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Acute intoxication with organophosphate (OP) cholinesterase inhibitors poses a significant public health risk. While currently approved medical countermeasures can improve survival rates, they often fail to prevent chronic neurological damage. Therefore, there is need to develop effective therapies and quantitative metrics for assessing OP-induced brain injury and its rescue by these therapies. In this study we used a rat model of acute intoxication with the OP, diisopropylfluorophosphate (DFP), to test the hypothesis that T2 measures obtained from brain magnetic resonance imaging (MRI) scans provide quantitative metrics of brain injury and therapeutic efficacy. Adult male Sprague Dawley rats were imaged on a 7T MRI scanner at 3, 7 and 28 days post-exposure to DFP or vehicle (VEH) with or without treatment with the standard of care antiseizure drug, midazolam (MDZ); a novel antiseizure medication, allopregnanolone (ALLO); or combination therapy with MDZ and ALLO (DUO). Our results show that mean T2 values in DFP-exposed animals were: (1) higher than VEH in all volumes of interest (VOIs) at day 3; (2) decreased with time; and (3) decreased in the thalamus at day 28. Treatment with ALLO or DUO, but not MDZ alone, significantly decreased mean T2 values relative to untreated DFP animals in the piriform cortex at day 3. On day 28, the DUO group showed the most favorable T2 characteristics. This study supports the utility of T2 mapping for longitudinally monitoring brain injury and highlights the therapeutic potential of ALLO as an adjunct therapy to mitigate chronic morbidity associated with acute OP intoxication.

Recent experimental evidence suggests combined treatment with midazolam and allopregnanolone is more effective than midazolam alone in terminating seizures triggered by acute organophosphate (OP) intoxication. However, there are concerns that combined midazolam and allopregnanolone increases risk of adverse cardiovascular events. To address this, we used telemetry devices to record cardiovascular responses in adult male Sprague-Dawley rats acutely intoxicated with diisopropylfluorophosphate (DFP). Animals were administered DFP (4 mg/kg, sc), followed immediately by atropine (2 mg/kg, i.m.) and 2-PAM (25 mg/kg, i.m.). At 40 min post-exposure, a subset of animals received midazolam (0.65 mg/kg, im); at 50 min, these rats received a second dose of midazolam or allopregnanolone (12 mg/kg, im). DFP significantly increased blood pressure by ~ 80 mmHg and pulse pressure by ~ 34 mmHg that peaked within 12 min. DFP also increased core temperature by ~ 3.5 °C and heart rate by ~ 250 bpm that peaked at ~ 2 h. Heart rate variability (HRV), an index of autonomic function, was reduced by ~ 80%. All acute (within 15 min of exposure) and two-thirds of delayed (hours after exposure) mortalities were associated with non-ventricular cardiac events within 10 min of cardiovascular collapse, suggesting that non-ventricular events should be closely monitored in OP-poisoned patients. Compared to rats that survived DFP intoxication without treatment, midazolam significantly improved recovery of cardiovascular parameters and HRV, an effect enhanced by allopregnanolone. These data demonstrate that midazolam improved recovery of cardiovascular and autonomic function and that the combination of midazolam and allopregnanolone may be a better therapeutic strategy than midazolam alone.

