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Organophosphate poisoning remains a global health crisis without efficacious treatments to prevent neurotoxicity. We examined whether antidotal tiger nut and coconut dietary intervention could ameliorate neurobehavioral deficits from organophosphate dichlorvos-induced gut-brain axis dysregulation in a mouse model. Mice were divided into groups given control diet, dichlorvos-contaminated diets, or dichlorvos plus nut-enriched diets. They were exposed to a DDVP-contaminated diet for 4 weeks before exposure to the treatment diets for another 8 weeks. This was followed by behavioural assessments for cognitive, motor, anxiety-, and depressive-like behaviours. Faecal samples (pre- and post-treatment), as well as blood, brain, and gut tissues, were collected for biochemical assessments following euthanasia. Dichlorvos-exposed mice displayed impairments in cognition, motor function, and mood along with disrupted inflammatory and antioxidant responses, neurotrophic factor levels, and acetylcholinesterase activity in brain and intestinal tissues. Weight loss and altered short-chain fatty acid levels additionally indicated gut dysfunction. However, intervention with tiger nut and/or coconut- enriched diet after dichlorvos exposure attenuated these neurobehavioral, and biochemical alterations. Our findings demonstrate organophosphate-induced communication disruptions between the gut and brain pathways that manifest in neuropsychiatric disturbances. Overall, incorporating fibre-rich nuts may represent an antidotal dietary strategy to reduce neurotoxicity and prevent brain disorders associated with organophosphate poisoning.

Objective: Organophosphates are the insecticides commonly used worldwide. Inadequate treatment in organophosphates poisoning increases morbidity, and mortality. Purpose of the work was to determine the effect of standard treatment alone versus standard treatment plus plasmapheresis on the levels of serum pseudo-cholinesterase, and erythrocyte acetyl cholinesterase in severe patients with organophosphates poisoning. Material and Method: This research is a prospective study. Patients diagnosed with organophosphates poisoning were included in the work. The patients were divided into two groups as the intervention group, and the standard group. The intervention group, plasmapheresis was performed in addition to the standard treatment. Results: The research was conducted with forty cases. (Intervention group n:21, standard group n:19). Serum pseudo-cholinesterase values were 482.5 u/L at baseline, 3723 u/L after plasmapheresis. Erythrocyte acetyl cholinesterase values were 1.91 u/mL on admission, 2.53 u/mL after plasmapheresis. Erythrocyte acetyl cholinesterase and serum pseudo-cholinesterase values were compared between the two groups daily from the admission of patients to intensive care units during the first 5 days, and on the last day in the intensive care units. There was no statistical difference between two groups (p gt; 0.05), except for the second day. It was observed that there was a statistically significant difference between the pseudo-cholinesterase values in the second day comparison of both groups (p=0.028). Conclusion: In conclusion, plasmapheresis treatment may contribute positively to pseudo-cholinesterase level. This treatment may have provided additional time for the organophosphates to be eliminated from the body. Although acetyl cholinesterase reactivation is achieved with oxime treatment, the clinical effect of this treatment is not clear.

Olesoxime, a cholesterol derivative with an oxime group, possesses the ability to cross the blood–brain barrier, and has demonstrated excellent safety and tolerability properties in clinical research. These characteristics indicate it may serve as a centrally active ligand of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), whose disruption of activity with organophosphate compounds (OP) leads to uncontrolled excitation and potentially life-threatening symptoms. To evaluate olesoxime as a binding ligand and reactivator of human AChE and BChE, we conducted in vitro kinetic studies with the active metabolite of insecticide parathion, paraoxon, and the warfare nerve agents sarin, cyclosarin, tabun, and VX. Our results showed that both enzymes possessed a binding affinity for olesoxime in the mid-micromolar range, higher than the antidotes in use (i.e., 2-PAM, HI-6, etc.). While olesoxime showed a weak ability to reactivate AChE, cyclosarin-inhibited BChE was reactivated with an overall reactivation rate constant comparable to that of standard oxime HI-6. Moreover, in combination with the oxime 2-PAM, the reactivation maximum increased by 10–30% for cyclosarin- and sarin-inhibited BChE. Molecular modeling revealed productive interactions between olesoxime and BChE, highlighting olesoxime as a potentially BChE-targeted therapy. Moreover, it might be added to OP poisoning treatment to increase the efficacy of BChE reactivation, and its cholesterol scaffold could provide a basis for the development of novel oxime antidotes.

Background: Organophosphorus compounds are widely used as pesticides in agriculture practicing countries like India. Since it is readily available and accessible, it is one of the most commonly used agents for suicidal poisoning. The current study was undertaken to evaluate the performance of the SOFA score (scoring system) and the serum lactate level (laboratory parameter) as a mortality predictor in organophosphorus poisoning. Material and Methods: This prospective observational study was conducted at AIIMS, Bhubaneswar, for 17 months. The study population included all patients with an alleged history of ingestion of organophosphorus (OP) compounds reporting to the casualty. The receiver operating characteristic (ROC) curve and the logistic regression analysis were used for the analysis. Results: In our study, 75 patients with OP poisoning were studied after satisfying the inclusion criteria. OP poisoning was commonly seen in married males aged 21–40 years. Twelve (16%) patients died during the process of treatment. There was a statistically significant difference in the mean SOFA score, serum lactate level, pH value, and mean duration of hospital stay between the discharged and the deceased patients. In the current study, the ROC curve analysis used to assess the predictor of the outcome of OP poisoning showed that the area under the curve for SOFA score and serum lactate level were 0.794 (95% CI 0.641–0.948) and 0.659 (95% CI 0.472–0.847), respectively. Conclusion: Sequential Organ Failure Assessment (SOFA) score is significantly associated with the outcome of organophosphate poisoning and can be utilized to predict mortality.

Introduction: Poisoning is a serious public health issue in developing countries like Nepal. Information about poisoning may be helpful for poisoning prevention and hospital treatment, aiding in the development of measures that lower the morbidity and mortality associated with poisoning. This study aimed to find out the prevalence of poisoning among autopsies conducted in the Department of Forensic Medicine and Toxicology in a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among autopsied cases in the Department of Forensic Medicine and Toxicology in a tertiary care centre. Data from 1 October 2020 to 1 April 2022 was collected between 22 December 2022 to 30 December 2022 from records after receiving ethical approval from the Institutional Review Committee. All autopsied cases during the study period were included with the exclusion of decomposed bodies. Convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. Results: Among 399 autopsies, 63 (15.79%) (12.21-19.37, 95% Confidence Interval) were found to be cases of poisoning. Among 63 cases, 35 (55.56%) were male and 28 (44.44%) were female. The most common substance causing poisoning was unknown with 31 (49.21%) cases, followed by organophosphates with 24 (38.10%) cases and rodenticide with 8 (12.70%) cases. Conclusions: The prevalence of poisoning among autopsies was found to be higher than similar studies conducted in similar settings.

Encapsulated phosphotriesterase nanoreactors show their efficacy in the prophylaxis and post-exposure treatment of poisoning by paraoxon. A new enzyme nanoreactor (E-nRs) containing an evolved multiple mutant (L72C/Y97F/Y99F/W263V/I280T) of Saccharolobus solfataricus phosphotriesterase (PTE) for in vivo detoxification of organophosphorous compounds (OP) was made. A comparison of nanoreactors made of three- and di-block copolymers was carried out. Two types of morphology nanoreactors made of di-block copolymers were prepared and characterized as spherical micelles and polymersomes with sizes of 40 nm and 100 nm, respectively. The polymer concentrations were varied from 0.1 to 0.5% (w/w) and enzyme concentrations were varied from 2.5 to 12.5 μM. In vivo experiments using E-nRs of diameter 106 nm, polydispersity 0.17, zeta-potential −8.3 mV, and loading capacity 15% showed that the detoxification efficacy against paraoxon was improved: the LD50 shift was 23.7xLD50 for prophylaxis and 8xLD50 for post-exposure treatment without behavioral alteration or functional physiological changes up to one month after injection. The pharmacokinetic profiles of i.v.-injected E-nRs made of three- and di-block copolymers were similar to the profiles of the injected free enzyme, suggesting partial enzyme encapsulation. Indeed, ELISA and Western blot analyses showed that animals developed an immune response against the enzyme. However, animals that received several injections did not develop iatrogenic symptoms.

