COMMON INTOXICATIONS IN KIDS

Blake Bulloch, MD

OBJECTIVES

• Review new recommendations for GI decontamination

• Review the common types of intoxications seen in children with recommendations on non-dialytic detoxifying therapies

GI DECONTAMINATION

• Ipecac

• Gastric Lavage

• Activated charcoal

• Cathartics

• Whole-Bowel irrigation

IPECAC

• 21% to 38% of drug is removed from the stomach if given in first hour

• Average child presents 1.5 hours post-ingestion, 3.5 hours for adults

• No evidence that ipecac improves outcome

• Use in the ED should be abandoned

GASTRIC LAVAGE

• 32% of drug removed if performed 1 hour• In ED studies no difference in outcomes

versus charcoal alone• Complication rate of 3% and includes:

– aspiration pneumonia– dysrhythmias– hypoxia and hypercapnia / laryngospasm

ACTIVATED CHARCOAL

• Mean in drug absorption is 89% if given within 30 min and 37% if given at 1 hour

• Complications minimal

• Insufficient data to support or exclude its use after 1 hour post-ingestion

CATHARTICS

• Two reasons cited for use of cathartics which are NOT true:– 1) Prevent charcoal induced constipation– 2) Decrease bioavailability of the ingestant

• Not recommended for GI decontamination

WHOLE-BOWEL IRRIGATION

• At 1 hour or longer after ingestion WBI decreases bioavailability 70%

• Long procedure and labor-intensive

• Limit to poisons not adsorbed by charcoal and to sustained release pharmaceuticals

• Should not be used routinely in poisonings

RCH POISONINGS (1997-2001)

• 2637 ER visits for poisoning

• 730 hospital admissions (28%)

• 53 ICU admissions– 2% of all poisonings– 7% of all admissions

RCH ICU ADMISSIONS

Antidepressants

Antihypertensives

Anticonvulsants

Alcohols

Iron

Benzodiazipines

Others

TRICYCLIC ANTIDEPRESSANTS

PATHOPHYSIOLOGY

Most toxic reactions are due to:

(1) Anticholinergic effects

(2) Excessive blockade of norepinephrine reuptake at the postganglionic synapse

(3) Direct quinidine-like effects on the myocardium

CLINICAL PRESENTATION

• Quinidine-like effects depress myocardial conduction – Prolonged QRS, QT or PR intervals– Torsade de pointes

• Ataxia, hallucinations, coma, seizures

• Other anticholinergic effects

MANAGEMENT

• Sodium bicarbonate: – Increases the plasma protein binding of TCAs– May help overcome sodium channel blockade

• If hypotensive may consider norepinephrine infusion (0.1-0.3 ug/kg/min)– Less ventricular arrhythmias than with

dopamine?

CARDIAC DRUGS

Beta-Adrenergic Blockers and Calcium Channel Blockers

PRESENTATIONS

• Bradycardia

• Hypotension

• Coma

• Convulsions

• Hypoglycemia: Beta-blockers

• Hyperglycemia: Calcium channel blockers

MANAGEMENT

• Atropine, fluid boluses and pressors to treat bradycardia and hypotension

• Glucagon 3-5 mg/kg IV bolus up to 10 mg followed by an infusion of 2-5 mg/h

• CCB: 10% Ca gluconate 0.6 ml/kg or 10% Ca chloride 0.2 ml/kg

• Pacemaker

CARBAMAZEPINE

CLINICAL PRESENTATION

• Coma

• Respiratory depression

• Seizures

• Ventricular arrhythmias

• Other anticholinergic effects (Ileus, hyperthermia, urinary retention)

MANAGEMENT

• Supportive

• Seizures: – Benzodiazepines – Phenobarbital– Not phenytoin.