Organophosphate (OP) poisoning can trigger cholinergic crisis, a life-threatening toxidrome that includes seizures and status epilepticus. These acute toxic responses are associated with persistent neuroinflammation and spontaneous recurrent seizures (SRS), also known as acquired epilepsy. Blood-brain barrier (BBB) impairment has recently been proposed as a pathogenic mechanism linking acute OP intoxication to chronic adverse neurologic outcomes. In this review, we briefly describe the cellular and molecular components of the BBB, review evidence of altered BBB integrity following acute OP intoxication, and discuss potential mechanisms by which acute OP intoxication may promote BBB dysfunction. We highlight the complex interplay between neuroinflammation and BBB dysfunction that suggests a positive feedforward interaction. Lastly, we examine research from diverse models and disease states that suggest mechanisms by which loss of BBB integrity may contribute to epileptogenic processes. Collectively, the literature identifies BBB impairment as a convergent mechanism of neurologic disease and justifies further mechanistic research into how acute OP intoxication causes BBB impairment and its role in the pathogenesis of SRS and potentially other long-term neurologic sequelae. Such research is critical for evaluating BBB stabilization as a neuroprotective strategy for mitigating OP-induced epilepsy and possibly seizure disorders of other etiologies. SIGNIFICANCE STATEMENT: Clinical and preclinical studies support a link between blood-brain barrier (BBB) dysfunction and epileptogenesis; however, a causal relationship has been difficult to prove. Mechanistic studies to delineate relationships between BBB dysfunction and epilepsy may provide novel insights into BBB stabilization as a neuroprotective strategy for mitigating epilepsy resulting from acute organophosphate (OP) intoxication and non-OP causes and potentially other adverse neurological conditions associated with acute OP intoxication, such as cognitive impairment.

We have shown that briefly inhaled isoflurane rapidly halts convulsions and protects the central nervous system (CNS) from organophosphate-induced neuronal loss when administered at 5% for 5 min, even as late as 1 h after organophosphate exposure. In the current study we investigated if an injectable form of isoflurane was as effective as inhaled isoflurane. We used a mixture of 10% isoflurane dissolved in an IV-compatible lipid-water emulsion for intravenous administration. Rats with an implanted jugular vein cannula were infused with 1,000 µL of the 10% isoflurane-lipid emulsion (ILE) mixture at a rate of 200 µL per minute, which achieved full anesthesia lasting approximately 10 min. When administered 30 min after a highly lethal dose of the organophosphate insecticide paraoxon (POX), the short-duration administration halted convulsions over the course of the study and prevented the great majority of neuronal loss as shown by Fluoro-Jade B staining (FJB). Our results indicate that injectable isoflurane is very effective for treating organophosphate poisoning, negating the need for vaporizer equipment and enabling intravenous therapy. [ABSTRACT FROM AUTHOR]

Introduction: Ethion is an organophosphate used as an acaricide and insecticide, that is restricted worldwide. In Colombia, pesticide poisoning is the third most common cause of chemical intoxication. On 9 October 2022, an outbreak of ethion poisoning occurred in Pereira. The aim of this study was to describe the clinical and epidemiological characteristics of the outbreak. Methods: This is a descriptive study of an outbreak of organophosphate poisoning. The onset of symptoms occurred on 9 October 2022, following the consumption of empanadas. Information was collected on sociodemographic characteristics and clinical manifestations, as well as from paraclinical examinations. Data were obtained from clinical histories, field epidemiological investigations, and inspection visits. Food samples were collected for analysis by gas chromatography-mass spectrometry. Attack rates, proportions, and measures of central tendency, dispersion, and position were calculated. Results: The case definition was met by 37 individuals with a median age of 30 years; all presented with muscarinic symptoms, 29 patients presented with nicotinic symptoms, and 20 patients presented with neurological symptoms. Males were the most affected (57%), and the most common time of symptom onset was 10:00 am. Twenty-three patients (62%) required intensive care unit admission, of whom 14 (38%) required mechanical ventilation. No deaths were reported. Erythrocyte acetylcholinesterase activity was reduced in all patients. Ethion was detected in mass-prepared maize and empanadas at concentrations greater than 0.1 mg/kg. The consumption of empanadas was identified as the common source. Discussion: In Colombia, pesticide poisonings are the third most common type of poisoning caused by chemical substances reported to the National Health Institute through the National Public Health Surveillance System. In the present outbreak, ethion was in empanadas, likely due to contamination of cooking oil. Conclusions: We describe a large ethion-contaminated food poisoning outbreak reported in Colombia. The main symptoms were muscarinic, and the main treatment measures employed were atropine and respiratory support. Increased awareness of pesticide poisoning and training for food handlers are needed. [ABSTRACT FROM AUTHOR]