Extracorporeal removal of organophosphate from blood has been proposed, but the efficacy of hemodialysis and hemoperfusion has not been established. We report a case of organophosphate poisoning in which continuous renal replacement therapy (CRRT) was applied with conventional indications and was found to increase plasma cholinesterase levels by hemodiafiltration. A 73-year-old male was found unconscious at home and was brought to the emergency department by ambulance. An empty bottle of Supracide insecticide, of which the active ingredient is methidathion, was found beside him. CRRT was initiated because he showed signs of oliguria and acidosis with an unstable hemodynamic condition. Although his condition improved temporarily after CRRT initiation, it subsequently deteriorated, and he died despite maximal supportive effort. His prefilter plasma cholinesterase levels remained at

Objective: There is insufficient evidence on the effectiveness of gastric lavage in organophosphorus poisoning. This study was done to quantitate the level of chlorpyrifos and quinalphos retrieved in gastric lavage fluid.Methods: Patients presenting within six hours of ingesting quinalphos or chlorpyrifos with International Program on Chemical Safety Poison Severity Score (IPCS PSS) grade 2 or more were included in the study. After the stabilisation of patients, gastric lavage was performed with alliquotes of 200 ml of normal saline till aspirate became clear. Quantification of the pesticide was done in the first 10 ml of lavage fluid aspirated out and in blood with gas chromatography with triple quadruple mass spectrometer (GC-MSMS).Results: There were six patients in each pesticide group. Mean time for reaching hospital after the ingestion of pesticide was 2.8 ± 1.1(range 1.25-6) hours. Median quantity of chlorpyrifos in the lavage fluid was 10.24 (IQR 14.36) µg/L and in quinalphos, it was 1360.62 (IQR 1691.2) µg/L. Other compounds detected in lavage fluid and confirmed in blood were endosulfan, diazinon, pirimiphos, pyridafenthion, pyrazophos, pirimiphos ethyl, and azinphos.Conclusion: Chlorpyrifos and quinalphos are detected in lavage fluid after one hour of ingestion and few milligrams are retrieved by gastric lavage. The presence of other pesticides including endosulfan were confirmed in lavage fluid.

Abstract Background Organophosphate poisoning is a serious issue and it results in significant casualties in developing countries. Since agriculture remains an important and necessary sector of human society and organophosphate are commonly used in agriculture, it is difficult to prevent organophosphate poisoning. Gastrointestinal bleeding is not a common but life threatening symptom of organophosphate poisoning. We report a rare case of gastrointestine bleeding due to organophosphate poisoning. Case presentation A 78-year-old woman presented to our hospital approximately 12 h after ingesting a mouthful of organophosphate and benzodiazepines in a suicide attempt. Six weeks after successful medical treatment for respiratory failure, she developed recurring melena. Colonoscopy and esophagogastroduodenoscopy findings were negative for ulcers or bleeding. Enteroscopy revealed severe circumferential ulcers with luminal narrowing 10 cm proximal to the ileocecal valve. The patient underwent a 100-cm ileum resection after failed medical treatment and recovered uneventfully. The resected terminal ileum demonstrated severe inflammation and a sharp transitional zone between the healthy and injured mucosa approximately 50 cm proximal to the ileocecal valve. Pathological examination revealed an injured mucosa with inflammatory cell infiltration and structural damage. This case highlights a rare event of OP poisoning with late-onset lower gastrointestinal bleeding, which prolonged the patient’s recovery course and parenteral alimentation period. Conclusion We report a rare case of a patient with organophosphate poisoning, with late-onset lower GI tract bleeding, which raised clinical awareness regarding the organophosphate poisoning that induce intestinal symptoms.

Introduction: Major cases of poisoning are associated with organophosphates. Cholinergic effects and an intermediate phase seen with organophosphate poisoning may implicate myopathy. Creatine kinase is a marker of muscle tissue damage. This study aimed to find out the mean serum creatine kinase among organophosphate poisoning cases in a tertiary care centre. Methods: A descriptive cross-sectional study was carried out among organophosphate poisoning cases in a tertiary care hospital from 13 October 2017 to 30 March 2018. Ethical approval was taken from the Institutional Review Committee [Reference number: 117(6-11-E) 2/074/075]. Blood samples were assayed for serum acetylcholinesterase in the pharmacology laboratory and for serum creatine kinase and lactate dehydrogenase in the biochemistry laboratory. Low serum acetylcholinesterase was taken as the basis for the establishment of organophosphate poisoning. A convenience sampling technique was used. Point estimate and 95% Confidence Interval were calculated. Results: Among 103 organophosphate poisoning cases, the mean serum creatine kinase was 931.35±446.60 IU/l (845.10-1017.60, 95% Confidence Interval). Conclusions: The mean serum creatine kinase level among organophosphate poisoning cases was higher than in other studies done in similar settings.

Industrial production of food for animals and humans needs increasing amounts of pesticides, especially of organophosphates, which are now easily available worldwide. More than 3 million cases of acute severe poisoning are estimated to occur worldwide every year, and even more cases remain unreported, while 200,000–350,000 incidentally or intentionally poisoned people die every year. Diagnostic and therapeutic procedures in organophosphate poisoning have, however, remained unchanged. In addition to several neurologic symptoms (miosis, fasciculations), hypersecretion of salivary, bronchial, and sweat glands, vomiting, diarrhea, and loss of urine rapidly induce dehydration, hypovolemia, loss of conscience and respiratory distress. Within hours, signs of acidosis due to systemic hypoxia can be observed at first laboratory investigation after hospitalization. While determination of serum-cholinesterase does not have any diagnostic value, it has been established that hypoalbuminemia alone or accompanied by an increase in creatinine, lactate, or C-reactive protein serum levels has negative prognostic value. Increased serum levels of C-reactive protein are a sign of systemic ischemia. Protective mechanical ventilation should be avoided, if possible. In fact, acute respiratory distress syndrome characterized by congestion and increased weight of the lung, accompanied by heart failure, may become the cause of death. As the excess of acetylcholine at the neuronal level can persist for weeks until enough newly, locally synthesized acetylcholinesterase becomes available (the value of oximes in reducing this time is still under debate), after atropine administration, intravenous albumin and fluid infusion should be the first therapeutic interventions to reestablish normal blood volume and normal tissue oxygenation, avoiding death by cardiac arrest.

Organophosphate pesticide (OP) poisoning is quite common and can cause cardiovascular complications and even direct myocardial injury. However, no guideline has included an acute poisoning as a potential cause for a type 2 myocardial infarction (MI) so far. Here we present a case of a 61-year-old woman brought by ambulance to emergency department one hour after accidental ingestion of an unknown quantity of a solution she used against flea infestation. The patient presented with dizziness, myosis, excessive sweating, hypersalivation, sphincteric incontinence, muscle fasciculation, tremor of the extremities, pale skin, alcoholic and pesticide breath odour. Even though we had no guidelines to fall back on, we successfully treated the patient with low-molecular-weight heparin, antiplatelets, statin, diltiazem, antidote therapy, and supportive care. Physicians should be aware that OP poisoning can induce type 2 MI as a complication within a few hours since exposure, and emergency management should always include close cardiac monitoring.

Abebe Getie, Yaschilal Muche Belayneh Department of Pharmacy, College of Medicine and Health Sciences, Wollo University, Dessie, EthiopiaCorrespondence: Yaschilal Muche BelaynehDepartment of Pharmacy, College of Medicine and Health Sciences, Wollo University, P.O. Box 1145, Dessie, EthiopiaTel +251918092466Email yaschilal.muche19@gmail.comBackground: Poisoning causes significant patient morbidity and mortality worldwide. It is a common reason for emergency department visits and hospitalizations. Acute poisoning needs immediate effective management to prevent patient mortality or sequela. This study was carried out to determine the pattern of acute poisoning cases and their management at the emergency department of Dessie referral hospital, northeast Ethiopia.Methods: A retrospective cross-sectional study of all registered poisoning cases managed at the emergency department of Dessie referral hospital was conducted from March 10 to May 2, 2018.Results: There were a total of 147 registered poisoning cases listed in the registry during the study period, of which 120 cases (81.6%) had complete data and were included in the study. Among the total of 120 studied poisoning cases, 66 (55%) were females, and 53 (44.2%) were in the age group of 21– 30 years. The causative poison was documented for 118 cases. Organophosphates were the most common poisoning agents involved in 54 (45%) of the cases followed by sodium hypochlorite, 27 (22.5%), and food poisoning, 19 (15.8%). Among the total patients, 77 (64.2%) were self-poisoned intentionally, 31 (25.8%) were poisoned in an unintentional manner and the rest, 12 (10%), had an unknown manner of poisoning. Mental disorder, 25 (20.8%); family disharmony, 23 (19.2%); and marital disharmony, 19 (15.8%) were the three most common causes of intentional poisoning. In all cases of acute poisoning, both pharmacological and non-pharmacological treatment approaches were used. Cimetidine was the most commonly used pharmacologic treatment, 118 (98.3%), followed by antiemetic, 107 (89.2%); proton pump inhibitor, 87 (72.5%), and atropine, 67 (55.8%). ANOVA did not show a statistically significant difference (P> 0.05) in the frequency of poisoning cases across seasons.Conclusion: Among 120 acute poisoning cases, 77 (64.2%) were intentional poisoning cases. Organophosphate poisoning accounts for 45% of the total poisoning cases. The three major reasons for intentional poisoning were mental disorders (20.8%), family disharmony (19.2%) and marital disharmony (15.8%). Cimetidine (98.3%) was the most commonly used pharmacologic treatment of the poisoning cases.Keywords: acute poisoning, emergency department, organophosphate poisoning

