Aluminum phosphide poisoning has high mortality resulting from cardiac impairment and hemodynamic disorders [1]. Aluminum phosphide is a rodenticide which is diffusely used in the world. Because of its severe toxicity, mortality is high. After ingestion, the phosphine gas is released on contact with stomach fluid. The released phosphine induces multi-organ failure. Circulatory failure and severe hypotension are common features .Free radicals have an important role in the pathogenesis of aluminum phosphate toxicity [2]. The high mortality of aluminum phosphide is due to cardiac impairment and hemodynamic disorders [1]. Although the majority of articles concentrate on the correction of side effects, nevertheless none of therapeutic planning was successful in improving the outcome of severe toxicity.

We believe that the acute cardiovascular injuries that characteristically occurs in severe poisoning with beta blockers and calcium channel blockers also happens in aluminum phosphide poisoning. This injury may play an important role in morbidity and mortality of this toxicity. Refractory hypotension and cardiovascular collapse are common causes of death. We hypothesized that glucagon along with other supportive managements can dominate the refractory hypotension and myocardial depression and decrease of mortality and morbidity of aluminum phosphide toxicity.

Aluminum phosphide poisoning is one of the most severe poisoning with multi-organ systems of the body involvement. Unfortunately, because of absence of any antidote for this toxicity, its mortality is high. Aluminum phosphide is sold as the tablets in the grocery market in Iran and uses as a rodenticide. Its high mortality can be due to increased incidence of severe heart failure, pulmonary edema and liver failure. Due to its cheapness and ease of accessibility it is relatively used high for the suicide attempt. Phosphate gas (phosphine) will be released after aluminum phosphate ingestion because of stomach acids. Released phosphine is rapidly absorbed and cause systemic toxicity through inhibition of oxidative phosphorylation, resulting in cellular hypoxia. Release phosphine affects primarily heart, lungs, gastrointestinal tract and the kidneys, although all organs can be involved. If there is any clinical suspicion for this toxicity diagnosis is made by the silver nitrate which is added to the stomach secretions. [3]. In the study of aluminum phosphide poisoning was reviewed in a 7-years study and early gastric lavage, oxygen, sufficient fluids and vasopressors, ventilator support and other supportive care have been proposed for treatment. It was reported that magnesium sulfate can be used as an antidote to stabilize the cell membrane and prevents heart conduction problems. One of the most frequent manifestations was cardiovascular (78.12%). Stomach decontamination with potassium permanganate and the use of gluconate calcium, magnesium, sodium bicarbonate and charcoal in many patients were considered [4]. There were ECG abnormalities in (65.6 %) cases [3]. In the study of Lourize et al. the mortality rate was 49 percent, with the association of shock and decreased levels of consciousness [5]. The mechanism of shock and myocardial damage is unclear. In some case reports myocardial necrosis and vacuolation is seen in myocardial biopsy. Frequency of hypotension and shock varied from 76% to 100% [6]. Hypovolemia due to vomiting associated with acute poisoning can also reduce blood pressure. Dysrhythmia encountered in phosphorus poisoning. The most common disorders are a bundle branch block, atrio-ventricular block, atrial fibrillation, ventricular and atrial extrasystoles, ventricular tachycardia and rarely sinoatrial block. Re-polarization abnormalities like depression or elevation of ST segment and T wave inversion are also noted. Echocardiography in many reports shows hypokinesia. [6,7].

Why glucagon?

Glucagon is given as a first antidote treatment for beta blocker overdose [8,9]. It activates adenylate cyclase at a site independent from beta-adrenergic agents, causing an increase in adenosine 3’-5’-cyclic monophosphate (cAMP). Elevations in cAMP increase the intracellular pool of calcium available for releasing during depolarization; augmenting contractility [10]. Glucagon appeared to consistently increase the heart rate at least transiently but appeared to have no effect on mean arterial pressure even though it possibly increases cardiac output. Its effect on the survival rate in animal models of betablocker overdose was unclear. In the six studies of animal models of calcium channel blocker overdose included, glucagon appeared to have increased the heart rate and cardiac output and reverse second and third degree AV blocks, all at least transiently [8,11]. Glucagon may decrease vasopressor requirements in calcium channel blocker toxicity [12]. Its infusion significantly increases mean blood pressure and heart rate in severe amitriptyline toxicity [13]. Comparing the efficacy of vasopressin and glucagon no overall differences were noted in mean arterial pressure, systolic blood pressure, cardiac output, heart rate, pH, or glucose levels, although vasopressin treatment yielded higher MAP and systolic BP early in resuscitation [14]. It is necessary to emphasize that in some studies of animal models of beta-blocker overdose included; glucagon appeared to have no effect on mean arterial pressure even though it possibly increased cardiac output. The effect of glucagon on calcium channel blocker overdose included is researched too and it is shown that heart rate and cardiac output are increased and second and third degree AV blocks are reversed, all at least transiently by glucagon. There appear to be no effect of glucagon on mean arterial pressure although it did increase in one model. Glucagon appeared to have no effect on survival rate [8]. The hyperglycemic effect of glucagon is transient and is virtually impossible if the stores of liver glycogen are depleted. It is suggested to eat some sugar or food to stop reactive hypoglycemia. The most common side effects are nausea and vomiting. Glucagon has been used in the treatment of spasticity associated with radiology, magnetic resonance imaging acute diverticulitis and biliary tract and sphincter of Oddi dysfunction. It is contraindicated in pheochromocytoma. This hormone is used as the treatment for shock, cardiac inotropic agent, especially when there is previous use of β-adrenergic receptor antagonists and adrenergic receptor agonist may be ineffective [15].

Because of effectiveness of glucagon on hypotension and myocardial contractility it may be useful in treating some aluminum phosphide toxicity side effects.

This concomitant evidence could lead to new therapeutic options in the management of acute phosphine toxicity.