 years, 8040 patients were admitted to the hospital with pesticide poisoning. The overall case fatality ratio was 22.6%. More detailed data from 2002 revealed that two-thirds of the patients were <30 years old, 57% were male and 96% had intentionally poisoned themselves. Two compounds, monocrotophos and endosulfan, accounted for the majority of deaths with known pesticides in 2002. Low fixed-dose regimens were used in the majority of cases for the most commonly used antidotes (atropine and pralidoxime). Inappropriate antidotes were also used in some patients.. It is likely that these findings reflect the situation in many rural hospitals of the Asia Pacific region. Even without an increase in resources, there appear to be significant opportunities for reducing mortality by better medical management and further restrictions on the most toxic pesticides.

Topics: Adolescent; Adult; Age Distribution; Antidotes; Atropine; Child; Endosulfan; Female; Humans; India; Insecticides; Length of Stay; Male; Middle Aged; Monocrotophos; Pesticides; Poisoning; Pralidoxime Compounds; Sex Distribution; Time Factors

To study the therapeutic efficacy and mechanism of oxime drug, pralidoxime chloride (PAM-Cl), on acute dichlorvos (DDV) poisoning.. The toxic signs and survival rate were recorded and ChE activity in blood was determined in treatment group with PAM-Cl and non-treatment group after DDV was given to rats and mice by gastrogavage; the therapeutic efficacy and reactivation of DDV-inhibited ChE by PAM-Cl were observed on the patients with acute DDV poisoning.. (1) The alleviated and delayed toxic signs as well as higher survival rate were found in PAM-Cl treatment group compared with non-treatment group. (2) After the rats were exposed to DDV, the ChE activities of whole blood in different time within 24 h were statistically significantly higher in PAM-Cl treatment group than in non-treatment group (P < 0.05). (3) After PAM-Cl treatment, muscular fasciculation and other nicotinic signs in poisoned patients were disappeared and the inhibited blood ChE activities were gradually reactivated to normal level.. PAM-Cl has therapeutic efficacy against acute toxicity of DDV through its reactivation of inhibited ChE.

Topics: Acute Disease; Adolescent; Adult; Animals; Antidotes; Cholinesterases; Dichlorvos; Female; Humans; Insecticides; Male; Mice; Mice, Inbred Strains; Middle Aged; Poisoning; Pralidoxime Compounds; Rats; Rats, Sprague-Dawley; Treatment Outcome

The objective of this study was to evaluate the effects of an adenosine A1 agonist, phenylisopropyl adenosine (PIA), on metamidophos poisoning compared to specific antidotes. Rats were poisoned with metamidophos (30 mg/kg, oral) and observed for 24 hours. One group received sodium chloride (1 mL/kg) and four experimental groups received atropine (5 mg/kg), pralidoxime (PAM, 20 mg/kg), atropine/PAM (5/20 mg/kg) or PIA (1 mg/kg) intraperitoneally. Atropine reduced salivation and prevented respiratory distress when compared to sodium chloride-treated rats. Treatment with PAM did not cause any suppression of cholinergic signs. Atropine and PAM combination prevented salivation, convulsion and respiratory distress. PIA delayed initial time of the salivation, convulsion and time to death. However, PIA was found ineffective against the metamidophos-induced cholinergic symptoms and mortality. All treatments, except PIA, lead to survival of these animals. Acetylcholinesterase (AChE) activity was not normalized by PIA or PAM. PIA prevented metamidophos-induced diaphragmatic muscle necrosis as much as PAM. In conclusion, a single dose of PIA was unable to protect the rats from metamidophos toxicity. Further studies are needed involving a combination of PAM and/or atropine with repeated doses of PIA to clarify the efficacy of adenosine agonists in OP poisoning.

Topics: Adenosine A1 Receptor Agonists; Animals; Antidotes; Atropine; Cholinesterase Reactivators; Cholinesterases; Diaphragm; Drug Interactions; Insecticides; Male; Models, Animal; Muscarinic Antagonists; Organothiophosphorus Compounds; Phenylisopropyladenosine; Poisoning; Pralidoxime Compounds; Rats; Rats, Wistar; Respiration; Salivation; Survival Rate; Time Factors

Topics: Agriculture; Antidotes; Cholinesterase Reactivators; Humans; India; Occupational Exposure; Organophosphate Poisoning; Organophosphates; Pesticides; Poisoning; Pralidoxime Compounds; Suicide, Attempted

Pralidoxime methylsulfate (Contrathion) is widely used to treat organophosphate poisoning. For the first time, we developed a specific assay for urinary pralidoxime using capillary zone electrophoresis (CZE) in the following conditions: fused-silica capillary (length: 47 cm, internal diameter: 75 microm), electrolyte solution: 25 mM sodium borate (pH 9.1), voltage: 15 kV, temperature: 25 degrees C, injection time: 1 or 2s, on-line UV detection: 280 nm. Sample preparation did not require a deproteinization step (1:5 dilution in water). The method was linear between 0.125 and 2 mg mL-1 of pralidoxime (quantification limit: 0.10 mg mL-1). Coefficients of variation for intra- and inter-assay precision were below 10% for all three control levels (0.15-1.15 mg mL-1). This assay was successfully applied to urine specimens from organophosphate poisoned patients treated by Contrathion (n=10). This CZE method allows the measure of pralidoxime in urine within 15 min with excellent precision, selectivity, and sensitivity. It is simple (no pretreatment) and convenient, thus suitable for the monitoring of Contrathion therapy in organophosphate poisoned patients.

