Acute Organophosphate Poisoning Research Articles

Shifts in the spatiotemporal profile of inflammatory phenotypes of innate immune cells in the rat brain following acute intoxication with the organophosphate diisopropylfluorophosphate

Acute intoxication with cholinesterase inhibiting organophosphates (OP) can produce life-threatening cholinergic crisis and status epilepticus (SE). Survivors often develop long-term neurological consequences, including spontaneous recurrent seizures (SRS) and impaired cognition. Numerous studies implicate OP-induced neuroinflammation as a pathogenic mechanism contributing to these chronic sequelae; however, little is known about the inflammatory phenotype of innate immune cells in the brain following acute OP intoxication. Thus, the aim of this study was to characterize the natural history of microglial and astrocytic inflammatory phenotypes following acute intoxication with the OP, diisopropylfluorophosphate (DFP). Adult male and female Sprague–Dawley rats were administered a single dose of DFP (4 mg/kg, sc) followed by standard medical countermeasures. Within minutes, animals developed benzodiazepine-resistant SE as determined by monitoring seizures using a modified Racine scale. At 1, 3, 7, 14, and 28 d post-exposure (DPE), neuroinflammation was assessed using translocator protein (TSPO) positron emission tomography (PET) and magnetic resonance imaging (MRI). In both sexes, we observed consistently elevated radiotracer uptake across all examined brain regions and time points. A separate group of animals was euthanized at these same time points to collect tissues for immunohistochemical analyses. Colocalization of IBA-1, a marker for microglia, with iNOS or Arg1 was used to identify pro- and anti-inflammatory microglia, respectively; colocalization of GFAP, a marker for astrocytes, with C3 or S100A10, pro- and anti-inflammatory astrocytes, respectively. We observed shifts in the inflammatory profiles of microglia and astrocyte populations during the first month post-intoxication, largely in hyperintense inflammatory lesions in the piriform cortex and amygdala regions. In these areas, iNOS+ proinflammatory microglial cell density peaked at 3 and 7 DPE, while anti-inflammatory Arg1+ microglia cell density peaked at 14 DPE. Pro- and anti-inflammatory astrocytes emerged within 7 DPE, and roughly equal ratios of C3+ pro-inflammatory and S100A10+ anti-inflammatory astrocytes persisted at 28 DPE. In summary, microglia and astrocytes adopted mixed inflammatory phenotypes post-OP intoxication, which evolved over one month post exposure. These activated cell populations were most prominent in the piriform and amygdala areas and were more abundant in males compared to females. The temporal relationship between microglial and astrocytic responses suggests that initial microglial activity may influence delayed, persistent astrocytic responses. Further, our findings identify putative windows for inhibition of OP-induced neuroinflammatory responses in both sexes to evaluate the therapeutic benefit of anti-inflammation in this context.

HI-6-Loaded Vehicle of Liposomes Mediated by an Amphiphilic Pillar[5]arene against Paraoxon Poisoning.

Organophosphate (OP) intoxication has become a severe common health matter all over the world. For the treatment of acute OP poisoning, the effective intracerebral delivery of acetylcholinesterase reactivators is crucial. Here, an amphiphilic hydrazide-pillar[5]arene (HP5A-6C), which could be readily integrated into liposomal bilayers' zwitterionic disaturated phosphatidylcholine (DSPC), was synthesized. A T7 peptide-containing guest (G) was attached on the surface via a noncovalent interaction to make mixed liposomes a particularly appealing candidate for brain-targeting delivery. Such coassembly could remain stable at room temperature for up to 6 weeks, and safety evaluations initially verified its fine biological compatibility. The hydrophilic interiors of T7/HP5A-6C@DSPC could further load HI-6 with 89.70% encapsulation efficiency. Support for brain-targeting potency came from imaging results. Notably, intravenous injection of HI-6-loaded vesicles exhibited a remarkable therapeutic effect on paraoxon (POX)-poisoned mice, effectively alleviating seizures and brain damage and significantly increasing the improving survival rate to 60% over the course of 7 days.

