How should lithium toxicity be identified and managed in a patient on lithium who presents with gastrointestinal upset, tremor, confusion, ataxia, seizures, or cardiac arrhythmias, including criteria for hemodialysis versus supportive care?

Lithium Toxicity: Identification and Management

Clinical Recognition and Severity Assessment

Lithium toxicity severity correlates with both serum levels and clinical presentation, with chronic toxicity being far more dangerous than acute overdose—patients with chronic toxicity require aggressive management even at lower serum levels, while acute overdose patients may tolerate levels >3.5 mEq/L with minimal symptoms. 1

Early Signs (Levels 1.5-2.0 mEq/L)

• Gastrointestinal: Diarrhea, nausea, vomiting 2
• Neurological: Fine tremor, muscular weakness, lack of coordination 2
• Renal: Polyuria-polydipsia 3
• General: Drowsiness, mild thirst 2

Moderate-to-Severe Toxicity (Levels >2.0 mEq/L)

• Neurological: Confusion, ataxia, giddiness, blurred vision, tinnitus, slurred speech 2
• Severe neurological: Seizures, stupor, coma, blackout spells 2
• Cardiovascular: Arrhythmias (including sinus bradycardia, advanced AV block), hypotension, peripheral circulatory collapse 3, 4
• Renal: Large output of dilute urine, oliguria 2

Critical Distinction: Acute vs. Chronic Toxicity

• Acute overdose: Patients frequently have mild symptoms despite potentially lethal levels (>3.5 mEq/L) and may not require hemodialysis 1
• Chronic toxicity: Develops during maintenance therapy, presents with more severe symptoms at lower serum levels, and carries higher risk of permanent neurological sequelae 1, 5

Immediate Management Algorithm

Step 1: Discontinue Lithium and Assess Severity

• Stop lithium immediately in all cases of suspected toxicity 2
• Obtain serum lithium level (drawn 8-12 hours post-dose if possible) 6
• Assess for precipitating factors: dehydration, NSAID use, renal impairment, intercurrent illness 3
• Check electrolytes (especially potassium and magnesium), renal function, and ECG 3

Step 2: Supportive Care (All Patients)

• Intravenous fluid resuscitation to correct dehydration and enhance renal lithium clearance 2
• Continuous cardiac monitoring for arrhythmias 3
• Correct electrolyte abnormalities, particularly potassium >4 mEq/L and magnesium 3
• Do NOT use activated charcoal—it does not bind lithium 7
• Consider gastric lavage only in acute ingestion presenting within 1-2 hours 2

Step 3: Hemodialysis Decision-Making

Hemodialysis is the definitive treatment for severe lithium toxicity and should be initiated urgently based on clinical presentation rather than serum level alone. 3

Absolute Indications for Hemodialysis:

• Serum lithium ≥3.5 mEq/L with ANY significant neurological symptoms (confusion, seizures, altered mental status) 3
• Severe cardiovascular manifestations at any level: symptomatic bradycardia, advanced AV block, refractory hypotension 3
• Chronic toxicity with severe symptoms regardless of serum level 1
• Refractory toxicity despite aggressive supportive care 3

Relative Indications (Clinical Judgment Required):

• Serum lithium 2.5-3.5 mEq/L in chronic toxicity with moderate symptoms 5
• Impaired renal function (GFR <30 mL/min) limiting lithium clearance 5
• Worsening clinical status despite supportive measures 5

Hemodialysis Protocol:

• Continue dialysis until serum lithium <1.0 mEq/L 3
• Duration typically 6-8 hours 3
• Recheck lithium level 4-6 hours post-dialysis to assess for rebound (redistribution from tissues) 3
• Repeat hemodialysis if rebound occurs with persistent symptoms 5

Step 4: Management of Specific Complications

Cardiac Arrhythmias:

• Correct electrolytes first (potassium, magnesium) 3
• Avoid QT-prolonging antiarrhythmics (amiodarone, sotalol) if QT prolongation present 3
• Consider temporary pacing for symptomatic bradycardia or advanced AV block 3, 4
• Hemodialysis is primary treatment for lithium-induced arrhythmias 3

Hypotension:

• Intravenous fluids as first-line 3
• Vasopressors (norepinephrine) if fluid-refractory 3
• Urgent hemodialysis if hypotension persists despite support 3

Seizures:

• Standard anticonvulsant therapy (benzodiazepines) 2
• Hemodialysis for definitive treatment 3

Critical Pitfalls to Avoid

Common Errors:

• Relying solely on serum lithium level without considering chronicity—chronic toxicity is more dangerous at lower levels 1, 5
• Delaying hemodialysis in chronic toxicity waiting for higher levels—severe symptoms warrant dialysis regardless of level 1
• Assuming acute overdose requires dialysis at levels >3.5 mEq/L—many tolerate this well with supportive care alone 1
• Using activated charcoal—completely ineffective for lithium 7
• Failing to check post-dialysis rebound—lithium redistributes from tissues requiring repeat level measurement 3

Risk of Permanent Neurological Damage:

• Irreversible cerebellar dysfunction (ataxia, dysarthria) can occur, particularly with chronic toxicity 8
• Risk appears lower in uncomplicated acute poisoning 5
• Early recognition and aggressive treatment reduce this risk 8

Post-Acute Management

Before Restarting Lithium:

• Identify and correct precipitating factors 3
• Ensure adequate hydration status 3
• Discontinue NSAIDs permanently if possible 3, 7
• Verify renal function has returned to baseline 3
• Consider dose reduction, especially if GFR <60 mL/min 7

Prevention of Recurrence:

• Regular monitoring: Lithium levels, renal function, electrolytes, thyroid function every 3-6 months 6
• Patient education on early toxicity signs and when to seek care 3
• Temporarily suspend lithium during intercurrent illness, dehydration, or before major surgery 3, 7
• Increase fluid intake by 0.5-1 L during hot weather 7