Background and Aim: Organophosphate compounds, including nerve agents, pesticides, chemical agent analogs, and Novichok, pose a serious health hazard to humans. Their use against humans was banned by 192 countries in 1993 under the Chemical Weapons Convention. The toxic effects of these compounds involve the phosphorylation and subsequent inhibition of the enzyme acetylcholinesterase, leading to the accumulation of acetylcholine in the synapses of the central and peripheral nervous systems, resulting in neurotoxic poisoning symptoms. The drugs used to treat this poisoning are compounds that can cross the blood-brain barrier by a maximum of 10% and therefore do not effectively detoxify the central nervous system. This research aims to design and synthesize a superparamagnetic nano-reactivator to activate the inhibited enzyme in the central nervous system. Methods: In this study, iron oxide nanoparticles conjugated with 2-pyridinium aldoxime were designed and synthesized in four steps. The characteristics of the nanoparticles were determined by infrared spectroscopy, energy-dispersive X-ray spectroscopy (EDS), elemental analysis, dynamic light scattering (DLS), and electron microscopy (SEM). Their activation effect was compared with pralidoxime, a commercially available drug, using the Ellman method in vitro. Results: The results of the Ellman method showed that the percentage of activation of the paraoxon-inhibited enzyme by pralidoxime as a commercially available antidote and the synthesized nanoparticles at a concentration of 5 mM over 30 minutes was 88.6% and 39.3%, respectively. Conclusion: This study demonstrated that the designed iron oxide nanoparticles conjugated with 2-pyridinium aldoxime can be synthesized and activate acetylcholinesterase inhibited by paraoxon. Therefore, future studies should investigate the effect of other groups such as 4-pyridinium aldoxime, 2,4-pyridinium aldoxime, etc., on the enzyme activation performance and the ability of these nanoparticles to cross the blood-brain barrier. [ABSTRACT FROM AUTHOR]

Paraquat is a widely used non-selective herbicide in Indian agriculture. It has gained popularity for its misuse in suicidal poisoning, primarily because it lacks an antidote, and ingestion often leads to death. When examining the historical trends of pesticide-related suicidal poisonings in India, there is a noticeable transition from endrin, organophosphates and rodenticides to the current prevalent use of paraquat. This review delves into globally reported cases of homicidal paraquat poisonings, which are sporadically reported in India as well, although not published in mainstream academia. Clinicians must remain vigilant in homicidal paraquat poisoning situations as there is often improper history at the time of presentation. Such cases typically present with some non-specific symptoms such as oral and pharyngeal burns and appear like any other typical acute gastroenteritis or a flu-like illness which ultimately leads to death as a result of pulmonary complications. At the same time, forensic pathologists need to be well versed in the characteristic autopsy findings and analytical toxicology considerations of paraquat-induced criminal poisoning, given the occasional incidents in India. The use of paraquat as a weapon in poisoning cases is a significant public health concern that underscores the need for a ban on paraquat in India.

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.

We have shown that briefly inhaled isoflurane rapidly halts convulsions and protects the central nervous system (CNS) from organophosphate-induced neuronal loss when administered at 5% for 5 min, even as late as 1 h after organophosphate exposure. In the current study we investigated if an injectable form of isoflurane was as effective as inhaled isoflurane. We used a mixture of 10% isoflurane dissolved in an IV-compatible lipid-water emulsion for intravenous administration. Rats with an implanted jugular vein cannula were infused with 1,000 μL of the 10% isoflurane-lipid emulsion (ILE) mixture at a rate of 200 μL per minute, which achieved full anesthesia lasting approximately 10 min. When administered 30 min after a highly lethal dose of the organophosphate insecticide paraoxon (POX), the short-duration administration halted convulsions over the course of the study and prevented the great majority of neuronal loss as shown by Fluoro-Jade B staining (FJB). Our results indicate that injectable isoflurane is very effective for treating organophosphate poisoning, negating the need for vaporizer equipment and enabling intravenous therapy.