Isolated Hypoglossal Nerve Palsy: A Rare Complication of Organophosphate Poisoning

Abstract 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.

Validity of different scoring systems in prediction of intensive care unit admission and mortality in acute organophosphate poisoning.

Organophosphate compounds (OPCs) pose significant health risks, especially in developing countries with limited resources. Predicting outcomes in OPCs poisoning is crucial for guiding clinical management and reducing mortality rates. The aim of this study to evaluate the validity of different scoring systems Rapid Emergency Medicine Score, Multiple Organ Dysfunction Score, Acute Physiology and Chronic Health Evaluation Score, and Poison Severity Score in prediction of intensive care unit (ICU) admission and mortality of acute OPCs poisoning patients. A cross-sectional study was conducted on 103 patients admitted to Xx Poison Control Center between May 2022 and June 2023. Scoring systems were applied at admission, and their performance in predicting the need for ICU admission and mortality was evaluated using receiver operating characteristic (ROC) curve analysis. Most patients survived (92.2%). Only 13.6% of the patients required ICU admission. Significant differences in median scores were observed between survivors and non-survivors and between patients requiring ICU admission and those who did not. Multiple Organ Dysfunction Score exhibited the highest discriminatory power for predicting both ICU admission (AUC=0.983) and mortality (AUC=0.999). The findings highlight the importance of utilizing scoring systems, particularly Multiple organ dysfunction score, for prediction of poor outcomes of acute OPCs poisoning.

Life-Saving Resin: Hemoperfusion's Role in Overcoming Acute Organophosphate and Carbamate Poisoning

Background: Acute poisoning from organophosphates and carbamates is a major public health concern. These poisons inhibit acetylcholinesterase, leading to severe clinical manifestations. Traditional treatments, such as atropine and oximes, often fall short in severe cases, necessitating alternative therapeutic approaches. Hemoperfusion, an extracorporeal blood purification technique, has shown promise in improving outcomes for poisoning cases. This study aimed to estimate the clinical outcomes of resin-based HOD in individuals with acute organophosphate and carbamate poisoning admitted to a South Asian tertiary care hospital. Methods: A prospective observational study was carried out involving 50 patients diagnosed with acute organophosphate (n=30) or carbamate (n=20) poisoning. Patients underwent standard treatment protocols, and eligible individuals received resin-based hemoperfusion. Data on demographic details, clinical outcomes, complications, and biochemical parameters were collected and analysed using SPSS version 25.0. Results: The study found an overall recovery rate of 84%, with 80% recovery in the organophosphate group and 90% in the carbamate group. The complication rate was 12%, and the mortality rate was 4%. Cholinesterase levels significantly increased post-hemoperfusion, with a mean rise of 600 U/L. Time to treatment was a significant predictor of positive outcomes (p=0.011). Conclusion: Resin-based hemoperfusion is effective in treating acute organophosphate and carbamate poisoning, significantly improving recovery rates and reducing mortality. Early intervention is crucial for optimal outcomes. This treatment modality should be considered a valuable component of poisoning management protocols, especially in resource-limited settings. Recommendations: Further research with larger sample sizes and randomized controlled trials is recommended to confirm these findings and explore additional factors influencing treatment outcomes. Implementation of resin-based hemoperfusion in standard treatment protocols for severe poisoning cases is advised to enhance patient care and survival rates. Keywords: Organophosphate poisoning, Carbamate poisoning, Hemoperfusion, Clinical outcomes

A Study on the Clinical Profile of Cholinergic Insecticide Poisoning in a Tertiary Care Centre in Kerala

Introduction In India, insecticides pose a significant risk of poisoning, particularly in rural households where they are readily accessible and frequently employed for deliberate self-harm. Acute organophosphate (OP) poisoning represents a critical medical emergency and stands as a significant contributor to both mortality and morbidity rates. Among the various insecticides, OP poisoning stands out as the most commonly encountered. Patients afflicted with OP poisoning may experience respiratory failure due to several factors, including the aspiration of gastric contents, excessive secretions, pneumonia, and septicemia, which can further escalate into acute respiratory distress syndrome1 . Objectives To determine the clinical profile of cholinergic insecticide poisoning at the Government Medical College, Alappuzha, in both medical wards and the ICU.

