Acute Organophosphate Poisoning Case Review With Consideration of Off-Gassing During Postmortem Examination.

ABSTRACT: Although self-harm via ingestion of organophosphorus compounds is relatively common in the developing world, it is rare in the United States. This article reviews the signs and symptoms associated with acute organophosphate poisoning and highlights the effects of organophosphate off-gassing during postmortem examinations to increase awareness of this potentially dangerous workplace exposure.Paramedics responded to a 42-year-old man with pulseless electrical activity. Spontaneous circulation was restored after aggressive resuscitation. Before loss of consciousness, the patient exhibited diaphoresis, vomiting, and diarrhea. Upon admission, the patient had a Glasgow Coma Scale score of 3. Significant laboratory values included a pH of 6.8, p co2 of 72 mm Hg, and lactic acid of 21.8 mmol/L. Electrocardiography suggested inferior ST-elevation myocardial infarction. Electroencephalogram revealed severe cerebral dysfunction. The patient died shortly thereafter.Scene investigation revealed suicidal ideations, which included a snapshot of a bottle containing granular sediment associated with statements that he had imbibed fertilizer. During the postmortem examination, the decedent exuded a petroleum-like odor. In addition, autopsy personnel developed symptoms consistent with organophosphate exposure.A reported history of suspected organophosphate exposure in a decedent should prompt increased safety practices to avoid potential harm to autopsy personnel.

Opsoclonus-myoclonus syndrome caused by organophosphate poisoning.

Opsoclonus-myoclonus syndrome is a combination of involuntary, arrhythmic, conjugate saccadic eye movements with myoclonus. The most common cause in adults is paraneoplastic encephalitis. Rarer causes include infections such as scrub typhus, and toxins such as organophosphates and cocaine. Organophosphates are one of the common poisonings in tropical countries such as India, causing both central and peripheral nervous system manifestations. We describe a middle-aged male farmer with unexplained altered consciousness and respiratory depression. After 2 days, he developed opsoclonus-myoclonus, and then bronchorrhoea and bradycardia, raising suspicion of organophosphate poisoning. After we had identified a very low serum cholinesterase concentration, he disclosed having consumed organophosphates.

Prolonged apnea after ECT in organophosphorus poisoning - the need to redefine norms.

BACKGROUND: Poisoning and deaths by organo-phosphorous (OP) compounds are one of the major causes of death in developing and poor countries, and a common admission in the emergency ward and the ICU. OP compounds act by irreversibly binding to pseudocholinesterase enzyme and hence prolong the apnea in patients being given suxamethonium. We present a unusual case of OP poisoning (OPP) in which prolonged apnea ensued in a patient of severe depression following MECT (modified electroconvulsive therapy) in which suxamethonium was used as muscle relaxant, in whom we were cautious of the side-effect of prior organophosphorus poisoning. Since the cases of OPP are very high worldwide, a thorough knowledge of the interaction of the action of the drug and the receptors on which it acts takes pride of place. This article highlights the nuances in the field of psychiatry and anaesthesia in diagnosis and management of prolonged apnea after ECT. CASE PRESENTATION: A 53/F patient consumed OP 38 days prior to MECT. Since existing literature recommend a delay of 4 weeks and a subminimal dose of suxamethonium to prevent prolonged apnea, both these points were taken into consideration. Despite 38 days post exposure to OP, and a dose of succinylcholine of < 0.3 mg/kg, the patient remained apneic for 3 h. Suxamethionum apnea was managed with elective ventilation. After recovery, patient had no residual effect. Subsequently her pseudocholinesterase levels were done which were found to be very low. CONCLUSION: This case is being presented to emphasize that behaviour of post synaptic receptors cannot be relied upon after OP poisoning and pseudocholinesterase levels needs to be mandatorily checked, irrespective of duration post-exposure. In strong suspects dibucaine number and fluoride number also needs to be estimated.

Novel therapeutics for treating organophosphate-induced status epilepticus co-morbidities, based on changes in calcium homeostasis.

