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The term "forced alkaline diuresis" is outdated and should be abandoned in favor of "urine alkalinization," which emphasizes that manipulating urine pH (not forcing diuresis) is the therapeutic goal. 1 Urine alkalinization (achieving urine pH ≥7.5-8.0) is first-line treatment for moderately severe salicylate poisoning in patients who do not meet criteria for hemodialysis, but has limited or no role for most other poisonings. 2, 3, 1
Historical Context and Terminology Shift
- The term "forced alkaline diuresis" has been replaced by "urine alkalinization" because the primary therapeutic mechanism is pH manipulation of urine, not the diuresis itself 1
- Terms like "forced alkaline diuresis" and "alkaline diuresis" should be discontinued from clinical practice 1
- Historical use of forced diuresis was based on indirect evidence from urinary excretion rates rather than controlled clinical trials, and its therapeutic effect was never properly validated 4
Current Role: Salicylate Poisoning
Primary Indication
Urine alkalinization is first-line treatment for moderately severe salicylate poisoning in patients who do not meet hemodialysis criteria. 2, 3, 1
Mechanism of Action
- Bicarbonate administration produces alkalemia, which minimizes salicylate passage into the central nervous system 2, 3
- It creates alkaluria (urine pH 7.5-8.0), which reduces renal tubular reabsorption and promotes renal excretion of salicylate 2, 3
- Salicylate excretion depends much more on urine pH than urine flow rate 5
When Hemodialysis Supersedes Alkalinization
Hemodialysis is the preferred treatment and should be initiated immediately for: 2, 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
- Fluid overload precluding bicarbonate administration
Critical Management Points
- Continue bicarbonate therapy between hemodialysis sessions until salicylate levels remain consistently below toxic thresholds 3
- Clinical symptoms must be resolved and patient clinically stable before discontinuing bicarbonate infusion 3
- Monitor for fluid overload as a potential complication of prolonged bicarbonate therapy 3
Limited Role: Barbiturate Poisoning
Phenobarbital
- Urine alkalinization was historically used for moderate phenobarbital poisoning because 20-25% is excreted unchanged in urine 2
- However, multiple-dose activated charcoal is superior to urine alkalinization and should be considered first-line treatment 1
- For life-threatening phenobarbital poisoning, hemodialysis with high-efficiency dialyzers is now preferred over forced alkaline diuresis 6
Short-Acting Barbiturates
- Urine alkalinization has no role for short-acting barbiturates (pentobarbital, secobarbital) as <5% is excreted unchanged 2
Other Poisonings with Potential Role
Chlorophenoxy Herbicides
- For severe 2,4-dichlorophenoxyacetic acid and mecoprop poisoning, both urine alkalinization AND high urine flow (approximately 600 mL/h) should be considered 1
- A substantial diuresis is required in addition to alkalinization for clinically important herbicide elimination 1
Limited Evidence Toxins
- Methotrexate toxicity: Urine alkalinization is employed clinically, but only one study supports its use 1
- The FDA label for methotrexate mentions "alkaline diuresis" as part of massive overdose management to prevent precipitation in renal tubules 7
- Fluoride: Volunteer studies suggest urine alkalinization increases fluoride elimination, but clinical confirmation is lacking 1
- Diflunisal: Urine alkalinization enhances excretion but is unlikely to be of clinical value in poisoning 1
Complications and Safety Considerations
Common Complications
- Hypokalemia is the most common complication but can be corrected with potassium supplements 1
- Alkalotic tetany occurs occasionally, but hypocalcemia is rare 1
- Fluid retention and biochemical disturbances can occur with aggressive fluid administration 5
Important Caveats
- Alkalemia (blood pH approaching 7.70) has been recorded, but there is no evidence that short-duration alkalemia poses risk to life in normal individuals or those with coronary/cerebral arterial disease 1
- Aspirin overdose itself causes sodium and fluid retention and may impair renal function, making forced diuresis potentially hazardous 5
- Haemodilution from forced diuresis causes a spurious fall in plasma salicylate concentration, giving a false impression of efficacy 5
What Does NOT Work
- Forced diuresis alone (without alkalinization) has little useful effect on salicylate removal 5
- Hemodialysis, hemofiltration, hemoperfusion, or plasmapheresis are not recommended for digoxin poisoning (digoxin-specific antibody fragments are preferred) 2
- Standard hemodialysis and peritoneal dialysis have not been shown to improve methotrexate elimination, though high-flux hemodialysis may be effective 7
Modern Alternatives to Consider
For Severe Poisonings
- Extracorporeal membrane oxygenation (VA-ECMO) is reasonable for persistent cardiogenic shock or cardiac arrest from poisoning not responsive to maximal treatment 2
- VA-ECMO should be started early in patients not responding well to other therapies as implementation takes time 2