ToxCard: Metal Phosphides

Authors: Forrest Turner, MD and Ann-Jeannette Geib, MD (Department of Emergency Medicine, Carolinas Medical Center, Charlotte, NC) // Reviewed by: Cynthia Santos, MD (@CynthiaSantosMD); Alex Koyfman, MD (@EMHighAK); and Brit Long, MD (@long_brit)

Case:

A 3-year-old (15kg) boy presents to the emergency department by EMS with frequent vomiting. The family had immigrated from India 2 years prior, but the patient has no prior past medical history and is fully immunized. Family states the patient was in normal state of health earlier when he was playing around the garage.  A few minutes later patient was noted to have frequent emesis and retching with associated ataxia and altered mental status. In his hand were some pellets that the parents identified as a rodenticide.  Upon arrival, patient has an episode of dark emesis that is notable for a foul garlicky odor. He is clutching his abdomen and moaning, GCS of 10. Initial vital signs are heart rate 170, BP 60/palp, respirations 40, O2 saturation 90%.


Question:

Which of the following rodenticide ingestions would be associated with the highest potential for death in this patient and is associated with garlicky breath?

  1. Cholecalciferol
  2. Aluminum phosphide
  3. Brodifacoum
  4. Bromethalin

Answer: B, the rodenticide with garlic breath.


Background:

  • Commonly available metal phosphides include Zinc phosphide, Aluminum phosphide, and Magnesium phosphide.
  • Cheap and frequently used insecticide and rodenticide. Typically tablet, pellet, or powder forms. Often added to grain supplies in enclosed spaces to act as a fumigant.
  • High concentration formulations are readily available to the public in India, Iran, Sri Lanka, Morocco, and other locales. It is a frequent agent for intentional ingestion/suicide in these countries, also seen in accidental ingestions and occupational exposure.
  • Metal phosphides are also available to the public in the US. Phosphine gas exposure is sometimes seen related to methamphetamine production.
  • Toxicity after ingestion is related to the liberation of phosphine gas when metal phosphides are exposed to water or acid. Phosphine gas is then absorbed through the GI mucosa and into the bloodstream.1

Al P + 3H2O → Al (OH)3 + PH3

Al P + 3H+ → Al+3 + PH3

  • Phosphine gas can also be inhaled and absorbed across the respiratory mucosa in settings of an occupational or chemical agent of opportunity exposure,2 with minimal risk of dermal exposure leading to toxicity.
  • The volume of distribution is unknown. Excreted as hypophosphite by the kidneys or exhaled as unmetabolized phosphine gas.
  • Phosphine is odorless; side reactions create compounds that lead to the characteristic garlicky/fishy odor.1
  • Mechanism of action is unknown although hypotheses include poisoning mitochondria and inhibition of oxidative respiration, increase in free radicals and depletion of glutathione, caustic effects especially in the GI tract, oxidation of hemoglobin, and methemoglobinemia. There is uncertainty as to the toxic dose, estimates from 150-500mg for AlP, 500-1000mg for ZnP. Rodent studies have shown 40mg/kg for both.
  • There is uncertainty regarding mortality, various estimates from 40-77%, with the majority of deaths in the first 12-24 hours. Death is usually attributed to multisystem organ failure, common features include cardiogenic shock, pulmonary edema, renal failure, and metabolic acidosis1,3,4,5.

Presentation:

  • Low dose inhaled toxicity which may be seen in agricultural occupational exposure is characterized by respiratory irritation, dyspnea, chest pain, nausea, vomiting, headache, and neurological findings (tremor, diplopia, weakness, etc.).
  • Symptoms from ingestion are rapid (10-15 minutes) and characterized by nausea, vomiting, hematemesis, abdominal pain, chest pain, shortness of breath, irritability, and garlicky breath. Predominant features of GI, cardiac, pulmonary, and electrolyte derangements, although almost any organ system can be affected.
  • GI – gastritis, ulcers, erosions, later can form strictures or fistulae, hepatitis, rarely pancreatitis.
  • Cardiac – hypotension, arrhythmias, acute heart failure.
  • Pulmonary – pulmonary edema, ARDS.
  • Electrolytes – high or low potassium, magnesium, sodium, glucose. Metabolic acidosis.
  • CNS – agitation, dizziness, ataxia, tremor, numbness, tremor, later seizure, and coma.
  • Hematologic – hemolysis, DIC, methemoglobinemia, although these are less common. Methemoglobinemia may reach levels that require treatment and correlate with survival.6,7
  • Renal – AKI and ATN, less common.8

Diagnosis:

  • History and the presence of garlic or fishy breath are helpful in determining a diagnosis. Readily available definitive testing is limited and unlikely to result in a time frame that would affect management. Paper infused with silver nitrate will turn black if exposed to phosphine, can be used on breath or gastric fluid to make 8
  • It is important to inquire about the exposure type (accidental or intentional), route of exposure, the concentration of the product, time of occurrence, and estimated amount ingested.

