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ORIGINAL ARTICLE
Year : 2018  |  Volume : 1  |  Issue : 2  |  Page : 30-34

Clinical benefits of magnesium sulfate in management of acute organophosphorus poisoning


1 Department of Forensic Medicine and Clinical Toxicology, Cairo University, Egypt
2 Department of Forensic Medicine and Clinical Toxicology, Cairo University, Egypt; Department of Forensic Medicine and Clinical Toxicology, Princess Nourah Bint Abdulrahman University, Riyadh, KSA
3 Department of Pharmacology, Cairo University, Egypt
4 National Environmental Center of Toxicological Research- Cairo University, Egypt

Date of Web Publication19-Feb-2019

Correspondence Address:
Dr. Samah F Ibrahim
Princess Nourah Bint Abdulrahman University, Riyadh

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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sjfms.sjfms_5_18

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  Abstract 


Background: Organophosphorus (OP) poisoning is a common health problem. Its diagnosis depends on clinical findings. The main treatment of OP poisonings is atropine and oximes. However, new adjunct therapy such as magnesium sulfate (MgSO4) has been introduced. Materials and Methods: To detect the effects of MgSO4, a case–control study was conducted on 100 patients intoxicated with OP compounds. All patients received standard care of treatment while half of them received MgSO4 given in a dose of 1 g/6 h for 24 h. Results: The given atropine and oximes doses, hospitalization period, and incidence of complications, especially cardiac arrhythmias, respiratory failure, and death were significantly reduced in Mg-treated group. Conclusion: Results suggest that magnesium could ameliorate OP toxic effects and could be considered in the management of patients intoxicated with these compounds.

Keywords: Cardiovascular, central nervous system, magnesium, organophosphate poisoning, respiratory


How to cite this article:
Elbarrany UM, Mohamed MA, Ibrahim SF, Elshekheby HA, Afify TA. Clinical benefits of magnesium sulfate in management of acute organophosphorus poisoning. Saudi J Forensic Med Sci 2018;1:30-4

How to cite this URL:
Elbarrany UM, Mohamed MA, Ibrahim SF, Elshekheby HA, Afify TA. Clinical benefits of magnesium sulfate in management of acute organophosphorus poisoning. Saudi J Forensic Med Sci [serial online] 2018 [cited 2019 May 26];1:30-4. Available from: http://www.sjfms.org/text.asp?2018/1/2/30/252536


  Introduction Top


Organophosphates are used as domestic and industrial pesticides since 1937.[1] Many opportunities for acute organophosphates (OP) poisoning are allowed due to its easy availability.[2] In 2014, more than 2900 cases of OP poisoning were reported to the American Association of Poison Control Centers with more than 700 cases had serious outcomes and three deaths.[3] In developing countries, pesticide poisonings were associated with high mortality rates, especially in rural areas.[4] In Egypt, more than 10% of the intoxicated cases consumed OP pesticides.[5]

Their acute toxic effects are related to irreversible inactivation of acetylcholine esterase enzyme (AChE) at a variety of neurotransmitter receptors; including sympathetic, parasympathetic, skeletal muscle, and central nervous system sites.[6]

Their nonpharmacologic treatment includes resuscitation and decontamination depending on the OP entrance route.[7]

However, their pharmacologic treatment includes symptomatic treatment, for example, atropine and diazepam, causal treatment, for example, AChE reactivators (oximes),[8] and other therapeutic toxicity ameliorating or reducing agents, for example, MgSO4 and clonidine.[9],[10]

Magnesium is an essential cofactor in several enzymatic reactions and maintains cellular homeostasis.[11] The role of magnesium in OP poisoning is not yet fully understood, but it inhibits acetylcholine release through blocking calcium channel.[12]

The aim of this study is to elaborate the clinical benefits of MgSO4 in management of OP intoxicated patients.


  Materials and Methods Top


A case–control study was approved by the Ethical Committee, Faculty of Medicine, Cairo University and was done in line with the ethical principles set out in Declaration of Helsinki. It was conducted at National Egyptian Center for Toxicological Research (NECTR)-Cairo University from August 2014 to October 2016. According to the clinical condition of the patient, the patient himself or his/her relative signed a written informed consent.

Any adult patient diagnosed as OP poisoning based on the history of exposure to OP, presence of known nicotinic and/or muscarinic manifestations on examination, and/or reduced levels of AChE at the time of presentation was included in the study.[6] Patients who had any concomitant ingestion, chronic disease, or received advanced medical care before admission were excluded from the study.

Included patients were randomly allocated to routine treatment (Mg-nontreated patients) or to routine treatment in addition to MgSO4 in a dose 1 g (intravenous [IV])/6 h for 4 doses (total dose 4 g) (Mg-treated patients).[10] Randomization was done by a stratified allocation procedure designed to balance the two groups.

