Activated charcoal

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Related FACEM curriculum (2022) learning objectives:

• ME 3.8.1.6(e) Principles of management of toxicological presentations including: Indications for antidotes
• ME 3.8.2.4 Identify the appropriate antidote or antivenom.

• AC is a nonspecific adsorbent, crucial for managing poisonings and overdoses.
• Utilized after evaluating risks and benefits considering patient-specific factors.
• Benefits include preventing absorption and aiding elimination by interfering with enterohepatic/enteroenteric recirculation.
• Risks include potential vomiting and aspiration pneumonitis.

History

• Known for over 200 years as an effective adsorbent.
• 1773: Scheele first used charcoal for gas absorption.
• 1791: Lowitz used it with colored liquids.
• 1811: Bertrand survived ingestion of toxic mercuric chloride and arsenic trioxide mixed with charcoal.
• 1830: Touery ingested lethal doses of strychnine mixed with charcoal without ill effects.
• 1834: Holt used charcoal for mercury bichloride poisoning.
• 1940s: Andersen proved AC’s broad-spectrum adsorbent properties.

Pharmacology

Chemistry and Preparation

• Created by pyrolyzing carbonaceous materials (wood, coconut, etc.) and activating with high heat (600°–900°C) and oxidizing agents (e.g., steam).
• Results in a high surface area (~800–1,200 m²/g).

Mechanism of Action

• Adsorption is via hydrogen bonding, ion–ion, dipole interactions, and van der Waals forces.
• Most effective when xenobiotics are dissolved and nonionized.

Pharmacokinetics

• Inert and unabsorbed; GI transit affected by factors such as the type and amount of ingested substance, hydration, and perfusion.
• Transit time: Varies between 17.3–29.3 hours in studies.
• Sorbitol addition: Speeds gastric emptying and transit times.

Pharmacodynamics

• Adsorptive properties depend on surface area and pore size (~10–1,000 Å), with pores 10–20 Å being most effective for moderate-weight molecules (100–800 Da).
• Adsorption is pH-dependent: weak bases adsorbed best at basic pHs; weak acids at acidic pHs.
• Nonpolar, poorly water-soluble substances are better adsorbed than polar ones.
• Efficacy: Best when AC-to-drug ratio is at least 10:1.
• Adsorption starts within ~1 minute but takes 10–25 minutes to reach equilibrium.
• Early administration crucial for rapidly absorbed substances.
• Desorption can occur due to pH changes, leading to possible reabsorption.

Concomitant Administration with Cathartics

• Single-dose cathartics (e.g., sorbitol) can be used but not repeatedly due to risks of electrolyte imbalance.
• Whole-bowel irrigation (WBI) may reduce AC’s effectiveness, especially with certain drugs. WBI can synergize with AC for specific cases like verapamil.

Role of Activated Charcoal in Gastrointestinal Decontamination

Dosing and Administration

• Single-dose AC: 1 g/kg body weight or 10:1 ratio to xenobiotic; typical dose 50-100 g in adults.
• Slurry: 1:8 ratio with water or cola.
• Prehospital use: May expedite treatment but carries risks.
• Hospital use: Enhance palatability with agents like syrups, ice cream; efficacy may be limited.
• Multiple-Dose Administration
  • Initial dose: 1 g/kg or 10:1 ratio to xenobiotic.
  • Subsequent doses: 0.5 g/kg (25-50 g) every 4-6 hours for 12-24 hours.
  • Continuous use: Nasogastric option; assess risks.

Single-Dose Activated Charcoal (SDAC)