Topics: Antidotes; Electrophoresis, Capillary; Humans; Organophosphate Poisoning; Poisoning; Pralidoxime Compounds; Reproducibility of Results; Sensitivity and Specificity

Topics: Anticonvulsants; Antidotes; Atropine; Chemical Warfare Agents; Child; Cholinesterase Reactivators; Disaster Planning; Humans; Muscarinic Antagonists; Neurotoxins; Pediatrics; Poisoning; Practice Guidelines as Topic; Pralidoxime Compounds; Terrorism; United States

Topics: Antidotes; Chemical Warfare Agents; Cholinesterase Inhibitors; Cholinesterase Reactivators; Humans; Neuroprotective Agents; Poisoning; Pralidoxime Compounds; Sarin

Topics: Adult; Antidotes; Female; Humans; Insecticides; Parathion; Poisoning; Pralidoxime Compounds; Treatment Outcome

We describe a case of intermediate syndrome after chlorpyrifos ingestion in a toddler, despite a continuous pralidoxime infusion. A 16-month-old girl ingested a pesticide containing chlorpyrifos. She was brought to an Emergency Department where she became lethargic and tachycardic, and subsequently developed pulmonary edema requiring mechanical ventilation. Pralidoxime 150 mg i.v. was administered twice, and an infusion begun at 15 mg/kg/h. At 24.5 h post-ingestion the child had a normal neurologic examination, showed no signs of cholinergic excess, and was extubated successfully. At 27.5 h post-ingestion the child became flaccid, bradycardic and apneic. She was emergently re-intubated. The child's delayed onset of respiratory arrest and flaccid paralysis after an asymptomatic period is consistent with Intermediate Syndrome. This is an unusual case in that it occurred in a young child, was related to chlorpyrifos, and occurred despite continuous and adequate oxime therapy.

Topics: Chlorpyrifos; Cholinesterase Inhibitors; Cholinesterase Reactivators; Female; Humans; Infant; Insecticides; Paralysis; Poisoning; Pralidoxime Compounds; Respiration, Artificial; Respiratory Insufficiency

Two cases of severe fenthion intoxication are presented. The first is a case of a psychiatric patient who attempted suicide with ingestion of the compound, and the second case was of a child exposed to the chemical agent by air spraying. Both patients were treated in the intensive care unit with atropine and pralidoxime and finally survived. Fenthion blood levels on admission were 2.7 and 0.95 microg/mL, respectively. Different concentrations of pralidoxime were added to the first patient's poisoned serum in order to assess in vitro the effect of pralidoxime on cholinesterase reactivation. The clinical and toxicological data of the poisonings are discussed, as well as the potential therapeutic use of pralidoxime in organophosphate intoxication.

Topics: Administration, Oral; Adolescent; Aged; Antidotes; Atropine; Environmental Exposure; Fenthion; Humans; Inhalation Exposure; Insecticides; Intensive Care Units; Male; Poisoning; Pralidoxime Compounds; Suicide, Attempted; Treatment Outcome

The temporal profile of butyrylcholinesterase (BuChE) and in vitro pralidoxime-reactivated BuChE was studied in a cohort of 25 organophosphate-poisoned patients to examine their relationship to the development of intermediate syndrome and to understand reasons for lack of efficacy of oxime treatment. The clinical severity of poisoning (assessed by the Namba Scale) correlated significantly with the severity of intermediate syndrome. BuChE activity increased significantly over time and showed significant relationship to muscle power. The temporal profile of the enzyme was correlated to the clinical severity of poisoning. Reactivation potentials of BuChE (the difference between oxime-reactivated and -unreactivated enzyme activity) declined significantly with time after organophosphate ingestion. The reactivation potential of the enzyme at admission decreased significantly with increasing severity of poisoning and was lower in patients who developed intermediate syndrome. Patients who received oxime prior to hospitalization had a higher rate of intermediate syndrome and lower levels of BuChE at admission than those who had not. The study suggests that (i) BuChE reflects the clinical course of poisoning, confirming earlier studies; (ii) intermediate syndrome may be associated with a persistent inhibition of BuChE; and (iii) the lack of oxime efficacy in our patients maybe due to their severity of poisoning and the timing of oxime treatment.

Topics: Adult; Antidotes; Butyrylcholinesterase; Cohort Studies; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Humans; Insecticides; Male; Muscles; Organophosphorus Compounds; Oximes; Poisoning; Pralidoxime Compounds; Severity of Illness Index; Suicide

To investigate the cholinesterase inhibition and effect of atropine and pralidoxime (PAM) treatment on the survival time in the rat model of aluminium phosphide (AlP) poisoning.. The rats were treated with AlP (10 mg/kg; 5.55 x LD50; ig) and the survival time was noted. The effect of atropine (1 mg/kg, ip) and PAM (5 mg/kg, ip) was noted on the above. Atropine and PAM were administered 5 min after AlP. Plasma cholinesterase levels were measured spectrophotometrically in the control and AlP treated rats 30 min after administration.. Treatment with atropine and PAM increased the survival time by 2.5 fold (1.4 h+/-0.3 h vs 3.4 h+/-2.5 h, P < 0.01) in 9 out of 15 animals and resulted in total survival of the 6 remaining animals. Plasma cholinesterase levels were inhibited by 47 %, (438+/-74) U/L in AlP treated rats as compared to control (840+/-90) U/L (P < 0.01).. This preliminary study concludes that AlP poisoning causes cholinesterase inhibition and responds to treatment with atropine and PAM.

Topics: Aluminum Compounds; Animals; Antidotes; Atropine; Blood Pressure; Cholinesterase Inhibitors; Cholinesterase Reactivators; Cholinesterases; Drug Interactions; Female; Male; Pesticides; Phosphines; Poisoning; Pralidoxime Compounds; Rats; Rats, Wistar

Topics: Adult; Antidotes; Cholinesterase Reactivators; Emergency Medical Technicians; Emergency Treatment; Humans; Insecticides; Malathion; Male; Poisoning; Pralidoxime Compounds; United States

A nonfatal case of poisoning involving aldicarb, an extremely toxic carbamate pesticide, is presented. A 39-year-old female ingested an unknown amount of aldicarb, together with alprazolam and sertraline. On admission to ICU (T0), she displayed marked cholinergic symptoms and a deep coma. The patient was given pralidoxime and atropine. Her condition gradually improved on days 2 and 3 and she was discharged at T0+80 h. Aldicarb was assayed by high-performance liquid chromatography on 21 blood and 8 urine samples successively taken during hospitalization. At the same time, serum pseudocholinesterase activity was followed on 21 successive samples. Blood aldicarb level was 3.11 microg/mL at T0 and peaked at T0+3.5 h (3.22 microg/mL), then followed a two-slope decay with a terminal half-life of ca. 20 h. Aldicarb was detected in all urine samples (peak level: 6.95 microg/mL at T0+31.5 h) and was still present at the time of discharge. Serum pseudo-cholinesterase activity remained low (< or = 10% of normal) until the 30th hour then rapidly increased and returned to normal after the 60th hour. The patient's clinical picture closely followed blood aldicarb levels and serum pseudo-cholinesterase activities. To our knowledge, this is the first report of an aldicarb poisoning documented by repeated measurements of the drug in the intoxicated person.