Organophosphate (OP) chemicals include pesticides such as parathion, and nerve gases such as sarin and soman and are considered major chemical threat agents. Acute OP exposure is associated with a cholinergic crisis and status epilepticus (SE). It is also known that the survivors of OP toxicity exhibit neurobehavioral deficits such as mood changes, depression, and memory impairment, and acquired epilepsy. Our research has focused on addressing the need to develop effective therapeutic agents that could be administered even after prolonged seizures and would prevent or lessen the chronic morbidity associated with OP-SE survival. We have developed rat survival models of OP pesticide metabolite paraoxon (POX) and nerve agent sarin surrogate diisopropyl fluorophosphate (DFP) induced SE that are being used to screen for medical countermeasures against an OP attack. Our research has focused on studying neuronal calcium (Ca2+) homeostatic mechanisms for identifying mechanisms and therapeutics for the expression of neurological morbidities associated with OP-SE survival. We have observed development of a "Ca2+ plateau" characterized by sustained elevations in neuronal Ca2+ levels in OP-SE surviving rats that coincided with the appearance of OP-SE chronic morbidities. These Ca2+ elevations had their origin in Ca2+ release from the intracellular stores such that blockade with antagonists like dantrolene, carisbamate, and levetiracetam lowered OP-SE mediated Ca2+ plateau and afforded significant neuroprotection. Since the Ca2+ plateau lasts for a prolonged period, our studies suggest that blocking it after the control of SE may represent a unique target for development of novel countermeasures to prevent long term Ca2+ mediated OP-SE neuropsychiatric comorbidities such as depression, anxiety, and acquired epilepsy (AE).

Antiseizure and neuroprotective effects of delayed treatment with midazolam in a rodent model of organophosphate exposure.

OBJECTIVE: Exposure to organophosphates (OPs) and OP nerve agents (NAs) causes status epilepticus (SE) and irreversible brain damage. Rapid control of seizure activity is important to minimize neuronal injury and the resulting neurological and behavioral disorders; however, early treatment will not be possible after mass release of OPs or NAs. METHODS: We utilized a delayed-treatment model of OP exposure in adult rats by administration of diisopropyl fluorophosphate (DFP) to study the relationship between the antiseizure and neuroprotective effects of the "standard-of-care" benzodiazepine, midazolam (MDZ), when given at 30, 60, and 120 minutes after SE onset. After electroencephalography (EEG) recordings, neural damage in serial brain sections was studied with Fluoro-Jade B staining. RESULTS: MDZ-induced seizure suppression was equivalent in magnitude regardless of treatment delay (ie, seizure duration). When assessed globally (ie, normalized across 10 different brain regions) for each treatment delay, MDZ administration resulted in only nonsignificant reductions in neuronal death. However, when data for MDZ treatment were combined from all three delay times, a small but significant reduction in global neuronal death was detected when compared to vehicle treatment, which indicated that the substantive MDZ-induced seizure suppression led to only a small reduction in neuronal death. SIGNIFICANCE: In conclusion, MDZ significantly reduced DFP-induced SE intensity when treatment was delayed 30, 60, and even up to 120 minutes; however, this reduction in seizure intensity had no detectable effect on neuronal death at each individual delay time. These data show that although MDZ suppressed seizures, additional neuroprotective therapies are needed to mitigate the effects of OP exposure.

Neurobiology of organophosphate-induced seizures.

This review summarizes the efforts of our laboratories to develop a mechanism-based therapy for the treatment of organophosphate (OP) nerve agent-induced seizures. Organophosphate poisoning can occur during warfare and terrorist attacks and in the civilian sphere because of intentional or unintentional poisoning. Persons exposed to OPs experience seizures. We developed animal models of OP poisoning and then evaluated the effects of OP on excitatory α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated glutamatergic neurotransmission in the hippocampus using patch-clamp electrophysiology. Organophosphate agents enhance glutamatergic transmission by enhancing neurotransmitter release. M1 muscarinic receptors mediate this effect, at least in part. Muscarinic receptors exert this action by inhibiting specific KCNQ2/3 potassium channels, which mediate the M-current. Flupirtine, a drug that open channels, is effective against OP-induced seizures. This article is part of the Special Issue"Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Efficacy and outcomes of lipid resuscitation on organophosphate poisoning patients: A systematic review and meta-analysis.