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. [ABSTRACT FROM AUTHOR]

Background and Aim: Organophosphate (OP) insecticides are important compounds as the most probable common cause of acute poisonings in developing countries. OP intoxication often presents as medical emergencies, and its related morbidity and mortality have not decreased despite major advances in critical care. The present study was conducted to find the incidence of increased levels of serum amylase and serum lipase in OPC poisoning and to identify the relation with prognosis and clinical outcome, out of which one outcome was acute pancreatitis. Material and Methods: The study was conducted at department of General Medicine, Tertiary care institute of Gujarat among the patients suffering from acute Organophosphate poisoning and admitted in emergency/ICU/medicine ward within 24 hours of intoxication event. This was an observational study conducted for the duration of 2 year with sample size of 85 patients out of which only 60 patients fulfill the inclusion and exclusion criteria. Patients were divided in 3 groups as mild, moderate and severe using q SOFA score at the time of admission. Results: Mean serum amylase level values in various q SOFA categories (0, 1, 2 and 3) were 65.03, 81.95, 118.8 and 330.78 IU/l respectively with p value < 0.001 and that of mean serum lipase level values were 41.45, 44.2, 38.9 and 115.69 IU/l respectively with p value 0.05. Serum amylase levels were positively correlated with duration of ICU stay and were better predictor for acute pancreatitis. Conclusion: Organophosphate poisoning is associated with multiple complications, including acute pancreatitis. The study found that levels of serum amylase & lipase were increased in statistically significant number of cases of acute organophosphate poisoning. [ABSTRACT FROM AUTHOR]

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.

Dichlorvos, an organophosphate compound, has the potential to cause acute kidney injury (AKI) besides its well-known neuromuscular complications. We report a case of severe-recurrent AKI that progressed to end-stage-renal-disease (ESRD) following accidental exposure to Dichlorvos. A 52-year-old male farmer presented with breathlessness after accidental exposure while spraying in the field. He required mechanical ventilation due to allergic pneumonitis and developed anuric AKI, requiring renal replacement therapy (RRT). Biopsy revealed severe acute tubulointerstitial nephritis (ATIN), which responded to steroids, and the patient became dialysis-independent by 4 weeks. Two weeks later, the patient had recurrent AKI requiring RRT. A repeat biopsy revealed severe ATIN. However, despite steroid treatment, he progressed to ESRD. Organophosphate compounds can cause renal injury with a wide spectrum of presentations, ranging from subclinical AKI to severe dialysis-dependent renal failure, which may eventually progress to end-stage renal disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To discuss the clinical presentation and successful treatment of a suspected case of intermediate syndrome due to organophosphate (OP) poisoning in a dog. Case summary: Two dogs presented with acute cholinergic signs after ingesting an OP insecticide containing 50% acephate. Clinical signs consistent with acute cholinergic crisis resolved in both dogs within 24 hours postingestion. One dog developed an onset of neurological signs consistent with intermediate syndrome approximately 24 hours postingestion. This patient's clinical signs resolved with the use of pralidoxime chloride. New or Unique Information Provided: OP poisoning most commonly presents as an acute cholinergic crisis, with rare instances of animals developing intermediate syndrome. Few reports of successful treatment and recovery from intermediate syndrome exist in the veterinary literature, particularly with instances in which 2 dogs within the same exposure setting were treated for acute cholinergic signs and only 1 progressed to an intermediate syndrome. This report also highlights the importance of early intervention with pralidoxime chloride prior to the onset of aging. [ABSTRACT FROM AUTHOR]

Objective: Organophosphates are the insecticides commonly used worldwide. Inadequate treatment for 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> 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. [ABSTRACT FROM AUTHOR]

Organophosphate poisoning is common poisoning seen in developing countries. Accidental poisoning is rare in children but adolescents consume it with suicidal intention. Complications following op compound poisonings are well known but children developing acute pancreatitis is a rare complication.[1-2] Hence we present a case series of children developing acute pancreatitis in op compound poisoning. All five cases were treated conservatively and successfully discharged. [ABSTRACT FROM AUTHOR]

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.