Topics: Adult; Aldicarb; Atropine; Butyrylcholinesterase; Chromatography, High Pressure Liquid; Female; Half-Life; Humans; Insecticides; Poisoning; Pralidoxime Compounds; Suicide, Attempted; Treatment Outcome

Aldicarb (2-methyl-2(methylthio) propanal o-[(methylamino)-carbonyl] oxime) is a pesticide manufactured since 1965. This carbamate ester is sold under the tradename, Temik, and is used as insecticide and nematicide. The Environmental Protection Agency has classified aldicarb in the highest toxicity category and has defined a strict control for its delivery and use. In Brazil and the Caribbean island, aldicarb is illegally used as a household rodenticide with a widespread risk of poisoning. Our study presents the first review of aldicarb poisoning circumstances associated with clinical and analytical findings. Moreover, the oxime treatment is discussed. Eighteen patients with cholinergic symptoms admitted to the Emergency Unit and two deceased with a history of aldicarb poisoning were included in the study. As agricultural workers, only two of them could legally use Temik. Seventy percent of the patients was managed by the Emergency Mobil Unit. Serum cholinesterase activity was always lower than 30% of the normal range and aldicarb was identified by UV spectra and retention time after liquid chromatography separation. The most common muscarinic effect was diarrhea, the main nicotinic sign fasciculation and almost half of the poisoned patients had central nervous system (CNS) depression (Glasgow Coma Score lower than 8). Four patients had serious conduction abnormalities and two of them died. These results suggest that aldicarb intoxication is always severe. Oxime treatment did not produce side effects and should be recommended whenever the pesticide involved is unknown. Effective measures should be implemented to stamp out the illicit use of aldicarb.

Topics: Adolescent; Adult; Aged; Aldicarb; Antidotes; Atropine; Child; Child, Preschool; Cholinesterases; Chromatography, High Pressure Liquid; Drug Therapy, Combination; Female; Humans; Infant; Male; Middle Aged; Pesticides; Poisoning; Pralidoxime Compounds; West Indies

Organophosphorus (OP) nerve agents are still used as warfare and terrorism compounds. Classical delayed treatment of victims of organophosphate poisoning includes combined i.v. administration of a cholinesterase reactivator (an oxime), a muscarinic cholinergic receptor antagonist (atropine) and a benzodiazepine anticonvulsant (diazepam). The objective of this study was to evaluate, in a realistic setting, the therapeutic benefit of administration of GK-11 (gacyclidine), an antiglutamatergic compound, as a complement to the above therapy against organophosphate poisoning. Gacyclidine was injected (i.v.) in combination with atropine/diazepam/pralidoxime at man-equivalent doses after a 45- or 30-min latency period to intoxicated primates (2 LD50). The effects of gacyclidine on the animals' survival, electroencephalographic (EEG) activity, signs of toxicity, recovery after challenge and central nervous system histology were examined. The present data demonstrated that atropine/diazepam/pralidoxime alone or combined with gacyclidine did not prevent signs of soman toxicity when treatment was delayed 45 min after poisoning. Atropine/diazepam/pralidoxime also did not control seizures or prevent neuropathology in primates exhibiting severe signs of poisoning when treatment was commenced 30 min after intoxication. However, in this latter case, EEG recordings revealed that additional treatment with gacyclidine was able to stop soman-induced seizures and restore normal EEG activity. This drug also totally prevented the neuropathology observed 5 weeks after soman exposure in animals treated with atropine/diazepam/pralidoxime alone. Overall, in the case of severe OP-poisoning, gacyclidine represents a promising adjuvant therapy to the currently available polymedication to ensure optimal management of organophosphate poisoning in man. This drug is presently being evaluated in a human clinical trial for a different neuroprotective indication. However, it should always be kept in mind that, in the case of severe OP-poisoning, medical intervention must be conducted as early as possible.

Topics: Animals; Anticonvulsants; Antidotes; Atropine; Brain; Cerebellum; Cerebral Cortex; Chemical Warfare Agents; Cholinesterase Reactivators; Cyclohexanes; Cyclohexenes; Diazepam; Drug Therapy, Combination; Electrocardiography; Excitatory Amino Acid Antagonists; Haplorhini; Macaca fascicularis; Male; Piperidines; Poisoning; Pralidoxime Compounds; Seizures; Soman; Time Factors

We investigated the failure of 2-PAM to protect honey bees against poisoning with paraoxon. The protective effect of the oxime 2-PAM against inhibition of acetylcholinesterase (AChE) by paraoxon was estimated in vitro and in vivo and was correlated with the mortality of paraoxon-treated bees. In vitro, 2-PAM protected 90% of AChE activity in the presence of paraoxon and reactivated more than 90% of inhibited AChE. Minor soluble and major membrane-bound forms of bee AChE presented about similar extents of reactivation, but the first order rate constant of reactivation (kobs) of the soluble form is threefold higher than that of the membrane-bound form. However, this difference did not significantly influence the reactivation kinetics of total AChE; the constant kobs of the membrane-bound form reflected that of total AChE. The linear kinetic profile of total AChE reactivation supported the conclusion that there was a single population of reactivatable species. The bimolecular rate constant of reactivation (kr), the dephosphorylation rate constant (k2), and the dissociation constant (Kd) were 646 M-1.min-1, 0.84 min-1 and 1. 30 mM, respectively. In vivo, administration of 2-PAM, after paraoxon exposure, induced a complete protection of AChE activity, but did not elicit any significant effect on mortality in paraoxon-treated bees. The inefficiency of 2-PAM to antagonize paraoxon-induced mortality was not changed by the administration of 2-PAM in pretreatment-therapy and in therapy treatments. These results indicated that the mortality of paraoxon-poisoned honey bees was not due to a lack of AChE reactivation.

