Toxicology

Whenever ingestion is suspected, contact local poison control at 1-800-222-1222.
Each year the American Association of Poison Control Centers records about 1.2 million childhood poisoning exposures. Of these exposures, 75% occur in children younger than the age of 6 years. Exposures in young children are often unintentional, whereas adolescents are more likely to have intentional ingestions.1

I. Initial Evaluation

When to suspect ingestion: always, but especially with altered mental status or seizure. Begin the evaluation with an assessment of circulation, airway and breathing, and manage accordingly.2

A. History
Keep in mind that history may be inaccurate and provide supportive care and treatment in accordance with clinical condition and toxidrome.2

  1. 1. Exposure history

Obtain history from witnesses and/or close contacts: Route, timing, and number of exposures (acute, chronic, or repeated ingestion), prior treatments or decontamination efforts.

  1. 2. Substance identification and quantity ingested

Attempt to identify exact name of substance(s) ingested, including product name, active ingredients, possible contaminants, expiration date, concentration, and dose. Attempt to estimate the missing volume of liquid or the number of missing pills from a container. Poison control can assist with pill identification.2,3

  1. 3. Environmental information

Accessible items in the house or garage, open containers, spilled tablets, household members taking medications, other caregivers, herbs, or other complementary medicines2,3

B. Workup and Laboratory Investigation

  1. 1. Electrocardiogram (ECG): Several medications will cause ECG changes, including QTc and QRS prolongation.
  2. 2. Blood tests
    1. a. Venous blood gas, blood glucose, and serum electrolytes
    2. b. Individual drug levels such as acetaminophen, aspirin, and ethanol are helpful general screenings in an acute, unknown ingestion.
    3. c. Acetaminophen levels are especially important to test in suicidal ingestions. Many medications for pain or upper respiratory symptoms contain acetaminophen.
  3. 3. Urine toxicology screens
    1. a. Basic screens include amphetamines, cocaine, opiates, phencyclidine (PCP), and tetrahydrocannabinol (THC).
    2. b. Positive results are presumptive only; must be confirmed by gas chromatography/mass spectrometry4

C. Clinical Diagnostic Aids: Table With Clinical Signs and Possible Intoxicants (eTable 3.1)

II. Toxidromes

See Table 3.1.

III. Ingestions and Antidotes

See Table 3.2.

A. Decontamination

  1. 1. Activated charcoal5
    1. a. Most effective when used within first hour after ingestion but can be given after first hour, especially for sustained-release preparations
    2. b. Should be given PO to an awake and alert patient. Nasogastric (NG) tube should be used only if a patient is intubated due to risk of aspiration.
    3. c. Substances not absorbed by charcoal: Iron, alcohols, lithium
    4. d. Contraindications: Unprotected airway, caustic ingestion, disrupted gastrointestinal tract, concern for aspiration
  2. 2. Whole bowel irrigation
    1. a. Indicated for evacuation of substances not bound to activated charcoal, such as iron, lead-containing foreign bodies, fatal sustained-release products, drug packing
    2. b. Use a polyethylene glycol electrolyte solution preparation to irrigate the bowel. Recommended rates: 9 months to 6 years (500 mL/hr), 6 to 12 years (1000 mL/hr), more than 12 years (1500 to 2000 mL/hr). Often will need two NG tubes and pumps to maintain these rates.6

B. Enhanced Removal

  1. 1. Hemodialysis or exchange transfusions may be indicated to remove a drug/toxin.
  2. 2. Ingestions that may require enhanced removal therapies: Salicylate, lithium, methanol, ethylene glycol, metformin-associated lactic acidosis, valproate, theophylline

C. Other Considerations

  1. 1. Many ingestions are managed primarily with supportive care of any associated toxic effects, such as hypotension or hyperpyrexia.
  2. 2. Seizures: First-line agents are benzodiazepines. Barbiturates or propofol should be considered as second-line agents. Phenytoin has no role in the treatment of toxin-induced seizures.7
  3. 3. Patients with severe poisoning and refractory cardiorespiratory failure after ingestion are potential extracorporeal membrane oxygenation (ECMO) candidates because the toxic effects are transient.