• Charcoal hemoperfusion and hemodialysis have reduced [serum] by 25-50%

METHANOL AND ETHYLENE GLYCOL

PATHOPHYSIOLOGY

• Metabolites cause the poisoning

• Ethylene glycol glycoaldehyde glycolic oxalic acids

• Methanol formaldehyde formic acid

• These cause metabolic acidosis, blindness, and cardiovascular instability

TRADITIONAL TREATMENT

• Ethanol administration to occupy binding sites on alcohol dehydrogenase and prevent generation of toxic metabolites

• Hemodialysis to eliminate parent compound

• Sodium bicarbonate to treat metabolic acidosis

FOMEPIZOLE

• Competitively inhibits alcohol dehydrogenase

• Loading dose 15 mg/kg followed by 10 mg/kg q12h for 4 doses then 15 mg/kg q12h

• Doses given intravenously over 30 minutes

FOMEPIZOLE VS ETOH

• Does not require separate preparation

• Adverse effects: HA, nausea and vertigo vs altered mental status and hypoglycemia

• Hemodialysis still useful

IRON

PATHOPHYSIOLOGY

• Excess iron is directly caustic to the GI mucosa hypovolemia and shock

• Free unbound iron:– Increases capillary permeability – Accumulates mainly in the liver and

concentrates in mitochondria disrupting oxidative phosphorylation lactic acidosis

CLINICAL STAGES

• Stage 1: GI phase (within hours)

• Stage 2: Latent (6 - 24 hours)

• Stage 3: Shock phase (variable)

• Stage 4: GI tract scarring (days to weeks)

MANAGEMENT

• WBI unless ileus, obstruction, perforation or GI hemorrhage

• Deferoxamine mesylate is a chelating agent that removes iron from tissues and free iron from plasma

• Dose: 15 mg/kg/hour

DFO INDICATIONS

1) Symptomatic patients with more than transient minor symptoms

2) Patients with lethargy, abdominal pain, hypovolemia or acidosis

3) Positive AXR

4) Any symptomatic patient with iron level > 300 ug/dl

BENZODIAZEPINES

PATHOPHYSIOLOGY

• Benzodiazepines act on the CNS by potentiating gamma-aminobutyric acid which renders the postsynaptic receptor sites to be less excitable

CLINICAL PRESENTATION

• Most commonly; ataxia, lethargy and slurred speech

• Respiratory depression and coma

• Hypotension and hypothermia are rare

MANAGEMENT

• Flumazenil – Competitive BDZ receptor antagonist

• Adult dose is 0.2 mg IV every minute until response achieved (maximum 3 mg)– Literature to support higher doses

• Pediatric dose recommendation:– 10 ug/kg for 2 doses

SULFONYLUREAS

BACKGROUND

• Sulfonylureas stimulate insulin secretion which results in hypoglycemia

• Most common are glyburide, glipizide and chlorpropamide

• Relatively uncommon poisoning but high morbidity and mortality

TRADITIONAL TREATMENT

• Routine treatments are often ineffective because they stimulate endogenous insulin secretion (dextrose and glucagon)

• Corticosteroids are unreliable

• Diazoxide (antihypertensive) is an inhibitor of insulin secretion and is effective

• Concern exists over possible hypotension

OCTREOTIDE

• Inhibits the secretion of insulin

• Stabilizes blood glucose levels and prevents rebound hypoglycemia

• Dose is 50 ug subcutaneously q8-12h

• Recommendation: Octreotide to all patients who remain hypoglycemic after a 1 g/kg dose of dextrose

ACETAMINOPHEN

PATHOPHYSIOLOGY

• Metabolized in 3 ways:– Glucuronidation– Sulfation– Via cytochrome P450 pathway to a toxic

intermediate that conjugates with glutathione

• In OD glutathione becomes depleted

MANAGEMENT

• GI decontamination

• Obtain 4 hour level

• N-Acetylcysteine (NAC):– United States: 140 mg/kg P.O. then 70 mg/kg

q4h for 17 doses (Total time 72 h)– Everywhere else: I.V. infusion x 3

(Total time: 21 h)