Topics: Acetylcholinesterase; Animals; Bees; Cholinesterase Inhibitors; Cholinesterase Reactivators; Dose-Response Relationship, Drug; Insecticides; Paraoxon; Poisoning; Pralidoxime Compounds; Survival Rate

This study paper reports on two cases of poisoning with the organophosphorus insecticides, fenthion and omethoate. The two victims were admitted in the Intensive Care Unit (ICU) a few hours after ingestion of the two insecticides. They received appropriate treatment for organophosphorous poisoning (gastric lavage, activated charcoal, atropine and pralidoxime) and supportive care. Both patients survived. Organophosphate blood levels were determined on admission (fenthion 2.9 micrograms/ml, omethoate 1.6 micrograms/ml) and during the hospitalisation and proved to be considerably high. Slow elimination rate of the poison already distributed in the body was indicated for both pesticides. The patient with omethoate poisoning remained clinically well (Glasgow Coma Scale: 15) and was discharged three days later. The patient with fenthion poisoning, who had also ingested 30 mg of bromazepam and 720 mg of oxetoron, developed cholinergic crisis six hours after admission and was intubated for 24 days, with concomitant complications.

Topics: Adult; Antidotes; Atropine; Charcoal; Cholinesterase Inhibitors; Cholinesterase Reactivators; Critical Care; Dimethoate; Female; Fenthion; Gastric Lavage; Greece; Humans; Insecticides; Male; Middle Aged; Poisoning; Pralidoxime Compounds; Treatment Outcome

Topics: Antidotes; Clinical Trials as Topic; Dose-Response Relationship, Drug; Follow-Up Studies; Guidelines as Topic; Humans; Organophosphate Poisoning; Patient Care; Poisoning; Pralidoxime Compounds; Severity of Illness Index; Treatment Outcome

Topics: Adolescent; Adult; Antidotes; Biomarkers; Butyrylcholinesterase; Controlled Clinical Trials as Topic; Female; Humans; India; Logistic Models; Male; Middle Aged; Organophosphate Poisoning; Poisoning; Pralidoxime Compounds; Risk Assessment; Severity of Illness Index; Treatment Outcome

Topics: Antidotes; Humans; Organophosphate Poisoning; Poisoning; Pralidoxime Compounds

We performed an experiment to characterize the toxicity of soman in cynomolgus monkeys when the organophosphorus intoxication was followed by a treatment with either the three-drug therapy atropine/pralidoxime/diazepam or the association atropine/HI-6/prodiazepam. Clinical, electrophysiological and histological approaches were combined. Our data demonstrate that the protection afforded against soman toxicity was better with the combination atropine/HI-6/prodiazepam compared to atropine/pralidoxime/diazepam. This was observed transiently in term of vigilance and respiratory function of intoxicated animals, but particularly in term of their EEG- and ECG disturbances. Moreover, compared to those treated with atropine/pralidoxine/diazepam, animals treated with atropine/ HI-6/prodiazepam recovered slightly sooner and did not exhibit prostration 2 days after intoxication although their rapidity of movements was not totally restored. The final recovery observed 3 weeks after intoxication was similar for the two groups. The value of the combination of atropine/HI-6/prodiazepam vs atropine/pralidoxime/diazepam to counteract soman toxicity was also confirmed in term of brain neuroprotection since greater lesions were observed with the second three drug treatment three weeks after intoxication.

Topics: Animals; Antidotes; Atropine; Cholinesterase Inhibitors; Diazepam; Dipeptides; Drug Therapy, Combination; Electrocardiography; Electroencephalography; Macaca fascicularis; Male; Oximes; Poisoning; Pralidoxime Compounds; Prodrugs; Pyridinium Compounds; Soman

To report a case of organophosphate poisoning treated with a continuous infusion of pralidoxime chloride.. A 27-year-old white man presented with extreme agitation, muscle weakness and fasciculations, and respiratory failure after ingesting an organophosphate pesticide (Dursban, active ingredients chlorpyrifos and xylene) as a suicide attempt. Atropine sulfate and pralidoxime chloride were administered intermittently, but the patient continued to be extremely agitated and have muscle fasciculations. Subsequently, a continuous intravenous infusion of pralidoxime (8 mg/mL concentration) at 500 mg/h was initiated to help control breakthrough nicotinic symptoms. Therapy with atropine and pralidoxime was continued for approximately 72 hours. Therapy was discontinued due to the predominance of anticholinergic symptoms and the patient's increased awareness.. Severe organophosphate poisoning with nicotinic and/or central manifestations should be treated with pralidoxime in addition to atropine. The rationale supporting the use of pralidoxime as a continuous infusion in this case includes: (1) slow absorption of organophosphate compounds following exposure to large quantities, (2) unknown quantity ingested, (3) delayed nicotinic effects from redistribution of lipid-soluble organophosphate and metabolic activation of phosphorothioates such as chlorpyrifos, and (4) intensive care monitoring. There is limited documentation in the literature of continuous infusions of pralidoxime used to treat organophosphate poisoning and the stability of the admixture is unknown.. A continuous pralidoxime infusion successfully managed the prolonged nicotinic symptoms seen after ingestion of an organophosphate. A continuous infusion of pralidoxime may be particularly useful in cases of organophosphate poisoning when the extent of chemical exposure or quantity of chemical ingested is unknown but potentially toxic and the therapy must be symptomatically managed.

Topics: Adult; Antidotes; Atropine; Chlorpyrifos; Drug Therapy, Combination; Humans; Infusions, Intravenous; Insecticides; Male; Muscarinic Antagonists; Poisoning; Pralidoxime Compounds

1 In vitro studies with human erythrocyte acetylcholinesterase (AChE) and the mouse diaphragm model were performed to unravel the various microscopic reaction parameters that contribute to the dynamic equilibrium of AChE inhibition, ageing and reactivation. These data may help to define more precisely the indications and limitations of oxime therapy in organophosphate (OP) poisoning. 2 Diethylphosphoryl-AChE resulting from intoxications with parathion, chlorpyrifos, chlorfenvinphos, diazinon and other OPs is characterized by slow spontaneous reactivation and low propensity for ageing. This kind of phosphorylated enzyme is particularly susceptible to reactivation by oximes. 3 None of the oximes tested (pralidoxime, obidoxime, HI 6 and HLö 7) can be regarded as a universally suitable reactivator. Obidoxime turned out to be the most potent and most efficacious oxime in reactivating AChE inhibited by various classes of OP insecticides and tabun. Obidoxime, however, was inferior to HI 6 against soman, sarin, cyclosarin and VX. Pralidoxime was generally less potent. 4 The kinetic data of reactivation established for diethylphosphoryl-AChE of human red cells indicate that the usually recommended dosage to attain a plasma concentration of 4 micrograms/ml does not permit exploitation of the full therapeutic potential of the oximes, in particular of pralidoxime. However, in suicidal mega-dose poisoning, oximes, even at optimal plasma concentrations, may be unable to cope with the fast re-inhibition of reactivated AChE in the first days following intoxication. 5 It is suggested that oximes be administered by continuous infusion following an initial bolus dose as long as reactivation can be expected and until permanent clinical improvement is achieved.