For the first time, the efficacy of post-exposure treatment of organophosphate (OP) poisoning was increased by transdermal delivery of acetylcholinesterase (AChE) reactivator pyridine-2-aldoxime methochloride (2-PAM) as a preventive countermeasure. By selecting the optimal ratio of components, classical transfersomes (based on soybean phosphatidylcholine and Tween 20) and modified transfersomes (based on soybean phosphatidylcholine, Tween 20 and pyrrolidinium cationic surfactants with different hydrocarbon tail lengths) were obtained for 2-PAM encapsulation. Transfersomes modified with tetradecylpyrrolidinium bromide showed the best results in encapsulation efficiency and sustained release of 2-PAM from vesicles. Using Franz cells, it was found that the incorporation of surfactants into PC liposomes results in a more prolonged release of 2-PAM through the rat skin. Transfersomes containing 2-PAM, after exhaustive physical and chemical characterization, were embedded in a gel based on Carbopol® 940. A significantly high degree of erythrocyte AChE reactivation (23 ± 7%) was shown for 2-PAM in unmodified transfersomes in vivo. Preliminary transdermal administration of 2-PAM 24 h before emergency post-exposure treatment of OP poisoning leads to an increase in the survival rate of rats from 55% to 90%.

Organophosphate (OP) compounds include highly toxic chemicals widely used both as pesticides and as warfare nerve agents. Existing countermeasures are lifesaving, but do not alleviate all long-term neurological sequelae, making OP poisoning a public health concern worldwide and the search for fully efficient antidotes an urgent need. OPs cause irreversible acetylcholinesterase (AChE) inhibition, inducing the so-called cholinergic syndrome characterized by peripheral manifestations and seizures associated with permanent psychomotor deficits. Besides immediate neurotoxicity, recent data have also identified neuroinflammation and microglia activation as two processes that likely play an important, albeit poorly understood, role in the physiopathology of OP intoxication and its long-term consequences. To gain insight into the response of microglia to OP poisoning, we used a previously described model of diisopropylfluorophosphate (DFP) intoxication of zebrafish larvae. This model reproduces almost all the defects seen in poisoned humans and preclinical models, including AChE inhibition, neuronal epileptiform hyperexcitation, and increased neuronal death. Here, we investigated in vivo the consequences of acute DFP exposure on microglia morphology and behaviour, and on the expression of a set of pro- and anti-inflammatory cytokines. We also used a genetic method of microglial ablation to evaluate the role in the OP-induced neuropathology. We first showed that DFP intoxication rapidly induced deep microglial phenotypic remodelling resembling that seen in M1-type activated macrophages and characterized by an amoeboid morphology, reduced branching, and increased mobility. DFP intoxication also caused massive expression of genes encoding pro-inflammatory cytokines Il1β, Tnfα, Il8, and to a lesser extent, immuno-modulatory cytokine Il4, suggesting complex microglial reprogramming that included neuroinflammatory activities. Finally, microglia-depleted larvae were instrumental in showing that microglia were major actors in DFP-induced neuroinflammation and, more importantly, that OP-induced neuronal hyperactivation was markedly reduced in larvae fully devoid of microglia. DFP poisoning rapidly triggered massive microglia-mediated neuroinflammation, probably as a result of DFP-induced neuronal hyperexcitation, which in turn further exacerbated neuronal activation. Microglia are thus a relevant therapeutic target, and identifying substances reducing microglial activation could add efficacy to existing OP antidote cocktails.

Introduction The development of an extrapyramidal syndrome (EPS) is assumed to be a potential and important consequence of organophosphate poisoning (OP). Even though its causal relationship is firmly established, the information available in the literature regarding the orientation to be given is scarce, and its approach remains shrouded in a significant degree of uncertainty. Catatonia, as a neuropsychiatric condition, may present a marked overlap with the set of extrapyramidal symptoms developed after OP. Does the overlap between the symptoms seen in catatonia and in EPS make differential diagnosis fundamental or does it have no relevance in relation to the approach to be established? Objectives To discuss the therapeutic approach to be implemented in the extrapyramidal symptoms resulting from OP and reflect on the overlap between catatonia and EPS. Methods Presentation of a clinical case and review of the literature. Results A 50-year-old woman with major depressive disorder developed a condition marked by exuberant extrapyramidal symptoms 3 weeks after OP. Significant stiffness, tremor, dysphagia and facial hypomimia were some of the symptoms observed. Therapy was started with amantadine 100mg daily, with complete resolution of the symptoms after 5 days. Follow-up revealed reversal of extrapyramidal symptoms, in the absence of any neuroimaging changes or any other neuropsychiatric manifestations. Conclusions The possible overlap between catatonia and EPS is remarkable. The two conditions, regardless of their differentiation, may benefit from an identical approach using dopaminergic drugs. The use of amantadine, even in low doses, may be an option in the rapid reversal of extrapyramidal symptoms resulting from OP. Disclosure No significant relationships.

Background: Human serum paraoxonase 1 (PON1) hydrolyzes organophosphate (OP) compounds and so significantly alters an individual’s susceptibility to the toxicity of these chemicals. The study was designed to assess the serum PON1 activity in a series of patients with OP poisoning. Methods: Suspected OP poisoning patients presented within 6 hours of consumption at emergency department were recruited. Demographic information of patients, clinical findings, treatments given, complications, length of hospital stay and clinical outcome were collected into datasheets. Patients were graded into moderate and severe poisoning. Serum PON1 was measured by ELISA method and serum cholinesterase by butyrylthiocholine method. Results: Mean serum PON1 level in patients with severe poisoning was significantly lower than those with moderate poisoning (426 ± 179 U/L vs. 868 ± 79 U/L, P < 0.001). Serum PON1 significantly correlated with serum cholinesterase levels (r = 0.400, P < 0.001) and negatively associated with total length of hospital stay (r = -0.338, P < 0.001), total atropine dose (r = -0.826, P < 0.001), serum amylase (r = -0.331, P < 0.001), lipase (r = 0.260, P = 0.011) and total creatinine kinase (r = -0.456, P < 0.001). Serum PON1 and cholinesterase levels were significantly lower in expired patients and those who required ventilation assistance as compared to recovered patients who did not require ventilation assistance. Conclusion: Lower PON1 activity was significantly associated with lower serum cholinesterase and poorer outcomes. PON1 activity may be considered as an indicator of prognosis in OP poisoning.

Objective: Organophosphates (OPs) are widely used for pest control worldwide, leading to increased risk for human exposure. The acute hormonal effects of OP include deficiencies in the thyroid-stimulating hormone (TSH), adrenocorticotropic hormone, and insulin-like growth factor 1 hormone correlated with the levels of cholinesterase. Most patients with OP-related hormone deficiency recover at 3 months of follow-up. However, the chronic effects of these chemicals are not clear. The aim of the present study was to determine the chronic influences of OP on pituitary functions in patients who had OP poisoning. Materials and Methods: This prospective study was performed in Erciyes University Medical School. All of the patients who had OP poisoning were followed up in the medical intensive care unit (MICU). They were evaluated after discharge from the MICU after at least 6 months with regard to pituitary functions. In all patients, data were extracted from the MICU records. Baseline hormone levels were assessed, and dynamic tests (insulin tolerance test and glucagon stress test) were performed. Results: Twenty-nine adult patients (13 women and 16 men) with OP poisoning were included in the study. The mean age of the patients was 41.9+-16.7 years. The mean time from hospitalization to assessment of pituitary functions was 43.9+-15.8 months in patients with OP poisoning. All patients had normal prolactin, TSH, follicle-stimulating hormone, and luteinizing hormone levels. Women had normal estrogen levels, and men had normal total testosterone levels. Cortisol deficiency was detected in only 1 (3.4%) patient, and growth hormone (GH) insufficiency was found in 3 (10.3%) patients. Conclusion: GH and cortisol axis may be affected by OP poisoning in the long term. Thus, pituitary hormone levels should be tested following an acute period in patients with OP.

