What is the treatment approach for drug toxicity requiring dialysis?

Treatment Approach for Drug Toxicity Requiring Dialysis

Intermittent hemodialysis is the preferred extracorporeal treatment modality for most dialyzable drug toxicities, with specific indications and cessation criteria varying by toxin. 1, 2, 3

General Principles of Extracorporeal Treatment Selection

Primary Modality Choice

• Intermittent hemodialysis should be used as first-line extracorporeal therapy when available for dialyzable poisons including salicylates, toxic alcohols (ethylene glycol, methanol), lithium, long-acting barbiturates, and hydrophilic beta-blockers (atenolol, sotalol). 1, 2, 3
• High-flux dialyzers with the largest available surface area provide superior clearance and should be selected over low-flux membranes. 2
• Continuous renal replacement therapy (CRRT) is the preferred alternative when intermittent hemodialysis is unavailable or cannot be initiated quickly enough. 1, 3
• Hemoperfusion can be used as a third-line option for specific toxins (barbiturates, highly protein-bound beta-blockers) when hemodialysis and CRRT are unavailable. 1

Optimization Parameters

• Maximize blood flow rates to 300-400 mL/min to enhance toxin clearance. 2
• Use higher dialysate/effluent flow rates to maintain concentration gradients. 1, 2
• Lower dialysate temperature to minimize hemodynamic compromise in unstable patients. 1, 2
• Prime the extracorporeal circuit and use dialysate with appropriate electrolyte concentrations (avoid low potassium, calcium, magnesium) to reduce dysrhythmia risk. 1
• Minimize net ultrafiltration in hemodynamically unstable patients not requiring volume removal. 1

Specific Drug Toxicities

Beta-Blocker Toxicity (Atenolol, Sotalol)

• Intermittent hemodialysis is strongly recommended for severe atenolol or sotalol poisoning requiring extracorporeal treatment. 1
• Indications include refractory bradycardia, hypotension despite vasopressors, or need for extracorporeal life support (ECLS). 1
• For sotalol specifically, maintain serum magnesium >1 mmol/L and potassium 4.5-5 mmol/L during dialysis to prevent torsades de pointes. 1, 2
• Magnesium can be added to dialysate or given intravenously to offset elimination during treatment. 1
• Cease dialysis based on clinical improvement (appropriate heart rate/blood pressure, weaning vasopressors, sustained cessation of torsades), not solely on drug concentrations. 1

Barbiturate Toxicity

• Intermittent hemodialysis is recommended for severe long-acting barbiturate (phenobarbital) poisoning. 1
• Indications include: prolonged coma, shock after fluid resuscitation, toxicity persisting despite multiple-dose activated charcoal (MDAC), rising serum concentrations despite MDAC, or respiratory depression requiring mechanical ventilation. 1
• Hemoperfusion or CRRT are acceptable alternatives if hemodialysis is unavailable. 1
• Short-acting barbiturates (pentobarbital) are less amenable to extracorporeal removal due to larger volume of distribution and higher lipid solubility. 1
• Stop dialysis when clinical improvement is apparent, not based on target concentrations. 1

Ethylene Glycol Toxicity

• Intermittent hemodialysis is strongly recommended when glycolate concentration >12 mmol/L, anion gap >27 mmol/L, or severe clinical features present (coma, seizures, acute kidney injury). 1, 3
• Conditional recommendation for hemodialysis when glycolate 8-12 mmol/L or anion gap 23-27 mmol/L. 1, 3
• CRRT is preferred over hemodialysis if marked brain edema is present (causes less intracranial pressure elevation) or if CRRT can be initiated faster. 1
• Increase fomepizole dosing frequency to every 4 hours during hemodialysis (from standard every 12 hours) as it is dialyzable. 3
• Continue dialysis until anion gap normalizes and clinical improvement occurs, not based solely on ethylene glycol concentration. 1, 3

Lithium Toxicity

• Hemodialysis is indicated for persistent shock after fluid resuscitation, significant renal dysfunction (GFR <60 mL/min/1.73 m²), or respiratory failure requiring mechanical ventilation. 4, 5
• Intermittent hemodialysis is preferred over CRRT due to higher efficacy. 4
• The FDA label confirms hemodialysis is "an effective and rapid means of removing the ion from the severely toxic patient." 5
• Monitor lithium levels every 2-4 hours until stabilization. 4
• Maintain potassium >4 mEq/L during treatment. 4

Methotrexate Toxicity

• Acute intermittent hemodialysis with a high-flux dialyzer should be used for methotrexate toxicity when indicated. 6
• The FDA label specifically recommends this modality as a corrective measure for serious toxicity. 6
• More frequent monitoring is indicated during periods of increased risk of elevated methotrexate levels (e.g., dehydration). 6
• Leucovorin calcium should be used in conjunction with dialysis. 6

Critical Pitfalls to Avoid

Timing and Modality Errors

• Never delay hemodialysis while attempting less effective modalities (urinary alkalinization alone, peritoneal dialysis) in severe poisonings with clear indications. 2, 3
• Do not use peritoneal dialysis when hemodialysis is available—it provides clearance ≤10 mL/min versus >100 mL/min with hemodialysis for many toxins. 2
• Avoid assuming CRRT is always better tolerated than intermittent hemodialysis in hemodynamically unstable patients not requiring net ultrafiltration. 1

Cessation Criteria Errors

• Do not cease dialysis based solely on toxin concentration—clinical improvement should guide cessation for most poisonings. 1, 2
• Do not stop dialysis for salicylate poisoning based on clinical improvement alone when concentrations remain >7.2 mmol/L. 3
• For ethylene glycol, do not assume adequate treatment based solely on improving pH; continue until anion gap normalizes. 3

Medication Management Errors

• Adjust antidote dosing during dialysis for dialyzable antidotes (fomepizole, ethanol). 3
• Ensure appropriate electrolyte concentrations in dialysate to minimize dysrhythmias, particularly for cardiotoxic drugs. 1, 2
• Do not forget to monitor and replace magnesium during sotalol dialysis. 1

Special Population Considerations

• Consider lower toxin thresholds for dialysis in children receiving ethanol (to minimize ethanol adverse effects) and pregnant patients (to reduce antidote exposure, though dialysis also carries risks). 1
• Use relatively low doses and close monitoring in elderly patients due to diminished hepatic/renal function. 6