Management Of Organophosphate Poisoning Research Articles

Atropine Induced Delirium in Organophosphate (OP) Insecticide Poisoning: A Case Report

: Delirium is a condition associated with disturbances in mental abilities attributing to the reduced awareness of one’s environment. The onset of delirium is usually rapid, which may last for hours or even few days. Organophosphate poisoning (OP poisoning) is one of the leading causes associated with suicidal attempts and major admissions in the intensive care unit. Few literatures have been reported regarding the use of atropine and the concurrent risk of adverse reactions. Manifestations of atropine overdose and misuse includes dryness of the mouth, tachycardia and in addition, psychotic symptoms such as restlessness and excitement, hallucinations, delirium etc. A 14 year-old female patient who manifested with delirium and associated symptoms after atropine administration during the management of OP poisoning. Atropine administrations should be monitored based on the acetyl cholinesterase enzyme estimation and the dose may be titrated to prevent the worsening of the present conditions. Monitoring of the signs and symptoms is the key element to prevent the adverse effects.Key words: Atropine, Organophosphate, Poison, Delirium, Adverse drug reaction, Acetyl cholinesterase estimation.

Possible role for anisodamine in organophosphate poisoning.

In cases of organophosphate poisoning, patients are treated with a combination of antidotes. In addition to these poison-directed antidotes, patients may require extra oxygen and artificial ventilation; other modalities may also be needed due to the wide range of toxic effects. Anisodamine is a belladonna alkaloid, and like other drugs from this family is non subtype-selective muscarinic, and a nicotinic cholinoceptor antagonist, which has been employed in traditional Chinese medicine. As a muscarinic antagonist, it displays similar pharmacological effects to atropine and scopolamine. However, anisodamine is not only less potent than atropine and scopolamine but also less toxic. Current in vitro and animal model studies have demonstrated that anisodamine has protective effects in a variety of diseases. Organophosphate poisoning involves not only the central and peripheral nervous systems, but also the cardiac and respiratory systems, as well as activation of inflammatory processes and oxidative stress. Therefore, the anticholinergic and additional activities of anisodamine appear to be relevant and justify its consideration as an addition to the existing remedies. However, more research is needed, as at present data on the role of anisodamine in the management of organophosphate poisoning are limited. Here, we review the beneficial effects of anisodamine on processes relevant to organophosphate poisoning.

A Study on Two Dose Regimens of Pralidoxime in the Management of Organophosphate Poisoning

Background: The role and proper dose of pralidoxime in the treatment of Organophosphorus (OP) compounds poisoning is an unresolved issue .This study was designed to compare the regimen recommended by the World Health Organization (WHO) with the commonly used standard regimen of pralidoxime. Methods: This was a randomized open labeled prospective study on OP poisoned patients admitted to JSS Hospital, Mysore, India during November 2009 to January 2012. WHO regimen of 2 g pralidoxime bolus followed by 8mg/kg/h infusion (study group) compared with standard regimen of 2 g pralidoxime bolus followed by 1g 6 hourly (control group). Results: In total, 82 patients were studied. Thirty-seven patients were randomized into the study group and 45 patients to the control group. All patients had moderate clinical severity. Although fewer patients in the study group required mechanical ventilation in comparison to the controls (12 vs. 22), the difference was not significant (P = 0.13). The death rate was lower in the study group though the difference was not also significant (P = 0.17). Mean (SD) duration of mechanical ventilation in the study group was significantly lower than controls (4.1 (1.6) vs. 6.6 (1.7) days; P = 0.01). Mean dosage of atropine administered was significantly lower in the study group compared to controls (345.0 (90.6) vs. 933.1 (162.3) mg; P = 0.001). Furthermore, 15 controls (33.3%) developed intermediate syndrome whereas no patient (0%) in the study group had such complication, which showed a significant difference (P < 0.001). Conclusion: A dose regimen of pralidoxime consisting of 2 g pralidoxime bolus followed by 8mg/kg/h infusion reduces morbidity and mortality in moderate cases of OP poisoning. The WHO dose regimen had significantly better outcomes compared to the standard dose regimen. How to cite this article: Mahesh M, Gowdar M, Venkatesh CR. A Study on Two Dose Regimens of Pralidoxime in the Management of Organophosphate Poisoning. Asia Pac J Med Toxicol 2013;2:121-5.

Letters to the Editor

Letters to the Editor

Homicidal Attempt by Injection of an Organophosphate Insecticide in a Seven Month-Old Baby

The present case reports the first ever case of homicidal poisoning due to injection of an organophosphate insecticide with successful resuscitation and reporting. Case: A 7-month-old baby presented to the emergency department with a history of insect bite since 5 hours by his relatives with a main complaint of irritability, disturbed conscious level, irregular respiration and wheezy chest. The injection site has appeared as oval area of redness and swelling at right elbow region that were noticed by the pediatric emergency department physician, with a medical history of resistance to medications for suspected insect bite (antihistaminic and corticosteroids in pediatric dosage) from referral hospital. By toxicological consultation, we revealed disturbed conscious level (GCS 10), pinpoint pupils and increase all body secretions, salivation, bronchorrhea and incontinence in urine and stools. The clinical toxicology consultant suspected a case of acute anticholine esterase toxicity and recommended a plasma pseudocholinesterase level that appeared to be very low, consistent with acute intoxication with organophosphate insecticide. The management of organophosphate poisoning was started, as airway management, administration of oxygen and fluids, as well as atropine in increasing doses and pralidoxime. Our case report emphasizes the necessity of a detailed history taken and careful smart medical examination for the possibility of homicide in such cases. Although injection sites may be the expected results of insect bite, medical treatment, dermal lesions also may be associated with injections of toxic substances.

