How is lithium toxicity severity classified by serum lithium concentration and clinical symptoms, and what are the recommended management steps for mild, moderate, and severe toxicity?

Lithium Toxicity Classification by Severity

Lithium toxicity severity is classified into mild, moderate, and severe categories based on serum lithium levels and clinical manifestations, with hemodialysis urgently indicated for severe toxicity (serum levels ≥3.5 mEq/L with significant symptoms or any level with cardiovascular compromise), while mild toxicity often requires only dose reduction or cessation. 1, 2, 3

Severity Classification

Mild Toxicity

• Serum lithium levels: 1.5-2.0 mEq/L 2
• Clinical manifestations:
  • Fine hand tremor 2
  • Nausea and diarrhea 1, 2
  • Polyuria and mild thirst 1, 2
  • Muscular weakness 2
  • Drowsiness and lack of coordination 2
  • General discomfort 2

Moderate Toxicity

• Serum lithium levels: 2.0-3.0 mEq/L 2
• Clinical manifestations:
  • Giddiness and ataxia 2
  • Blurred vision 2
  • Tinnitus 2
  • Large output of dilute urine 2
  • Slurred speech 2
  • Confusion 2

Severe Toxicity

• Serum lithium levels: >3.0 mEq/L (particularly ≥3.5 mEq/L) 1, 2, 4
• Clinical manifestations:
  • Complex multi-organ involvement 2
  • Seizures 1, 2
  • Stupor or coma 2
  • Significant arrhythmias 1
  • Symptomatic bradycardia or advanced AV block 1
  • Refractory hypotension 1
  • Myocardial dysfunction 1
  • Acute renal failure 5

Critical Distinction: Acute vs. Chronic Toxicity

Patients with chronic toxicity (developing during maintenance therapy) typically have more severe symptoms at lower serum levels compared to acute overdose patients, who may have mild symptoms despite potentially lethal levels. 4, 6

• Acute intoxication patients frequently have milder symptoms even with levels >3.5 mEq/L 4
• Chronic intoxication patients are more likely to have severe neurologic and cardiovascular symptoms at therapeutic or slightly elevated levels 4, 6
• The severity depends on serum lithium concentration, duration of intoxication, and individual tolerance 6

Management Algorithm by Severity

Mild Toxicity Management

• Discontinue or reduce lithium dose 2, 3
• Resume treatment at lower dose after 24-48 hours 2
• Monitor serial serum lithium levels 7
• Ensure adequate hydration 1
• Monitor renal function tests frequently 7
• These symptoms usually subside with continued treatment or temporary dose reduction 2

Moderate Toxicity Management

• Discontinue lithium immediately 2
• Correct fluid and electrolyte imbalance 2
• Monitor cardiac rhythm continuously 1
• Correct electrolytes, especially potassium and magnesium 1
• Serial serum lithium measurements 7
• Consider hemodialysis if symptoms progress or levels continue rising 1

Severe Toxicity Management

Hemodialysis is the treatment of choice and should be initiated urgently in the following situations: 1, 2, 6

• Serum lithium ≥3.5 mEq/L with significant neurological or cardiovascular symptoms 1
• Any serum level with significant cardiovascular compromise (symptomatic bradycardia, advanced AV block, refractory hypotension) 1
• Severe neurologic symptoms with levels above therapeutic range, regardless of whether toxicity is acute or chronic 4

Hemodialysis protocol:

• Continue dialysis until serum lithium <1.0 mEq/L is achieved after redistribution 1, 6
• Duration typically 6-8 hours 1
• Measure lithium level 4-6 hours post-dialysis to evaluate for rebound 1
• High-flux hemodialysis membranes with bicarbonate dialysate are most effective 5
• Multiple consecutive sessions may be needed 5

Additional supportive measures for severe toxicity:

• Gastric lavage if recent ingestion 2
• Intravenous fluids for hypotension 1
• Vasopressors (norepinephrine) if hypotension persists despite fluids 1
• Avoid antiarrhythmic drugs that prolong QT interval (amiodarone, sotalol) if QT prolongation present 1
• Infection prophylaxis and regular chest X-rays 2
• Preservation of adequate respiration 2

Critical Pitfalls to Avoid

Do not use sodium chloride infusion as specific treatment - it has no specific effect on lithium excretion and can lead to hypernatremia 6

Do not rely solely on serum lithium levels to determine severity - patients sensitive to lithium may exhibit toxic signs at levels below 1.5 mEq/L, and chronic toxicity patients have more severe symptoms at lower levels than acute overdose patients 2, 4

Do not delay hemodialysis in severe cases - peritoneal dialysis is only appropriate if hemodialysis facilities are unavailable, as it is far less effective 6

Monitor for post-dialysis rebound - lithium redistributes from tissues, requiring measurement 4-6 hours after dialysis completion 1

Prevention and Monitoring

• Educate patients and caregivers about early signs of toxicity (tremor, nausea, diarrhea, polyuria) 1, 7
• Regular monitoring of serum lithium levels, especially during acute treatment phases 1, 7
• Temporarily suspend lithium during intercurrent illness, IV radiocontrast administration, bowel preparation, or prior to major surgery 1
• Avoid concomitant NSAIDs which increase lithium levels 1
• Maintain adequate hydration, especially during illness 1
• Regular monitoring of renal function and electrolytes 1, 7