Role of Combination Therapy of Glucose Insulin Potassium Infusion (GIK), Intravenous Hydrocortisone and Oral Sevelamer in Treatment of Acute Aluminum Phosphide Poisoned Cases Admitted to Intensive Care Unit (ICU) at Sohag University Hospitals.

Обзор

Metal phosphides are commonly utilized for safeguarding stored grains due to their desirable characteristics. They have high potency and the ability to combat different pests and produce non-toxic residues in crops . In countries like Iran, India, and Egypt, metal phosphides are extensively employed in agriculture. Some examples of metal phosphides are aluminum phosphide (ALP), zinc phosphide, magnesium phosphide, and calcium phosphide . ALP poisoning is a prevalent method for suicide in most of developing countries such as North India, Iran, and Egypt . ALP poisoning is becoming more common in Egypt, and poison control centers are seeing an increase in cases . ALP which is a potent poison with an oral LD50 of 11.5 mg/kg, is utilized as an insecticide, rodenticide, and fumigant. It is available in the form of tablets, commonly referred to as rice tablets or wheat bills. The rice tablet weighs three grams and contains 56% ALP and 44% aluminum carbonate. When it comes into contact with moisture, it releases one gram of Phosphine (PH3) . PH3 is rapidly absorbed from the respiratory or gastrointestinal tract to reach the systemic circulation. PH3 is a toxic substance that can cause various harmful effects . The cause of hypotension in ALP poisoning is thought to be due to the direct toxic effects of phosphine on cardiac myocytes, fluid loss and adrenal gland damage . PH3 causes collapse of the cardiovascular system, damage to the lungs, and liver dysfunction. Additionally, it can lead to significant imbalances in the body's acid-base and electrolyte levels, resulting in conditions such as metabolic acidosis and hypokalemia As a result, fatalities resulting from metal phosphide exposure are usually caused by a combination of cardiogenic shock, metabolic acidosis, acute pulmonary edema, and liver failure that are difficult to treat There is no known antidote for ALP poisoning, so treatment is only supportive. The success of treatment depends on the severity of the poisoning and how quickly the patient receives medical attention Although no specific antidote for ALP poisoning is available, glucose-insulin-potassium (GIK) infusion precipitating hyperinsulinemia-euglycemia. It is supposed to improve cell carbohydrate metabolism, increases both cardiac inotropy and systemic vascular resistance, and corrects acidosis. As carbohydrates are preferable fuel substrates of the myocardium under stressful conditions. GIK infusion assists in enhanced uptake of carbohydrates and, therefore, results in improved cardiac function GIK infusion therapy has been advised in the additional management of ischaemia and reperfusion disturbances in ischaemic heart diseases. GIK therapy has been reported to be beneficial in cardiac surgeries.Although the GIK regime, along with supportive care, results in a longer duration of hospital stay, the ultimate outcome of the results is beneficial Adrenal insufficiency may occur as a result of shock; thus, a hydrocortisone infusion is given. Hydrocortisone combats shock; reduces the dose of dopamine; and it additionally checks capillary leakage in the lungs to prevent ARDS Use of hydrocortisone in treatment of shocked patients has a promising outcome as it stabilizes cell membranes, reduces systemic inflammation, and helps manage refractory hypotension Sevelamer (SVLM) is approved by the US Food and Drug Administration for the treatment of hyperphosphatemia in patients with chronic kidney disease or end-stage renal disease (De Santi et al., 2024). Sevelamer is being "repurposed" as a potential oral antidote for treating aluminum phosphide poisoning. Sevelamer may serve as an effective antidote by its interaction with phosphine gas. While GIK and Hydrocortisone address the effects of the poison (shock and metabolic collapse), Sevelamer is unique because it may directly target and neutralize the toxic phosphine gas itself

Вмешательства

• Препарат Gastric lavage with paraffin oil
  with paraffin oil about 6 bottles (3 for lavage and 3 left in the stomach) then Nil Per Os (NPO) for 48 hrs.
• Препарат GIK solution
  bolus of 1-3 IU/kg regular insulin together with 0.5-1 gm/kg dextrose followed by an intravenous infusion of 0.2 to 1 IU/kg/hr of regular insulin and a dextrose infusion will be started at 0.5gm/kg/hr. The dextrose infusion rate will be adjusted to maintain blood glucose between 140-180 mg/dL. Potassium will be given at dose of 20-80 meq/L of potassium chloride to maintain serum potassium at 3.5 to 4.5 meq/L. GIK will be administered via a central line

Первичные конечные точки

• change in mortality rate in acute aluminum phosphide poisoned cases admitted to intensive care unit (ICU). [Срок оценки: 1 year]

Критерии участия

Критерии включения

• Confirmed history of ALP ingestion and clinical symptoms and signs of toxicity.
• Age of Cases (12 - 60 years).
• Shocked cases (Mean arterial blood (MAP) less than 70 mmHg).
• Presentation within 12 hours of ingestion.

Критерии исключения

• Co-ingestion of other toxins.
• Chronic cardiac/renal/hepatic failure and diabetic patients.
• Pregnancy.
• Cases arriving in terminal cardiac arrest.
• Cases refused to participate in the trial.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Египет · 1 центр

• Sohag university hospital — Sohag

Публикации

• Adel B, Elgharbawy NM, Shahin MM, Abo-Elfadl AA, Saad KM. Insulin-euglycemia therapy in acute aluminum phosphide poisoning: a randomized clinical trial. Clin Toxicol (Phila). 2023 Dec;61(12):1032-1039. doi: 10.1080/15563650.2023.2279495. Epub 2024 Jan 25. PMID 38096041
• Agrawal VK, Bansal A, Singh RK, Kumawat BL, Mahajan P. Aluminum phosphide poisoning: Possible role of supportive measures in the absence of specific antidote. Indian J Crit Care Med. 2015 Feb;19(2):109-12. doi: 10.4103/0972-5229.151019. PMID 25722553
• Bagherian F, Kalani N, Rahmanian F, Abiri S, Hatami N, Foroughian M, Mehramiz NJ, Shahi B. Aluminum Phosphide Poisoning Mortality Rate in Iran; a Systematic Review and Meta-Analysis. Arch Acad Emerg Med. 2021 Oct 3;9(1):e66. doi: 10.22037/aaem.v9i1.1396. eCollection 2021. PMID 34870232
• Bogale DE, Ejigu BD, Muche TA. Clinical Profile and Treatment Outcome of Aluminum Phosphide Poisoning in Felege Hiwot Referral Hospital, Northwest Ethiopia: A Retrospective Study. Open Access Emerg Med. 2021 Jun 16;13:239-248. doi: 10.2147/OAEM.S313181. eCollection 2021. PMID 34163261
• Bogle RG, Theron P, Brooks P, Dargan PI, Redhead J. Aluminium phosphide poisoning. Emerg Med J. 2006 Jan;23(1):e3. doi: 10.1136/emj.2004.015941. PMID 16373788

Идентификаторы

NCT: NCT07451561 · Soh-Med--26-2-4MD

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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