Background: Organophosphates (OPs) are regularly utilized as pesticides all over the world. Exposures to OPs cause countless cases of poisoning and death annually. Organophosphates inebriation generates a range of muscarinic, nicotinic, and cholinergic side effects including both central and peripheral nervous systems. OP compound’s simple accessibility is responsible for expanding rates of pesticide poisoning and the fact that it is a noteworthy reason for morbidity and mortality that presents general medical issues in a growing district. Methods: I performed a review of the published literature. The databases Medline, Embase, Scopus and Google Scholar were searched using the terms intermediate syndrome, organophosphate induces intermediate syndrome and organophosphate poisoning. Databases were merged and a duplicate was removed. Results: In intense organophosphate poisoning, serious and delayed acetylcholinesterase restraint comes with oxidative stress, identified in erythrocyte membranes, that takes place in the initial phases of poisoning and may add to the progress and seriousness of intermediate syndrome (IMS). Conclusion: It normally appears 2-4 days after presentation when the side effects and indications of the intense cholinergic disorder (e.g., muscle fasciculations, muscarinic signs) are not evident anymore. However, IMS has been considered as a noteworthy causative factor of organophosphate-related morbidity and mortality due to its incessant presence and potential occurrence of breathing malfunction. The aim of the article is to bring down the clear idea about the IMS.

Introduction: Acute organophosphate (OP) poisoning is one of the most common poisoning causing significant morbidity and mortality in developing countries. Acute cholinergic manifestations predominate with many patients requiring intensive care management and ventilator support. Nerve conduction studies including repetitive nerve stimulation can evaluate the altered neuromuscular transmission and peripheral nerve function by OPs. Objective: To evaluate the electrophysiological abnormalities in patients with acute OP poisoning and correlate with clinical status. Materials and Methods: Patients with acute OP poisoning admitted from August 2016 to August 2017 were prospectively studied. Nerve conduction studies including phrenic nerve conduction were performed within 24 h of admission. Repetitive nerve stimulation was performed at 3 and 30 Hz. Nerve conduction findings were compared with data from age-matched healthy controls. Results: Thirty patients were included (18 men and 12 women) in the study. Their age ranged from 16 to 47 years (30 ± 9.2). The first assessment revealed a mild reduction of compound muscle action potential (CMAP) amplitude and reduced F-wave persistence. Eleven patients had repetitive CMAPs suggesting cholinergic excess. Seven among the 11 patients requiring mechanical ventilation had decrement–increment response with 30 Hz stimulation and reduced diaphragmatic CMAP amplitude (P = 0.02). Conclusion: The presence of repetitive CMAPs, decrement–increment response to tetanic stimulation and reduced diaphragmatic CMAP amplitude in OP poisoning patients correlate with neuromuscular paralysis and need for mechanical ventilation.

Background: Acute organophosphate poisoning (AOPP) is related to several clinical complications that may be fatal. The aim of this study was to evaluate the effects of demographic, clinical and laboratory findings on AOPP outcome. Methods: In this retrospective cross-sectional study, medical records of all patients with AOPP admitted to Imam Reza Hospital, Mashhad, Iran, were reviewed from January 2016 to December 2017. Demographic data, clinical presentations, erythrocyte cholinesterase (RBC-ChE) and serum cholinesterase (S-ChE) activities were studied and evaluated in relation to clinical outcome of the patients. Results: A total of 64 patients (37 male, 27 female) were evaluated from whom 6 patients (9.4%) died. Statistically significant relationships were found between the outcome of the patients and RBC-ChE activity (p =0.008), intratracheal intubation (p=0.003), and abnormal blood pressure (p =0.009). Despite the lower mean S-ChE levels in the deceased patients and loss of consciousness in 42.2% (n=27) of patients, there was no statistically significant correlations between these factors and patients’ outcome (p =0.147, p =0.075, respectively). Conclusion: RBC-ChE activity, need for intratracheal intubation, and abnormal blood pressure on admission were important predictive factors in the clinical outcome of AOPP. Although S-ChE activity, level of consciousness, white blood cell count and blood glucose level on admission provide useful information, these data had no prognostic value in patients with AOPP.

Background: Organophosphate (OP) poisoning is a global issue, causing over 200,000 deaths annually especially in developing countries, such as Sri Lanka and India. Clinical presentation of a typical OP poisoning may follow three well-defined phases. The initial phase is an acute cholinergic crisis, after that Intermediate Syndrome (IMS) may develop within 24-96 hours, and lastly, Organophosphate-Induced Delayed Polyneuropathy (OPIDPN) may present after 2-3 weeks. The signs and symptoms of the IMS are weakness of the respiratory muscles, including the diaphragm, intercostal, accessory, neck, and proximal limbs muscles. The aim of this study was to highlight the clinical profile of the IMS following organophosphate poisoning. Methods: This descriptive, prospective, and cross-sectional study was conducted at the Teaching Hospital, Batticaloa, Sri Lanka, over a period of 6 months from March 1, 2017 to August 31, 2017. Results: Of the total 65 enrolled patients, 60% (n=39) were male. All patients ingested OP pesticide for deliberate self-harm and all of them had some degrees of initial cholinergic crises. The prevalence of IMS in the studied patients was 5.88%. All 5 patients with IMS had neck, facial and proximal limbs muscle weakness from whom, two cases (40%) had extra-ocular muscle paralysis. There was no in-hospital fatality among IMS patients. Conclusion: IMS is a rare and life-threatening problem in OP intoxication. Early diagnosis and intensive care management can prevent further complications and mortality. Prevalence of IMS in this study was lower than previous reports with almost similar clinical features.

Organophosphate (OP) poisoning is prevalent in developing countries. Toxicity occurs by voluntary injection, inhalation, and absorption. Self-injection is rare. The current case report describes a 61-y/o male with subcutaneous self-injected one cc OP poisoning presenting with delayed drowsiness, nausea, and vomiting. He was treated and presented a good clinical response to treatment with pralidoxime and had a successful recovery. Diagnosis of OP compound toxicity by the parenteral route is a challenge. By observing patients, the dose, and the time between poisoning until the time to start treatment, we can conclude different presentations and outcomes of OP poisoning.

Although methidathion is an organophosphate insecticide, it is different from the other organophosphates in terms of toxicity. Because of its relatively high fat solubility, the apparent volume of methidathion distribution throughout the body is very high, indicating that hemoperfusion is not effective in removing this organophosphate from the body. Redistribution of methidathion from fat to blood can also occur when plasma levels diminish. Additionally, acetylcholinesterase aging, which is the loss of an alkyl side chain that prevents reactivation by oximes, is very rapid so that the effective reactivation by oximes is thwarted. Thus, methidathion’s effect on acetylcholinesterase inhibition is long lasting, particularly with a high dose. In addition to its parasympatholytic effect and ability to induce muscle paralysis, methidathion poisoning is associated with a profound and long-lasting circulatory collapse due to sympathetic ganglion blockade. This report presents the case of a 55-year-old man who accidentally ingested a high dose of methidathion. He later developed enteroinvasive aspergillosis infection-induced multiple bowel perforations on two separate occasions while on mechanical ventilator support, resulting in a fatal outcome. The renin-angiotensin axis activated by sympathetic ganglion blockade may have reduced the patient’s splanchnic blood flow, contributing to translocation of endotoxin. Also, the effect of excessive acetylcholine on non-neuronal acetylcholine receptors may have contributed to the development of fatal enteroinvasive aspergillosis in this patient.

Background: Exposure to environmental toxins such as organophosphates poses a great threat to the health of the public. In this work, we investigated the effects of continuous exposure to dichlorvos (DDVP) on kidney function and hematological parameters, and the possible antidote activity of Nigella sativa oil (NSO). Methods: This research was conducted in 2016, at The Animal Holding and Research Laboratory of Faculty Basic Medical Sciences, University of Ilorin, Ilorin, Nigeria. Twenty-four Wistar rats were randomly divided into four groups, six rats each. The four groups received: 1. phosphate buffer solution as controls, 2. DDVP, 3. DDVP+NSO and 4. NSO alone. After 2 wk of treatment, blood samples were collected and hematological profile (RBC, Hb), erythrocyte indices (MCV, MCH, MCHC, and Plt), renal function parameters (albumin, urea, total protein, chloride, sodium, and potassium ions) and nonspecific immune response (WBC) were measured. Results: Rat exposed to DDVP showed red blood cell count, hemoglobin, packed cell volume, albumin, and total protein levels was reduced from control, while white blood cell count and urea significantly increased as compared to controls, the change in K+ level was not significant. NSO maintained optimal levels of red blood cell count, hemoglobin, packed cell volume, albumin, white blood cell count, and urea, indicative of its protective effect against hemo-, immuno- and nephrotoxicity of DDVP. Conclusion: N. sativa (Black Caraway) oil might be a potential antidote in hematotoxicity, immunosuppression and renal dysfunction in organophosphate poisoning, especially dichlorvos. The protective effect of NSO against dichlorvos toxicity can be attributed to its antioxidant capacity.