Acute intoxication with diisopropylfluorophosphate promotes cellular senescence in the adult male rat brain.

Acute intoxication with high levels of organophosphate (OP) cholinesterase inhibitors can cause cholinergic crisis, which is associated with acute, life-threatening parasympathomimetic symptoms, respiratory depression and seizures that can rapidly progress to status epilepticus (SE). Clinical and experimental data demonstrate that individuals who survive these acute neurotoxic effects often develop significant chronic morbidity, including behavioral deficits. The pathogenic mechanism(s) that link acute OP intoxication to chronic neurological deficits remain speculative. Cellular senescence has been linked to behavioral deficits associated with aging and neurodegenerative disease, but whether acute OP intoxication triggers cellular senescence in the brain has not been investigated. Here, we test this hypothesis in a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP). Adult male Sprague-Dawley rats were administered DFP (4mg/kg, s.c.). Control animals were administered an equal volume (300µL) of sterile phosphate-buffered saline (s.c.). Both groups were subsequently injected with atropine sulfate (2mg/kg, i.m.) and 2-pralidoxime (25mg/kg, i.m.). DFP triggered seizure activity within minutes that rapidly progressed to SE, as determined using behavioral seizure criteria. Brains were collected from animals at 1, 3, and 6months post-exposure for immunohistochemical analyses of p16, a biomarker of cellular senescence. While there was no immunohistochemical evidence of cellular senescence at 1-month post-exposure, at 3- and 6-months post-exposure, p16 immunoreactivity was significantly increased in the CA3 and dentate gyrus of the hippocampus, amygdala, piriform cortex and thalamus, but not the CA1 region of the hippocampus or the somatosensory cortex. Co-localization of p16 immunoreactivity with cell-specific biomarkers, specifically, NeuN, GFAP, S100β, IBA1 and CD31, revealed that p16 expression in the brain of DFP animals is neuron-specific. The spatial distribution of p16-immunopositive cells overlapped with expression of senescence associated β-galactosidase and with degenerating neurons identified by FluoroJade-C (FJC) staining. The co-occurrence of p16 and FJC was positively correlated. This study implicates cellular senescence as a novel pathogenic mechanism underlying the chronic neurological deficits observed in individuals who survive OP-induced cholinergic crisis.

Quantitative T2 mapping-based longitudinal assessment of brain injury and therapeutic rescue in the rat following acute organophosphate intoxication

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.

Cardiovascular responses of adult male Sprague–Dawley rats following acute organophosphate intoxication and post-exposure treatment with midazolam with or without allopregnanolone

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.

Comparative Analysis of Outcomes in Acute Organophosphate Poisoning With and Without N-acetyl Cysteine Intervention.