OBJECTIVE: Organophosphate (OP) pesticides are still widely available in developing countries, leading to numerous accidental or suicidal poisonings every year. Lipid emulsion treatments are commonly used in resuscitating OP poisoning patients but few studies regarding their use have been reported. Our meta-analysis aimed to analyze the efficacy and outcomes of lipid resuscitation on OP poisoning patients. METHODS: A systematic search for associated studies was conducted in Pubmed, EMBASE, MEDLINE, the Cochrane Library and the Chinese National Knowledge Infrastructure. Collected data was pooled using Revman v5.3. Outcomes included prognosis (cured vs. mortality rates), hepatic function (serum ALT, AST, Total Bilirubin (TBIL) level), serum acetylcholinesterase (AchE) level and respiratory function (rate of respiratory muscular paralysis). RESULTS: Seven randomized controlled studies consisting of 630 patients meeting inclusion criteria were identified. Lipid emulsion helped to improve the cure rate [OR = 2.54, 95% CI (1.33, 4.86), p = 0.005] and lower the mortality rate [OR = 0.31, 95% CI (0.13, 0.74), p = 0.009]. Serum ALT, AST and TBIL in patients undergoing lipid resuscitation were lower than those in the control groups [ALT, SMD = -1.52, 95% CI (-2.64, 0.40), p = 0.008; AST, SMD = -1.66, 95% CI (-3.15, 0.16), p = 0.03; TBIL, SMD = -1.26, 95% CI (-2.32, 0.20), p = 0.02]. Serum AchE level were increased in patients treated with lipid emulsion [SMD = 2.15, 95% CI (1.60, 2.71), p < 0.00001]. Rate of respiratory muscular paralysis was lower in patients undergoing lipid resuscitation than those in the control groups [OR = 0.19, 95% CI (0.05, 0.71), p = 0.01]. CONCLUSION: Based on our meta-analysis of included RCT reports, lipid resuscitation seems likely to help improve prognosis and liver function of OP poisoning patients. However, larger multi-center RCTs are still recommended.

Case Control Study of Impulsivity, Aggression, Pesticide Exposure and Suicide Attempts Using Pesticides among Farmers.

A case-control study was conducted to investigate associations between organophosphate pesticide (OP) exposure, aggression, impulsivity, and attempted suicide. Questionnaires were used to collect information; impulsivity and aggression were measured by the Barratt Impulsivity Scale (BIS) and the Aggression Inventory (AI). A greater number of OP symptoms was associated with an increased odds of a suicide attempt after adjusting for marital status and income (OR = 1.45; CI 1.14-1.86). Attempted suicide was significantly associated with high impulsivity scores (means: 72.4 vs. 60.6, P < 0.0001) and high aggression scores (means: 38.5 vs. 26.1, P < 0.0001). Suicide attempters had a higher number of OP exposure symptoms than controls and scored higher on scales of impulsivity and aggression.

Prolonged Apnea During Modified Electroconvulsive Therapy in a Patient of Suicidal Attempt by Organophosphorus Poisoning: A Case Report.

Organophosphorus (OP) pesticides are commonly used in agricultural fields to control pests in India. However, exposure to it can cause poisoning in humans and animals, or it can be taken intentionally as poison to commit suicide. We present a case of a 35-year-old suicidal man who developed prolonged apnea for almost 4 hours on day 13 of OP poisoning after brief general anesthesia induced by propofol and 1 mg/kg of suxamethonium, during the first session of the third cycle of modified electroconvulsive therapy, despite all due precautions. Such prolonged apnea secondary to complex interactions has been reported very rarely in literature. This case therefore, highlights the importance of careful evaluation and monitoring while giving anesthesia to OP-poisoning patients.

Midazolam as an anticonvulsant antidote for organophosphate intoxication--A pharmacotherapeutic appraisal.

OBJECTIVE: This review summarizes the therapeutic potential of midazolam as an anticonvulsant antidote for organophosphate (OP) intoxication. METHODS: Benzodiazepines are widely used to treat acute seizures and status epilepticus (SE), a neurologic emergency of persistent seizures that can lead to severe neuronal damage or death. Midazolam is a benzodiazepine hypnotic with a rapid onset and short duration of action. RESULTS: Midazolam is considered the new drug of choice for persistent acute seizures and SE, including those caused by neurotoxic OPs and nerve agents. Midazolam is a positive allosteric modulator of synaptic γ-aminobutyric acid (GABA)A receptors in the brain. It potentiates GABAergic inhibition and thereby controls hyperexcitability and seizures. Midazolam is administered intravenously or intramuscularly to control acute seizures and SE. Due to its favorable pharmacokinetic features, midazolam is being considered as a replacement anticonvulsant for diazepam in the antidote kit for nerve agents. Clinical studies such as the recent Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) trial have confirmed the anticonvulsant efficacy of midazolam in SE in prehospital settings. SIGNIFICANCE: In experimental models, midazolam is effective when given at the onset of seizures caused by nerve agents. However, benzodiazepines are less effective at terminating seizures when given 30 min or later after OP exposure or seizure onset, likely because of internalization or downregulation of synaptic, but not extrasynaptic, GABAA receptors, which can lead to diminished potency and seizure recurrence.

Clinical management of organophosphate poisoning in pregnancy.

