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Magnesium sulfate in the management of acute Organophosphate poisoning: A Case Report

Mohammadreza Mohammadi1, Arman Hakemi2, Alireza Ghassemi Toussi3, Bita Dadpour4, Reza Mousavi5, Sadaf Rafati 6 and Anahita Alizadeh Ghamsari7

1Tehran University of Medical Sciences, Tehran, Iran
2Fellowship of Clinical toxicologist, Emergency medicine specialist, Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
3clinical toxicologist, Forensic medicine specialist, Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
4Clinical toxicologist, Internal medicine specialist, Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
5Clinical toxicologist, Forensic medicine specialist, Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
6Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
7Clinical toxicologist, Pediatrician, Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

*Corresponding author

*Mohammadreza Mohammadi, Medical student, Medicine Department, Tehran University of Medical Sciences, Iran

Abstract

Background Organophosphate (OP) poisoning is a critical global health concern, particularly in regions with extensive agricultural activities. OPs inhibit acetylcholinesterase, resulting in excessive cholinergic stimulation. Despite standard treatments, including atropine and oximes, high morbidity and mortality rates necessitate the exploration of adjunctive therapies.

Case Presentation We report the case of a 40-year-old male who deliberately ingested 100 ml of organophosphorus poison in a suicide attempt. On admission, the patient presented with acute cholinergic symptoms including dizziness, anxiety, pallor, tremor, diaphoresis, sialorrhea, lacrimation, bradycardia, and hypopnea. Initial management included oxygen therapy, intravenous fluids, and atropine. Due to severe respiratory distress, the patient was intubated and admitted to the ICU. Despite extubation after 72 hours, cholinergic symptoms persisted and significant muscle weakness was noted. Due to the unavailability of pralidoxime, a daily dose of 2 grams of intravenous magnesium sulfate was administered. The patient showed remarkable improvement in muscle strength and overall clinical condition, with acetylcholinesterase levels returning to normal. He was discharged after 10 days without complications.

Discussion This case highlights the potential efficacy of magnesium sulfate as an adjunctive treatment for OP poisoning. Magnesium sulfate may alleviate nicotinic symptoms and improve neuromuscular function, offering a promising complementary approach to conventional therapies. Previous studies have suggested its beneficial role, but further large-scale research is needed to establish optimal dosing, timing, and safety.

Conclusion Magnesium sulfate shows potential as an effective adjunctive therapy for surgical poisoning, improving patient outcomes and reducing healthcare burden. Further studies are essential to validate these findings and integrate magnesium sulfate into standard treatment protocols.

Introduction

Organophosphate compounds (OPs) are one of the most important agricultural insecticides used since the mid-1940s. Poisoning with organophosphates occurs for occupational, accidental, or intentional reasons. Intentional consumption of these substances is a major cause of death in developing countries due to their easy availability and the lack of a monitoring system to control them. approximately one-third of suicides in the world are due to intentional consumption of pesticides. Systemic absorption of the OPs occurs through the skin, gastrointestinal tract, conjunctiva, and respiratory system exposure [1]. OP poisoning either intentional or accidental, is a significant global health concern, particularly in regions with extensive agricultural activities [2].OP poisoning leads to the phosphorylation and inhibition of acetylcholinesterase (AChE), the enzyme responsible for the termination mechanism of cholinergic signaling in synapses. This inhibition causes a marked increase in synaptic acetylcholine levels, which in turn leads to uncontrolled cholinergic action mediated through both muscarinic and nicotinic receptors. The diagnosis of OP poisoning is mainly based on clinical signs and symptoms as well as direct measurement of erythrocyte AChE activity which provides an estimate of the degree of toxicity. Particularly, in the absence of known exposure, the clinical features of excessive cholinergic activity may indicate OP poisoning [3]. Standard management of OP poisoning typically includes intravenous administration of atropine (a competitive antagonist of muscarinic receptors) to counteract the muscarinic side effects and oximes, including pralidoxime, to regenerate the AChE enzyme, along with appropriate supportive care. However, despite these interventions, morbidity and mortality rates remain high, prompting research into adjunctive therapies to improve treatment efficacy. Magnesium sulfate, a well-known therapeutic agent with various medical applications, has gained attention for its potential neuroprotective and muscle relaxant properties. Its ability to mitigate the severe effects of OP poisoning has been investigated in animal studies and human-controlled trials [1]. In this case report, we present a unique instance of intentional organophosphate poisoning managed with the addition of magnesium sulfate to the conventional treatment regimen. The patient exhibited a remarkable recovery, highlighting the potential benefits of magnesium sulfate as an adjunctive therapy in OP poisoning cases.