Regeneration of Red Cell Cholinesterase Activity Following Pralidoxime (2-PAM) Infusion in First 24 h in Organophosphate Poisoned Patients

Oximes such as pralidoxime chloride reactivate acetylcholinesterase. However their role in management of organophosphate poisoning is controversial. The study was carried out to find effectiveness of pralidoxime chloride (2-PAM) in regenerating red cell acetyl cholinesterase in first 24h following administration of it in dose recommended by WHO. Eight patients with OPP [chlorpyriphos (3), phorate (3), dichlorvos (1) and monocrotophos (1) who fulfilled the criteria for inclusion were investigated. In addition to decontamination and atropine, all these patients were administered 30mg/kgbodywt of 2-PAM as bolus dose followed by 7.5mg/kgbodywt/h with maximum dose being 500mg/h as continuous infusion till first 24h. Red cell AChE activity was estimated every 15min for first 4h, one hourly for next 4h and then 2 hourly till 24h and subsequently without 2-PAM every 12h till 7days or discharge or death which ever earlier. In all the patients maximum increase in activity was observed in first 4h following which rise was very slow despite continued 2-PAM infusion and reaching a steady state in 20h in all the cases. The increase in red cell AChE activity observed in diethyl group at 24h of 2-PAM infusion was 154% vs. 81% in dimethyl group. At 7days the increase in activity was 215% vs. 118% respectively. However on multiple repeated ANOVA, no statistically significant difference was observed between diethyl and dimethyl groups at admission and discharge (P>0.05). Similarly no significant difference was observed in three groups when patients were categorized according to WHO classification of organophosphates (P>0.05). The maximum increase in red cell AChE activity occurs in first 4h of 2-PAM administration followed by a slow increase despite 2-PAM infusion till 24h.

Cardiac Effects of Magnesium Sulfate Pretreatment on Acute Dichlorvos-Induced Organophosphate Poisoning: An Experimental Study in Rats

Although atropine and oximes are traditionally used in the management of organophosphate poisoning, investigations have been directed to finding additional therapeutic approaches. Thus, the aim of this study was to evaluate the cardiac effects of magnesium sulfate pretreatment on dichlorvos intoxication in rats. Rats were randomly divided into three groups as control, dichlorvos, and magnesium sulfate groups. After 6 h of dichlorvos or corn oil (as a vehicle) injection, venous blood samples were collected, and cardiac tissue samples were obtained. Biochemical analyses were performed to measure some parameters on serum and cardiac tissue. Immunohistochemical analyses of apoptosis and inducible nitric oxide (NO) synthase showed no change in cardiac tissue. Serum cholinesterase levels were markedly depressed with dichlorvos, and further suppressed markedly with magnesium sulfate pretreatment. Although we have demonstrated that serum NO levels in dichlorvos and magnesium sulfate groups were lower than the control group, cardiac tissue NO levels in magnesium sulfate group were higher than the other two groups. Mortality was not significantly affected with magnesium sulfate pretreatment. Uncertainty still persists on the right strategies for the treatment of organophosphate acute poisoning; however, it was concluded that our results do not suggest that magnesium sulfate therapy is beneficial in the management of acute dichlorvos-induced organophosphate poisoning, and also further studies are required.

Imidazenil, a non-sedating anticonvulsant benzodiazepine, is more potent than diazepam in protecting against DFP-induced seizures and neuronal damage

Organophosphate (OP)-nerve agent poisoning may lead to prolonged epileptiform seizure activity, which can result in irreversible neuronal brain damage. A timely and effective control of seizures with pharmacological agents can minimize the secondary and long-term neuropathology that may result from this damage. Diazepam, the current anticonvulsant of choice in the management of OP poisoning, is associated with unwanted effects such as sedation, amnesia, cardio-respiratory depression, anticonvulsant tolerance, and dependence liabilities. In search for an efficacious and safer anticonvulsant benzodiazepine, we studied imidazenil, a potent anticonvulsant that is devoid of sedative action and has a low intrinsic efficacy at α1- but is a high efficacy positive allosteric modulator at α5-containing GABA A receptors. We compared the potency of a combination of 2 mg/kg, i.p. atropine with: (a) imidazenil 0.05–0.5 mg/kg i.p. or (b) equipotent anti-bicuculline doses of diazepam (0.5–5 mg/kg, i.p.), against diisopropyl fluorophosphate (DFP; 1.5 mg/kg, s.c.)-induced status epilepticus and its associated neuronal damage. The severity and frequency of seizure activities were determined by continuous radio telemetry recordings while the extent of neuronal damage and neuronal degeneration were assessed using the TUNEL-based cleaved DNA end-labeling technique or neuron-specific nuclear protein (NeuN)-immunolabeling and Fluoro-Jade B (FJB) staining, respectively. We report here that the combination of atropine and imidazenil is at least 10-fold more potent and longer lasting than the combination with diazepam at protecting rats from DFP-induced seizures and the associated neuronal damage or ongoing degeneration in the anterior cingulate cortex, CA1 hippocampus, and dentate gyrus. While 0.5 mg/kg imidazenil effectively attenuated DFP-induced neuronal damage and the ongoing neuronal degeneration in the anterior cingulate cortex, dentate gyrus, and CA1 hippocampus, 5 mg/kg or a higher dose of diazepam is required to produce similar protective effects. These finding suggests that imidazenil, a non-sedating anticonvulsant BZ ligand, is a more potent, effective, and safer drug than diazepam in protecting rats from DFP-induced seizures and the associated neuronal damage and/or ongoing neuronal degeneration.

