When is dialysis indicated for a drug overdose?

Drugs Amenable to Dialysis in Overdose Situations

Hemodialysis should be initiated for drug overdoses involving substances with specific pharmacokinetic properties (low volume of distribution, low protein binding, water solubility) and when patients demonstrate severe toxicity, metabolic derangements, or organ dysfunction despite supportive care.

Pharmacokinetic Properties That Make Drugs Amenable to Dialysis

Drugs most effectively removed by dialysis share these characteristics:

• Low molecular weight (<500 Da)
• Low volume of distribution (<1 L/kg)
• Low protein binding (<80%)
• High water solubility
• Limited endogenous clearance

Specific Drugs Requiring Dialysis in Overdose

First-Line Indications (Strong Evidence)

1. Toxic Alcohols

   • Ethylene glycol: Initiate hemodialysis when:
     • Concentration >50 mmol/L (>310 mg/dL)
     • Osmol gap >50
     • Anion gap >27 mmol/L
     • Severe acidosis, coma, seizures, or acute kidney injury 1
   • Methanol: Similar criteria as ethylene glycol
   • Treatment approach: Administer fomepizole (15 mg/kg loading dose) AND initiate hemodialysis 2

2. Lithium

   • Indications for hemodialysis:
     • Severe symptoms (altered mental status, seizures)
     • Levels >4 mEq/L in acute poisoning
     • Levels >2.5 mEq/L in chronic users with symptoms
     • Impaired kidney function with prolonged elimination half-life 3

3. Salicylates

   • Indications for hemodialysis:
     • Levels >100 mg/dL (acute) or >60 mg/dL (chronic)
     • Altered mental status
     • Severe acidosis (pH <7.2)
     • Pulmonary edema
     • Renal failure

4. Valproic Acid

   • Indications for hemodialysis:
     • Levels >1000 μg/mL
     • Coma or hemodynamic instability
     • Severe metabolic acidosis
     • Hyperammonemia 4

Second-Line Indications

1. Aminoglycosides (gentamicin, tobramycin)

   • Consider hemodialysis for extremely high levels (>100 μg/mL)
   • Particularly important in patients with renal impairment 5

2. Metformin

   • Indications: Severe lactic acidosis (pH <7.1) with elevated metformin levels

3. Theophylline

   • Levels >80-100 μg/mL (acute) or >60 μg/mL (chronic)
   • Seizures or life-threatening arrhythmias

4. Phenobarbital and other barbiturates

   • Levels >100 μg/mL with severe CNS depression
   • Hemodynamic instability

5. ACE Inhibitors (e.g., lisinopril)

   • Consider in cases with severe kidney injury, hyperkalemia, and metabolic acidosis unresponsive to conventional therapy 6

Drugs Poorly Removed by Dialysis

• Tricyclic antidepressants
• Calcium channel blockers (except diltiazem)
• Beta-blockers (except atenolol and sotalol) 7
• Benzodiazepines
• Most antipsychotics
• Digoxin

Dialysis Modality Selection

Intermittent hemodialysis is the preferred modality for drug removal in poisoning due to higher clearance rates compared to other techniques 7.

1. Intermittent Hemodialysis (IHD):

   • First-line for most drug overdoses requiring extracorporeal removal
   • Highest clearance rates
   • Use high-flux dialyzers with maximum blood and dialysate flow rates

2. Continuous Renal Replacement Therapy (CRRT):

   • Consider for hemodynamically unstable patients
   • Less efficient than IHD but may be used when IHD is unavailable
   • Higher doses (35-45 mL/kg/h) recommended for toxin removal

3. Hemoperfusion:

   • Limited availability but may be superior for highly protein-bound toxins
   • Consider for specific overdoses (e.g., theophylline) if available

4. Peritoneal Dialysis:

   • Least effective method, rarely used for toxin removal
   • Should only be considered when other modalities are unavailable 7

When to Stop Dialysis

Discontinue dialysis when:

• Drug levels fall below toxic threshold
• Clinical improvement occurs (resolution of symptoms)
• Acid-base and electrolyte abnormalities normalize
• For ethylene glycol: anion gap <18 mmol/L and concentration <4 mmol/L 1

Common Pitfalls to Avoid

1. Delayed initiation: Don't wait for confirmatory drug levels if clinical presentation strongly suggests dialyzable toxin overdose

2. Inadequate dialysis parameters: Use high blood flow rates (300-400 mL/min), high-flux dialyzers, and maximize treatment time

3. Premature discontinuation: Monitor for post-dialysis rebound in drug levels, particularly for drugs with large volume of distribution

4. Overlooking concurrent therapies: Continue antidotes (e.g., fomepizole, NAC) during dialysis with appropriate dose adjustments

5. Forgetting post-dialysis dosing: Administer medications after hemodialysis to avoid premature removal 7

Remember that dialysis is an adjunctive therapy to supportive care and specific antidotes when available. The decision to initiate dialysis should be made in consultation with nephrology and toxicology specialists whenever possible.