Objectives: Organophosphate (OP) pesticides inhibit both red blood cell (RBC) and plasma cholinesterases (ChEs). Oximes, especially pralidoxime (2-PAM), are widely used as antidotes to treat OP poisoning. In addition, N-acetylcysteine (NAC) is sometimes used as an adjuvant antidote. The current study aimed to assess the feasibility of using NAC as a single therapeutic agent for OP poisoning in comparison to in vitro 2-PAM. Methods:This study was carried out at the Razi Drug Research Center of Iran University of Medical Sciences, Tehran, Iran, between April and September 2014. A total of 22 healthy human subjects were recruited and 8 mL citrated blood samples were drawn from each subject. Dichlorvos-inhibited blood samples were separately exposed to low and high doses (final concentrations of 300 and 600 μmol.L-1, respectively) of 2-PAM, NAC and cysteine. Plasma and RBCs were then separated by centrifugation and their ChE activity was measured using spectrophotometry. Results: Although cysteine—and not NAC—increased the ChE activity of both plasma and RBCs over those of dichlorvos, it did not increase them over those of a high dose of 2-PAM. Conclusion:These results suggest that the direct reactions of 2-PAM and cysteine with dichlorvos and the reactivation of phosphorylated ChEs occurr via an associative stepwise addition-elimination process. High therapeutic blood concentrations of cysteine are needed for the elevation of ChE activity in plasma and RBCs; however, both this agent and NAC may still be effective in the reactivation of plasma and RBC ChEs.

Introduction: Atropine is not recommended in organophosphorus (OPs) poisoning cases without any obvious clinical signs. This study aimed to evaluate the clinical utility of Atropine challenge test in screening OPs poisoning cases with atypical presentation. Methods: In this prospective cross sectional study, after primary supportive care, patients with atypical pretentions of OPs poisoning underwent Atropine challenge test (1 mg intravenously) and demographic parameters, clinical presentations, and serum level of cholinesterase enzyme were compared between cases with positive and negative test results. Results: 20 patients with the mean age of 47.60 ± 13.25 years were studied. The mean time since exposure and initial symptoms was 6.17 ± 2.99 hours. The most common clinical presentations were tachycardia (55%) and flushing (35%). The atropine challenge test was positive in 3 (15.00%) cases. The two groups were the same regarding gender distribution (p = 0.582), mean age (p = 0.957), clinical presentation (p > 0.05), and mean PR interval (p = 0.729). The level of cholinesterase was 220.00 ± 15.52 U/mL and 332.17 ± 143.99 U/mL in patients with positive and negative Atropine challenge test, respectively (p = 0.006). Conclusion: Patients with positive Atropine challenge test had a significantly lower level of serum cholinesterase and response to Atropine in their therapeutic management. Hence, Atropine challenge test could be considered as a useful clinical test in the setting of acute OPs poising.

Background: Deliberate self-harm (DSH) is a global problem which has steadily increased over the past few years in developing countries and has become as one of the major causes of morbidity and mortality in these countries. The aim of this prospective study was to analyze the prevalence of organophosphate poisoning among other acute DSH cases admitted to the medical ward at Batticaloa Teaching Hospital, Sri Lanka. We report the socio-demographic, and outcome of organophosphate poisoning. Method: The prospective study comprises of 121 cases of acute poisoning admitted at Batticaloa Teaching Hospital (BTH), Sri Lanka. This study was conducted for a period of three months from April 12 through July 12, 2017. Results: Among the subjects, 119 (98.34%) cases had intentional poisoning and only two cases (1.65%) accidental poisoning. Poisoning with organophosphate compounds (OP) 23 (19%) was the second leading type. There were 13 (56.5%) males and 10 (43.5%) females. Most of the patients were under the age group of 20-29 years old. 21 cases lived in rural areas and 2 in urban areas. Out of 23 patients, there were 2 (8.7%) deaths, 18 (78.3%) were discharged without any complications. Conclusion: DSH in Sri Lanka is reported to be associated with interpersonal conflict, short premeditation, as well as alcohol misuse among males.

OBJECTIVE: This study aims to determine the frequency of organophosphate poisoning outcomes at tertiary care hospital at Nawabshah. DESIGN: Descriptive Study. SETTING: Intensive Care Unit at Peoples University of Medical and Health Sciences for Women, Nawabshah. MATERIAL AND METHOD: A retrospective study of 387 patients of organophosphate poisoning admitted in Intensive Care Unit at Peoples University of Medical and Health Sciences for Women, Nawabshah, catering all cases from urban and rural areas, during the years January 2013 to December 2015. The Intensive Care Unit is fully equipped with all modern equipment to treat cases of poisoning. The record of the patients were reviewed and the data was entered in proforma for further analysis. The variable considered were gender, age and yearly outcome was presented as frequencies and percentage whereas age was presented as mean ±SD. RESULTS: A total of 387 cases organophosphate poisoning were reported in our hospital between 2013 and 2015. The age of study population in our study was 26.14 ±10.086 years with predominance of males (62.5%). The highest number of cases (42.1%) were reported during 2013 with the least (23.3%) in 2014. Moreover, 275 (71.1%), 105 (27.1%) and 7 (1.8%) cases were cured, expired and referred during the period of three years i.e. 2013 to 2015. CONCLUSION: Organophosphate poisoning cases were more common among males. Youth is predominant population for organophosphate poisoning which draws immediate attention for public health policy makers, by educating the public through print and electronic media specially television with dramatize shots.

In this issue of the Biomedical Journal, we highlight new data supporting the use of pralidoxime in the treatment of cases of organophosphate poisoning, which also suggest that WHO treatment guidelines should be updated. We also learn about a modified surgical technique to repair severe spinal injuries, as well as new insight into the structure of human adenovirus that could inform vaccine development.

Atropine is a drug of choice for muscarinic effects in organophosphate (OP) poisoning. Allergic reaction to atropine is rare. Here, we report a case of a 17-year-old male who was admitted with clinical manifestations of acute OP poisoning. After intravenous atropine injection, cutaneous signs of hypersensitivity including erythema and urticarial were observed on his body. Atropine injection was stopped, and antihistamines and hydrocortisone were administered. His condition was improved, and he discharged with a good condition after 2 days hospitalization. Adverse allergic reaction to atropine should be in mind when managing OP poisoning cases.

Chlorpyrifos is an organophosphate compound recognized as causing acute toxicity. However, organophosphate-induced delayed polyneuropathy (OPIDP), although rare, has also been described. We describe an unusual presentation of OPIDP with flaccid quadriplegia progressing to a locked-in-like syndrome, 30 days after a 60-year-old man voluntarily ingested chlorpyrifos. In the absence of specific treatment, the patient only recovered partial motor responses and the ability to communicate. The authors present this report in order to highlight a form of OPIDP which can hinder diagnosis due to its atypia and the delay in the onset of symptoms from initial contact with the toxicant.

Organophosphate (OP) compounds are frequently used agorchemicals for deliberate self-harm in some parts of the world resulting in high mortality and morbidity. Pralidoxime (2PAM) is the most widely used and trialed oxime for treatment of OP poisoning. There have been variations over the results of trials using 2PAM for OP poisoning. 2PAM therapy has led to favorable outcomes in some studies, whereas it has been associated with unfavorable outcomes or without benefit in the others. Why 2PAM works in some trials and why it does not in the others, has been a key question for medical toxicologists with no definite answer. In this systematic review, we sought to investigate possibilities of the variations in the results of different studies conducted on the effectiveness of 2PAM therapy for OP poisoning and we tried to provide solutions for future studies.