Topics: Acetylcholinesterase; Animals; Antidotes; Cholinesterase Reactivators; Erythrocyte Membrane; Humans; Mice; Obidoxime Chloride; Organophosphate Poisoning; Organophosphorus Compounds; Poisoning; Pralidoxime Compounds

Although rodenticides historically have been among the most toxic substances available to the public and have been implicated as agents in both unintentional and suicidal exposures, the anticoagulant agents currently in use, such as coumadin and their long-acting derivatives (e.g., brodifacoum), are relatively safe. In 1995, most persons who reported exposure to anticoagulant rodenticides did not develop symptoms or require specific therapy. However, during 1994-1997, the New York City Poison Control Center (NYCPCC) was consulted about 25 patients, primarily persons who had emigrated from the Dominican Republic, who had manifestations consistent with the cholinergic toxidrome, which is not characteristic of poisoning by the anticoagulant rodenticides, after ingesting a rodenticide known as Tres Pasitos ("Three Little Steps"). In each case, the product had been purchased at a neighborhood store for use as a household rodenticide. The Environmental Investigation Unit of the New York State Department of Environmental Conservation (NYDEC) investigated the poisoning incidents. Laboratory analysis indicated that the product contained the carbamate pesticide aldicarb (2-methyl-2-(methylthio)-propionaldehyde O-(methylcarbamoyl) oxime), which is not registered for use as a rodenticide in the United States. This report presents a detailed description of two of these cases and a summary of the remaining cases.

Topics: Adult; Aldicarb; Anti-Arrhythmia Agents; Atropine; Child, Preschool; Cholinesterase Reactivators; Female; Humans; Insecticides; Male; New York City; Pest Control; Poisoning; Pralidoxime Compounds; Rodenticides

The acute toxicity of chlorpyrifos, methylchlorpyrifos, parathion and methylparathion to three age classes of Artemia salina was determined. In general, A. salina 24-h old was less sensitive to these organophosphorous insecticides (OPI) than A. salina 48-h old and A. salina 48-h old was significantly more tolerant than A. salina 72-h old, in contrast, chlorpyrifos was equally toxic to A. salina 48- and 72-h old. There were some differences among the three age classes of A. salina in the relative order of toxicity of OPI tested. The rank order of toxicity to A. salina 48-h old was methylparathion < parathion < methyl-chlorpyrifos < chlorpyrifos, while to A. salina 24- and 72-h old it was methylparathion = parathion < methyl-chlorpyrifos < chlorpyrifos. The protective effect of the cholinergic antagonists atropine, hexamethonium, pirenzepine and 11-(2-((diethyl-amino)methyl)-1-piperidinylacetyl)-5, 11-dihydro-6H-pyrido(2,3-b)-(1,4)-benzodiazepine-6-one (AF-DX 116) and a cholinesterase-reactivating oxime 2-pyridine aldoxime methochloride (2-PAM) on the mortality due to four selected OPI in Artemia salina 24-h old was investigated. The lethal action of OPI tested was completely prevented by pretreatment of Artemia salina 24-h old with 2-PAM (10(-5) M) and atropine (10(-4 )M). However no concentration of hexamethonium, pirenzepine or AF-DX 116 protected 100% of the animals poisoned by LC84 of the OPI selected, maximum protection obtained was 71 to 88%. In contrast, the maximum inhibition of mortality obtained with AF-DX 116 pretreatment was about 55% because this compound was used at concentrations which were non toxic to control Artemia salina. Atropine, hexamethonium, pirenzepine, AF-DX 116 and 2-PAM afforded 50 % protection (IC50) of Artemia salina against mortality by LC84 of the OPI selected at concentrations in the range of 6.62x10(-7)-1.6x10(-6) M, 2. 38x10(-4)-2.05x10(-3)M, 8.91x10(-7)-1.24x10(-6) M, 9.66x10(-8)-1. 34x10(-7 )M, and 1.95x10(-8)-2.73x10(-8 )M, respectively. Pretreatment of atropine plus 2-PAM to determine whether this combination afforded greater inhibition of the lethality induced by four OPI tested than pretreatment with either atropine or 2-PAM alone was investigated. Atropine (10(-5) M) in combination with 2-PAM (10(-7 )M) inhibited completely the acute toxicity of all OPI tested, while the pretreatment with atropine (10(-6) M) plus 2-PAM at the same concentration gave a inhibition of mortality (about 62%) significantly greater than

Topics: Animals; Artemia; Atropine; Chlorpyrifos; Cholinergic Antagonists; Cholinesterase Reactivators; Cysts; Hexamethonium; Insecticides; Larva; Methyl Parathion; Parasympatholytics; Parathion; Pirenzepine; Poisoning; Pralidoxime Compounds; Species Specificity; Structure-Activity Relationship

We report a 60-yr-old woman with schizophrenia, who manifested a neuroleptic malignant (NM)-like syndrome after acute organophosphate poisoning (OPP). She attempted suicide by ingesting 40% emulsions of DMTP (S-2,3-dihydro-5-methoxy-2-oxo-1,3,4-thiadizol-3-yl-methyl O,O-dimethyl phosphorodithioate) 100 ml. On admission, she was unconscious and demonstrated convulsions, depressed respiratory movements, miosis and profuse salivation. Plasma cholinesterase concentration (842 IU.L-1) was very low and OPP was diagnosed. She was treated with gastric lavage, atropine and pralidoxime (PAM). By the seventh day after admission, symptoms of OPP disappeared and serum ChE had recovered to a sub-normal level. On the 13th day, she demonstrated coma, high fever (41.0 degrees C) and lead-pipe rigidity. Serum CPK was increased (1631 IU.L-1). Dantrolene sodium iv was administered for three days. Body temperature began to decrease in 24 hr, and her consciousness, muscle rigidity and other neurological symptoms returned to normal by the 16th day after admission. She was discharged from the hospital without sequelae 55 days after admission. We conclude that OPP can predispose to an NM-like syndrome and that dantrolene may be effective in the management.

