How should lithium toxicity be managed in an adult patient on lithium for bipolar disorder who presents with tremor, nausea, vomiting, diarrhea, confusion, ataxia, seizures, or cardiac arrhythmias?

Management of Lithium Toxicity

Immediate Recognition and Discontinuation

Stop lithium immediately in any patient presenting with clinical signs of toxicity—tremor, nausea, vomiting, diarrhea, confusion, ataxia, or seizures—regardless of serum lithium level. 1, 2, 3, 4

Clinical lithium toxicity can occur even at therapeutic serum levels (0.6–1.2 mEq/L), and treatment decisions must be based on clinical presentation rather than laboratory values alone. 3, 4 Patients sensitive to lithium may exhibit toxic signs at levels below 1.5 mEq/L, and diarrhea, vomiting, drowsiness, muscular weakness, and lack of coordination can occur at levels below 2.0 mEq/L. 2

Severity-Based Treatment Algorithm

Mild Toxicity (Fine tremor, nausea, mild GI symptoms, lithium <2.5 mEq/L)

• Discontinue or reduce lithium dose 5
• Ensure adequate hydration with normal saline IV to maintain urine output 2500–3000 mL/day 2
• Correct electrolyte abnormalities, particularly sodium, potassium, and magnesium 1
• Monitor serum lithium levels every 4–6 hours until declining 6
• Monitor renal function (BUN, creatinine) frequently 6

Moderate Toxicity (Coarse tremor, confusion, ataxia, significant GI symptoms)

• Discontinue lithium immediately 1, 2
• Aggressive IV hydration with normal saline 5
• Sodium administration and maintenance of high-normal sodium levels may reduce intracellular lithium and severity of toxicity 5
• Consider gastric lavage if acute ingestion within 1–2 hours 5
• Serial lithium levels every 2–4 hours 6
• Evaluate for precipitating factors: dehydration, medication interactions (NSAIDs, ACE inhibitors, diuretics), renal impairment 1, 2

Severe Toxicity (Seizures, cardiac arrhythmias, severe confusion/coma, lithium ≥3.5 mEq/L, or any level with cardiovascular compromise)

Hemodialysis is the definitive treatment for severe lithium intoxication and should be initiated urgently. 1, 7

• Indications for hemodialysis: 1

  • Serum lithium ≥3.5 mEq/L with significant neurological or cardiovascular symptoms
  • Any lithium level with symptomatic bradycardia, advanced AV block, or refractory hypotension
  • Severe neurological symptoms (seizures, coma) regardless of level
  • Renal failure preventing lithium elimination

• Use high-flux hemodialysis membranes with bicarbonate dialysate for maximum lithium clearance 8, 7

• Continue hemodialysis until lithium level <1.0 mEq/L after redistribution (generally 6–8 hours) 1

• Measure lithium level 4–6 hours post-dialysis to evaluate for rebound elevation 1

• Multiple consecutive hemodialysis sessions may be required 8

Management of Specific Complications

Cardiac Arrhythmias

• Correct electrolytes (potassium, magnesium) as primary treatment 1
• Avoid antiarrhythmic drugs that prolong QT interval (amiodarone, sotalol) if QT prolongation present 1
• Hemodialysis is the definitive treatment 1

Hypotension

• IV fluids and vasopressors (norepinephrine) 1
• Urgent hemodialysis if hypotension persists despite support 1

Seizures

• Standard anticonvulsant therapy (benzodiazepines first-line) 1
• Hemodialysis to remove lithium 1

Acute Renal Failure

• Often reversible with hemodialysis and volume repletion 8
• Hemodialysis both treats toxicity and supports renal function 8

Critical Pitfalls to Avoid

• Never rely solely on serum lithium levels—clinical toxicity can occur at "therapeutic" levels, particularly in chronic toxicity or patients with renal impairment 3, 4
• Do not delay hemodialysis in severe cases waiting for conservative measures to work; lithium's narrow therapeutic index and potential for irreversible neurological damage demand aggressive intervention 1, 7
• Avoid NSAIDs, ACE inhibitors, and diuretics during and after toxicity, as these increase lithium levels 1, 2
• Monitor for post-dialysis rebound—lithium redistributes from intracellular compartments, and levels may rise again 4–6 hours after dialysis 1, 8
• Peritoneal dialysis and continuous arteriovenous hemofiltration are inferior to hemodialysis for lithium removal 7

Post-Toxicity Management

• Regular monitoring of lithium levels, electrolytes, and renal function to prevent recurrence 1, 6
• Patient and caregiver education about early signs of toxicity (tremor, nausea, diarrhea, polyuria) 1, 6
• Temporarily suspend lithium during intercurrent illness, IV radiocontrast administration, bowel preparation, or major surgery 1
• Maintain adequate hydration (2500–3000 mL/day) and normal salt intake 2
• Consider alternative mood stabilizers (valproate, atypical antipsychotics) if recurrent toxicity or inability to maintain therapeutic window 1

Special Considerations

• Chronic kidney disease: Patients with stage 3 CKD or worse are at higher risk for toxicity even at normal levels 3
• Elderly patients: Lower lithium doses and more frequent monitoring required due to decreased renal clearance 2
• ECT: Discontinue lithium during electroconvulsive therapy if clinically possible, as concurrent use is associated with acute brain syndrome 6