Lithium Toxicity Management

Lithium has a narrow therapeutic window (target 0.6-1.0 mEq/L for maintenance bipolar treatment, 0.8-1.2 in acute mania) and toxicity can occur at modest elevations above therapeutic level. Three patterns are recognized: acute toxicity (single overdose in non-lithium-naive or naive patient), acute-on-chronic (overdose superimposed on chronic therapy), and chronic toxicity (gradual accumulation due to dehydration, renal impairment, drug interactions, sodium depletion, or dose increase).

Mechanisms of toxicity involve neuronal hyperexcitability, interference with sodium and inositol pathways, and cardiac and renal effects. Severity depends on lithium level, duration of exposure, baseline renal function, and central nervous system penetration. Chronic toxicity is more dangerous than acute at similar levels because tissue lithium has equilibrated with serum.

Clinical features progress from mild (tremor, nausea, diarrhea, polyuria) to moderate (confusion, ataxia, dysarthria, fasciculations, hyperreflexia) to severe (seizures, coma, cardiovascular collapse, renal failure). Cardiac effects include T-wave changes, QT prolongation, and arrhythmia. Diagnosis combines history, examination, serum lithium level (with caveats of timing), electrolytes, renal function, ECG. Management is supportive (IV fluids, electrolyte correction, airway protection), gastrointestinal decontamination in acute ingestion (whole-bowel irrigation for sustained-release preparations; activated charcoal generally not effective), and hemodialysis for level >4 mEq/L, severe symptoms, renal failure, or impaired consciousness. Long-term, address precipitants, education, dose adjustment, and monitoring.