Topics: Atropine; Cholinesterase Reactivators; Cholinesterases; Dantrolene; Female; Humans; Middle Aged; Miosis; Muscarinic Antagonists; Muscle Relaxants, Central; Neuroleptic Malignant Syndrome; Organophosphate Poisoning; Organothiophosphorus Compounds; Poisoning; Pralidoxime Compounds; Respiration; Salivation; Schizophrenia; Seizures; Suicide, Attempted; Therapeutic Irrigation

Insecticide poisoning is an increasing event which requires a thorough knowledge base for diagnosis and management. Awareness of the importance of decontamination is fundamental not only in the prehospital care phase but also in the emergency department. A thorough knowledge of the essentials of emergency and critical care is indispensable for the management and support of ventilatory and circulatory functions. Specific antidotal therapy utilizing atropine and pralidoxime is usually necessary in the immediate care of acute cases. In addition, use of pralidoxime after acute exposure may contribute to a beneficial outcome. Appropriate laboratory determinations in the acute phase are necessary parameters for successful outcomes. The use of cholinesterase determinations for diagnostic and prognostic purposes is discussed.

Topics: Antidotes; Atropine; Blood Circulation; Carbamates; Cholinesterases; Critical Care; Decontamination; Emergency Medical Services; Emergency Service, Hospital; Humans; Insecticides; Organophosphorus Compounds; Poisoning; Pralidoxime Compounds; Respiration; Treatment Outcome

Topics: Animals; Antidotes; Carbamates; Cat Diseases; Cats; Poisoning; Pralidoxime Compounds

(1) Retrospective evaluation of the clinical course of carbamate poisoning and the effect of oxime therapy in children. (2) In vitro study of the effect of oximes on the reactivation of carbamylated cholinesterase.. (1) Clinical survey: The records of 26 children intoxicated with carbamates were examined retrospectively. The poisoning agents in all cases were positively identified as methomyl or aldicarb by gas chromatography-mass spectrometry. (2) Laboratory study: The direct effect of obidoxime and of pralidoxime on acetylcholinesterase activity in vitro was investigated in normal human packed red blood cells pretreated with an organophosphate (paraoxon) or a carbamate (aldicarb or methomyl).. Pediatric intensive care unit of a teaching hospital.. Twenty-six infants and young children (aged 1 to 8 years) admitted to the pediatric intensive care unit with severe carbamate intoxication.. All cases had been treated with repeated doses of atropine sulfate (0.05 mg/kg) administered every 5 to 10 minutes until muscarinic symptoms disappeared. Obidoxime chloride (Toxogonin, 6 mg/kg) was administered on admission, and again after 4 to 5 hours.. Predominant symptoms were related to central nervous system and nicotinic effects. All the patients showed marked improvement within several hours and recovered completely within 24 hours. None of the children deteriorated and none showed exacerbation of cholinergic symptoms after obidoxime treatment. In vitro, oximes reactivated acetylcholinesterase inhibited with paraoxon, whereas no significant effect of oximes on carbamylated enzyme activity was observed.. Based on the recovery of all cases, as compared with other reports of carbamate poisoning treated with atropine alone, it is concluded that, in the case of aldicarb or methomyl poisoning, oxime therapy apparently does not contribute to the recovery of poisoned patients. In cases of poisoning by an unknown pesticide or of mixed poisoning, oxime therapy can prove beneficial because no negative effects of the therapy can be discerned.

Topics: Aldicarb; Antidotes; Atropine; Carbamates; Child; Child, Preschool; Cholinesterases; Drug Therapy, Combination; Female; Humans; Infant; Male; Methomyl; Obidoxime Chloride; Oximes; Paraoxon; Poisoning; Pralidoxime Compounds; Retrospective Studies

This study compared the efficacy of HI6 and 2-PAM against nerve agent (soman, tabun, sarin, and VX)-induced lethality in the atropinesterase-free rabbits pretreated with vehicle (controls) or pyridostigmine. Treatment was administered at signs or 2 min after agent challenge and consisted of oxime (100 mumol/kg) + atropine (13 mg/kg) (alone or together with diazepam). Twenty-four-h LD50 values were calculated for soman- and tabun-intoxicated animals, whereas 24-h survival was noted in animals given 10 LD50s of sarin or VX. In pyridostigmine and control rabbits intoxicated with soman and treated with oxime + atropine (alone or together with diazepam), HI6 was 3-5 times more effective than 2-PAM. In contrast, HI6 was less effective than 2-PAM against tabun poisoning. In pyridostigmine-pretreated animals exposed to tabun, efficacy was increased more than 3-fold when compare to tabun-challenged animals treated with atropine + HI6 alone. Both oximes were highly effective against sarin and VX. These findings suggest that HI6 could replace 2-PAM as therapy for nerve agent poisoning, because it is superior to 2-PAM against soman, and when used in pyridostigmine-pretreated animals, it affords excellent protection against all four nerve agents when used in combination with atropine (alone or together with diazepam) therapy.

Topics: Animals; Antidotes; Atropine; Chemical Warfare Agents; Cholinesterase Inhibitors; Cholinesterase Reactivators; Diazepam; Lethal Dose 50; Male; Organophosphate Poisoning; Organophosphates; Organophosphorus Compounds; Organothiophosphorus Compounds; Oximes; Poisoning; Pralidoxime Compounds; Pyridinium Compounds; Pyridostigmine Bromide; Rabbits; Sarin; Soman; Specific Pathogen-Free Organisms

We report severe organophosphate poisoning complicated by hypotension and ischemic sequelae in two patients with pre-existing vascular disease. Both patients had a low total peripheral resistance and high cardiac output that were significantly reversed by doses of atropine in excess of those required to control other muscarinic symptoms. Cerebral infarcts and gangrene requiring a below knee amputation were complications of the poisonings. It is proposed that the ischemic complications are due to paradoxical vasoconstriction by acetylcholine at sites of endothelial injury. One patient, who had taken fenthion, also had a significantly delayed peak and prolonged, 2-3 week, systemic toxicity. We propose that stability of the plasma cholinesterase at 6 to 8 h after temporarily suspending oxime provides a rapid guide to the duration of therapy, especially in patients whose complications make clinical assessment difficult.