Introduction: Paraoxonase 1 (PON1) is a high-density lipoproteinassociated enzyme with both aryl esterase and lactonase activity, and it possesses significant antioxidant and anti-inflammatory properties. PON1 hydrolyzes the active metabolites of several organophosphorus (OP) insecticides, including parathion, diazinon, and chlorpyrifos. This widely studied enzyme is recognized for its protective role against organophosphate poisoning and vascular diseases, as well as its potential as a biomarker for conditions related to oxidative stress, inflammation, and liver disease. However, limited knowledge exists regarding PON1 activity status following acute organophosphate intoxication. The aim of the present study was to investigate changes in serum PON1 activity after acute chlorpyrifos poisoning and its relationship with acetylcholinesterase (AChE) activity. Method: Rats were orally given a single dose of chlorpyrifos (160 mg/kg), and blood samples were collected before treatment, as well as at 6 and 96 hours post-treatment. We measured serum cholinesterase, paraoxonase, and arylesterase activity of PON1. Results: Signs of OP poisoning, including miosis, salivation, tremors, fasciculation, and paralysis, were observed following intoxication, accompanied by a significant inhibition of AChE activity. All symptoms resolved after 48 hours, and AChE activity returned to baseline levels at 96 hours. In contrast, paraoxonase and arylesterase activities progressively increased after 6h and 96h treatment respectively. Conclusion: The results of our study indicated that serum cholinesterase activity and paraoxonase activity negatively associated in OP poisoning. Based on these findings, monitoring paraoxonase activity after OP intoxication may serve as a valuable biomarker for assessing intoxication. [ABSTRACT FROM AUTHOR]

Poisoning cases of sika deer (Cervus nippon) due to grazing organophosphorus pesticide-contami-nated pasture occur frequently in the wild and in nature reserves. Acute organophosphate poisoning is characterized by symptoms such as parasympathetic excitement, diarrhea, salivation, and muscle tremors, which can lead to death in severe cases. Sika deer often die suddenly because of untimely treatment, and the disease often occurs in groups, which seriously affects the health and protection of sika deer. This article reports a case of acute organophosphorus poisoning in sika deer in a wildlife protection base of Heilongjiang Province. Through medical history investigation, clinical examination, case autopsy, field investigation and laboratory examination, it was diagnosed as organophosphorus poisoning caused by pesticidecontaminated pasture. For the deer herd, multiple diagnosis and treatment measures are taken to eliminate the source of toxins in the base to prevent ingestion, restrict breeding, detoxify the symptoms, increase the body's immunity, and put forward targeted preventive measures. We successfully controlled the mass poisoning of sika deer in the wildlife protection base, and provide reference for the treatment and prevention of such poisoning cases in the wildlife protection area. [ABSTRACT FROM AUTHOR]

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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

The uncontrolled use of pesticides signifies a substantial health hazard. This study was designed to explore the prognostic role of on-admission hepatic aminotransferases [alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and the reversed De Ritis ratio (ALT/AST)] in the prediction of in-hospital mortality among patients with acute organophosphate (OP) poisoning. We conducted a retrospective study based on extracting the required information from the specific medical records for acutely OP-intoxicated patients admitted to the intensive care unit. A total of 49 acutely malathion-intoxicated patients were enrolled in the study. The in-hospital mortality rate was 32.7%. Patients were stratified into survivors and non-survivors. Compared to the survivors, the non-survivors had significantly lower Glasgow coma scale scores, mean arterial blood pressure, significantly higher reversed De Ritis ratio (ALT/AST), and ALT and AST activities. The reversed De Ritis ratio (ALT/AST) and ALT demonstrated good discrimination between the survivors and the non-survivors with an area under the curve (AUC) of 0.708 vs 0.781, respectively, however, AST showed satisfactory discrimination, AUC of 0.694. Hepatic aminotransferases are useful in predicting in-hospital mortality in acute OP poisoning. ALT is the most specific biomarker. However, the reversed De Ritis ratio (ALT/AST) is the most sensitive one. [ABSTRACT FROM AUTHOR]