Case Presentation

A 40-year-old male patient was referred to the emergency department of Imam Reza Hospital in Mashhad after deliberately ingesting 100 ml of organophosphorus poison in a suicide attempt. On arrival, the patient was conscious but presented with acute cholinergic symptoms including dizziness, anxiety, pallor, tremor, diaphoresis, sialorrhea, lacrimation, bradycardia, and hypopnea. His initial vital signs were as follows: blood pressure 105/70 mmHg, heart rate 65 beats per minute, respiratory rate 10 breaths per minute, oxygen saturation 96%, and body temperature 37.3°C. Immediate management included oxygen therapy, intravenous fluids, and atropine to relieve cholinergic symptoms. Comprehensive laboratory tests were performed, including measurement of acetylcholinesterase levels in red blood cells and serum. Due to the severity of the patient's symptoms and significant respiratory distress, he was intubated, placed on mechanical ventilation, and admitted to the Intensive Care Unit (ICU). After 72 hours, with improved vital signs and regained consciousness, the patient was extubated. Despite extubation, cholinergic symptoms persisted, requiring continued atropine therapy. The patient reported severe muscle weakness, with strength scores of 1/5 in the upper limbs and 2/5 in the lower limbs. Due to the unavailability of pralidoxime and based on previous studies suggesting the efficacy of magnesium sulfate, a daily dose of 2 grams of intravenous magnesium sulfate was administered. Throughout the treatment, the patient's vital signs, electrocardiogram, and deep tendon reflexes were carefully monitored to avoid potential side effects of magnesium sulfate, and no pathological findings were observed. Paraclinical investigations, including complete blood count, urea, creatinine, coagulation factors, and venous blood gas analysis, were within normal ranges. Initial acetylcholinesterase levels were critically low at 517 U/L (normal range: 4620-11500) in serum and 0.6 IU/ml (normal range: >4.2) in red blood cells. These enzyme levels gradually normalized with continued treatment. The patient's chest radiograph showed no specific pathology. Notably, his muscle strength improved significantly 72 hours after starting magnesium sulfate therapy, with upper limb strength increasing to 3/5. Intravenous atropine and magnesium sulfate infusions were continued until the patient's full recovery. The patient was discharged after 10 days in good general condition with no complications. This case highlights the potential efficacy of magnesium sulfate in alleviating cholinergic symptoms and improving proximal muscle weakness in organophosphate poisoning. However, further studies are needed to determine the optimal dose, timing, and safety profile of magnesium sulfate in such cases.

Multidisciplinary approach

Inclusion of a psychological examination in the diagnosis of children with post-COVID syndrome is dictated by practical necessity. Neuropsychological symptoms reflect “subtle” functional changes in brain tissue. Currently, in psychiatry and neurology, studies of the cognitive and emotional sphere, which based on the neuropsychological method, have become firmly established in the scientific and research practice of medical specialists and psychologists. New research in these areas is relevant for clinical psychology (primarily neuropsychology), pediatrics, psychiatry and neurology [23-26].

The neuropsychological approach is the most promising way to evaluate disorders in the formation of higher mental functions, opening the following possibilities: the study of changes in the structure of mental functions; the relationship between maturing brain structures and developing mental functions; the correlation of the revealed deficit of mental activity with specific brain dysfunctions or immaturity of brain activity.

Discussion

Organophosphates are chemical compounds used worldwide as insecticides, fungicides, and herbicides to control pests. Their neurotoxic effects are well-documented, and chronic exposure has been associated with a range of neurological disorders, including Parkinson's disease, as well as reproductive issues, respiratory diseases, endocrine disorders, skin problems, and leukemia. The severity and nature of these adverse effects depend on the specific type of organophosphate and the dose of exposure [4].

The pathophysiology of OP poisoning involves the inhibition of acetylcholinesterase, an enzyme crucial for terminating neurotransmission at cholinergic synapses by hydrolyzing acetylcholine. The accumulation of acetylcholine leads to overstimulation of muscarinic and nicotinic receptors, manifesting as a cholinergic crisis with symptoms such as dizziness, anxiety, tremors, salivation, sweating, bradycardia, and respiratory depression [5].