BACKGROUND: Acute organophosphorus pesticide poisoning during pregnancy may lead to spontaneous abortion. Now, there is no definite strategy focused on maintaining pregnancy. METHOD: This is a retrospective analysis of 2 cases of organophosphorus poisoning during pregnancy. All patients received penehyclidine hydrochloride injection,until the tracheobronchial tree is cleared of the secretions, and most secretions were dried. In addition, magnesium sulfate was used in one woman for the correction of hyperdynamic uterine activity. RESULTS: Two women all survived, one fetus died of spontaneous abortion, and one fetus died of incoordinate uterine action. The 2 women had no significant complications during postpartum period. CONCLUSION: Penehyclidine hydrochloride and magnesium sulfate may be used to treat organophosphorus during pregnancy. However, futher study and new experimental need to be designed.

Coronary artery bypass grafting in a patient with organophosphate poisoning.

A 43-year-old male, with no previous history of mental illness, was diagnosed with coronary heart disease, after which he became acutely depressed and attempted suicide by ingesting an organophosphate pesticide. He was admitted to an intensive care unit and treated with pralidoxime, atropine, and oxygen. His coronary occlusion pattern required early coronary artery bypass grafting (CABG) surgery. His family, apprehensive of a repeat suicidal attempt, requested surgery be performed as soon as possible. He recovered well from the OP poisoning and was mentally fit to express informed consent 2 weeks after admission. Seventeen days after poisoning, he underwent coronary artery bypass grafting and recovered uneventfully. Six years later, he remains in excellent health. We report this case because to the best of our knowledge there is no literature regarding CABG performed soon after organophosphate poisoning.

Animal models that best reproduce the clinical manifestations of human intoxication with organophosphorus compounds.

The translational capacity of data generated in preclinical toxicological studies is contingent upon several factors, including the appropriateness of the animal model. The primary objectives of this article are: 1) to analyze the natural history of acute and delayed signs and symptoms that develop following an acute exposure of humans to organophosphorus (OP) compounds, with an emphasis on nerve agents; 2) to identify animal models of the clinical manifestations of human exposure to OPs; and 3) to review the mechanisms that contribute to the immediate and delayed OP neurotoxicity. As discussed in this study, clinical manifestations of an acute exposure of humans to OP compounds can be faithfully reproduced in rodents and nonhuman primates. These manifestations include an acute cholinergic crisis in addition to signs of neurotoxicity that develop long after the OP exposure, particularly chronic neurologic deficits consisting of anxiety-related behavior and cognitive deficits, structural brain damage, and increased slow electroencephalographic frequencies. Because guinea pigs and nonhuman primates, like humans, have low levels of circulating carboxylesterases-the enzymes that metabolize and inactivate OP compounds-they stand out as appropriate animal models for studies of OP intoxication. These are critical points for the development of safe and effective therapeutic interventions against OP poisoning because approval of such therapies by the Food and Drug Administration is likely to rely on the Animal Efficacy Rule, which allows exclusive use of animal data as evidence of the effectiveness of a drug against pathologic conditions that cannot be ethically or feasibly tested in humans.

Body mass index as a prognostic factor in organophosphate-poisoned patients.

Organophosphate poisoning is a serious clinical entity and considerable morbidity and mortality. Several factors have been identified to predict outcomes of organophosphate poisoning. Organophosphates are lipophilic and therefore predicted to have a large volume of distribution and to rapidly distribute into tissue and fat. Thus, toxic effects of organophosphate would be expected to last longer in obese patients. We investigated the relationship between obesity and clinical course in 112 acute organophosphate-poisoned patients from an initial medical record review of 234 patients. One hundred twenty-two patients were excluded: 6 were children, 14 had an uncertain history of exposure and of uncertain agent, 10 were transferred to another hospital, 67 were discharged from the emergency department because their toxicity was mild, 21 had carbamate poisoning, and 4 did not have height or weight checked. Clinical features, body mass index, Glasgow Coma Scale, laboratory findings, serum cholinesterase activity, electrocardiogram finding, management, and outcomes were examined. The lipid solubility of the implicated organophosphate was characterized by its octanol/water coefficient. Forty of 112 patients were obese. Obese patients who were poisoned by high lipophilicity organophosphate compounds had a need for longer use of mechanical ventilation, intensive care unit care, and total length of admission. Body mass index can provide a guide to physicians in predicting clinical course and management in organophosphate-poisoned patients.

A 48-year-old man with severe shortness of breath.

A 48-year-old man was found by his neighbor unconscious on the floor at his residence. Earlier in the day, his neighbor reported noticing the patient was becoming more short of breath and having some trouble speaking. The neighbor alerted EMS. Upon EMS arrival, the patient was tachypneic with a room air O2 saturation in the 60s. A LifeFlight helicopter responded to transfer this patient to a tertiary care center from his home in a rural farming community.

