Acute poisoning is a severe global public health issue that involves injury or death caused by exposure to an exogenous substance through any route. This study evaluated the most common poisons, reasons for poisoning, clinical management of poisoning cases, and their associated outcomes. One-year prospective cohort study executed at an academic medical center in Sindh, Pakistan. The predictors of outcomes are examined using a binary logistic regression model. Among 1404 enrolled patients, the majority were male (57.1%), aged 16-30 years (63.2%) and married (77.6%). Organophosphate compounds (42.8%) were the primary reasons for poisoning. Clinical manifestations as abnormalities in blood pressure (AOR = 1.76; 95% CI: 1.04-2.97; p = 0.034), abnormal consciousness (AOR = 10.41; 95% CI: 5.91-18.35; p < 0.001), dyspnea (AOR = 3.20; 95% CI: 1.72-5.96; p < 0.001), bronchorrhea (AOR = 1.99; 95% CI: 1.06-3.74; p = 0.032) and salivation (AOR = 2.70; 95% CI: 1.38-5.29; p = 0.004) were associated with higher odds of death. Symptomatic management was achieved through the administration of proton pump inhibitors (89.0%) and antidotes, such as pralidoxime (49.9%). The findings highlight the need for stricter regulation of organophosphate storage and sales, alongside community awareness campaigns. Establishing regional poison and antidote centers, ensuring early recognition of clinical manifestations, and implementing standardized management protocols may reduce mortality risk.

Nausea and vomiting in pregnancy is a common affliction, especially in the early trimesters. This is typically managed at home with doxylamine-pralidoxime or other home remedies. Many women, however, require additional adjuncts to control their symptoms. In this case we present a G2P0 female at 7 weeks gestation who arrived in the emergency department with persistent vomiting for several days. This patient already had a home medication regimen of multiple antiemetics. Additional treatment with ondansetron, prochlorperazine, and metoclopramide via IV administration as well as fluid administration resulted in minimal improvement in her symptoms in the emergency department. After stepwise escalation of antiemetic therapy and fluid resuscitation failed to provide relief, droperidol administration resulted in the rapid and complete resolution of her symptoms. This allowed for a safe discharge rather than admission for hyperemesis gravidarum. This case highlights the utility of droperidol as a rescue antiemetic in pregnancy when conventional therapies prove to be ineffective. This adds to the evidence supporting consideration of droperidol for refractory cases of nausea and vomiting and hyperemesis gravidarum in pregnancy. The purpose of this case report is to describe the safety and efficacy of droperidol in the treatment in refractory nausea and vomiting in pregnancy.

Organophosphorus compounds (OP), like pesticides and nerve agents, are potent inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) due to the phosphylation of their catalytic serine. Current treatment is limited, as approved oximes lack broad-spectrum efficacy and are poor reactivators of inhibited BChE. An alternative approach is pseudo-catalytic OP bioscavenging in which BChE and an efficient reactivator rapidly degrade OP in circulation, preventing it from reaching target tissues enriched with AChE. As imidazolium oximes were previously identified as potent BChE reactivators, we prepared eight novel N-substituted imidazolium oximes and tested them as reactivators of both human AChE and BChE inhibited by pesticide derivative paraoxon, and nerve warfare agents (sarin, cyclosarin, tabun VX, and five A-series agents). Oxime 3 (1,3-dibenzyl-2-hydroxy (imino)methylimidazolium bromide) was identified as the most potent reactivator, showing nanomolar affinity with native BChE and reactivation efficacy superior to standard oximes for cyclosarin-, sarin-, and tabun-BChE conjugate that was 1400-fold, 20-fold and 40-fold higher, respectively. In human whole blood, 30 μM cyclosarin was pseudo-catalytically decomposed by supplemented BChE and oxime 3, restoring 65% of total cholinesterase activity within 10 min. Although less potent, we identified two oximes capable of reactivating A-230-BChE conjugate. Furthermore, oxime 3 was not toxic to neural SH-SY5Y and hepatic HepG2 cells in concentrations relevant for biological activity. These findings highlight oxime 3 as well as the N,N'-dibenzyl imidazolium scaffold as the most potent BChE reactivators reported to date, providing a critical foundation for the advancement of bioscavenging-based therapies for OP poisoning.

Although acetylcholinesterase (AChE) is the primary inhibitory target for organophosphate (OP) insecticides and chemical warfare nerve agents, research supports the concept that the wide range of systems affected by OPs are not solely dependent on the anticholinesterase activity of OPs but are attributable to the inhibition of other serine hydrolases. Oxime reactivators play an integral role in the treatment of acute OP exposure by returning function to OP-inhibited AChE. Our laboratory has synthesized and patented a platform of oxime reactivators (US Patent 9,227,937) that have provided central neuroprotection through returning function to OP-inhibited AChE in the brain and preservation of neuronal and glial structures from damage in a rat model; the current US-approved oxime, pralidoxime, does not provide central neuroprotection. Thus, returning function to other OP-inhibited serine hydrolases by these novel oximes could provide additional secondary neuroprotection. Rat brain proteins were studied using activity-based protein profiling (ABPP) for serine hydrolase targets of a highly relevant sarin surrogate, nitrophenyl isopropyl methylphosphonate (NIMP), alone or in combination with Oxime 20, our lead novel AChE reactivator. ABPP indicated that NIMP significantly inhibited 6 serine hydrolases, and of these were the well-known serine hydrolases fatty acid amide hydrolase and monoacylglycerol lipase, which are important in endocannabinoid signaling. Oxime 20 administration after NIMP treatment showed only limited remediation of the inhibition experienced by these targets. The impact of this study is the identification of secondary serine esterase targets that could be explored for esterase reactivating therapeutics for the treatment of OP poisoning.

