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, advanced AV block, and cardiac arrest 1, 6
• Severe neurological symptoms such as seizures, deep coma, or quadriplegia indicate critical toxicity 6, 4

Initial Stabilization and Supportive Care

Immediate Interventions:

• Discontinue lithium immediately upon suspicion of toxicity 2, 3
• Perform gastric lavage if presentation is within hours of acute ingestion 2, 3
• Initiate aggressive IV fluid resuscitation to correct dehydration and maintain adequate hydration 1, 6, 3
• Correct fluid and electrolyte imbalances, particularly maintaining high-normal sodium levels to facilitate lithium removal from intracellular compartments 2, 3
• Correct potassium and magnesium deficiencies, especially if arrhythmias are present 1
• Monitor and support respiratory function with mechanical ventilation if needed 2

Cardiovascular Support:

• For hypotension refractory to IV fluids, administer vasopressors such as norepinephrine 1
• For symptomatic bradycardia or advanced AV block, consider temporary pacemaker insertion 1, 6
• Avoid antiarrhythmic drugs that prolong QT interval (amiodarone, sotalol) if QT prolongation is already present 1
• Perform chest compressions and manual ventilation for cardiac arrest 6

Hemodialysis: The Definitive Treatment

Absolute Indications for Urgent Hemodialysis:

• 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
• Severe neurological symptoms (seizures, coma, progressive deterioration) regardless of serum level 4
• Refractory toxicity despite conservative management 1
• Acute renal failure complicating lithium toxicity 7

Hemodialysis Protocol:

• Use high-flux hemodialysis membranes with bicarbonate dialysate for maximum lithium clearance 7
• Continue hemodialysis until serum lithium <1.0 mEq/L is achieved after redistribution 1
• Duration typically 6-8 hours, with serum lithium measurement 4-6 hours post-dialysis to evaluate for rebound 1, 7
• High-flux membranes provide greater lithium elimination per hour than conventional hemodialysis and reduce risk of post-dialysis rebound elevations 7
• Consecutive hemodialysis sessions may be necessary if rebound occurs or if renal function remains impaired 7

Alternative Enhanced Elimination:

• Peritoneal dialysis is less effective than hemodialysis but can be used if hemodialysis is unavailable 3
• Urea, mannitol, and aminophylline produce significant increases in lithium excretion but are secondary to hemodialysis 2

Monitoring During Treatment

Essential Laboratory Monitoring:

• Serial serum lithium levels: initially every 4-6 hours, then 4-6 hours post-dialysis to assess for rebound 1, 7
• Electrolytes (sodium, potassium, magnesium) frequently during resuscitation 1, 2
• Renal function (BUN, creatinine) to assess for acute kidney injury 7, 5
• Thyroid function (TSH, free T4, free T3) as thyrotoxicosis can precipitate lithium toxicity 6

Clinical Monitoring:

• Continuous cardiac monitoring for arrhythmias and conduction abnormalities 1, 6
• Serial neurological examinations to assess for improvement or deterioration 4, 5
• Regular chest X-rays for infection prophylaxis 2
• Vital signs including temperature, as febrile episodes can complicate toxicity 6

Special Considerations and Precipitating Factors

Evaluate and Address Precipitating Causes:

• Dehydration from lithium-induced nephrogenic diabetes insipidus or intercurrent illness 1, 4
• Medication interactions, particularly NSAIDs which increase lithium levels 1
• Impaired renal function from volume depletion or intrinsic kidney disease 7, 4
• Thyrotoxicosis (including silent thyroiditis) which increases tubular reabsorption of lithium 6
• Recent cessation of lithium with compromised renal function can still result in toxicity 6

Thyroid Assessment:

• Thyroid function should be assessed immediately in all patients with suspected lithium toxicity, as thyrotoxicosis may be a contributing cause even with recent lithium cessation 6
• If thyrotoxicosis is present, treat with glucocorticoids and inorganic iodine (100 mg) until thyroid function normalizes 6

Recovery and Prognosis

Expected Clinical Course:

• Lithium toxicity has a low mortality rate with appropriate treatment 4
• Chronic lithium poisoning may require prolonged hospitalization due to impaired mobility, cognition, and nosocomial complications 4
• Neurological recovery can be gradual, with some patients requiring weeks to fully recover from severe toxicity 6, 5

Persistent Neurological Deficits:

• Persistent cerebellar deficits are described but appear uncommon in uncomplicated acute poisoning 4
• Risk factors for permanent neurological sequelae are poorly understood but may relate to severity and duration of toxicity 4

Prevention of Future Toxicity

Patient and Caregiver Education:

• Educate patients and families to watch for early symptoms (tremor, nausea, diarrhea) and discontinue lithium immediately if they occur 1, 2
• Emphasize the importance of maintaining adequate hydration, especially during illness 1
• Careful supervision is essential, particularly in children and adolescents, as lithium overdoses can be lethal 1

Medication Management:

• 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
• Regular monitoring of serum lithium concentrations, especially during acute treatment phase (twice weekly until stabilized) 1
• Regular monitoring of lithium levels, electrolytes, and renal function to prevent future toxicity 1

Critical Pitfalls to Avoid

• Never delay hemodialysis in severe toxicity waiting for conservative measures to work—cardiovascular collapse and irreversible neurological damage can occur rapidly 1, 6
• Do not rely solely on serum lithium levels to determine severity, as clinical symptoms (especially in chronic toxicity) may not correlate with serum concentrations 1, 4
• Always measure lithium levels 4-6 hours post-dialysis to detect rebound elevations requiring additional dialysis sessions 1, 7
• Do not overlook thyroid function testing as thyrotoxicosis can precipitate and perpetuate lithium toxicity even after lithium cessation 6
• Avoid underdialysis—continue hemodialysis until post-redistribution lithium level is <1.0 mEq/L, not just until the immediate post-dialysis level appears acceptable 1