Laboratory Testing:

Broad workup to determine derangements from toxicity: CBC, CMP, lipase, magnesium, coagulation studies, lactate. VBG or ABG with co-oximetry to examine for methemoglobin should be obtained.8

Imaging:

  • ECG may demonstrate sinus tachycardia early on, can see QRS, PR widening, heart blocks, or STEMI mimics, after 6 hours one may see supraventricular tachycardias, ventricular tachycardia, or ventricular fibrillation.
  • Bedside echo may demonstrate systolic dysfunction, wall motion abnormalities, or pericardial effusion.
  • Chest x-ray may demonstrate evidence of pulmonary edema or ARDS.5,8

Clinical Management:

  • Don’t forget PPE and eye protection for the healthcare team. Be mindful that standard ED respiratory protection (eg, N-95) will not prevent phosphine exposure. Patients should be fully unclothed and decontaminated.
  • ABC’s with good supportive care is the mainstay of treatment; no antidote exists. There is no proven role of hemodialysis to remove phosphine.
  • GI decontamination is performed frequently in these cases around the world although data showing benefit is scarce. A variety of agents have been described to reduce the systemic absorption of phosphine including potassium permanganate, bicarbonate, lipids such as coconut oil, vegetable oil, or liquid paraffin, and activated charcoal. Several case reports and small studies demonstrate survival with the administration of some cocktail of these, although controlled studies do not exist.3,4,5,8,9 While the evidence is not well-established, it would be reasonable to deploy GI decontamination with activated charcoal as it is readily available in the ED environment.
  • Antidotal therapies: The antioxidants vitamin E and N-acetylcysteine have shown some promising preliminary data.
  • NAC – There is data from 3 controlled studies, with 2 showing mortality benefit and 1 not. Studies used a variety of regimens; it would be reasonable to select an IV regimen routinely used at your facility.4,10
  • Vitamin E – A controlled study of 36 critically ill patients in Turkey saw significant improvements in mortality and the need for mechanical ventilation with 400mg IM vitamin E BID for 3 days.11
  • Continuous magnesium infusions have shown differing results in the 2 controlled studies, one showed mortality benefit and the other did not.1
  • Several other adjuncts show promise, but data does not extend beyond in vitro or animal studies including melatonin, sodium selenite, triiodothyronine, acetyl-L-carnitine, pralidoxime, and others.
  • Rescue maneuvers
  • High-dose insulin can be considered. 88 patients in a controlled study showed significant mortality benefit (72% vs 50%).12
  • Case reports document successful deployment of intra-aortic balloon pumps and ECMO.8

Case Conclusion:

The emergency department physician was astute in suspecting toxic ingestion with special concern for metal phosphide poisoning. Intravenous access was obtained, and a broad set of labs were drawn. The patient was placed on oxygen, although due to waning mental status and O2 saturation, as well as ongoing dark emesis, the decision was made to proceed with endotracheal intubation. With airway secured and suspected recent ingestion, a nasogastric tube was placed, the patient’s gastric contents were aspirated, and a dose of activated charcoal was administered. Labs were significant for hypokalemia to 3.0, hypomagnesemia to 1.1, mild elevations in LFTs, normal renal function, and anion gap acidosis pH 7.18, bicarb 14, AG 18 attributed to elevated lactate of 5.6. Chest x-ray showed bilateral opacifications concerning for ARDS or infectious process. Bedside point of care echocardiogram demonstrated a moderate degree of systolic dysfunction. An IV fluid bolus was given, empiric antibiotics were initiated, and electrolyte replacement was started.

Upon arrival to the PICU, NAC was started. A central line and norepinephrine infusion were started for down trending blood pressure. The family confirmed the presence of an aluminum phosphide containing rat poison stored in their garage. Over the course of the night, the patient had increasing vasopressor requirements despite the addition of epinephrine infusion. ECMO was considered but the team opted to trial high dose insulin therapy. Over the next 24 hours, the patient was able to be weaned from vasopressors and he was extubated on hospital day 3. Ultimately, he was discharged without sequelae.