In this paper we have made efforts to compile and critically review the existing scientific evidence on the efficacy of combined oxime treatment as potential alternative or interim solution in organophosphate poisonings in the absence of universal single oxime. Literature review identified binary combinations of oximes that included apart from standard four (pralidoxime, trimedoxime, obidoxime and asoxime) also promising experimental oximes (K203 and phenoxyalkyl pyridinium oximes). Their effectiveness was confronted to nerve agents, and some organophosphate insecticides. Although few in vitro studies were found, the most studies were done in vivo on intoxicated mice, rats or guinea pigs. Some beneficial effects of combined oxime treatment were found for particular organophosphate poisonings. However, the majority of studies are incomparable due to interspecies differences or differences in the experimental setups. The need for appropriate oxime dosing was found via extrapolation of animal doses to human relevant doses. Thus, the further and rational approach is need to confirm or disprove advantages of the combined oxime treatment for organophosphate poisoning.

Resurgence of sarin use in the Syrian conflict demonstrates that chemical weapons are a vivid threat. Like other organophosphate compounds, sarin inhibits acetylcholinesterase resulting in cholinergic crisis. The current antidote therapy includes atropine (a muscarinic cholinergic antagonist) + an oxime (e.g., pralidoxime) to reactivate the inhibited cholinesterases. Long-term sequelae reported in victims of the 1995 Tokyo subway sarin attack emphasize the need to improve neuroprotection and to delineate more precise biomarkers of intoxication severity. Previously, we proposed that brain oscillations could indicate exposure severity to a sublethal dose of a neurotoxic agent. In the present study, we evaluated the effects of atropine + pralidoxime in mice exposed to a sublethal dose of sarin (0.9 LD50) on changes in short-term recovery, brainwaves and behavioral patterns. We demonstrated the benefits of the antidotes on alleviation of the sarin-induced encephalopathy, stabilization of brain oscillations, and attenuation of anhedonia behavior. Nevertheless, mice exhibited work memory impairments associated with the disruption of theta oscillations during the task, the disruption of sleep architecture and the anxiety-like behavior when exposed to the non-convulsive sarin dose. These outcomes were not mitigated by atropine + pralidoxime administration. Our findings suggest that the currently recommended antidote for sarin poisoning provides only partial neuroprotection. Despite stabilizing brain waves in resting state, current antidote is not effective in preventing long-term neurobehavioral complications.

Neurotoxicity induced by organophosphorus (OP) compounds such as paraoxon (POX) leads to severe brain damage and cognitive impairments. Although current treatments alleviate acute cholinergic symptoms, they fail to address secondary neurotoxicity. This study investigated the therapeutic potential of N-acetylcysteine-amide (AD4), a blood-brain-barrier permeable antioxidant, in a survival mouse model of acute POX intoxication. Male Swiss CD-1 mice received POX (4 mg/kg) followed by standard emergency therapy (atropine, pralidoxime and diazepam). AD4 (150 mg/kg) was administered 2 and 6 h post-exposure. AD4 treatment effectively prevented oxidative stress by reducing lipid peroxidation and restoring the expression in hippocampus (HP) and/or prefrontal cortex (PFC) of key antioxidant enzymes such as glutathione peroxidase-1 (GPx-1) and catalase (CAT) suppressed by POX acute exposure. Moreover, AD4 attenuated neuroinflammation in specific hippocampal subregions, as evidenced by reduced Glial Fibrillary Acidic Protein (GFAP) and Ionized Calcium Binding Adaptor Molecule 1 (Iba-1) immunoreactivity. Importantly, AD4 also rescued recognition memory deficits, as assessed by the Novel Object Recognition Test (NORT). In summary, these findings demonstrate that AD4 mitigates oxidative stress, neuroinflammation, and cognitive dysfunction following acute POX intoxication, supporting its potential as an adjuvant therapy for mitigating the secondary neurotoxicity derived from organophosphorus poisoning.

Organophosphate poisoning can precipitate acute atrial fibrillation even in previously healthy individuals. This first documented case from Pakistan of Malathion-induced atrial fibrillation emphasizes the need for early recognition, continuous cardiac monitoring, prompt atropine and pralidoxime therapy, electrolyte correction, and timely cardioversion to ensure full recovery.