Initial treatment protocols for OP poisoning focus on decontamination, including removal of contaminated clothing and gastric lavage with activated charcoal if ingestion is recent. Supportive measures such as maintaining ventilation and cardiovascular monitoring are critical. Atropine is administered to counteract muscarinic symptoms by reducing secretions and controlling bradycardia and bronchial secretions. However, atropine does not treat nicotinic symptoms such as muscle weakness. Oximes, including pralidoxime, obidoxime, and others, have been used for decades to reactivate acetylcholinesterase by removing the phosphorylated group added by OPs. These agents are crucial in restoring neuromuscular function, although their effectiveness can vary depending on factors such as the type of OP, dosage, and timing of administration. Pralidoxime, the most commonly used oxime, is recommended by WHO guidelines with an initial bolus followed by continuous infusion until clinical improvement. However, the efficacy of oximes is often limited by inhibition of the enzyme by high concentrations of OPs and their inability to adequately penetrate the central nervous system due to low lipid solubility [6-8].

A 2010 review discussed the efficacy of various drugs, including activated charcoal, atropine, benzodiazepines, butyrylcholine, glycopyrronium bromide, magnesium sulfate, organophosphorus hydrolases, oxime, and sodium bicarbonate, in improving the symptoms of organophosphate poisoning. In this study, it was mentioned that magnesium sulfate is an inhibitor of acetylcholine release in the central nervous system and peripheral sympathetic and parasympathetic synapses [9]. In a study by Kiss and Fazekas, intravenous magnesium sulfate led to the disappearance of premature ventricular contractions. Magnesium was also found to inhibit the direct effect of organophosphates on the sodium-potassium ATPase pump, preventing the release of acetylcholine into the synaptic space [10,11]. In another study, Singh et al. administered 4 grams of magnesium sulfate intravenously to patients with organophosphorus poisoning and observed an improvement in neuro-electrophysiological deficits. Other studies also showed that on the first day after the patient's admission, intravenous injection of magnesium sulfate (4 grams) will lead to a reduction in hospitalization and improvement of symptoms [12,13]. Magnesium sulfate has also been used to control tachycardia, ventricular arrhythmias, and muscle fasciculations, therefore preferred to traditional treatments [14].

Our case report demonstrates the successful use of magnesium sulfate as adjunctive therapy in a patient with severe OP poisoning. Despite conventional treatment with atropine and supportive care, the patient presented with significant muscle weakness and respiratory distress. Administration of 2 grams of intravenous magnesium sulfate daily resulted in a marked improvement in muscle strength and overall clinical condition. This is consistent with previous studies suggesting that magnesium sulfate may improve neuromuscular function and reduce mortality in OP poisoning. The patient's acetylcholinesterase levels, initially severely depressed, gradually returned to normal ranges with continued treatment, correlating with clinical recovery. Throughout treatment, careful monitoring of vital signs, electrocardiograms, and deep tendon reflexes ensured the safe administration of magnesium sulfate without adverse effects. These findings support the potential role of magnesium sulfate in reducing nicotinic symptoms, particularly proximal muscle weakness, in OP poisoning.

Although our findings are promising, they indicate the need for further research. Large-scale randomized controlled trials are essential to determine the optimal dose, timing, and safety of magnesium sulfate in the management of OP poisoning. In addition, understanding the interactions between magnesium sulfate and standard treatments such as atropine and oximes will be crucial in developing comprehensive treatment protocols [15].

conclusion

In conclusion, this case demonstrated the potential of magnesium sulfate as a valuable adjunctive therapy in the management of organophosphate poisoning. It offers a promising avenue for improving patient outcomes and reducing the burden of this critical condition on healthcare systems. Further studies are essential to validate these findings and to incorporate magnesium sulfate into standard treatment protocols for organophosphate poisoning.

Ethics approval

This case report was conducted under the ethical standards of the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Ethical approval was granted by the Ethics Committee of Mashhad University of Medical Sciences, Mashhad, Iran. Written informed consent was obtained from the patient for publication of this case report and any accompanying data.

Data availability declaration

Due to the sensitive and confidential nature of the data associated with this case report, detailed clinical data, including laboratory results and patient history, are not publicly available. However, de-identified data that support the findings of this study are available from the corresponding author upon reasonable request. Requests for access to these data will be reviewed by the corresponding author and will require compliance with applicable privacy regulations and approval by the institutional review board.

Conflicts of interest
The authors declare that there are no conflicts of interest regarding the research, authorship, and/or publication of this article.

Funding declaration
The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Authors contributions
Conceptualization Mohammadreza Mohammadi, Arman Hakemi
Writing – original draft Mohammadreza Mohammadi
Data curation Arman Hakemi, Reza Mousavi
Critical revision: Alireza Ghassemi Toussi, Bita Dadpour, Reza Mousavi, Anahita Alizadeh Ghamsar

Acknowledgments
Not applicable

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