Background:Organophosphates are commercially available agrochemicals for pest control, but may be abused for deliberate self-poisoning. We report a case of suicidal ingestion of dimethoate, a moderately toxic organophosphate insecticide, which can cause refractory hemodynamic instability, and the successful use of methylene blue (MB) for counteracting this complication. Case Presentation: An unconscious 47-year-old man was referred to emergency department with history of dimethoate ingestion. He rapidly developed hypotension that was refractory to antidotes, resuscitative hydration and multiple vasopressors including norepinephrine, epinephrine and vasopressin. Pulmonary artery catheterization revealed high cardiac output and low peripheral vascular resistance consistent with distributive shock, a complication previously reported in the setting of acute dimethoate toxicity. MB was initiated for the patient and improved hemodynamic status (increased MAP, systolic and diastolic blood pressures) and seized vasopressor requirement. Laboratory tests revealed that on-admission plasma cholinesterase level and dimethoate serum level were 2247 U and 56 μg/mL, respectively. The patient required 2 week ICU course with eventual tracheotomy for ventilation and later transferred to step down level of care. Discussion:Although MB therapy has been reported to be useful in managing sepsis-induced hypotension, there has been no similar report of its use in organophosphate poisoning. Our patient had no objective evidence for sepsis, and MB infusion improved hemodynamics within 6 hours and the effect was continued even after discontinuation of the therapy. The underlying mechanism of dimethoate-induced hypotension might be related to increase in nitric oxide (NO) formation. MB is effective to inhibit NO synthase. Conclusion:MB treatment was effective to reverse hypotension and restore hemodynamic instability caused by dimethoate poisoning. This index case may pave way to further investigation of MB therapy for OP-induced hemodynamic instabilities.

Background: Organophosphate compound (OPC) poisoning is common in the developing countries such as India. The acute and later effects of OPC poisoning on pituitary and target gland hormones is largely unknown. Materials and Methods: This prospective study was conducted at Postgraduate Institute of Medical Education and Research between January 2012 and March 2013. Fourteen patients (8 males, age 18-50 years) with acute OPC poisoning were included in the study based on the history and clinical features, documented decreased in plasma cholinesterase activity or presence of the OPC in gastric lavage/blood samples. The hormonal parameters were done at baseline, at the time of discharge and at three months of follow-up. Results: A total of 14 patients out of 46 with the mean age of 30.1 ± 10.3 years were finally eligible for the study. Hormonal alterations at admission were similar to sick euhormonal syndrome. Overall 7 of them had nine hormonal deficits at three months of follow up, 4 having sub normal basal cortisol level and two each had low testosterone and growth hormone and only one had thyroxine deficiency. Conclusion: Acute organophosphate poisoning results in endocrine dysfunction akin to sick euhormonal syndrome. However, in a small subset of patients, varying level of hormonal insufficiency may occur either at admission or later. These observations need re-validation in a larger group of patients with specific OPC.

Introduction: Toxicity resulting from pesticides is an important global public health hazard concern, particularly in developing countries. The objectives of this retrospective study were to determine the presenting clinical features, complications and length of stay of patients poisoned with organophosphates (OP). Materials and Methods : The medical records of all OP poisoning patients admitted to King Fahd Hospital of the University in the period between 2000 and 2010 were reviewed. Results: There was a total of 50 patients: Thirty-four males (68%) and 16 females (32%), 39(78%) of whom were >18 years of age. The most common route of exposure was ingestion, which was observed in 20 patients; vomiting was the most common clinical presentation. Thirteen patients were intubated at the Emergency Department on account of respiratory failure. Thirty-two patients required admission to the Intensive Care Unit and the mean length of stay in the hospital was 5 days. Two patients had cardiac arrest. Conclusion: This relatively high prevalence of OP poisoning makes it necessary to have tighter governmental controls and awaken public awareness to this problem.

Background: For effective treatment of organophosphate (OP) poisoning, development of a standardized protocol with flexible dose regimen for atropine and pralidoxime is an essential step. In this study, we aimed to assess the protocol devised in our setting; Bach Mai Hospital Poison Treatment Center, for treatment of OP poisoning that included a higher dose regimen of pralidoxime (2PAM). Methods: A protocol for treatment of OP poisoning was developed during 1995 to 1996, which included an atropinization scoring scale and a modification of 2PAM dose regimen. In this study, OP poisoned patients who were treated during 1997 to 2002 with the new protocol (study group or cases) were compared with historical control group which included OP poisoned patients treated between 1993 and 1994 prior to establishment of the new protocol. Results: One-hundred and eight cases and 54 controls were included. The cases and controls were not significantly different according to age, gender and plasma cholinesterase activity on admission from each other. There was no significant difference of mean duration of 2PAM therapy between the two groups. The controls received mean total 2PAM dose of 7.2±4.1 g, while the patients in the study group received 20.0±12.7 g which was 2.77 times higher than the dose for control group (P

Organophosphate (OP) poisoning is one of the most common causes of poisoning in developing countries especially in Southeastern Asia. Poisoning with phosphorus-containing organic chemicals or OP compounds can be managed with antidotes like oximes which are potential reactivators of acetylcholinesterase (AChE). The efficacy of oxime therapy in OP poisoned patients mainly depends upon various factors such as different dose plans, infusion rate of oximes, genetic differences of patients, type of oxime used and chemical nature of the OP compound ingested. Studies on pralidoxime kinetics in OP poisoned patients have shown that reactivation of AChE depends on the plasma concentration of oximes as well as OP compounds. The plasma concentration of oximes mainly depends on the dose plan from intermittent injection to continuous infusion after a loading dose. The incontrovertible fact is that the intermittent dosing of oximes results in deep troughs in blood pralidoxime/oxime levels (BPL) whereas continuous infusion of oximes maintains steady state plasma concentrations. Many published literature also highlighted pralidoxime via continuous infusion results in better outcomes with minimum fluctuation in BPL compared to intermittent dosing. At therapeutic doses, adverse effects of oximes are reported to be minimal. But high BPL is associated with some common adverse effects including dizziness, blurred vision and diastolic hypertension. Considering all the facts, it is important to note that kinetic studies of oximes are useful not only in deciding the dose regimen, but also in predicting the possible side-effects.

Purpose: The knowledge about neuromuscular effects of organophosphate poisoning depends on limited publications and case reports. In this study, we aimed to determine the neuromuscular effects of organophosphate poisoning and the influence of these information in clinical approach and treatment modalities that will guide further studies to prement disability. Materials and Methods: In this prospective study conducted for 2 years with the approval of ethical comittee, 20 patients older than 15 years old who were admitted with cholinergic complaints with suspected organophosphate poisoning were evaluated. After proper primary assesment and treatment Electromyography, Visuel evoked potential, Somatosensory evoked potential were performed to evaluate the neuromuscular affect. Results: Twenty patients, 12 (60%) females and 8 (40%) males were included in our study. Electromyograhy of 20 patients were normal with normal neuromuscular junction functions. Latancy and/or amplitude asymmetry were found in 4 (20%) patients in Visuel evoked potential and 3 (15%) patients in Somatosensory evoked potential. All of the patients were discharged without sequela. Conclusion: There is no evoked potential studies performed in organophosphate poisoning althoung electroneurography repetitive and P300 studies exist in literature. More further studies are needed to evaluate the cardiac and neuromuscular effects of organophosphate poisoning. [Cukurova Med J 2014; 39(4.000): 795-800]

Background: It is becoming apparent that although inhibition of cholinesterase plays a key role in organophosphate (OP) toxicity, other factors are also important. One of the contributing factors for severity of OP poisoning is electrolyte imbalances such as hypokalemia. This study was aimed at evaluating the value of hypokalemia in association with plasma cholinesterase (PChE) levels in predicting morbidity and mortality of acute OP poisoning. Methods: In this cross sectional study patients with definitive diagnosis of OP poisoning were enrolled. Pre-interventional clinical features were observed and noted with severity assessment as per Proudfoot classification, along with measurement of serum potassium ion ([K+]) concentration and PChE level. Results: Fifty OP poisoned patients (33 men, 17 women) were enrolled with median age of 27.1 years. The most common clinical manifestation was congested conjunctiva (82%) followed by miosis (78%) and bronchorrhea (78%). A total of 21 cases presented with one or more severe clinical features according to Proudfoot classification. Among them, 61.9% of cases (13 out of 21) developed hypokalemia. Muscle weakness or fasciculation developed with mean serum [K+] of 3.31 ± 0.11. Ventilatory support was required at the mean serum [K+] of 3.27 ± 0.10 mmol/L. Fatality was noted when the mean serum [K+] reduced to 2.90 ± 0.06 mmol/L. Correlation of the clinical effects and serum [K+] was significant (P < 0.001). In addition, muscle weakness, fasciculation, convulsion and respiratory distress were associated with marked suppression of PChE (>75%). Death was mostly observed among patients who had respiratory distress associated with hypokalemia and grossly reduced PChE. Conclusion: For severe clinical features of OP poisoning, serum [K+] and PChE level are greatly reduced. Hence, these biochemical findings can be proposed as OP poisoning predictive markers. Clinicians and medical toxicologists should consider hypokalemia associated with reduced PChE level as alarming signs of poor prognosis in OP poisoned patients.