Organophosphorus poisoning (OPP) stands as a significant health concern in numerous regions, especially in developing nations. Despite the rising complexities and case fatalities associated with exposure, the treatment approach has remained unchanged for many years. Based on clinical insights, certain pharmacologic agents have demonstrated utility in enhancing outcomes and reducing complications arising from this type of exposure. The objective of this study is to compare the outcome of N-acetyl cysteine in the treatment of acute organophosphate poisoning cases. In terms of a) its impact on the requirement of atropine, b) Length of hospital stay, and mortality. The study was conducted in the intensive care unit (ICU) of the General Hospital Lahore. Thirty patients with a history and clinical presentation indicative of acute organophosphorus poisoning were randomly divided into two groups in a 1:1 ratio. The treatment group received parenteral administration of atropine, pralidoxime, and N-acetylcysteine (NAC) as an adjuvant, and the control group received standard treatment for acute organophosphate (OP) toxicity. Throughout the study duration, 30 patients suffering acute organophosphate (OP) toxicity (14 men, 16 women) were examined, with an age mean of (25.83±11.59) years. In the interventional group, only four patients required ICU admission, but in the control group, eight patients were admitted to ICU. The correlation result between the dose of atropine and length of hospital stays was not statistically significant between both study groups (<0.005). Plasma Cholinesterase (PChE) level (KU L-1) and total dose of Pralidoxime (g) were statistically significant in the length of hospital stay. The data was not normally distributed, so the non-parametric tests were applied. The Wilcoxon ranked test showed significant improvement in both the controlled and interventional groups because the p-value was (<0.005). Intergroup comparison analyzed by using the Mann-Whitney U test showed a significant reduction in the severity and other associated symptoms in the interventional group because the p-value was (0.001). The outcome demonstrated that the NAC group had a decreased demand for atropine rather than Pralidoxime. In the NAC group, the length of hospital stay and mortality was decreased. The administration of NAC to the present study procedure for acute organophosphate (OP) poisoning is suggested.

Acute Poisoning Emergencies at Gulu University Teaching Hospitals in Northern Uganda: Prevalence, Outcomes and Clinical Challenges

Acute poisonings, including envenomation as well as toxicological emergencies stemming from accidental or intentional ingestion of poisonous substances or drug overdose, are significant worldwide causes of morbidity and mortality. The study aimed to characterise acute poisoning emergencies admitted to two major hospitals in Northern Uganda. We conducted a retrospective review of charts of all patients admitted with acute poisoning emergencies between January and December 2021, as well as a structured interview of hospital staff working in these hospitals on challenges faced while managing these emergencies. Of the total 40,653 patient admissions, 416 (1%) were due to acute poisonings. The majority were admitted to SMHL (71.4%), 43.3% were between 20 and 40 years of age, and 59.9% were males. The average length of hospital stay was 1 (0-3). The most frequent diagnoses were acute alcohol intoxications (27.2%, n=113), snake bites (26.0%, n=108), and organophosphate poisonings (21.2%, n=88). Only 29.6% (n=123) of patients received antidotes. Peak admissions were observed in February, May, and July. The majority of poisonings were intentional (61.3%), resulting in a Case Fatality Rate of 6.3%. In the qualitative findings, participants highlighted key challenges in managing these conditions, including the lack of antidotes, patients presenting late at the hospital, economic barriers, staff shortages, and limited community awareness. Acute poisoning, especially acute alcoholic intoxication, snake bites and organophosphate poisoning, are common in northern Uganda, with significant numbers dying from it. The lack of antidotes remains a problem in these hospitals. Restriction of alcohol consumption use of agricultural organophosphates, and training of healthcare workers in managing these emergencies are recommended

Neuroprotectant Activity of Novel Water-Soluble Synthetic Neurosteroids on Organophosphate Intoxication and Status Epilepticus-Induced Long-Term Neurological Dysfunction, Neurodegeneration, and Neuroinflammation.

