Pediatric Emergency Medicine Clinical Case Presentation Rudi-Ann Graham, PGY-1, Pediatrics

Case Scenario 1 A 16 year old female with known history of major depression, is brought to the emergency room by her parents, after having sudden onset of abdominal pain and vomiting. She admits to intentional ingestion of approximately 50 Pre-natal vitamin tablets, 3 hours prior to presentation. On arrival, her vital signs are BP 102/66, P 105, RR 24, Oxygen Saturations 99%, and T 38. 3˚. Weight 55kg. She is awake and alert, but diaphoretic, with moderate epigastric tenderness on palpation. Heart sounds are normal, and lungs are clear to auscultation. Which of the following are the most important initial investigations to obtain for this patient:

Case Scenario 1 CBC, urinalysis, blood and urine cultures CBC, Serum Iron Level, TIBC, BMP CBC, CMP, serum amylase and lipase levels VBG, Serum iron levels, PT/INR, PTT and Liver Enzymes, and abdominal XR

Case Scenario 1 CBC, urinalysis, blood and urine cultures CBC, Serum Iron Level, TIBC, BMP CBC, CMP, serum amylase and lipase levels VBG, Serum iron levels, PT/INR, PTT and Liver Enzymes, and abdominal XR

Acute Iron Poisoning Iron toxicity is the leading cause of poisoning deaths in children. Over 15000 cases of iron exposure reported to poison control centers annually Most ingestion occurs unintentionally Pre-natal vitamins or Ferrous sulphate pills Excess intake of children's chewable vitamins unlikely to cause death Intentional ingestion also occurs Higher mortality rates than accidental exposure The most serious exposures involve pre-natal vitamins and pure iron preparations that contain ferrous sulphate, which typically have significant levels of elemental iron. Epidemiology of intentional overdose differs from unintentional: female, mean age 19 years. Mortality rates increased among children with interntional ingestions (10 percent vs 1 percent)

Acute Iron Poisoning Toxicity depend on amount of elemental iron ingested Most common preparations are iron salts Ferrous Gluconate (12 percent) Ferrous Sulphate (20 percent) Ferrous Chloride (28 percent) Ferrous Fumarate (33 percent) Pre-natal vitamins generally contain 65 mg elemental iron MVT typically contain 15-18mg of elemental iron Placebo pills in 28 day OCP packages contain iron Iron also found in plant fertilisers, and snail baits

Iron Toxicity Minimal toxic dose and lethal dose not firmly established: Ingestion greater than 20mg/kg will often produce GI upset Exposures above 60mg/kg are potentially fatal Iron ingestions between 20-60mg/kg may or may not lead to toxicity

Iron Toxicity Ferric iron is toxic to cellular processes: Free radical production Lipid peroxidation Toxic effects seen when TIBC becomes overwhelmed Local Toxicity: Iron is corrosive to GI mucosa Abdominal pain, vomiting, diarrhea, GI hemorrhage Hypovolemia GI perforation Systemic Toxicity: Injury to cardiovascular system and liver Major cause of death is shock or liver failure

Stages of Iron Poisoning Time Post-Ingestion Description 1 < 6 hours Vomiting, hematemesis, explosive diarrhea, melena, abdominal pain, lethargy; Tachypnea, tachycardia, hypotension, coma 2 6-36 hours Resolution of GI symptoms (latent period) 3 2-5 days Shock, metabolic acidosis, liver failure, coagulopathy, hypoglycemia 4 2-5 weeks Gastric outlet or duodenal obstruction secondary to scarring Symptoms of iron poisoning occur in 4 stages: The progression of these phases may occur rapidly depending on the severity of the ingestion. The clinical phase should therefore be determines by the patients clinical and laboratory manifestations, not by the time since ingetion. Vomiting is the most serious indicator of serious ingestion in the early phase. Hypovolemic shock is most common cause of death. Quiesent phase: period of apparent recovery. Important to distinguish patients who are in this phase from patients with low-dose ingestion whos toxicity is actually resolved. Stage 3: Cardiogenic, hypovolemic and distributive shock. Metabolic acidosis is often profound and is an indicator of iron induced toxicity.