Background:Acute poisoning with organophosphorus (OP) pesticides is a common method of suicide and entails considerable mortality in Bangladesh. The objective of this study was to evaluate the effects and outcomes of a protocol for treatment of OP poisoning that included titrated incremental atropine as loading dose and slow infusion for maintenance. Methods:In this prospective descriptive case series, definitive OP poisoned patients were enrolled in an adult medicine unit of Dhaka Medical College Hospital from April 2006 to April 2007. Clinical examinations were done as soon as the patient entered the ward. Patient’s demographics, comorbid conditions and the occurrence of specific clinical outcomes including death, need for assisted ventilation and clinical complications were recorded. The patients were treated according to the protocol. Results: A total of 56 patients were enrolled over the study period. The median age of the study population was 22.5 years. Most patients were men (67.8%). The most common clinical presentation was miosis (58.9%). In total, 11 patients died (19.6%). Intermediate syndrome developed in 12 patients (21.4%) and 6 of them died. Assisted ventilation was required in 16 cases (28.5). Patients with diastolic blood pressure ≤ 70 mmHg and/or GCS ≤ 10 were significantly less likely to survive (P = 0.02, 0.006, respectively). Moreover, early respiratory failure (P < 0.001) and the need for assisted ventilation (P < 0.001) were significantly higher among deceased cases. The mortality rate in this study was similar to previous studies. The frequency of atropine toxicity in the present study (1.8%) was considerably lower than conventional regimen used in previous studies. Conclusion:Using the new protocol, lower rate of atropine toxicity developed in victims. Hence, the new protocol appears to be safer and its effectiveness should be further evaluated in case control studies in Bangladesh. How to cite this article: Ahmed AS, Basher A, Amin MR, Faiz MA. Effect of Intensive Atropine Doses (Rapid Incremental Loading and Titration) for Management of Organophosphorus Pesticide Poisoning: a Case Series. Asia Pac J Med Toxicol 2014;3:23-6.

Introduction: Poisoning with various substances is a major public health problem and a reason for significant morbidity and mortality throughout the globe. It is one of the most common presentation in an emergency department. This study was conducted to determine the sociodemographic, poisoning types, and mode of poisoning in cases attending a tertiary hospital of Western Nepal. Methods: A retrospective observational study of two years was conducted from July 2014 to June 2016. Demography details, name of poisonous substance, and reasons for poisoning were reviewed and analyzed using descriptive statistics. Results: A total of 65 cases of poisoning were recorded. The occurrence was more common in female (n=44, 67.7%) than in male (n=21, 32.3%) with a F:M ratio of 2.1:1. Poisoning was most common in the age group of 11-20 years (32.3%). Most of the cases were students (37%) followed by farmers (26%). The most commonly abused poisoning substance were organophosphorous compounds, zinc-phosphate, and kerosene in adults, adolescents, and children respectively. Oral route was the most common (99%) route of administration. Suicidal attempt, as a mode of poisoning, accounted for 70.8% of total poisoning cases. Conclusion: Female and young people are at greater risk of acute poisoning. Insecticide was the most common agent and self administer poisoning was the most common mode of poisoning. The occurrence of poisoning and its morbidity and mortality can be reduced by developing and implementation of effective prevention strategies like restricting easy poison sales, establishing drug and poison information centers, and community awareness programs.

Background: The effective therapeutic dose of pralidoxime methylsulphate for organophosphate (OP) poisoning is necessary to be clarified. This study was designed to comparatively assess the blood level of pralidoxime (BPL) and clinical outcomes in OP poisoned patients treated with intermittent dosing and patients treated with continuous infusion. Methods: This was a prospective, open labelled, cross-sectional, nonrandomized observational study which was done from 2009 to 2012 in a tertiary care hospital in Manipal, India. A high-performance liquid chromatography (HPLC) method with prominence diode array (PDA) detector was developed to measure BPL. Patients were categorized into study and control groups. Patients in study group were divided into 3 subgroups as they were treated with (a) intermittent pralidoxime dosing (1 g/q8h) or (b) continuous pralidoxime infusion (500 mg/h) or (c) continuous pralidoxime infusion (1 g/h). Patients who were not treated with pralidoxime were considered as the control group. The level of acetylcholinesterase (AChE) was measured before and pralidoxime therapy. Results: The developed HPLC method was linear over the range of 0.5-50 µg/mL and the correlation coefficient was found to be greater than 0.99. The median (IQR) of BPL in intermittent dosing (4.63 (5.26)) was comparatively lower than patients treated with continuous infusion. The highest BPL was maintained in 1 g/h group with median (IQR) serum level of 38.86 (16.75). The reactivation rate of AChE was higher in continuous infusion groups compared to intermittent dosing. Comparison of AChE before and after pralidoxime therapy showed that higher BPL was associated with greater reactivation of AChE. Conclusion: HPLC can be used as alternative method for measurement of pralidoxime level in blood. Continuous infusion of pralidoxime maintained a steady higher blood concentration compared to intermittent dosing with vast fluctuations. The reactivation rate of AChE was higher in continuous infusion compared to intermittent dosing. Hence, continuous infusion of pralidoxime can more rapidly recover the OP poisoned patients with less morbidity. How to cite this article: Thunga G, Pandey S, Nair S, Mylapuri R, Vidyasagar S, Kunhikatta V, et al. Comparative Study of Continuous Pralidoxime Infusion versus Intermittent Dosing: Application of High-Performance Liquid Chromatography Method on Serum of Organophosphate Poisoned Patients. Asia Pac J Med Toxicol 2013;2:105-10.

Giriş: Çalışmamızda akut organofosfat zehirlenmesine bağlı elektrokardiyografik (EKG) değişiklikler ile kolinesteraz düzeylerinin mortaliteye etkilerini araştırmayı amaçladık. Materyal ve Metod: Prospektif, randomize olarak 2 yıl süresince, 01.08.2009 – 31.08.2011 tarihleri arasında acil tıp kliniği’ne organik fosfat zehirlenmesi ile gelen hastaların alınmasının planlandığı çalışmaya Etik Kurul’dan onay alındıktan sonra başlandı. Acile başvuru sonrası, tedavi (atropin ve pralidoksim uygulaması) öncesinde çalışmada kullanılmak üzere EKG çekildi ve kan örneği alınarak, serum ve eritrosit kolinesteraz düzeyleri hastanemiz laboratuvarı’nda çalışıldı. Hastaların EKG bulguları, kolinesteraz değerleri, sonlanım durumu standart veri giriş formuna kayıt edildi. Verilerin istatistiksel analizinde SPSS 18.0 paket programı kullanıldı. Bulgular: Çalışmaya alınan 39 hastanın 5’i (% 12.8) tedavileri sırasında eksitus oldu. Hastalarda görülen elektrokardiyografik bulgular sıklık sırasına göre; sinüs taşikardisi (% 48.7), uzamış QT mesafesi (% 20.5) ve sağ dal bloğu (% 20.5), ST-T dalga değişikliği (% 12.8), atriyal fibrilasyon (% 7.7), sağ aks sapması (% 5.1), uzamış PR mesafesi (% 2.5) idi. Eksitus ve taburcu edilen hastaların acile ilk başvurusu sonrasında çekilen EKG bulguları karşılaştırıldığında gruplar arasında istatistiksel olarak fark olmadığı tespit edildi (p ≥ 0.05). Eksitus olan hastaların ilk geliş anında bakılan ortalama serum kolinesteraz düzeyleri ortalaması taburcu edilen hastalara göre düşüktü ve aralarında istatistiksel olarak anlamlı bir fark mevcuttu (p=0.006). Ancak eksitus ve taburcu edilen hastaların eritrosit kolinesteraz düzeyleri arasında anlamlı farklılık yoktu (p= 0.984). Sonuç: Organofosfat zehirlenmesinin şiddeti ile EKG bulguları arasında mortalite açısından anlamlı bir ilişki olmadığı, şiddetli zehirlenmelerde serum kolinesteraz düzeyi düşüklüğü ile mortalite arasında istatistiksel olarak anlamlı bir ilişki olduğu belirlendi. Organofosfat zehirlenmelerinde görülebilecek EKG bulguları ve mortaliteye etkileri hakkında acil hekimlerine fikir vermesi, klinik deneyimlerine katkıda bulunması açısından bu çalışmanın faydası olacaktır. Ancak bu konuda yapılacak daha detaylı çalışmalara ihtiyaç vardır.