• Efficacy:
  • Prospective studies hard to conduct due to exclusions (e.g., multiple agents, sustained-release).
  • Minimal benefits in asymptomatic patients; limited improvements in symptomatic cases.
• Clinical Studies:
  • No significant effect in overdoses of benzodiazepines, APAP, SSRIs regarding mortality, ICU use, etc.
  • No outcome difference when comparing SDAC alone to SDAC with gastric emptying (except within 1 hour of ingestion).
• Meta-analysis Findings:
  • Effective if administered within 240 minutes of exposure, especially with 10:1 ratio.
• Pharmacokinetic Studies:
  • Reduces absorption of APAP, oxycodone, lamotrigine, oxcarbazepine within optimal timeframe (30 mins to 3 hours post-ingestion).
• Specific Overdose Benefits:
  • Escitalopram: 31% absorption reduction, 35% lower QT prolongation risk for high doses.
  • Venlafaxine: Fewer seizures when paired with whole-bowel irrigation (WBI).
  • Quetiapine: Lower intubation rates in large ingestions.
  • Factor Xa Inhibitors: Reduced AUC, extended half-life with delayed use.
• Limitations:
  • No clear benefit in organic phosphorus/carbamate poisonings.
  • Reduced efficacy with substances not adsorbed by AC or combined decontamination techniques (e.g., lavage).
• Updated Recommendations:
  • Expanded "window" supports AC use past 1 hour, even with antidotes like APAP.

Multiple-Dose Activated Charcoal (MDAC)

• Function:
  • Reduces absorption of slowly absorbed agents; enhances elimination of already absorbed substances.
• Mechanisms of Action:
  • Effective for delayed dissolution (e.g., bezoars), prolonged-release forms, impaired GI motility, enterohepatic circulation.
• Historical and Experimental Evidence:
  • Initial 1982 study on IV phenobarbital in healthy volunteers showed MDAC's role in clearance.
  • Concept of “gastrointestinal dialysis”: AC acts as an "infinite sink," pulling drugs from blood into GI tract.
• Clinical Applications:
  • Effective for amitriptyline, cyclosporine, carbamazepine, dapsone, digitoxin, phenobarbital, theophylline, etc.
  • Limited evidence linking xenobiotic properties to MDAC effectiveness
• Studies and Results:
  • MDAC reduced half-lives for drugs with long plasma half-lives.
  • Theophylline/aminophylline overdoses showed reduced half-lives.
  • Neonatal hyperbilirubinemia: MDAC plus phototherapy more effective than phototherapy alone.
  • Phenobarbital overdoses: MDAC lowered half-life but no major clinical endpoint changes.
  • Shown to reduce serum phosphate in haemodialysis patients.
  • Sri Lankan Study:
    • Fewer deaths, life-threatening dysrhythmias in yellow oleander seed poisoning.
    • No mortality rate reduction in broader self-poisoned patient cohort.
• Clinical Decision Considerations:
  • Risk–benefit analysis based on patient factors (e.g., ingested amount, formulation, time, coingestants, severity).
  • Best when xenobiotic is in blood, low protein binding, and slow endogenous clearance.
  • Prioritise clinical interventions over decontamination in severe cases.
• Complications: Increased with MDAC; risk of diarrhoea, vomiting, ileus, obstruction, reduced serum levels.
  • 0.6% aspiration, 0% GI obstruction, 6% hypernatremia, 3.1% hypermagnesemia.
  • Electrolyte risk: Potentially severe, especially in children.

Adverse Effects and Safety Issues

• Contraindications: GI perforation, need for endoscopy.
• Aspiration risk: Requires airway assessment and management.
• GI motility: Ensure normal peristalsis; delay if compromised.
• Side effects:
  • Common: Emesis, constipation, diarrhoea.
  • Serious: Pulmonary aspiration, ARDS, bronchiolitis obliterans, peritonitis, intestinal obstruction, pseudo-obstruction.
• Aspiration incidence: 4%-25%; 1.6% in overdosed patients.
• Sorbitol caution: Avoid in fructose intolerance.

Pregnancy and Lactation

• Category: Safety undetermined; benefits should outweigh risks.
• Vomiting risk: Higher in pregnancy.
• Teratogenicity: No risk in animal studies.
• Lactation: No evidence of excretion in breast milk.

Formulation

• Types: Ready-to-use suspensions (15-50 g) at 208 mg/mL concentration.
• Sorbitol mix: Some preparations include sorbitol (400 mg/mL).
• Preparation: Mix non-premixed AC 1:8 with liquid (e.g., water, cola).
• **### Related Formulations
  • Porous carbon microspheres (e.g., AST-120): used to adsorb uremic toxins and slow chronic kidney disease progression.