Key Points:     

  • Metal phosphides are potent pesticides with disproportionate numbers of poisonings in countries such as India and Iran.
  • Toxicity stems from the production of phosphine gas when a metal phosphide contacts water or acids, particularly in the stomach when ingested, with rapid onset of symptoms by this route.
  • Predominant symptoms involve garlicky or fishy breath or vomitus, GI irritation often with dark emesis, hepatopathy, acute heart failure, shock, arrhythmias, ARDS, and electrolyte derangements, although any organ system can be affected.
  • Obtain a full panel of labs, ECG, CXR, and bedside echo if able.
  • Management is focused on ABCs and good supportive care. GI decontamination with a variety of agents including bicarb, potassium permanganate, lipids, and charcoal are given frequently around the world although data supporting their use is scarce. Some small studies show benefits with NAC, vitamin E, and high-dose insulin.

References:

  1. Proudfoot AT. Aluminium and zinc phosphide poisoning. Clin Toxicol (Phila). 2009 Feb;47(2):89-100. doi: 10.1080/15563650802520675. PMID: 19280425.
  2. 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; PMCID: PMC2564148.
  3. Shadnia S, Soltaninejad K. Fumigants. In: Nelson LS, Howland M, Lewin NA, Smith SW, Goldfrank LR, Hoffman RS. eds. Goldfrank’s Toxicologic Emergencies, 11e. McGraw-Hill; Accessed January 25, 2021. https://accessemergencymedicine-mhmedical-com.libproxy.lib.unc.edu/content.aspx?bookid=2569&sectionid=210275622
  4. Karimani A, Mohammadpour AH, Zirak MR, et al. Antidotes for aluminum phosphide poisoning – An update. Toxicol Rep. 2018;5:1053-1059. Published 2018 Oct 28. doi:10.1016/j.toxrep.2018.10.009
  5. Moghadamnia AA. An update on toxicology of aluminum phosphide. Daru. 2012 Sep 3;20(1):25. doi: 10.1186/2008-2231-20-25. PMID: 23351193; PMCID: PMC3555759.
  6. Soltaninejad K, Nelson LS, Khodakarim N, Dadvar Z, Shadnia S. Unusual complication of aluminum phosphide poisoning: Development of hemolysis and methemoglobinemia and its successful treatment. Indian J Crit Care Med. 2011 Apr;15(2):117-9. doi: 10.4103/0972-5229.83021. PMID: 21814377; PMCID: PMC3145296.
  7. Mostafazadeh B, Pajoumand A, Farzaneh E, Aghabiklooei A, Rasouli MR. Blood levels of methemoglobin in patients with aluminum phosphide poisoning and its correlation with patient’s outcome. J Med Toxicol. 2011 Mar;7(1):40-3. doi: 10.1007/s13181-010-0121-7. PMID: 21057909; PMCID: PMC3614104.
  8. Hashemi-Domeneh B, Zamani N, Hassanian-Moghaddam H, Rahimi M, Shadnia S, Erfantalab P, Ostadi A. A review of aluminium phosphide poisoning and a flowchart to treat it. Arh Hig Rada Toksikol. 2016 Sep 1;67(3):183-193. doi: 10.1515/aiht-2016-67-2784. PMID: 27749266.
  9. Trakulsrichai S, Kosanyawat N, Atiksawedparit P, et al. Clinical characteristics of zinc phosphide poisoning in Thailand. Ther Clin Risk Manag. 2017;13:335-340. Published 2017 Mar 14. doi:10.2147/TCRM.S129610
  10. Agarwal A, Robo R, Jain N, Gutch M, Consil S, Kumar S. Oxidative stress determined through the levels of antioxidant enzymes and the effect of N-acetylcysteine in aluminum phosphide poisoning. Indian J Crit Care Med. 2014 Oct;18(10):666-71. doi: 10.4103/0972-5229.142176. PMID: 25316977; PMCID: PMC4195197.
  11. Halvaei Z, Tehrani H, Soltaninejad K, Abdollahi M, Shadnia S. Vitamin E as a novel therapy in the treatment of acute aluminum phosphide poisoning. Turk J Med Sci. 2017 Jun 12;47(3):795-800. doi: 10.3906/sag-1512-6. PMID: 28618724.
  12. Hassanian-Moghaddam H, Zamani N. Therapeutic role of hyperinsulinemia/euglycemia in aluminum phosphide poisoning. Medicine (Baltimore). 2016 Aug;95(31):e4349. doi: 10.1097/MD.0000000000004349. PMID: 27495040; PMCID: PMC4979794.

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