Topics: Acetylcholinesterase; Aged; Alprazolam; Atropine; Cholinesterase Inhibitors; Cholinesterase Reactivators; Dimethoate; Drug Interactions; Fenthion; Humans; Male; Middle Aged; Poisoning; Pralidoxime Compounds; Vascular Diseases; Vascular Resistance

Various organophosphorus compounds with low acute toxicity levels are widely used as insecticides. Human acute poisoning by organophosphates has often occurred accidentally. We determined the activity and isoenzyme patterns of serum cholinesterase (ChE) obtained from 13 human patients who attempted suicide with various organophosphates, i.e. Fenitrothion, Malathion, Isoxathion, Pyridaphenthion and Trichlorfon, and studied on the changes in the activity and isoenzyme patterns of serum ChE after ingestion. The following results were obtained. 1) Twenty ChE isoenzyme bands from normal human serum were detected by electrophoretic separation on polyacrylamide gradient gel. The main bands in the ChE isoenzyme pattern in normal serum were bands 4 and 5 which had the highest activity of acetylcholinesterase (AChE) with a molecular weight of 600,000-800,000, and bands 7, 12, 14, 17 and 18. 2) Inhibition of serum ChE activity was more severe as the amount ingested increased in patients who took Fenitrothion and Malathion. Reactivation of serum ChE activity was very slow in patients treated with PAM (2-pyridine aldoxime methiodide) in the late stage of ingestion or whose symptoms reappeared. 3) There were no differences in the patterns of serum ChE isoenzyme by organophosphorus compound. Band 7 disappeared in the serum ChE isoenzyme of almost every patient, and bands 12, 18, 14 and 17 of the serum ChE isoenzyme disappeared successively with the decline of serum ChE activity. Only band 5 of the isoenzyme remained in cases who had serum ChE activity lower than 5% of normal. 4) All 13 patients were treated with PAM and atropine immediately after being admitted to hospitals. We could not clearly determine the efficacy of PAM on reactivation of serum ChE activity and isoenzyme, because it was impossible in human poisoning to compare PAM efficacy with no treatment and with pre- and post-PAM treatment. 5) The activity and isoenzyme patterns of serum ChE recovered rapidly after combined hemoperfusion and hemodialysis treatment (HP-HD treatment) of the patients poisoned with Malathion. But HP-HD treatment had no effect on poisoning by Fenitrothion and Isoxathion. These findings demonstrated the changes in the activity and isoenzyme pattern of serum ChE in patients poisoned with several organophosphates after PAM and HP-HD treatment.

Topics: Acute Disease; Adult; Aged; Animals; Cholinesterases; Female; Hemoperfusion; Humans; Isoenzymes; Male; Middle Aged; Organophosphate Poisoning; Poisoning; Pralidoxime Compounds; Rats; Renal Dialysis

The metabolic fate of 2-PAM and its antidotal effect on organophosphorus compound poisoning in rats were studied. When 14C-2-PAM was administered intravenously, the amount of 14C reaching the brain was small. Following administration by intramedullary injection, 14C was present in high concentrations in the brain, and 72-90% of the 14C present in the brain corresponded to the unchanged form of 2-PAM. 2-PAM was rapidly excreted into the urine and feces following either intramedullary or intravenous administration. The half-life of 2-PAM in the brain following intramedullary administration was 1.52 hr. Intramedullary administration of 2-PAM to rats poisoned with fenitrothion or malathion enabled their survival and induced reactivation of brain cholinesterase.

Topics: Animals; Antidotes; Brain; Cholinesterase Reactivators; Cholinesterases; Enzyme Activation; Fenitrothion; Half-Life; Injections; Injections, Intravenous; Malathion; Male; Organophosphate Poisoning; Poisoning; Pralidoxime Compounds; Rats; Rats, Sprague-Dawley; Subarachnoid Space; Tissue Distribution

Topics: Antidotes; Humans; Infusions, Intravenous; Organophosphate Poisoning; Poisoning; Pralidoxime Compounds

This study was done to assess the effects of pyridostigmine (PYR) on a) the accumulation of labelled VX and soman within the brain, b) the therapeutic efficacy of atropine and oxime (2-PAM or HI-6) against intoxication by VX and soman and c) oxime-induced reactivation of inhibited acetylcholinesterase (AChE). In all experiments, rats were given PYR (131 micrograms/kg, im; I70 dose for whole blood AChE) or vehicle 30 min prior to nerve agent. In estimating 3H-agent the accumulation in the brain or estimating blood AChE activity, sufficient soman (47 micrograms/kg, iv) or VX (21.3 micrograms/kg, iv) was given to inhibit 50% of brain AChE activity. In assessing therapeutic efficacy and oxime-induced reactivation of blood AChE, rats were pretreated with PYR, challenged with agent and treated with atropine (16 mg/kg, im) and HI-6 or 2-PAM (100 umoles/kg, im) 30 sec post agent. Whole blood was collected by tail bleeding to monitor peripheral AChE activity at various time points before and after PYR and challenge. Pyridostigmine failed to alter covalent binding of labelled VX or soman in the brain. The 24-hr survival data showed that PYR reduced the therapeutic benefit of atropine and oxime against VX intoxication (but not soman). Protective ratios in VX-challenged rats given vehicle or PYR and treated with atropine + 2-PAM decreased slightly from 2.5 to 2.1 (p > .05), whereas with atropine + HI-6 they decreased significantly from 3.8 to 2.4. Also, AChE reactivation by HI-6 in VX-challenged rats was greater (p < .05) in vehicle- than in PYR-pretreated rats. HI-6 significantly reactivated AChE activity in both pretreatment groups (PYR or vehicle) given soman. The data suggest that PYR decreases the overall recovery of inhibited AChE in VX-challenged rats given HI-6; under the conditions used, this adverse effect decreases atropine+oxime efficacy against VX-induced lethality.

