What is the treatment approach for a patient with suspected lithium toxicity, particularly one with a history of bipolar disorder and potential impaired renal function?

Treatment of Lithium Toxicity

Immediate Management Based on Severity

For suspected lithium toxicity, immediately discontinue lithium, assess severity through serum lithium levels and clinical symptoms, initiate supportive care with IV fluids and electrolyte correction, and proceed urgently to hemodialysis for severe cases (serum lithium ≥3.5 mEq/L with significant symptoms, cardiovascular compromise, or refractory toxicity despite conservative management). 1, 2

Recognition of Toxicity Severity

Early/Mild Toxicity:

• Clinical manifestations include tremor, nausea, diarrhea, and polyuria-polydipsia 1
• These symptoms can often be managed by cessation or reduction of lithium dosage, with resumption at a lower dose after 24-48 hours 2, 3

Moderate to Severe Toxicity:

• Presents with confusion, ataxia, lethargy, muscle weakness, or altered consciousness 4, 5
• Cardiovascular manifestations include arrhythmias, ECG alterations, hypotension, myocardial dysfunction, symptomatic bradycardia, and advanced AV block 1
• Can progress to seizures, cardiac arrest, prolonged sinus arrest, and coma 6, 4
• Severity of symptoms does not always correlate with serum lithium levels, particularly in chronic versus acute intoxication 1

Initial Stabilization and Supportive Care

Immediate interventions include:

• Gastric lavage if presentation is within hours of acute ingestion 2, 3
• Aggressive IV fluid resuscitation to correct dehydration and maintain adequate hydration 1, 2
• Correction of fluid and electrolyte imbalances, particularly potassium and magnesium 1, 2
• Maintenance of high-normal sodium levels, which may reduce intracellular lithium accumulation in excitable cells 3
• Regulation of kidney function and monitoring of renal parameters 2

For cardiovascular complications:

• Correct electrolytes (especially potassium and magnesium) as primary treatment for arrhythmias 1
• Avoid antiarrhythmic drugs that prolong QT interval (amiodarone, sotalol) if QT prolongation is present 1
• Use IV fluids and vasopressors (norepinephrine) for hypotension 1
• Insert temporary pacemaker for severe sinus bradycardia or advanced AV block 6
• Perform chest compression and manual ventilation for cardiac arrest 6

Hemodialysis Indications and Protocol

Hemodialysis is the definitive treatment for severe lithium toxicity and should be initiated urgently when: 1, 2, 3, 7, 4

• Serum lithium ≥3.5 mEq/L with significant neurological or cardiovascular symptoms 1
• Any lithium level with significant cardiovascular compromise (symptomatic bradycardia, advanced AV block, refractory hypotension) 1
• Moderate to severe toxicity with refractory symptoms despite conservative management 1, 3
• Acute renal failure complicating lithium toxicity 7

Hemodialysis technique and duration:

• High-flux hemodialysis membranes with bicarbonate dialysate provide superior lithium elimination rates compared to conventional hemodialysis 7
• Continue hemodialysis until serum lithium <1.0 mEq/L is achieved after redistribution 1
• Duration typically 6-8 hours, with measurement 4-6 hours post-dialysis to evaluate for rebound 1
• Consecutive hemodialysis sessions may be necessary to prevent rebound elevations in lithium concentration 7
• High-efficiency dialyzers eliminate lithium more rapidly than previously reported with conventional techniques 7

Alternative extracorporeal treatment:

• Peritoneal dialysis can eliminate lithium but is less effective than hemodialysis 3

Adjunctive Pharmacological Measures

Agents that enhance lithium excretion include: 2

• Urea
• Mannitol
• Aminophylline

These produce significant increases in lithium excretion but are secondary to hemodialysis for severe toxicity 2

Special Clinical Considerations

Thyrotoxicosis as precipitating factor:

• Thyroid hormone increases tubular reabsorption of lithium, and thyrotoxicosis can precipitate lithium toxicity even after lithium cessation if renal function is compromised 6
• Assess thyroid function (free T3, free T4, TSH, thyroglobulin, TSH receptor antibody) immediately in patients with suspected lithium toxicity 6
• Consider silent thyroiditis as a cause, particularly with abrupt onset thyrotoxicosis 6
• Administer glucocorticoid therapy and inorganic iodine (100 mg) for thyrotoxicosis-associated lithium toxicity 6

Acute renal failure:

• May develop from volume depletion and is often rapidly reversible with hemodialysis and infusion therapy 7
• Improvement of renal function combined with consecutive hemodialysis sessions allows rapid decrease in serum lithium without hemodynamic instability 7

Monitoring and Supportive Measures

Essential monitoring includes:

• Infection prophylaxis 2
• Regular chest X-rays 2
• Preservation of adequate respiration 2
• Serial serum lithium levels, particularly 4-6 hours post-dialysis to detect rebound 1
• Continuous cardiac monitoring for arrhythmias 1, 6
• Electrolytes (sodium, potassium, magnesium) 1, 3
• Renal function (BUN, creatinine) 1, 7

Prevention of Future Toxicity

Critical preventive measures include: 1

• Regular monitoring of serum lithium concentrations, especially during acute phase (twice weekly until stabilized) 1
• Temporarily suspend lithium during intercurrent illness, planned 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 lithium levels, electrolytes, and renal function 1
• Educate patients and caregivers about early signs of toxicity (tremor, nausea, diarrhea) to allow rapid intervention 1

Common Pitfalls to Avoid

Never delay hemodialysis in severe toxicity - waiting for conservative measures when cardiovascular compromise or severe neurological symptoms are present increases risk of permanent neurological deficits, prolonged hospitalization, and mortality 1, 4

Do not assume symptom severity correlates with serum lithium level - chronic toxicity can present with severe symptoms at lower serum levels than acute overdose 1, 4

Avoid overlooking thyroid dysfunction - thyrotoxicosis can precipitate lithium toxicity even after lithium cessation, and failure to assess thyroid function delays appropriate treatment 6

Do not use single hemodialysis session without post-dialysis monitoring - rebound elevations in lithium concentration can occur due to redistribution from intracellular compartments, requiring measurement 4-6 hours post-dialysis and potentially additional sessions 1, 7

Never restart lithium at previous dose after toxicity - evaluate precipitating factors (dehydration, medication interactions, renal impairment, thyroid dysfunction) and restart at lower dose only after complete resolution and correction of contributing factors 1

Expected Clinical Course and Prognosis

• Lithium poisoning has a low mortality rate with appropriate treatment 4
• Chronic lithium poisoning can require prolonged hospital length of stay from impaired mobility and cognition with associated nosocomial complications 4
• Persistent neurological deficits, particularly cerebellar dysfunction, are described but appear uncommon in uncomplicated acute poisoning 4
• Gradual recovery is expected with appropriate treatment, though neurological symptoms may initially deteriorate before improvement 6, 5
• Both patients in reported case series recovered without sequelae following dialysis 5