On admission to the emergency department, blood samples were withdrawn from patients, after detailed history and clinical examination, to determine Mg++ level using a flame atomic absorption spectrometric method[13] and plasma cholinesterase (PChE) level using a kinetic colorimetric method.[14]

Moreover, arterial blood gases using blood gas analyzer, Bayer 855;[15] liver function tests; including alanine aminotransferase and aspartate aminotransferase using NADH Kinetic UV method,[16] kidney function tests; including blood urea nitrogen and serum creatinine; using colorimetric method according to Houot;[17] and baseline 12-lead electrocardiography with a paper speed of 25 mm/s were performed for each patient.

All patients received routine nonpharmacological and pharmacological treatment; atropine (1 mg IV bolus every 5 min to 30 min time interval till resolution of muscarinic manifestations, for example, secretions, bradycardia, and miosis). Then, 10%–20% of the total amount of required atropine was continued as infusion and gradually reduced[18] and pralidoxime (30 mg/kg over 60 min followed by 8 mg/kg/h until recovery or death).[10]

The patients were monitored every 15 min in 1st h, then every 30 min in 2nd h, then every 1 h for 24 h after admission. A workup sheet [vital signs, nicotinic, muscarinic manifestations, signs of atropinization, biochemical, hematological investigations, medical, and pharmacological management] was used. Mg++ level was repeated 24 h after administration while PChE levels were repeated daily till normalization.

Statistical analysis

All statistical calculations were done using Statistical Package for the Social Science version 15 (IBM, Armonk, NY, United States of America). The data were statistically described in terms of mean ± standard deviation, frequencies and percentages. Comparison of numerical variables was done using Student's t-test for independent samples while comparison of categorical data was done using Chi-square test. P < 0.05 was considered statistically significant.


  Results Top


One hundred patients with acute OP poisoning presented to (NECTR) from August 2014 to October 2016. Fifty patients were allocated to be in Mg-treated group (25 males and 25 females). The main manner of intoxication was suicidal ingestion. Their mean age was 27.54 ± 11.71 years. Regarding demographic data, no significant difference was observed between two groups [Table 1].
Table 1: Demographic data of the studied patients

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The clinical presentation in the studied groups was presented in [Table 2]. Constricted pupils (89%), muscle fasciculation (79%), chest crepitation (64%), normal blood pressure (75%), and vomiting (87%) were the most prominent presentations among studied patients [Figure 1], [Figure 2], [Figure 3].
Table 2: Prevalence of complication among the studied patients

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Figure 1: Prevalence of the central nervous system and pupillary manifestations among the studied groups

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Figure 2: Prevalence of cardiovascular and respiratory manifestations among the studied groups

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Figure 3: Prevalence of gastrointestinal and urinary manifestations among the studied groups

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During the hospitalization, both groups developed many complications. The hospitalization period and complications, especially cardiac arrhythmias (e.g., premature ventricular contraction, premature atrial contractions, and ventricular tachycardia), respiratory failure, and death were significantly lower in Mg-treated patients [Table 2].

In both groups, plasma cholinesterase level was <3000 U/L and Mg++ serum level was within normal range. In Mg-treated group, the difference in Mg++ level before and after Mg infusion did not show any significant difference (P < 0.05) [Table 3].
Table 3: Laboratory results, given medication among the studied patients

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Mg-treated group required less frequent doses of atropine and pralidoxime; 4 ± 1.01 mg and 690 ± 170 mg, respectively. The difference between two groups was statistically significant [Table 3].


  Discussion Top


Acute OP poisoning is an important cause of morbidity and mortality worldwide.[19] Treatment of OP poisoning conventionally involves atropine for reduction of muscarinic signs and oximes to increase the activation of (AChE) enzyme before aging.[20] It is documented that hypomagnesemia could cause cell resistance to atropine.[21] Thus, MgSO4 could be considered as a pharmacotherapeutic agent that could prevent or ameliorate the toxicity of OP insecticides.[22]

This study among adult patients (28.11 ± 11.5 years) with acute OP poisoning explored the ability to use MgSO4 as pharmacotherapeutic agent to ameliorate the OP toxicity.

Most of the patients were intentionally poisoned. On admission, there was no statistical difference between the Mg-treated and Mg-nontreated patients in plasma cholinesterase level as it is considered as a marker of exposure to OP compounds. We were inconsistent with Leibson and Lifshitz.[23]

Plasma magnesium level was within normal range in both groups and did not vary significantly before and after Mg treatment within Mg-treated group.