Topics: Animals; Antidotes; Cholinesterase Inhibitors; Male; Organothiophosphorus Compounds; Oximes; Poisoning; Pralidoxime Compounds; Pyridinium Compounds; Pyridostigmine Bromide; Rats; Rats, Sprague-Dawley; Soman

Using pharmacokinetic data from healthy human volunteers in a bicompartmental pharmacokinetic model, a repeated dose scheme for pralidoxime methylsulphate (Contrathion) was developed producing plasma levels remaining above the assumed "therapeutic concentration" of 4 mg.l-1. Using the same data, it was found that a concentration of 4 mg.l-1 could also be obtained by a loading dose of 4.42 mg.kg-1 followed by a maintenance dose of 2.14 mg.kg-1.h-1. In order to study the pharmacokinetic behaviour of pralidoxime in poisoned patients, this continuous infusion scheme was then applied in nine cases of organophosphorus poisoning (agents: ethyl parathion, ethyl and methyl parathion, dimethoate and bromophos), and the pralidoxime plasma levels were determined. The mean plasma levels obtained in the various patients varied between 2.12 and 9 mg.l-1. Pharmacokinetic data were calculated, giving a total body clearance of 0.57 +/- 0.27 l.kg-1.h-1 (mean +/- SD), an elimination half-life of 3.44 +/- 0.90 h, and a volume of distribution of 2.77 +/- 1.45 l.kg-1.

Topics: Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Insecticides; Male; Organothiophosphorus Compounds; Poisoning; Pralidoxime Compounds

The efficacy of 2-Pyridine aldoximide methiodide (PAM) for lethal acute poisoning by fenitrothion (FNT) was investigated in mice and dogs. Sumithion (FNT 51.7%, emulsifiers 12.5% and xylol 35.8%) was used as fenitrothion. 1. FNT at 1500 mg/kg was administered orally to mice. After ten minutes 50 mg/kg of PAM was injected once iv, and plasma, erythrocyte, brain, liver and kidney ChE activities were investigated 30 and 60 min later. Recovery in ChE activity was found in every organ but the brain at 30 min, but no efficacy of PAM was observed at 60 min. 2. After administering 1500 mg/kg of FNT orally to mice, the life-saving effect was studied from the changes in mortality due to variation of PAM route, dosage and number of administrations. With oral administration of 1500 mg/kg of FNT, 75 to 85% of the animals died. The mortality ranged from 80 to 95% when the animals received a single intravenous injection of 50 mg/kg of PAM between zero and 60 min following the FNT administration. Thus, a single intravenous administration of PAM at 50 mg/kg showed no life-saving effect on the animals given FNT. However, the mortality was reduced to 45% when the animals received repeated subcutaneous injections of 20 mg/kg of PAM at a 3-hr interval from just after administration of FNT over 24-hr. In other repeated subcutaneous injection experiments, the mortality ranged from about 55 to 65%. In any PAM-treated group, the survival time was prolonged. This life-prolonging effect was more marked in the case of repeated subcutaneous injections of PAM by 12-hr and even more by 24-hr, than in the case of a single intravenous injection. FNT treatment caused marked salivation and watery diarrhea, and PAM clearly inhibited these signs of the muscarinic action of FNT. There was a high relationship between this inhibitory effect of PAM on the muscarinic action and its life-prolonging or life-saving effect. 3. PAM (150 mg/animal/shot, iv) was given 12 or 13 times during 7 hr from 10 min (4 animals), 3 hr (1 animal) and 6 hr (2 animals) after administration of FNT at 150 mg/kg. The effects of PAM on survival, plasma ChE activity, plasma protein (TP) and hematocrit (Ht) values were examined. The 3 dogs given FNT alone all died within 53 hr of administration, whereas 6 out of 7 animals treated with PAM survived.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Antidotes; Cholinesterase Reactivators; Cholinesterases; Dogs; Drug Evaluation, Preclinical; Fenitrothion; Male; Mice; Poisoning; Pralidoxime Compounds

Twenty two cases of endosulfan poisoning with their symptomatology are reported. The management and lack of awareness regarding specific treatment are highlighted.

Topics: Adult; Antidotes; Atropine; Cholinesterase Reactivators; Endosulfan; Humans; Male; Poisoning; Pralidoxime Compounds

1. The dispositions of the acetylcholinesterase reactivators: 2PAM-I, TMB4 and R665, labelled with 14C on the oxime group, have been studied in normal rats and rats poisoned by the organophosphates Soman and A4. 2. For all three compounds, radioactivity was eliminated mostly in the urine (60-90% dose in 24 h). Faecal elimination was low (5.8-17.2% in 72 h). 3. All three compounds concentrated in kidney, but only 2PAM-I and R665 concentrated in liver. TMB4 and R665 concentrated in mucopolysaccharide-containing tissues such as cartilage and intervertebral disc. Other tissues were weakly and uniformly labelled. Soman poisoning does not modify the kinetic parameters of both compounds, but A4 poisoning increases 2PAM-I tissue concentration. 4. Chromatography of urine and plasma showed only unchanged 2PAM-I, TMB4 and R665 in both healthy and poisoned animals. Despite the high concentration of 2PAM-I and R665 in liver, these oximes are not metabolized.

Topics: Acetylcholinesterase; Animals; Carbon Radioisotopes; Cholinesterase Reactivators; Male; Organophosphate Poisoning; Oximes; Poisoning; Pralidoxime Compounds; Rats; Rats, Inbred Strains; Tissue Distribution; Trimedoxime

Topics: Adolescent; Antidotes; Bronchopneumonia; Drug Therapy; Insecticides; Malathion; Poisoning; Pralidoxime Compounds; Toxicology

Topics: Animals; Atropine; Cattle; Cattle Diseases; Cholinesterases; Clinical Enzyme Tests; Goats; Insecticides; Livestock; Pharmacology; Phosphates; Poisoning; Pralidoxime Compounds; Sheep; Sheep Diseases; Statistics as Topic; Toxicology