We report a case of systemic organophosphate (OP) poisoning in a young child following the use of a household shampoo containing diazinon. In previous reported cases, diagnosis is typically made rapidly and indirectly through decreased cholinesterase activity and identification of OPs in commercial containers. In our case, however, the diagnosis was significantly delayed due to nonspecific clinical signs and a language barrier between the family and medical staff, resulting in the development of an intermediate syndrome. Initial symptoms included gastrointestinal disturbances, followed several hours later by neurological and respiratory complications. Plasma, urinary, and hair arsenic levels were first investigated due to the use of a product which may contain organometallic copper acetoarsenite complex. All arsenic concentrations were within physiological concentrations. Clinical presentation and biological cholinesterase activity (313 U/L vs. reference 1900-3800 U/L) later supported the diagnosis of OP poisoning. This hypothesis was reinforced by the analysis of the household shampoo indicating the presence of diazinon. Furthermore, despite the delayed diagnosis, non-targeted high-resolution mass spectrometry (LC-HR-MS/MS) identified diazinon in plasma and multiple phase I metabolites, including the specific marker IMPY, in both plasma and urine. Four previously undescribed metabolites and one phase II metabolite, hydroxy-IMPY-glucuronide, were also detected. Pralidoxime methylsulfate (Contrathion™) was administered on day 4, following toxicological confirmation and lack of clinical improvement. Although late, this treatment led to gradual neurological recovery, suggesting possible slow "aging" of diazinon-inhibited acetylcholinesterase. Nonetheless, the child developed persistent sequelae including hypotonia, peripheral neuropathies, and respiratory dysfunction consistent with intermediate syndrome. This case highlights the importance of considering OP poisoning even in atypical presentations and illustrates the utility of non-targeted HRMS screening in providing direct evidence of exposure when conventional approaches are inconclusive.

Lethal organophosphate (OP) exposure leads to status epilepticus (SE), which, despite standard-of-care (SOC) therapy, is associated with acute mortality and long-term morbidities. Neuronal injury and inflammation are reported following OP-SE, and drugs targeted at these processes have produced beneficial outcomes. Verapamil (VPM) is a calcium-channel blocker used as an antihypertensive drug and has been shown to exhibit neuroprotective and anti-inflammatory actions in experimental models of CNS injuries. Here, we investigated the feasibility of an adjunctive intramuscular (i.m.) VPM therapy in OP Diisopropyl Fluorophosphate (DFP)-induced SE. We also investigated the safety and toxicity of i.m. VPM and compared its pharmacokinetic (PK) profile to oral (p.o.) administration. Rats were injected with DFP (4 mg/kg, s.c.). One minute later, SOC treatment consisting of atropine (0.5 mg/kg, i.m.) and pralidoxime chloride (2-PAM; 25 mg/kg, i.m.) were administered, and at 1-hour post-SE, midazolam (1.78 mg/kg, i.m.) was given. Rats that met the behavioral SE severity criteria (Racine 4-5) were randomized into two treatment groups: those receiving saline (SAL) or VPM (10 mg/kg, i.m. bid, 3 days). Histological analysis was conducted to assess neuronal injury and injection-site pathology. In a separate group of rats, PK studies were conducted on blood and brain homogenates treated once with saline or VPM (10 mg/kg, p.o. or i.m.). Our data demonstrated that following DFP-SE, i.m. VPM achieved higher blood and brain levels and exhibited a favorable PK profile compared to p.o. route. VPM therapy did not cause significant muscle pathology and produced a robust neuroprotective response. Neuroinflammatory markers and long-term behavioral outcomes were not included in this study. Our studies provide evidence that the i.m. route is an effective method for delivering VPM following SE, producing significant neuroprotective outcomes compared to treatment with the standard-of-care alone in OP-SE.

Organophosphate (OP) pesticides are widely used in agriculture and can cause acute cholinergic toxicity by inhibiting the enzyme acetylcholinesterase, leading to an accumulation of acetylcholine. A 45-year-old male plumber was admitted to the emergency department 4 h after ingesting an unknown quantity of a 50% emulsifiable concentration of diazinon. He presented with sialorrhea, excessive tearing, emesis, and constricted pupils. Laboratory tests revealed a significant reduction in serum cholinesterase activity. A chest X-ray showed no signs of pulmonary edema or lung abnormalities. The patient was found to be moderately dehydrated and was managed with intravenous normal saline (20 mL/kg) during the first 4 h of treatment. He received 1770 mg of pralidoxime over the first 12 h, along with 9.44 mg of atropine in the first 8 h, followed by 84.96 mg of atropine over the next 3 days. The patient's condition significantly improved after 48 h of intensive treatment, with symptom resolution and normalization of cholinesterase levels. His neurological function progressively returned to normal, and he was discharged on day seven without any lasting complications, having made a full recovery. This case highlights the critical importance of prompt diagnosis and immediate treatment of organophosphate poisoning to prevent life-threatening outcomes. Continuous monitoring and appropriate supportive care are essential for ensuring a successful recovery.