The Potential Therapeutic Role of Hydroxyethyl Starch and Hydrocortisone in Acute Aluminum Phosphide Poisoning

Study Overview
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Brief Summary
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Aluminum phosphide (ALP) is a widely used fumigant due to its efficiency as pesticides. It is available as tablets of Celphos, Alphos or Quickphos which are known as rice tablets. Each tablet weights 3 grams and contains 56% ALP and 44% of aluminum carbonate and paraffin. The incidence of ALP poisoning increased steadily specially in developing countries . ALP poisoning is considered to be one of the major causes of suicidal poisoning owing to its wide accessibility and low cost. However, accidental poisoning may occur during occupational exposure

Detailed Description
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Aluminum phosphide (ALP) is a widely used fumigant due to its efficiency as pesticides. It is available as tablets of Celphos, Alphos or Quickphos which are known as rice tablets. Each tablet weights 3 grams and contains 56% ALP and 44% of aluminum carbonate and paraffin. The incidence of ALP poisoning increased steadily specially in developing countries . ALP poisoning is considered to be one of the major causes of suicidal poisoning owing to its wide accessibility and low cost. However, accidental poisoning may occur during occupational exposure. Signs and symptoms of acute AlP poisoning include gastrointestinal, cardiovascular, hepatic, renal, and neurologic (1). Ingestion of ALP causes mild gastrointestinal (GIT) manifestations as nausea, vomiting, abdominal pain, in addition to chest tightness, hypotension, headache and dizziness. In severe cases, GIT hemorrhage, shock, severe metabolic acidosis, cardiac arrhythmia, convulsions and coma may occur. Later, signs of hepatic damage and renal insufficiency may develop. Death usually occurs in 30-70% of cases within the first 24 hours resulting from refractory cardiogenic shock, cardiac arrhythmia, severe hypotension and metabolic acidosis.The main causes of cardiovascular collapse are increase capillary permeability, insufficient systemic vasoconstriction with low ventricular ejection fraction. On autopsy examinations, point to extravasation of fluid into the third space. The management is exclusively supportive as gastric lavage with KMnO4 solution, treatment of hypotension and acidosis in view of the fact that there is no specific antidote available.

Official Title
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The Potential Therapeutic Role of Hydroxyethyl Starch and Hydrocortisone in Acute Aluminum Phosphide Poisoning: A Randamized Controlled Clinical Trial

Conditions
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Potential Therapeutic Role

Intervention / Treatment
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* Drug: Hydroxyethyl Starch 130-0.4 60 MG/ML [Voluven]
* Drug: Hydrocortisone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with severe acute aluminum phosphide poisoning systolic blood pressure (SBP) ≤90 mmHg PH ≤ 7.2 HCO3 ≤15 meq/L during the first six hours of admission Exclusion Criteria: Pregnant and lactating women Asymptomatic patients with history of acute aluminum phosphide exposure. Patients with co-ingestion to other substances in addition to aluminum phosphide. Patients with other major medical conditions (e.g. cardiovascular disease, renal or hepatic failure). Patients with previous medical intervention (fluid therapy and vasopressors).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: control group<br>received the standard ALP treatment according to TUPTC protocol as follows: patient resuscitation, care of airway, breathing and circulation, gastric decontamination with 2 ampoules sodium bicarbonate (each ampoule 25 ml containing 2.1 gm sodium bicarbonate) followed by activated charcoal in dose of 1 g/Kg orally, adequate hydration, normal saline administration (0.9% Sodium Chloride IV), vasopressors IV infusions, inhalation of 100% oxygen, ranitidine IV, magnesium sulfate IV infusion and other supportive treatment. | Drug: Placebo<br>* received the standard ALP treatment according to TUPTC protocol as follows: patient resuscitation, care of airway, breathing and circulation, gastric decontamination with 2 ampoules sodium bicarbonate (each ampoule 25 ml containing 2.1 gm sodium bicarbonate) followed by activated charcoal in dose of 1 g/Kg orally, adequate hydration, normal saline administration (0.9% Sodium Chloride IV), vasopressors IV infusions, inhalation of 100% oxygen, ranitidine IV, magnesium sulfate IV infusion and other supportive treatment.<br>|
| Experimental: Hydroxyethyl starch group):<br>Patients will start therapy with Hydroxyethyl starch instead of normal saline (6% hetastarch 600/0.75 in 0.9% sodium chloride) with a dose of 500 cc in 6 hours. Additionally, patient will receive the standard ALP treatment according to TUPTC protocol in the same order of placebo. | Drug: Hydroxyethyl Starch 130-0.4 60 MG/ML [Voluven]<br>* Hydroxyethyl starch dose is 500 cc in 6 hours<br>Drug: Placebo<br>* received the standard ALP treatment according to TUPTC protocol as follows: patient resuscitation, care of airway, breathing and circulation, gastric decontamination with 2 ampoules sodium bicarbonate (each ampoule 25 ml containing 2.1 gm sodium bicarbonate) followed by activated charcoal in dose of 1 g/Kg orally, adequate hydration, normal saline administration (0.9% Sodium Chloride IV), vasopressors IV infusions, inhalation of 100% oxygen, ranitidine IV, magnesium sulfate IV infusion and other supportive treatment.<br>|
| Experimental: Combined Hydroxyethyl starch and hydrocortisone group<br>Patients will start therapy with combined Hydroxyethyl starch (Voluven®, fresenius kabi, Germany) and hydrocortisone (SOLU-CORTEF 100 mg ampoule) instead of normal saline of normal saline as follow: Hydroxyethyl starch dose is 6% hetastarch 600/0.75 in 0.9% sodium chloride with a dose of 500 cc in 6 hours. Hydrocortisone dose is 200-300 mg /day intravenously until normalization of blood pressure. Additionally, patient will receive the standard ALP treatment according to TUPTC protocol in the same order of placebo. | Drug: Hydroxyethyl Starch 130-0.4 60 MG/ML [Voluven]<br>* Hydroxyethyl starch dose is 500 cc in 6 hours<br>Drug: Hydrocortisone<br>* Hydrocortisone dose is 200-300 mg /day intravenously<br>Drug: Placebo<br>* received the standard ALP treatment according to TUPTC protocol as follows: patient resuscitation, care of airway, breathing and circulation, gastric decontamination with 2 ampoules sodium bicarbonate (each ampoule 25 ml containing 2.1 gm sodium bicarbonate) followed by activated charcoal in dose of 1 g/Kg orally, adequate hydration, normal saline administration (0.9% Sodium Chloride IV), vasopressors IV infusions, inhalation of 100% oxygen, ranitidine IV, magnesium sulfate IV infusion and other supportive treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality | mortality rate of patients | 28 days from start of management | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Need for mechanical ventilation | incidence of need for intubation and mechanical ventilation for each patient | Through study completion up to 6 months | 
| need for ICU admission | the incidence of need for ICU admission for each patient | Through study completion up to 6 months |