In poisoning with organophosphorus compounds (OP), patients can only profit from the regeneration of acetylcholinesterase, when the poison load has dropped below a toxic level. Every measure that allows an increase of synaptic acetylcholinesterase (AChE) activity at the earliest is essential for timely termination of the cholinergic crisis. Only drug‐induced reactivation allows fast restoration of the inhibited AChE. Obidoxime and pralidoxime have proved to be able to reactivate inhibited cholinesterase thereby saving life of poisoned animals. A plasma level of obidoxime or pralidoxime allowing reactivation in humans poisoned by OP can be adjusted. There is no doubt that obidoxime and pralidoxime are able to reactivate OP‐inhibited AChE activity in poisoned patients, thereby increasing AChE activity and contributing substantially to terminate cholinergic crisis. Hence, a benefit may be expected when substantial reactivation is achieved. A test system allowing determination of red blood cell AChE activity, reactivatability, inhibitory equivalents and butyrylcholinesterase activity is available for relatively low cost. If any reactivation is possible while inhibiting equivalents are present, oxime therapy should be maintained. In particular, when balancing the benefit risk assessment, obidoxime or palidoxime should be given as soon as possible and as long as a substantial reactivation may be expected. [ABSTRACT FROM AUTHOR]

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%. [ABSTRACT FROM AUTHOR]

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.

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.

Purpose: This case report aims to describe a rare manifestation of isolated hypoglossal nerve palsy (HNP) resulting from organophosphate poisoning (OP), specifically organophosphate- induced delayed neuropathy (OPIDN). The primary objective of this case report is to highlight this unusual manifestation and discuss its potential underlying mechanisms, emphasizing the importance of timely diagnosis and appropriate management., Case Report: A 31-year-old male with a history of consuming a commercial chlorpyrifos formulation presented with acute organophosphate poisoning symptoms that improved with appropriate treatment. However, two weeks later, the patient developed neurological deficits (numbness and weakness spreading from the plantar region to the upper limbs) involving the hypoglossal nerve, manifesting as left-sided tongue deviation, fasciculation, and atrophy, resulting in speech and swallowing difficulties. A comprehensive workup ruled out other potential causes of HNP, supporting the link between OPIDN and isolated HNP. Despite regaining limb strength, the patient's speech and swallowing issues persisted, prompting a follow-up visit to our hospital for further management and rehabilitation., Conclusion: This case report highlights a unique manifestation of OPIDN, resulting in isolated HNP, a rare phenomenon. The correlation between exposure to chlorpyrifos, acute organophosphate poisoning, and delayed onset of HNP suggests a causative relationship. Prompt diagnosis, appropriate treatment, and timely speech and swallowing rehabilitation are vital for optimizing outcomes in such cases. Further research is needed to understand the mechanisms underlying this selective vulnerability of OPIDN and to develop targeted interventions.

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.