Does organophosphate poisoning cause cardiac injury?

Organophosphates are insecticides which are widely used as a suicidal agent in Iran. They are associated with different types of cardiac complications including cardiac arrest and arrhythmia, however their role in cardiac injury is not known yet. The aim of this study was to investigate the presence of myocardial damage in patients with cholinesterase poisoning.It was a prospective study conducted from January 2008 to March 2010. Cohorts of patients with cholinesterase poisoning due to suicidal attempt who have been referred to Loghman hospital were selected. Patients who have taken more than one poison or were used concomitant drugs were excluded. Physical examination was performed on admission to discover warning sign. Peripheral arterial blood gases, creatine kinase, creatine kinase-myocardial band, troponin-T measurements were performed in all cases. There were 24 patients, 7 of them women, with the mean age of 41.2±15.05 who were included in this study. Non-survivors had significantly higher levels of systolic blood pressure, partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide, bicarbonate Glasgow Coma Scale scoring and longer duration of mechanical ventilation. Our findings showed that cardiac injury is an important cause of death in organophosphate poisoning. It could be hypothesized that cardiac injury is a strong predictor of death in patients with organophosphate poisoning.

Organophosphorus poisoning induced delayed neurotoxicity: a report of two cases.

INTRODUCTION: Organophosphorus compounds (OPC) are one of the most commonly used pesticides worldwide and are often misused for suicidal poisoning due to their easy availability. Acute manifestations and management of organophosphorus (OP) poisoning have been reported several times. Organophosphorus-induced delayed neurotoxicity (OPIDN) is a rare delayed presentation of OP poisoning that involves central-peripheral distal axonopathy. CASE PRESENTATION: In this study, we report two cases of OPIDN developed after a few weeks of OP poisoning. Clinical features, electrodiagnostic study findings, and rehabilitative measures adopted for the patients and their follow-up have been described in the report. DISCUSSION: Organophosphorus (OP) poisoning may rarely produce features of delayed neurotoxicity, which may gradually appear after acute cholinergic symptoms. This report shows the importance of considering the delayed presentation of possible OPC toxicity in patients with neurological symptoms and a history of OPC exposure.

Mean Serum Creatine Kinase among Organophosphate Poisoning Cases in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

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. Keywords: acetylcholinesterase; creatine kinase; organophosphate poisoning; rhabdomyolysis.

Neuroleptic malignant syndrome associated with acute organophosphate poisoning: Case report / Síndrome neuroléptico maligno asociado con intoxicación aguda por un organofosforado: reporte de caso.

Neuroleptic malignant syndrome is a rare and potentially fatal clinical condition frequently associated with the use of antipsychotics. In the literature, there is only one case report associated with the intake of organophosphates. We present the case of a patient who presented with a clinical picture compatible with neuroleptic malignant syndrome, after the ingestion of an organophosphate (chlorpyrifos). A 57-year-old man who consulted for attempted suicide, acute deterioration of consciousness, torpid neurological evolution, and associated autonomic instability associated with rigidity, persistent hyperthermia, and elevated CPK. Bromocriptine treatment was offered, which resolved the clinical picture. The association with the ingestion of an organophosphate was established, and he was discharged without sequelae. The diagnosis of neuroleptic malignant syndrome is clinical and should be considered in any case of exposure to substances that may lead to dysregulation of dopaminergic neurotransmission in order to initiate timely therapy and impact outcomes.

El síndrome neuroléptico maligno es una condición clínica rara y potencialmente letal que frecuentemente se asocia con el uso de antipsicóticos. En la literatura especializada se encontró únicamente un reporte de caso relacionado con la ingestión de organofosforados. Se presenta un paciente con un cuadro clínico correspondiente al síndrome neuroléptico maligno posterior a la ingestión de clorpirifós. Como resultado de un intento de suicidio con el mencionado organofosforado, el hombre de 57 años presentó deterioro agudo del estado de consciencia, evolución neurológica tórpida e inestabilidad autonómica asociada a rigidez e hipertermia persistentes, así como incremento de la creatina-fosfocinasa (creatine phosphokinase, CPK). Se le administró tratamiento con bromocriptina, con lo cual el cuadro clínico remitió, y fue dado de alta sin secuelas. El diagnóstico del síndrome neuroléptico maligno es clínico y debe contemplarse en cualquier caso de exposición a sustancias que puedan resultar en una desregulación de la neurotransmisión dopaminérgica, con el fin de iniciar el tratamiento oportuno y contrarrestar efectivamente los efectos.