Urine Alkalinization in Drug Overdose and Poisoning
Urine alkalinization (not "forced alkaline diuresis") is first-line treatment for moderately severe salicylate poisoning that does not meet hemodialysis criteria, targeting a urine pH of 7.5-8.0, while the term "forced diuresis" should be abandoned as the critical therapeutic mechanism is pH manipulation, not fluid volume. 1
Key Terminology and Mechanism
The term "forced alkaline diuresis" is outdated and should be discontinued—the correct term is urine alkalinization, which emphasizes that urine pH manipulation rather than diuresis is the primary therapeutic objective 2
Urine alkalinization works through two mechanisms: producing alkalemia (which minimizes salicylate passage into the CNS) and creating alkaluria (which reduces renal tubular reabsorption and promotes renal excretion of salicylate) 1, 3
Alkalinization is achieved by administering intravenous sodium bicarbonate to produce urine with a pH ≥7.5, ideally 7.5-8.0 1, 2
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 1
Renal excretion of salicylate depends much more on urine pH than flow rate—forced diuresis alone has little useful effect and is potentially hazardous due to fluid retention and haemodilution 4
Alkali administration alone is at least as effective, and possibly more effective, than forced alkaline diuresis in enhancing salicylate removal, without causing fluid retention or biochemical disturbances 4
When to Use Hemodialysis Instead
Hemodialysis is the preferred treatment (not urine alkalinization) for salicylate poisoning when patients have: 1, 3
- Altered mental status
- Acute respiratory distress syndrome or new hypoxemia requiring supplemental oxygen
- Severe acidemia (pH ≤7.20)
- Salicylate concentrations >7.2 mmol/L (>100 mg/dL)
- Clinical deterioration despite standard therapy
- High salicylate concentrations (>6.5 mmol/L or >90 mg/dL) with impaired kidney function
Other Poisonings Where Urine Alkalinization May Be Used
Phenobarbital poisoning: Multiple-dose activated charcoal is superior to urine alkalinization and should be considered first-line treatment, though urine alkalinization may still be used for moderate poisoning 1, 2
Chlorophenoxy herbicides (2,4-dichlorophenoxyacetic acid and mecoprop): Urine alkalinization combined with substantial diuresis (approximately 600 mL/h) should be considered in severe poisoning 2
Methotrexate overdose: Hydration and urinary alkalinization may be necessary to prevent precipitation of methotrexate and/or its metabolites in the renal tubules 5
Other drugs with enhanced elimination: Chlorpropamide, diflunisal, and fluoride show increased urine elimination with alkalinization, though clinical benefit varies 2
Drugs Where Urine Alkalinization Has NO Role
- Short-acting barbiturates (pentobarbital, secobarbital) have no benefit from urine alkalinization as less than 5% is excreted unchanged in urine 1
Monitoring and Safety Considerations
Continue bicarbonate infusion until clinical symptoms of toxicity resolve and the patient is clinically stable 3
Monitor for hypokalemia (the most common complication), which can be corrected with potassium supplements 2
Alkalotic tetany occurs occasionally, but hypocalcemia is rare 2
Fluid overload is a potential complication of prolonged bicarbonate therapy 3
Serial blood gases should track acid-base status, as pH is more important than salicylate levels for management decisions 3
Critical Pitfall to Avoid
Never suppress compensatory hyperventilation in salicylate toxicity—if intubation becomes necessary, maintain aggressive hyperventilation to prevent catastrophic acidemia, as acidemia promotes CNS salicylate accumulation 3