IV. Acetaminophen Overdose

Section references: 8
NAPQI metabolite is hepatotoxic.

A. Four Phases of Intoxication

  1. 1. Phase 1 (first 24 hours): Nonspecific symptoms such as nausea, malaise, vomiting
  2. 2. Phase 2 (24 to 72 hours): Above symptoms resolve; right upper quadrant pain, hepatomegaly, and increasing transaminases develop
  3. 3. Phase 3 (72 to 96 hours): Return of nonspecific symptoms as well as evidence of liver failure (increased prothrombin time, lactate, phosphate), renal failure, and encephalopathy
  4. 4. Phase 4 (4 days to 2 weeks): Recovery or death

B. Treatment Criteria

  1. 1. Serum acetaminophen concentration above the possible toxicity line on the Rumack-Matthew nomogram after single acute ingestion (Fig. 3.1)
  2. 2. History of ingesting more than 200 mg/kg or 10 g (whichever is less) and serum concentration not available or time of ingestion not known
  3. 3. If time of ingestion is unknown or multiple/chronic ingestion, check acetaminophen level and AST. Treat if either is elevated.

C. Antidote: N-Acetylcysteine (See Formulary in Chapter 30)

  1. 1. PO: 140 mg/kg loading dose (max 15 g/dose) followed by 70 mg/kg/dose (max 7.5 g/dose) Q4 hours continue treatment until transaminases and INR have peaked and are decreasing substantially towards normal. Repeat dose if vomiting occurs within 1 hour of administration.
  2. 2. Intravenous (IV): 150 mg/kg N-acetylcysteine IV loading dose (max 15 g/dose) over 60 minutes, followed by 50 mg/kg/dose (max 5 g/dose) over 4 hours, followed by 100 mg/kg/dose (max 10 g/dose) over 16 hours for a total infusion time of 21 hours. Some patients may require more than 21 hours of N-acetylcysteine administration. See Formulary for weight-based drug dilution volumes.
  3. 3. Liver failure: Continue the 100 mg/kg over 16 hours infusion until resolution of encephalopathy, AST less than 1000 units/L, and INR less than 2.

D. Consider Referral to Liver Transplant Center if Patient Meets King’s College Criteria

Descriptive text is not available for this image

FIGURE 3.1
Rumack-Matthew nomogram. Semilogarithmic plot of plasma acetaminophen levels versus time. This nomogram is valid for use after single acute ingestions of acetaminophen. The need for treatment cannot be extrapolated based on a level before 4 hr.

Data from Pediatrics 1975;55:871, and Micromedex.

V. Lead Poisoning

Section references: 9

A. Definition
Centers for Disease Control and Prevention (CDC) defines a reference level of 3.5 μg/dL to identify children with elevated blood lead levels (BLLs).10

B. Sources of Exposure
Paint, dust, soil, drinking water, cosmetics, cookware, toys, caregivers with occupations and/or hobbies using lead-containing materials or substances, and bullets if in joint spaces or pleura

C. Overview of Symptoms by Blood Lead Level

  1. 1. BLL ≥ 40 μg/dL: Irritability, vomiting, abdominal pain, constipation, anorexia
  2. 2. BLL ≥ 70 μg/dL: Lethargy, seizure, and coma. Note: Children may be asymptomatic with lead levels greater than 100 μg/dL.