These results can be explained as stated in a previous study that the presence of normal range of plasma magnesium (1.8–2.4 mg/dl) did not exclude magnesium deficiency and insignificant difference within Mg-treated group was related to short half-life of magnesium.[10]

Regarding the pupil size, results in the current study are consistent with some previous researches,[24] while other studies reported that patients with severe OP poisoning showed pupil dilatation (mydriasis) due to excessive nicotinic stimulation.[25] However, pupil constriction (miosis) that reverses following atropine administration appears to be a reliable indicator of OP poisoning.[26]

As regards chest manifestations, crepitation was the most prominent finding followed by wheezes and MgSO4 significantly reduced incidence of respiratory failure in patients with OP poisoning. To the best of our knowledge, no study addressed the respiratory effects of MgSo4 in treatment of the OP-poisoned patients. Magnesium causes bronchodilation through modulation of calcium ion flow, which inhibits the release of acetylcholine from nerve terminals. Magnesium stabilizes T-cells, preventing their activation, and inhibits mastocyte degranulation, therefore, limiting the production of inflammatory mediators. It also acts to stimulate nitric oxide and prostacyclin production, possibly reducing the severity of bronchial constriction.[11]

As regards nervous and musculoskeletal manifestations, 79% of admitted patients had fasciculation, 7% had seizures, and 9% presented with disturbed conscious level.

Fasciculation is a part of nicotinic manifestations of OP poisoning. Reactivation of the cholinesterase enzyme either spontaneously or by oximes administration can resolve it.[27] Magnesium sulfate (MgSO4) has precurarization effects that reduce fasciculation and increases in serum potassium concentration.[28] Moreover, it could reverse the neuroelectrophysiological effects, for example, seizures of organophosphate poisoning.[29]

Concerning cardiovascular system, most of the patients (75%) were normotensive. This finding favored MgSO4 usage. In addition, incidence of arrhythmia, for example, premature ventricular contraction, premature atrial contraction, and ventricular tachycardia were significantly reduced in Mg-treated patients (16%). Shock was found only in 3 patients; one of them was in Mg-treated group.

Magnesium deficiency is one of important pathogenetic factors responsible for supraventricular and ventricular arrhythmias. Magnesium, intracellular ion, plays a crucial role in the functioning of many ion channels, including cardiac potassium channels.[30] Despite normal magnesium blood levels, intracellular and systemic deficiency may occur. Hence, intravenous magnesium seems to be useful in prevention and treatment of various cardiac arrhythmias. Moreover, magnesium therapy is well tolerated, with sporadic, mild, and quickly subsiding adverse effects (heat, flushing, hypotension).[31] A research did not find any Mg adverse effects in OP-poisoned patients treated with high magnesium infusion up to 16 g.[10]

On studying the cardiotoxicity of OP poisoning, it was found that patients with OP poisoning had QTc prolongation that was correlated with patients' prognosis.[32],[33] Magnesium counteracts the direct toxic inhibitory action of organophosphate compounds on the heart and inhibits acetylcholine release.[31]

Most of admitted patients had vomiting, diarrhea, and abdominal pain, while 29% of them had urinary incontinence. These are consistent with adverse cholinergic actions of the cholinesterase inhibitors compounds.[6] Magnesium deficiency is linked to gastrointestinal problems. Drugs containing magnesium can improve gastrointestinal disorders.[34] In Mg-nontreated group, two patients had liver impairment and five patients had renal impairment. The incidence of liver impairment in this study was lower than its incidence in another study done by Wang et al.[35] This difference may be due to the formulation of consumed OP agent, impurities, and delay time. Renal impairment was consistent with other study stated that renal failure is rarely caused by OP poisoning,[36] but still its pathogenesis is unknown due to lack of experimental data;[37] however, it could be caused by direct toxic effect of OP agents rather than increase acetylcholine or oxidative stress[37]

The present study showed MgSO4 therapy to significantly reduce atropine and oxime requirements. These findings were inconsistent with some other studies.[10],[12] This difference may be due to careful observation and dose adjustment minimized overuse of these therapies.[2] Moreover, atropine infusion was largely determined by the initial loading dose.[10]

The duration of hospitalization and mortality rate were lower in Mg-treated patients that is in the same line with other studies[10],[12]

These findings could be explained by ability of Mg to inhibit acetylcholine release from motor nerve terminals, to antagonize the effects of OP, to control premature ventricular contractions, and to counteract the direct toxic inhibitory action of OP on sodium–potassium ATPase,[38] hence Mg-nontreated patients showed higher incidence of complications.

Magnesium has many side effects including respiratory depression and peripheral vasodilatation resulting in sudden drop of blood pressure, but we tested the least effective dose to prevent undesirable toxic effects. Moreover, careful monitoring and calcium gluconate can reverse these effects.[10]


  Conclusion and Recommendation Top


MgSO4, when given to OP-intoxicated patients within 24 h of admission as a total 4 g dose, reduces the requirement of atropine and oximes, duration of hospital stay, and incidence of cardiac and respiratory complications. The results of the present study suggest that magnesium could ameliorate organophosphorus toxic effects. However, for these results to be generalized, there should be more studies with large sample size and studies to determine the most appropriate durations and doses for MgSO4 administration with different types and amounts of consumed OP.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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