Organophosphates (OPs) and nerve agents are potent neurotoxic compounds that cause seizures, status epilepticus (SE), brain injury, or death. There are persistent long-term neurologic and neurodegenerative effects that manifest months to years after the initial exposure. Current antidotes are ineffective in preventing these long-term neurobehavioral and neuropathological changes. Additionally, there are few effective neuroprotectants for mitigating the long-term effects of acute OP intoxication. We have pioneered neurosteroids as novel anticonvulsants and neuroprotectants for OP intoxication and seizures. In this study, we evaluated the efficacy of two novel synthetic, water-soluble neurosteroids, valaxanolone (VX) and lysaxanolone (LX), in combating the long-term behavioral and neuropathological impairments caused by acute OP intoxication and SE. Animals were exposed to the OP nerve agent surrogate diisopropylfluorophosphate (DFP) and were treated with VX or LX in addition to midazolam at 40 minutes postexposure. The extent of neurodegeneration, along with various behavioral and memory deficits, were assessed at 3 months postexposure. VX significantly reduced deficits of aggressive behavior, anxiety, memory, and depressive-like traits in control (DFP-exposed, midazolam-treated) animals; VX also significantly prevented the DFP-induced chronic loss of NeuN(+) principal neurons and PV(+) inhibitory neurons in the hippocampus and other regions. Additionally, VX-treated animals exhibited a reduced inflammatory response with decreased GFAP(+) astrogliosis and IBA1(+) microgliosis in the hippocampus, amygdala, and other regions. Similarly, LX showed significant improvement in behavioral and memory deficits, and reduced neurodegeneration and cellular neuroinflammation. Together, these results demonstrate the neuroprotectant effects of the novel synthetic neurosteroids in mitigating the long-term neurologic dysfunction and neurodegeneration associated with OP exposure. SIGNIFICANCE STATEMENT: Survivors of nerve agents and organophosphate (OP) exposures suffer from long-term neurological deficits. Currently, there is no specific drug therapy for mitigating the impact of OP exposure. However, novel synthetic neurosteroids that activate tonic inhibition provide a viable option for treating OP intoxication. The data from this study indicates the neuroprotective effects of synthetic, water-soluble neurosteroids for attenuation of long-term neurological deficits after OP intoxication. These findings establish valaxanolone and lysaxanolone as potent and efficacious neuroprotectants suitable for injectable dosing.

Evidence Implicating Blood-Brain Barrier Impairment in the Pathogenesis of Acquired Epilepsy following Acute Organophosphate Intoxication.

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.

Time- and region-dependent blood-brain barrier impairment in a rat model of organophosphate-induced status epilepticus

Acute organophosphate (OP) intoxication can trigger seizures that progress to status epilepticus (SE), and survivors often develop chronic morbidities, including spontaneous recurrent seizures (SRS). The pathogenic mechanisms underlying OP-induced SRS are unknown, but increased BBB permeability is hypothesized to be involved. Previous studies reported BBB leakage following OP-induced SE, but key information regarding time and regional distribution of BBB impairment during the epileptogenic period is missing. To address this data gap, we characterized the spatiotemporal progression of BBB impairment during the first week post-exposure in a rat model of diisopropylfluorophosphate-induced SE, using MRI and albumin immunohistochemistry. Increased BBB permeability, which was detected at 6 h and persisted up to 7 d post-exposure, was most severe and persistent in the piriform cortex and amygdala, moderate but persistent in the thalamus, and less severe and transient in the hippocampus and somatosensory cortex. The extent of BBB leakage was positively correlated with behavioral seizure severity, with the strongest association identified in the piriform cortex and amygdala. These findings provide evidence of the duration, magnitude and spatial breakdown of the BBB during the epileptogenic period following OP-induced SE and support BBB regulation as a viable therapeutic target for preventing SRS following acute OP intoxication.

Organophospate-Induced Pathology: Mechanisms of Development, Principles of Therapy and Features of Experimental Studies

