What is the role of forced alkaline diuresis in treating drug overdose or poisoning?

Forced Alkaline Diuresis in Drug Overdose and Poisoning

Direct Answer

The term "forced alkaline diuresis" is outdated and should be abandoned in favor of "urine alkalinization," which emphasizes pH manipulation rather than aggressive fluid administration—the latter adds unnecessary risk without additional benefit. 1

Current Terminology and Rationale

• Urine alkalinization is the preferred term, defined as administration of intravenous sodium bicarbonate to achieve urine pH ≥7.5, with a target range of 7.5-8.0 2, 1
• The mechanism involves two distinct effects: alkalemia minimizes drug passage into the central nervous system, while alkaluria reduces renal tubular reabsorption and promotes renal excretion 2
• The forced diuresis component is unnecessary and potentially harmful, as it causes fluid retention, haemodilution (giving false impression of efficacy), and biochemical disturbances without enhancing drug elimination 3

Primary Indication: Salicylate Poisoning

The American College of Emergency Physicians recommends urine alkalinization as first-line treatment for moderately severe salicylate poisoning in patients who do not meet hemodialysis criteria. 2

• Volunteer and clinical studies support this as the primary indication 1
• Urine alkalinization alone is at least as effective—and possibly more effective—than forced alkaline diuresis for salicylate removal 3
• Renal excretion of salicylate depends much more on urine pH than flow rate 3

When to Use Hemodialysis Instead

Hemodialysis is preferred for salicylate poisoning when patients have: 2

• Altered mental status
• Acute respiratory distress syndrome
• Severe acidemia
• Salicylate concentrations >7.2 mmol/L
• Clinical deterioration despite standard therapy

Other Specific Poisonings

Phenobarbital Poisoning

• Multiple-dose activated charcoal is superior to urine alkalinization and should be considered first-line treatment 2
• Urine alkalinization may still be used for moderate poisoning, but is not the preferred approach 2
• Modern high-efficiency hemodialysis with high blood flow rates achieves excellent phenobarbital clearance and should be considered for life-threatening cases 4
• Urine alkalinization has no role for short-acting barbiturates (pentobarbital, secobarbital) as <5% is excreted unchanged in urine 2

Chlorophenoxy Herbicides (2,4-D and Mecoprop)

• Both urine alkalinization AND substantial diuresis (approximately 600 mL/h) are required for clinically important herbicide elimination in severe poisoning 2, 1
• This is one of the few scenarios where high urine flow remains relevant 1

Methotrexate Toxicity

• The FDA label specifically recommends hydration and urinary alkalinization to prevent precipitation of methotrexate and its metabolites in renal tubules in cases of massive overdosage 5
• Leucovorin administration should begin as promptly as possible 5
• Glucarpidase is indicated for toxic methotrexate concentrations with delayed clearance due to impaired renal function 5
• Only one clinical study supports urine alkalinization use, though it is employed clinically 1

Other Drugs with Enhanced Elimination

Urine alkalinization increases elimination of: 1

• Chlorpropamide (though supportive care with dextrose is usually adequate)
• Diflunisal (unlikely to be clinically valuable)
• Fluoride (supported by volunteer studies, not yet confirmed clinically)

Sodium Channel Blocker Poisoning: Important Distinction

Sodium bicarbonate boluses are used for sodium channel blocker poisoning (tricyclic antidepressants, class Ia/Ic antiarrhythmics), but NOT for alkalinization purposes. 6, 2

• The mechanism here is sodium loading and pH correction to treat hypotension and dysrhythmia 6
• Target serum pH should not exceed 7.50-7.55 to avoid iatrogenic harm 6
• This is a different therapeutic goal than urine alkalinization for enhanced renal excretion 2

Safety Considerations and Monitoring

Common Complications

• Hypokalemia is the most common complication and requires potassium supplementation 1
• Alkalotic tetany occurs occasionally, but hypocalcemia is rare 1
• Monitor and treat hypokalemia during alkalemia therapy 6

Safety Limits

• Avoid extremes of hypernatremia (serum sodium should not exceed 150-155 mEq/L) 6
• Avoid extremes of alkalemia (serum pH should not exceed 7.50-7.55) 6
• Blood pH values approaching 7.70 have been recorded, but there is no evidence that relatively short-duration alkalemia poses risk to life in normal individuals or those with coronary/cerebral arterial disease 1

Clinical Pitfalls to Avoid

• Do not pursue aggressive fluid loading ("forced diuresis") as this causes fluid retention and biochemical disturbances without benefit 1, 3
• Do not confuse sodium bicarbonate use for sodium channel blocker poisoning with urine alkalinization for enhanced renal excretion 2
• Do not use urine alkalinization as first-line for phenobarbital when multiple-dose activated charcoal is available 2
• Haemodilution from excessive fluids causes spurious falls in plasma drug concentrations, giving false impression of treatment efficacy 3