Poison ingestion is a medical emergency requiring immediate care in the emergency department. Respiratory symptoms with ingested poisons can occur due to aspiration, cardiopulmonary effects, or direct lung toxicity due to injury of the alveolar epithelium. Chest imaging (chest radiographs/CT) is usually performed in the emergency setting to evaluate such symptoms. It is often impossible to elicit the nature of the poison ingested by the patients due to their unconscious state. Identification of the culprit poison can expedite the patient's management towards a specific antidote or help understand the underlying mechanism causing the pulmonary symptoms. The imaging manifestations depend on the underlying mechanisms, varying for each ingested poison, forming an imaging signature which has not been adequately discussed in existing literature. Poisons like paraquat and organophosphate are important to differentiate as indiscriminate use of oxygen therapy in the former can exacerbate the lung injury caused by redox cycling. In this pictorial assay, we present the chest imaging spectrum of commonly ingested poisons, and further suggest algorithmic approach towards identification of common poisons based on their chest imaging. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We designed this study to identify the factors associated with time to successful weaning in mechanically ventilated organophosphate (OP)-poisoned patients as the primary outcomes while duration of mechanical ventilation (MV) support, intensive care unit (ICU), and hospital length of stay (LOS) and in-hospital mortality as the secondary outcomes. We conducted a retrospective study of mechanically ventilated OP-poisoned patients admitted to the ICU of Poison Control Center of Ain Shams, Cairo, Egypt, starting from January 2019 to December 2019. Weaning was considered successful if the patient succeeded in the first spontaneous breathing trial of weaning and did not need reinstitution of MV. We used Cox proportional hazards regression models to identify factors associated with time to successful weaning in the studied patients. A total of 55 patients were enrolled in the study. Thirty-eight patients were weaned successfully. Lower initial red cell distribution width (RDW) levels [adjusted hazard ratio (HR), 0.299, 95% confidence interval (CI) (0.184–0.486)] and lower initial doses of atropine [adjusted HR, 0.97, 95% CI (0.935–0.999)] were independently associated with shorter time to achieve successful weaning. Successfully weaned patients had significantly longer hospital LOS (p = 0.019) and no reported in-hospital mortality (p < 0.001) compared with patients who failed to wean. We concluded that initial RDW and initial doses of atropine were found to be the strongest factors associated with time to successful weaning in mechanically ventilated OP-poisoned patients. RDW and atropine can be used as simple risk assessment tools in OP poisoning. [ABSTRACT FROM AUTHOR]

Introduction: Organophosphorus compounds are pesticides commonly used for agricultural purposes. However, by nature they are poisonous, and administration either accidental or intentional is a medical emergency requiring prompt evaluation and treatment, and can even lead to death. In addition due to the ease of their availability, they are commonly used for self-harm/suicidal purposes. Many of the patients are initially managed at primary or secondary healthcare setups before being referred to tertiary care hospitals. The purpose of our study is to find a prognostic marker in the initial blood work of these patients. Materials and Methods: A total of 46 patients were included in this retrospective cross-sectional survey conducted at the Department of Emergency Medicine, Holy Family Hospital, Rawalpindi. Data were collected from patient files using specific questionnaires. Outcomes were defined in terms of Emergency Department disposition. Data were analysed using SPSS v25. A univariate analysis, followed by Spearman's Correlation was used. Results: Patients with a higher WBC to Platelet ratio had worse outcomes. The Spearman's rho correlation coefficient was calculated and a moderately strong correlation (rho = .458, p < .001) was found. Conclusion: WBC to Platelet ratio is a hematological parameter determined to be most strongly correlated with adverse outcomes in Organophosphate Poisoning. It has a statistically significant stronger correlation than the WBC count alone. However, further extensive and focused studies are needed to corroborate these findings and substantiate them as a definite marker of prognostic significance. [ABSTRACT FROM AUTHOR]

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.