Organophosphates (OP) are one of the most common neurotoxic xenobiotics. In acute OP poisoning, as a result of suppression of synaptic acetylcholinesterase (AChE) activity, a cholinergic syndrome develops, which can transform into status epilepticus. Within a few days after acute poisoning, the so-called an intermediate syndrome can develop, which is associated with prolonged inhibition of AChE, desensitization of nicotinic receptors, and functional degradation of synapses and muscle fibers. In 10–20 days after a single acute or repeated subacute poisoning, OP-induced delayed polyneuropathy (OPIDN) can develop – a neurodegenerative disease, the signs of which are ataxia, loss of function of the distal sensory and motor axons of peripheral nerves. The occurrence of a neuropsychiatric disorder (NPD) caused by chronic exposure to relatively low-toxicity organophosphorus compounds is usually not associated with acute poisoning; symptoms include cognitive impairment, chronic fatigue, and extrapyramidal symptoms. The list of possible diseases or pathological conditions (syndromes) that develop as a result of acute, subacute or chronic effects of OP on the human body has expanded in recent years due a number of known neurodegenerative diseases (Alzheimer’s, Parkinson’s, multiple sclerosis, etc.). The aging of the body in general and the aging of the brain in particular are considered in the review from the point of view of the consequences of OP poisoning, which can serve as a nonspecific trigger of aging and related neurodegenerative diseases. Gulf syndrome is not a consequence of OP intoxication, but is also of interest and is considered in the context of OP-induced pathology, since its etiology and pathogenesis are associated with the exposure to cholinesterase inhibitors. The review presents data indicating the important role of the vascular endothelium in the development of OP-induced pathology; The first suggestions were made by clinicians in the late 1980s, and the first experimental data were obtained in the early 2000s. The principles of therapy for acute poisoning are outlined, taking into account experimental data from recent years. Some methods for studying OP in experiments in vitro, ex vivo and in vivo with laboratory animals, including the use of carboxylesterase inhibitors, are presented. The most important part of in vivo investigations has been and remains the search for new biomarkers to assess the effectiveness of adjuvant and regenerative therapies.

Acute pancreatitis, a significant mortality predictor in acute organophosphate poisoning: an observational study in a tertiary care centre in north India

Background: Organophosphate compounds are one of the most common agents used as poison and acts by accumulation of acetylcholine hormone at neuronal synapses resulting in the symptoms like excessive salivation, vomiting, urination, and increased serum amylase and lipase levels. APACHE 2 score along with ultrasound modality can be used to assess the acute pancreatitis. The primary aim of the study is to find correlation of serum amylase and lipase levels with duration of ICU stay and with radio-logical variables like bulky pancreas. Methods: This observational study conducted at GSVM medical college, Kanpur from December 2020 to October 2022 included 58 out of total 94 admitted patients with acute organophosphate intoxicationn on the basis of 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: Acute organophosphate poisoning was more prevalent among 20-40 years of age group. Mean serum amylase level values in q SOFA category 0, 1, 2, 3 were 65.2, 82.0, 118.4, 329.9 IU/l respectively and that of mean serum lipase levels on day 1 of admission values were 42.0, 44.3, 38.6 and 115.5 IU/l respectively. Serum amylase levels were positively correlated with duration of ICU stay and were better predictor for acute pancreatitis. Conclusions: In this study we concluded that serum amylase is a better predictor of duration of ICU stay and acute pancreatitis in patients admitted with acute organophosphate poisoning.

The role of a combination of N-acetylcysteine and magnesium sulfate as adjuvants to standard therapy in acute organophosphate poisoning: A randomized controlled trial