Advances in the management of organophosphate poisoning

Organophosphate (OP) poisoning is commonly encountered in agricultural communities. The mainstay of therapy in OP poisoning is the use of atropine. However, several other therapies have been evaluated. Although oxime has been the most studied antidote, results in humans have been disappointing and limited by the lack of well-designed, prospective, randomised controlled trials. The key factor in determining outcomes in OP poisoning appears to be the timing of antidote administration. Other adjuvants, such as magnesium, fresh frozen plasma and haemoperfusion appear promising, and need to be explored further. A multi-faceted approach may be the answer to improving outcomes in OP poisoning. This review evaluates the advances in OP management over the last 20 years.

Increased morbidity and mortality in acute human organophosphate-poisoned patients treated by oximes: a meta-analysis of clinical trials

Organophosphates are one of the most common causes of poisoning, especially in the Third world, with high morbidity and mortality. The treatment of this type of poisoning involves the use of atropine and oximes. Atropine has been used successfully in large doses to counteract the muscarinic effects of organophosphate poisoning, but the efficacy of oximes in the management of this poisoning remains under question. In this study, we undertook a meta-analysis by reviewing all clinical trials to evaluate the efficacy of oximes in the management of organophosphate poisoning. The databases of PUBMED, EMBASE, Cochrane, SCOPUS, and the search engine of Google were searched for all clinical trials on the use of oximes in organophosphate poisoning. The inclusion criteria were death, development of intermediate syndrome, and need for ventilation. Six clinical trials met the inclusion criteria and were included in the metaanalysis. The chi2 tests for heterogeneity (P = 0.25, 0.16, and 0.33, respectively) indicated that the included studies were not significantly heterogeneous and could be combined. A significant relative risk (P = 0.0017) for death among oxime-exposed was 2.17 (95% CI of 1.34-3.51). The 'need for ventilation' in patients who received oxime was higher (P = 0.03) than those who did not receive oxime with a relative risk of 1.53 (1.16-2.02). The incidence of 'intermediate syndrome' for oxime-exposed patients was significantly higher (P = 0.01) than oxime non-exposed patients with a relative risk of 1.57 (95% CI 1.11-2.11). It can be concluded that oximes are not effective in the management of organophosphate-poisoned patients and, surprisingly, they can be dangerous and worsen the patient's clinical situation.

Organophosphate poisoning.

Organophosphates are commonly used as pesticides around the world. Exposures to organophosphates cause a significant number of poisonings and deaths each year. Organophosphates bind and inhibit cholinesterase enzymes. Acute toxicity manifests as a cholinergic crisis with excessive glandular secretions, altered mental status, and weakness. Several delayed syndromes have also been associated with organophosphate exposure, including a myasthenic-like syndrome, peripheral neuropathies, neuropsychiatric abnormalities, and extrapyramidal disorders. Clinical features and management of organophosphate poisoning is reviewed with emphasis on those affecting the central and peripheral nervous system.

Organophosphate poisoning in the intensive care unit

Organophosphate pesticides are widely used agricultural products that act as acetycholinesterase inhibitors. This study aimed to describe the presentation and management of organophosphate poisoning (OPP) in the intensive care unit (ICU).

Prevention and Management of Organophosphate Poisoning

The organophosphates are the pesticides most often involved in serious human poisoning. That involvement is likely to increase, because recent governmental actions against the use of DDT and related organochlorine pesticides will likely increase the domestic and agricultural use of the organophosphate pesticides. Accordingly, practicing physicians in all communities should know how to diagnose and treat organophosphate intoxication and how to advise patients on the principles of poisoning prevention. The organophosphate pesticides, a closely related family of chemicals, share a number of characteristics which are of considerable importance to the clinician. They are widely used as insecticides, and all are cholinesterase inhibitors of varying potency. All may penetrate the intact skin but do not accumulate in body tissues as do many of the chlorinated hydrocarbon pesticides. The organophosphates are nonpersistent in the environment; that is, after application they rapidly break down into relatively nontoxic substances. Lastly, all are capable of

Prevention and management of organophosphate poisoning

Prevention and management of organophosphate poisoning