Background and Objective: Organophosphates poisoning is among the most prevalent forms of intentional and unintentional poisoning in Pakistan. However, the actual burden of AKI secondary to organophosphate poisoning in Pakistani population is still not known. This study aimed to determine the actual burden of AKI among patients admitted at National Poison Control Centre, Karachi. Methods: A cross-sectional survey was conducted at National Poison Control Centre, Karachi November, 2013 to April, 2014. A sample of 300 patients of age 18 years and above, presenting with organophosphate poisoning within 24 of exposure or ingestion were included in the study. Frequency of acute kidney injury was calculated using the diagnostic criteria of serum creatinine level of >1.4 mg/dL. Data was analyzed using SPSS version 19. Results: The frequency of AKI which was defined as creatinine level >1.4 mg/dL was 22.3% (n=67). However, there was no statistically significant difference was found in frequency of AKI on the basis of age, sex, amount of organophosphates ingested and BMI. This study found statistically significant differences in the AKI frequency on the basis of lag time. Those who presented earlier after poisoning had relatively low frequency of AKI. Conclusion: This study concludes that AKI is a common complication among patients presenting with organophosphate poisoning at National Poison Control Center, Karachi. Lag time is a key determinant of AKI among patients with organophosphate poisoning. Timely treatment can prevent this critical complication among patients with organophosphate poisoning. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

On March 4, 2018, two casualties collapsed on a park bench in Salisbury, Wiltshire, UK. They were later discovered to have been the victims of an attempted murder using the Soviet-era Novichok class of nerve agent. The casualties, along with three further critically ill patients, were cared for in Salisbury District Hospital's Intensive Care Unit. Before the COVID-19 pandemic, the Salisbury and Amesbury incidents were the longest-running major incidents in the history of the UK National Health Service. This narrative review seeks to reflect on the lessons learned from these chemical incidents, with a particular focus on hospital and local organisational responses. [ABSTRACT FROM AUTHOR]

Organophosphate (OP) poisoning is a critical public health issue, particularly in agricultural regions where these compounds are extensively used as pesticides. The toxic effects of OP compounds arise from their inhibition of acetylcholinesterase, leading to an accumulation of acetylcholine and a subsequent cholinergic crisis, which can be fatal if not promptly treated. Traditional management of OP poisoning includes the administration of atropine and pralidoxime; however, these treatments often fall short of reducing the high morbidity and mortality associated with severe cases. Recent research has highlighted the potential of magnesium sulfate as an adjunctive treatment for OP poisoning. Magnesium sulfate exerts its beneficial effects through mechanisms such as calcium channel blockade and stabilization of neuromuscular junctions, which help mitigate the cholinergic hyperactivity induced by OP compounds. Clinical studies have shown that magnesium sulfate can significantly reduce the duration of intensive care unit (ICU) stays and improve overall patient outcomes. This narrative review aims to comprehensively analyze current insights into using magnesium sulfate to manage OP poisoning. It discusses the pathophysiology of OP poisoning, the pharmacological action of magnesium sulfate, and the clinical evidence supporting its use. Furthermore, the review will address the safety profile of magnesium sulfate and its potential role in current treatment guidelines. By synthesizing available evidence, this review seeks to establish magnesium sulfate as a game-changer in the management of OP poisoning, ultimately contributing to better clinical practices and patient outcomes., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Nelakuditi et al.)

Organophosphate poisoning (OPP) remains a significant public health issue globally, particularly in middle- and low-income countries. This study aimed to assess the effectiveness of physiotherapy interventions in managing patients with OPP, focusing on reducing the severity of intermediate syndrome symptoms and associated complications such as respiratory muscle weakness and bilateral loculated pleural effusions. A 48-year-old male with a history of alcohol consumption was transferred to the medicine intensive care unit due to poison ingestion. The patient exhibited symptoms of respiratory distress and decreased consciousness, necessitating intubation and mechanical ventilation. Physiotherapy interventions included patient education, secretion mobilization, vital capacity improvement, secondary complication prevention, chest expansion exercises, dyspnea-relieving positions, and mobilization. The patient's progress was monitored using various scales, including the Functional Independence Measure Scale, ICU Mobility Scale, and Chelsea Critical Care Physical Assessment Tool. Significant improvements in functional independence, mobility, and psychological well-being were observed throughout the intervention period. This study highlights the importance of physiotherapy in the comprehensive management of OPP, emphasizing its role in mitigating respiratory complications and improving overall functional outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Vikhe et al.)