Acute Iron Poisoning Thorough history of amount of elemental iron and timing of ingestion What type and how much? When did ingestion occur? Intentional or accidental exposure? Other toxic substances? Patients asymptomatic 6 hours after ingestion unlikely to become symptomatic, unless enteric-coated tablets Evaluate serum iron concentrations after 8 hours

Acute Iron Poisoning Asymptomatic Patients: If tablet ingestion Abd Xray. If Abd Xray negative, no further investigation or observation If unknown amount or >40mg/kg ingested, measure serum iron concentration q4h until falling

Acute Iron Poisoning All symptomatic patients: Abdominal XR if tablet ingestion Venous blood gas (anion gap metabolic acidosis) Serum glucose (hyperglycemia) Serum Iron Usually peaks at 4-6 hours after ingestion Enteric-coated tablets, absorption may be erratic and delayed Serum electrolytes and creatinine PT/INR, PTT, liver enzymes (reversible early coagulopathy and late coagulopathy secondary to hepatic injury) Type and Screen

Acute Iron Poisoning Additional tests: EKG Urine Toxicology Serum Drug levels

Serum Iron Concentration Peak serum iron concentrations correlate with levels of toxicity Less than 350 mcg/dl: Minimal toxicity Between 350-500 mcg/dl: Mild to moderate GI symptoms Greater than 500 mcg./dl: Serious systemic toxicity Greater than 1000 mcg/dl: Significant morbidity and mortality

Radiographic Evaluation Indication: Ingestion more than 40mg/kg Significant symptoms Depends on type of formulation and content of elemental iron

Index Case Patient is symptomatic, and has potentially ingested 59mg/kg of elemental iron!!! Although patient has a low-grade fever, there is no history suggestive of infectious exposure. Iron toxicity, which is more likely, may also present with pyrexia. Urinalysis, blood and urine cultures are not the most appropriate initial investigations in this case. CBC may show leucocytosis; BMP may show hyperglycemia. But absence does not exclude iron toxicity. Acute pancreatitis is a likely differential for epigastric abdominal pain with vomiting. But given history, this is much less likely, and amylase and lipase would not be initially ordered.

Case Scenario 2 A 3 year old boy is brought to the emergency room, after being found with an open container of Pre- natal vitamins. His weight is 15kg. His parents estimate that 20 pills are missing from bottle. He has had 5 episodes of large hematemesis prior to arrival. On presentation, his vital signs are BP 66/45, P 125, RR 26, Oxygen Saturation 98%, T 37.9 ˚. POC glucose is 102 mg/dl. He is lethargic and pale, with a tender, distended abdomen. His airways are patent, and chest is clear to auscultation Which of the following is the best initial management for this patient.

Case Scenario 2 Treat with activated charcoal immediately for gastric decontamination Whole bowel irrigation (WBI) with nasogastric colonic lavage solution at 30 cc/kg/hr until rectal effluent is clear Establish IV access, fluid resuscitation with Normal Saline bolus at 20cc/kg, and prepare for chelation therapy Administer of 125mg/5ml syrup of ipecac to induce gastric emptying

Case Scenario 2 Treat with activated charcoal immediately for gastric decontamination Whole bowel irrigation (WBI) with nasogastric colonic lavage solution at 30 cc/kg/hr until rectal effluent is clear Establish IV access, fluid resuscitation with Normal Saline bolus at 20cc/kg, and prepare for chelation therapy Administer of 125mg/5ml syrup of ipecac to induce gastric emptying Airway protection and respiratory support should be provided as needed. Volume resuscitation to maintain euvolemia.

Treatment of Iron Poisoning Decontamination: Activated charcoal does not bind iron and is of no use in a pure ingestion!!!

Treatment of Iron Poisoning Whole bowel irrigation has been shown to be effective in reducing toxicity, especially of tablets on plain radiograph Awake and alert No evidence of GI dysfunction Intractable vomiting Ileus Significant bleeding Bowel obstruction or perforation Administer 25-40 cc/kg/hour of polyethylene glycol by NGT until effluent clear and radiograph no longer shows iron tablets

Treatment of Iron Poisoning Antidote: Deferoxamine is chelating agent; forms water-soluble deferoxamine-iron complex Consider deferoxamine if: Serum iron concentration > 500 mcg/dl Estimated dose > 60mg/kg elemental iron Patient has significant symptoms (altered conscious state, hypotension, tachycardia, tachypnea) irrespective of ingested dose, or serum iron concentrations Significant pills seen on xray Do not wait for iron concentrations if severe symptoms

Treatment of Iron Poisoning Dose 15mg/kg/hr IV Deferoxamine. Total dose should not exceed 80mg/kg/24 hours. Deferoxamine iron complex excreted renally. Patient’s urine will turn pink ‘vin rose’ If oliguria or anuria, may need peritoneal or hemodialysis End-point for chelation therapy: Patient is asymptomatic Decontamination complete (urine no longer pink) Anion gap acidosis resolved Serum iron concentration < 335 mcg/dl

Treatment of Iron Poisoning Chelation therapy side-effects Hypotension ARDS

References Erica L Liebelt, MD; Rana Kronfol, MD; www.uptodate.com: Acute Iron Poisoning Gerald F O’Malley, DO; Rika O’Malley, MD Merck Manual: Iron Poisoning https://pedclerk.bsd.uchicago.edu/page/iron-toxicity

QSL!