Management of Drug Overdose

Indications for Hemodialysis

• Hemodialysis is indicated for toxic alcohols (ethylene glycol and methanol) with high concentration, osmol gap, anion gap, severe acidosis, coma, seizures, or acute kidney injury, as recommended by the American College of Medical Toxicology and the American College of Emergency Physicians 1, 2, 3
• Hemodialysis is recommended for lithium poisoning with severe symptoms, high levels, or impaired kidney function, according to the American Academy of Clinical Toxicology 1
• Hemodialysis is indicated for salicylate poisoning with high levels, altered mental status, severe acidosis, pulmonary edema, or renal failure, as suggested by the American College of Medical Toxicology 1
• Hemodialysis is recommended for valproic acid poisoning with high levels, coma, hemodynamic instability, severe metabolic acidosis, or hyperammonemia, according to the European Association of Poison Centres and Clinical Toxicologists 1

• The following criteria are used to initiate hemodialysis:

  Criteria	Value
  Ethylene glycol/methanol concentration	>50 mmol/L (>310 mg/dL)
  Osmol gap	>50
  Glycolate concentration	>12 mmol/L
  Anion gap	>27 mmol/L

Dialysis Modalities

• Intermittent hemodialysis is the preferred modality for drug removal in poisoning due to higher clearance rates, as recommended by the American Society of Nephrology and the European Renal Association 1, 2, 4
• Continuous Renal Replacement Therapy (CRRT) is considered for hemodynamically unstable patients, with higher doses recommended for toxin removal, according to the European Renal Association 5
• Hemoperfusion may be superior for highly protein-bound toxins and is considered for specific overdoses, such as theophylline, if available, as suggested by the International Society of Nephrology 5
• Peritoneal dialysis is the least effective method and should only be considered when other modalities are unavailable, as stated by the National Kidney Foundation 5

Management of Dialysis

• Hemodialysis should be discontinued when drug levels fall below toxic threshold, clinical improvement occurs, or acid-base and electrolyte abnormalities normalize, as recommended by the American College of Physicians 6
• Delayed initiation of dialysis should be avoided if clinical presentation strongly suggests dialyzable toxin overdose, as advised by the American Academy of Emergency Medicine 6
• Inadequate dialysis parameters, such as low blood flow rates or inadequate treatment time, should be avoided, and high-flux dialyzers should be used, as recommended by the American Society of Nephrology 6
• Premature discontinuation of dialysis should be avoided, and post-dialysis rebound in drug levels should be monitored, particularly for drugs with large volume of distribution, as suggested by the European Association of Poison Centres and Clinical Toxicologists 6
• Cessation criteria for hemodialysis include anion gap <18 mmol/L, ethylene glycol concentration <4 mmol/L, and acid-base abnormalities corrected, as recommended by the Critical Care society 2

Concurrent Therapies and Post-Dialysis Care

• Antidotes, such as fomepizole and NAC, should be continued during dialysis with appropriate dose adjustments, as recommended by the American College of Medical Toxicology 6
• Post-dialysis dosing of medications should be administered after hemodialysis to avoid premature removal, as advised by the American Society of Health-System Pharmacists 6
• Fomepizole is the first-line antidote for ethylene glycol poisoning, with a loading dose of 15 mg/kg IV over 30 minutes, and maintenance dose of 10 mg/kg IV every 12 hours for 4 doses, then 15 mg/kg every 12 hours, until ethylene glycol levels are <20 mg/dL and the patient is asymptomatic with normal pH, as recommended by the Critical Care society and the 2023 EXTRIP guidelines 2, 7
• Fomepizole dosing should be increased to every 4 hours during hemodialysis, and a continuous infusion at 1 mg/kg/h may be required to compensate for its elimination, as recommended by the Critical Care society 2
• Ethanol is an alternative treatment if fomepizole is unavailable, but it has less predictable efficacy and requires more intensive monitoring, according to the Critical Care society 2
• Poor prognostic indicators for ethylene glycol poisoning include delayed presentation, severe acidosis at presentation, elevated glycolate levels, and pre-existing renal dysfunction, as stated by the Critical Care society and the American College of Medical Toxicology 2
• Supportive care should include IV fluids, correction of electrolyte abnormalities, management of metabolic acidosis, and monitoring for hypoglycemia, according to the American College of Medical Toxicology and the European Renal Association 4, 2
• Sodium bicarbonate supplementation should be continued until tubular function recovers, with close monitoring of electrolytes, especially potassium, calcium, and phosphate, as recommended by the American College of Medical Toxicology 2
• Activated charcoal is ineffective for these poisonings, as stated by the American College of Medical Toxicology and the European Renal Association 4, 2