D. Management

  1. 1. See TABLE 3.3 TABLE 3.4 for general management and repeat testing guidelines.
  2. 2. Chelation therapy2
    1. a. Asymptomatic children with BLL 45 to 69 mCg/dL
    2. Succimer: 1050 mg/m2/day PO divided Q8 hours × 5 days, then 700 mg/m2/day divided Q12 hours × 14 days. See Formulary for more details.
    3. b. Asymptomatic children with BLL ≥70 mCg/dL
      1. (1) Succimer: Per above dosing
      2. (2) Edetate (EDTA) calcium disodium: 1000 mg/m2 (max dose 2 to 3 g) as 24-hour IV infusion × 5 days. Begin 2 hours after first dose of succimer. Monitor renal function closely.
    4. Warning: Do not mistake edetate disodium for edetate calcium disodium. Edetate calcium disodium is the correct medicine used for the treatment of lead poisoning.
    5. c. Symptomatic children unable to take PO (e.g., lead encephalopathy, seizure)
      1. (1) Dimercaprol (BAL): 450 mg/m2/day IM divided Q4 hours × 3 to 5 days (number of days based on clinical course). Do not give to patients with peanut allergy. Do not use concomitantly with iron, as BAL-iron complex is a potent emetic. Use with caution in patients with G6PD deficiency, as it may cause hemolysis.
      2. (2) Edetate (EDTA) calcium disodium: 1500 mg/m2 (maximum dose 2 to 3 g) as 24-hour IV continuous infusion × 5 days. Begin 4 hours after first dose of BAL.

VI. Web Resources

Author(s)

Sophie Crinion, MD

References

  1. D.D. Gummin, J.B. Mowry, M.C. Beuhler, et al. 2020 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 38th Annual Report. Clin Toxicol (Phila). 2021;59(12):1282-1501.
  2. L.S. Nelson, R.S. Hoffman, M.A. Howland, et al. Goldfrank’s Toxicologic Emergencies. 11th ed.. McGraw-Hill; 2019.
  3. G. Wang, R.C. Dart, B.H. Rumack Poisoning. M.Bunik, W.W.Hay, M.J.Levin, M.J.Abzug, eds. Current Diagnosis and Treatment: Pediatrics. 26e. McGraw-Hill; 2022.
  4. K.E. Moeller, K.C. Lee, J.C. Kissack Urine drug screening: practical guide for clinicians. Mayo Clin Proc. 2008;83(1):66-76.
  5. G.R.Fleisher, S.Ludwig, eds. Textbook of Pediatric Emergency Medicine. 7th ed.. Lippincott Williams & Wilkins; 2016.
  6. R. Thanacoody, E.M. Caravati, B. Troutman, et al. Position paper update: whole bowel irrigation for gastrointestinal decontamination of overdose patients. Clin Toxicol (Phila). 2015;53(1):5.  [PMID:26174744]
  7. H.Y. Chen, T.E. Albertson, K.R. Olson Treatment of drug-induced seizures. Br J Clin Pharmacol. 2016;81(3):412-419.
  8. Theobald JL, Kostic MA. Poisoning. In: Kleigman RM, St Geme JW, et al., eds. Nelson Textbook of Pediatrics 21st ed. Philadelphia: Elsevier 77: 490–510.
  9. Advisory Committee on Childhood Lead Poisoning Prevention of the Centers for Disease Control and Prevention Low Level Lead Exposure Harms Children: A Renewed Call for Primary Prevention. January 2012. http://www.cdc.gov/nceh/lead/ACCLPP/Final_Document_030712.pdf.
  10. Blood Lead Levels in Children. (2022 August 29). Centers for Disease Control and Prevention. Retrieved 2022 September 15 from https://www.cdc.gov/nceh/lead/prevention/blood-lead-levels.htm.
  11. Recommended Actions Based on Blood Lead Level. (2022 September 8). Centers for Disease Control and Prevention. Retrieved 2022 September 15 from https://www.cdc.gov/nceh/lead/advisory/acclpp/actions-blls.htm.
  12. K.M. Engebretsen, K.M. Kaczmarek, J. Morgan, J.S. Holger High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning. Clin Toxicol. 2011;49(4):277-283.