Aim: In our study, we aimed to investigate the relationship between the mortality and acute inflammatory markers, serum - erythrocyte cholinesterase levels in patients with organophosphorus poisoning. Material and Methods: We planned to take patients who administered to emergency department with organic phosphorus poisoning prospectively for 2 years after approval by the Ethics Committee of Cukurova University. Patients with hereditary cholinesterase deficiency, liver disorders, malnourished, anemia, using cocaine, morphine, codeine, and medications such as succinylcholine were excluded from the study. A total of 39 patients were included in the study. Standard data entry form has been created. Blood samples were taken from all of the patients included in the study for use in study after diagnosis. White blood cell (WBC) and platelet counts, fibrinogen, ferritin, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-á), interleukin-1 (IL-1), interleukin 6 (IL-6), interleukin 10 (IL-10), erythrocyte and serum cholinesterase levels were determined from blood samples in Central Laboratory of Hospital of Balcali in Cukurova University School of Medicine. SPSS 18.0 package program was used for statistical analysis of data. The statistical significance level of all tests was p

Aim: In our study we aimed to investigate the relationship between electrocardiographic (ECG) changes, cholinesterase levels and mortality due to acute organophosphate poisoning. Material and Methods: We planned to take patients who administered to emergency department with organic phosphorus poisoning randomized and prospectively for 2 years between 01.08.2009 – 31.08.2011 after approval by the Ethics Committee. The electrocardiograms of the patients were taken after admission to the emergency department, before the treatment (atropine and pralidoxime application). Blood samples were taken and studied in the laboratory of our hospital. ECG findings, cholinesterase values and the final situation of the patients were recorded at the standard data entry form. SPSS 18.0 package program was used for statistical analysis of data. The statistical significance level of all tests was p < 0.05. Results: The five of thirty nine patients (12.8 %) included in the study have died during the treatment. The electrocardiographic findings seen in patients in order of frequency; sinus tachycardia (48.7 %), prolonged QT interval (20.5 %), and right bundle branch block (20.5 %), ST-T wave changes (12.8 %), atrial fibrillation (7.7 %), right axis deviation (5.1 %), prolonged PR (2.5 %). There was no statistically significant difference between the ECG findings of the patient groups who died or discharged (p ≥ 0.05). The mean serum cholinesterase levels of the patients who died were statistically lower than the discharged patients (p = 0.006). Conclusion: There is not a significant relationship between ECG findings and the severity of organophosphate poisoning.There is a statistically significant relationship between mortality and low levels of serum cholinesterase due to severe poisoning. ECG findings and their effects to the mortality in organophosphate poisoning can give an opinion to the emergency physicians and contribute to their clinical experiences. However, more detailed studies are needed in this matter. [Cukurova Med J 2013; 38(2.000): 181-188]

Background: Cardiac manifestations that occur in a majority of patients with organophosphate (OP) poisoning may range from innocuous electrocardiographic manifestations, such as sinus tachycardia, to life-threatening complications, including cardiogenic pulmonary edema and myocardial necrosis. In this study, we evaluated the various electrocardiographic manifestations in patients with OP poisoning. Methods: This retrospective-descriptive study was performed by reviewing the medical records from all patients poisoned with organophosphate admitted to Razi Educational Hospital, Rasht, Iran, from April 2008 to March 2011. Patients with incomplete records were excluded from the study. Histories of all patients were collected and ECG analysis was conducted including the rate, rhythm, ST-T abnormalities, conduction defects, and measurement of PR and QT intervals by a cardiologist. Descriptive statistical analysis was conducted by SPSS software version18. Results: Of the total 100 patients (75 were male) with OP poisoning that referred to the Emergency Ward of Razi Hospital, 63 patients presented ECG abnormalities. The mean age of the patients was 35.78 ± 12.91 years. The causes of poisoning were occupational in 71 patients, suicidal in 26 patients, and accidental in 3 patients. Sinus tachycardia (31%) was the most common ECG abnormality, followed by non-specific ST-T changes (24%). Overall, mortality rate was 5% and all of the deceased patients presented changes in ECG. Conclusion: OP poisoning is associated with significant ECG abnormalities, especially tachycardia and non-specific ST-T changes.

Descreve-se um surto de intoxicação por organofosforado (ORF) em bovinos na mesorregião centro ocidental do Rio Grande do Sul. A água fornecida a 49 bovinos foi contaminada com ORF e carbamato (CM). Vinte bovinos morreram após quadro clínico de poucas horas. Foram observados os clássicos sinais clínicos de hiperestimulação do sistema parassimpático incluindo incoordenação motora, agressividade, sialorreia, tremores musculares e, em alguns casos, diarreia. Na necropsia e histopatologia não foram observadas alterações morfológicas significativas. ORF e CM foram detectados por cromatografia em camada delgada em amostras de tecido de dois bovinos afetados. Adicionalmente, uma amostra da água consumida pelos bovinos foi positiva para ORF e CM e outras duas foram positivas para ORF. Uma análise quantitativa realizada por cromatografia gasosa no conteúdo do abomaso de um bovino afetado, revelou 0,93µg/g de mancozebe (CM) e 0,07 µg/g de forato (ORF).An outbreak of organophosphate (ORF) poisoning in cattle occurred in the central-midwestern region of Rio Grande do Sul, Brazil. The water available for 49 cattle was contaminated with ORF and carbamate (CM). Twenty cows died after a clinical course that lasted for few hours. The classical clinical signs of over stimulation of the parasympathetic nervous system were observed, including motor incoordination, aggressiveness, drooling, muscle tremors and, on occasion, diarrhea. Significant morphological changes were not observed at necropsy or at histopathological examination. ORF e CM were detected by thin layer chromatography in tissue samples of two affected cattle and in a sample from the water consumed by the affected cattle. Additionally, two other water samples accessed by the affected cattle were positive for ORF. A quantitative analysis carried out by gas chromatography in the abomasum contents of an affected cow revealed 0.93µg/g of mancozebe (CM) and 0.07µg/g of phorate (ORF).

Poisoning due to organophosphate pesticides is an important cause of morbidity and mortality worldwide. Although standard treatments involving the administration of atropine and oximes have been used, there remain many controversial areas concerning organophosphate poisoning (OPP). Herein, we present our 10 years of experience in assessing the severity of OPP in southern Taiwan. A retrospective study was performed on patients admitted with OPP. A total of 75 patients (50 males and 25 females) were studied between January 1996 and December 2005. Diagnosis was based on a clinical assessment and serum acetylcholinesterase (AChE) level at the time of hospital admission. The severity of OPP was assessed using the grading system of Bardin et al. The duration and dosage of atropine and palidroxime were recorded. All the biochemical data were analyzed. Sixty-one of the patients had attempted suicide and 14 patients had accidental exposure. The overall mortality rate was 8%. Muscarinic effects were observed in 66 (88%) of the OPP patients and the most frequent symptom was bronchial hypersecretion (52%). Among these three different severity groups, prolonged length of stay, higher infection rates, and higher mortality were found in the life- threatened group. The initial serum C-reactive protein (CRP) level was strongly correlated to the severity grading of the OPP. Nearly half of the patients were admitted to the intensive care unit (ICU) and, of this, 21 patients developed respiratory failure within 72 hours. Low serum AChE levels support the diagnosis of OPP, but no significant association was found between the severity of OPP and serum AChE levels. The grading system of Bardin et al is very helpful for physicians to facilitate the recognition of seriously poisoned subjects, and to permit their early admission to an ICU. Initial serum CRP, an acute phase reactant, had significant value in assessing the severity of the OPP. Although the management of acute OPP is supportive and the recovery rate is high, anti-cholinergic therapy should be used as soon as possible to counteract muscarinic effects. Physicians must be aware of the potential dangers of respiratory failure, which could occur within 72 hours of OPP.

Abstract This resource is a high-fidelity simulation case on organophosphate poisoning. It follows a 40-year-old adult male with complaints of dimmed vision, watery eyes, shortness of breath, nausea, vomiting, diarrhea, and sweating. The simulation uses a manikin and includes all the necessary materials for learners to complete the scenario. The case is intended to teach teamwork and clinical skills in a realistic emergency department setting, with an underlying emphasis on the physiology of the autonomic nervous system. Students should be able recognize the signs and symptoms of organophosphate poisoning, and select the appropriate personal protective gear for the situation. They should also be able to assign roles to group members, and address the basic airway, breathing, and circulation on the simulated patient. This simulation was used for first-year medical students. The students had a few introductory lectures on the autonomic nervous system and autonomic drugs prior to the simulation event. This was crucial for the students to be able to recognize the autonomic signs and symptoms the simulated patient is exhibiting, and know what to use for treatment. In addition, all of the students had previously completed a Medical First Responders course, which utilized high-fidelity simulators. Due to this training, the students were familiar with basic medical terminology, teamwork as medical professionals, basic first response care, the high-fidelity simulators, and the use of personal protective equipment.