BackgroundMortality in acute organophosphate (OP) poisoning remains high despite current standard therapy with atropine and oximes. Due to dose-limiting side effects of atropine, novel therapies are targeting other putative mechanisms of injury, including oxidative damage, to reduce atropine dosage. ObjectivesN-acetylcysteine (NAC) and magnesium sulfate (MgSO4) have different mechanisms of actions and should act synergistically in OP poisoning. In this study, we wanted to evaluate whether this novel combination, used as an adjuvant to standard care, could improve clinical outcomes. MethodsThe study was conducted in the Emergency Department and ICU of AIIMS Bhubaneswar (a tertiary care center and government teaching institute) between July 2019 and July 2021. Eighty-eight adult patients with history and clinical features of acute OP poisoning were randomly allocated (1:1) into two groups. The Study group received 600 mg NAC via nasogastric tube thrice daily for 3 days plus a single dose of 4 g Inj. MgSO4 IV on first day and the Control group received suitably matched placebo (double-blinding) – in addition to standard care in both the groups. The primary outcome measure was to compare the total dose of Inj. Atropine required (cumulative over the entire treatment duration) between the control group and the study group receiving NAC and MgSO4. The secondary outcome measures were lengths of ICU and hospital stays, need and duration of mechanical ventilation, the differences in BuChE activity, oxidative stress biomarkers – MDA and GSH levels, the incidences of adverse effects including delayed sequalae like intermediate syndrome and OPIDN, and comparison of mortality between the two groups. ResultsData from 43 patients in Control and 42 patients in Study group was finally analyzed. The baseline parameters were comparable. Total atropine requirements were lower in the Study group [175.33 ± 81.25 mg (150.01–200.65)] compared to the Control [210.63 ± 102.29 mg (179.15–242.11)] [Mean ± SD (95% CI)], but was not statistically significant. No significant differences in any of the other clinical or biochemical parameters were noted. ConclusionThe N-acetylcysteine and MgSO4 combination as adjuvants failed to significantly reduce atropine requirements, ICU/hospital stay, mechanical ventilatory requirements, mortality and did not offer protection against oxidative damage.

ChatGPT in Clinical Toxicology.

ChatGPT has recently been shown to pass the United States Medical Licensing Examination (USMLE). We tested ChatGPT (Feb 13, 2023 release) using a typical clinical toxicology case of acute organophosphate poisoning. ChatGPT fared well in answering all of our queries regarding it.

STUDY OF SERUM AMYLASE LEVELS IN ORGANOPHOSPHATE POISONING

Organophosphate (OP) insecticides are 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.This study aims to determine the impact of serum amylase level for estimation of prognosis in patients with acute OP poisoning. Method: This prospective observational hospital-based study was performed on 100 patients with acute OP poisoning. Demographics data, clinical profile, serum amylase levels, complications,hospital stay and outcome were determined.Data were analyzed in the form of a frequency distributions using SPSS 26.0 version software.Result: Most patients were young adults with mean age of 29yrs ± 11yrs with slightly male predominance. Mean serum amylase level was significantly higher among patients with morbidity and mortality. Conclusion: Among patients with OP poisoning,higher serum amylase than normal was associated with severe clinical course and increased risk for mortality.Determination of serum amylase can be an effective marker of the prognosis and clinical course among OP poisoning patients.

Performance of new Poisoning Mortality Score in comparison with SOFA and APACHE II scores in acute organophosphate poisoning

Introduction: Organophosphate (OP) poisoning is a serious public health problem in underdeveloped nations. Many cases of severe poisoning and more than 220,000 deaths are recorded every year. Early detection and treatment can save lives because OP poisoning has a significant fatality rate. The new Poisoning Mortality Score (PMS) has been developed for clinical decision-making and therapeutic guidance in patients with acute poisoning. Methods: This is a retrospective study that included 236 patients with acute OP poisoning who got admitted to a tertiary care hospital over two years after obtaining permission from the institutional ethical committee. The PMS, Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were calculated based on patient details. Results: The results showed that the mean age of patients was 32.8 ± 13.4 years; 50.8% were men and 49.2% were women. Out of 236 patients, 214 got discharged and 22 died. The mean ± SD of PMS, SOFA score, and APACHE II scores among the discharged patients were 51±7, 1 ± 2, and 5 ± 5, respectively, and those among the expired patients were 70 ± 12, 7 ± 3, and 28 ± 9, respectively. The best cut-off points for predicting mortality in acute OP poisoning patients for PMS, SOFA score, and APACHE II scores were &gt;65, &gt;3, and &gt;15 with sensitivities of 77.27%, 95.45%, and 95.45%, specificities of 96.26%, 91.59%, and 95.79%, and areas under the receiver operating characteristic curve of 0.917, 0.970, and 0.984, respectively. Conclusion: The study showed that the new PMS is significantly associated with the prediction of mortality in acute OP poisoning in comparison with SOFA and APACHE II scores.