What are the clinical presentation, adverse effects, and management of lithium toxicity?

Lithium Toxicity: Clinical Presentation, Side Effects, and Management

Clinical Presentation of Lithium Toxicity

Lithium toxicity is closely related to serum concentrations, with toxicity risk beginning at 1.5 mEq/L and serious toxicity at levels >2.0 mEq/L, though sensitive patients may exhibit toxic signs even below 1.5 mEq/L. 1, 2

Early/Mild Toxicity (levels <2.0 mEq/L):

• Gastrointestinal symptoms: Diarrhea, nausea, vomiting 3, 2
• Neuromuscular signs: Fine hand tremor, muscular weakness, lack of coordination 2
• Renal manifestations: Polyuria-polydipsia 3, 2
• Drowsiness and general discomfort 2

Moderate Toxicity (levels 2.0-3.0 mEq/L):

• Giddiness and ataxia 2
• Blurred vision and tinnitus 2
• Large output of dilute urine 2
• Slurred speech and confusion 2

Severe Toxicity (levels >3.0 mEq/L):

• Neurological: Seizures, stupor, coma, somnolence, psychomotor retardation, incontinence 2
• Cardiovascular: Arrhythmias (including severe bradycardia and sinus node dysfunction), hypotension, peripheral circulatory collapse 3, 2, 4
• Complex multi-organ involvement affecting multiple organ systems 2

Critical distinction: Patients with chronic toxicity (developing during maintenance therapy) typically present with more severe symptoms compared to acute overdose patients, even at similar serum levels. 5 In acute intoxication, patients may have mild symptoms despite potentially lethal levels (≥3.5 mEq/L). 5

Adverse Effects and Side Effects

Cardiovascular Effects:

• Cardiac arrhythmias, including severe bradycardia requiring pacemaker placement 3, 4
• ECG changes: T-wave flattening/inversion, QT prolongation, PR interval prolongation, sinoatrial block 2, 4
• Hypotension and syncope 2, 4
• Sinus node dysfunction 2, 4

Neurological Effects:

• Tremor, muscle fasciculations, twitching, clonic movements 2
• Ataxia, choreo-athetotic movements, hyperactive deep tendon reflexes 2
• Seizures, blackout spells, vertigo, dizziness 2
• Acute dystonia, downbeat nystagmus 2
• Pseudotumor cerebri (increased intracranial pressure) which can lead to blindness if undetected 2

Renal Effects:

• Nephrogenic diabetes insipidus (polyuria, polydipsia) 3, 6
• Acute renal failure, particularly with volume depletion 7
• Albuminuria, oliguria, glycosuria 2

Endocrine Effects:

• Hypothyroidism with euthyroid goiter, lower T3 and T4 2
• Rare cases of hyperthyroidism 2

Dermatologic Effects:

• Hair thinning and alopecia 2
• Exacerbation of psoriasis 2
• Chronic folliculitis, xerosis cutis 2

Other Effects:

• Weight gain, edema of ankles or wrists 2
• Metallic taste 2
• Fatigue, lethargy, dehydration 2

Treatment of Lithium Toxicity

Immediate Management Based on Severity:

Mild Toxicity (levels <2.0 mEq/L with minimal symptoms):

• Discontinue or reduce lithium dose 2, 8
• Resume treatment at lower dose after 24-48 hours 2
• Ensure adequate hydration 3
• Monitor serum lithium levels, electrolytes, and renal function 3

Moderate to Severe Toxicity:

1. Discontinue lithium immediately 2

2. Supportive care:

   • Correct fluid and electrolyte imbalance 2
   • Maintain adequate hydration and high-normal sodium levels to facilitate lithium removal from cells 8
   • Correct electrolytes, especially potassium and magnesium 3
   • Monitor cardiovascular status for arrhythmias and hypotension 1

3. Gastric decontamination (if recent ingestion):

   • Gastric lavage may be helpful 2, 8
   • Do NOT use activated charcoal - it does not bind lithium 1

4. Enhanced elimination:

   • Urea, mannitol, and aminophylline increase lithium excretion 2
   • Sodium administration and maintenance of high-normal sodium levels 8

Hemodialysis Indications:

Hemodialysis is the definitive treatment for severe lithium toxicity and should be initiated urgently in the following situations: 3

• Serum lithium ≥3.5 mEq/L with significant neurological or cardiovascular symptoms 3
• Any lithium level with significant cardiovascular compromise: symptomatic bradycardia, advanced AV block, refractory hypotension 3
• Severe neurological symptoms (confusion, seizures, coma) regardless of level in chronic toxicity 5
• Refractory toxicity despite conservative management 3

Hemodialysis technique:

• Use high-flux membranes with bicarbonate dialysate for optimal lithium removal 7
• Continue dialysis until level <1.0 mEq/L is achieved 3
• Measure lithium level 4-6 hours post-dialysis to evaluate for rebound (redistribution from tissues) 3
• Duration typically 6-8 hours, but may require consecutive sessions 3, 7

Important caveat: In acute overdose with levels ≥3.5 mEq/L but mild symptoms, hemodialysis may not be necessary. 5 These patients often recover without dialysis or permanent sequelae. 5 However, patients with chronic toxicity and severe symptoms should receive hemodialysis even with lower levels. 5

Management of Specific Complications:

Cardiovascular complications:

• For arrhythmias: Correct electrolytes and proceed with hemodialysis 3
• Avoid antiarrhythmic drugs that prolong QT interval (amiodarone, sotalol) if QT prolongation present 3
• For hypotension: IV fluids and vasopressors (norepinephrine); urgent hemodialysis if refractory 3

Renal support:

• Hemodialysis addresses both toxicity and acute renal failure 7
• Volume repletion for dehydration-induced renal impairment 7

Prevention of Future Toxicity:

• Evaluate and address precipitating factors: dehydration, medication interactions (especially NSAIDs), renal impairment 3
• Temporarily suspend lithium during intercurrent illness, IV radiocontrast administration, bowel preparation, or prior to major surgery 3
• Avoid concomitant NSAIDs which increase lithium levels 1, 3
• Educate patients about early warning signs: fatigue, reduced urine output, dizziness, muscle weakness, diarrhea, vomiting, excessive sweating 1
• Increase fluid intake by 0.5-1 L during hot weather (beyond standard 2.5-3 L daily) 1
• Regular monitoring: lithium levels, electrolytes, renal function, thyroid function every 3-6 months once stable 9

Common Pitfalls to Avoid:

• Do not rely solely on serum lithium levels to determine severity in chronic toxicity - clinical symptoms are more important 5, 6
• Do not use activated charcoal - it is ineffective for lithium 1
• Do not delay hemodialysis in patients with severe symptoms and chronic toxicity, even if levels are <3.5 mEq/L 5
• Monitor for post-dialysis rebound - lithium redistributes from tissues, requiring level checks 4-6 hours after dialysis 3
• Recognize that cardiac manifestations are often overlooked but can be life-threatening 4