A 52-year-old man with bipolar disorder has been on lithium 900 mg/day for 3 years with good mood stabilization. He presents to the emergency department with confusion, coarse tremor, ataxia, and diarrhea. Serum lithium level is 2.8 mEq/L (normal: 0.6–1.2 mEq/L). What is the drug of choice for acute management of his lithium toxicity?

## Acute Lithium Toxicity Management **Key Point:** Hemodialysis is the gold standard for severe lithium toxicity (serum level >2.5 mEq/L or symptomatic toxicity with level >1.5 mEq/L) because lithium is a small ion that is efficiently removed by dialysis. ### Mechanism of Toxicity Lithium toxicity occurs due to: 1. Narrow therapeutic window (0.6–1.2 mEq/L) 2. Accumulation in cells, particularly in the CNS and kidneys 3. Interference with second-messenger systems (phosphoinositol pathway) 4. Dehydration and reduced renal clearance increase risk ### Clinical Features of Severe Toxicity - **Neurological:** Confusion, ataxia, coarse tremor, seizures, coma - **Gastrointestinal:** Nausea, vomiting, diarrhea, abdominal pain - **Cardiac:** Arrhythmias, hypotension - **Renal:** Polyuria, nephrogenic diabetes insipidus ### Management Algorithm ```mermaid flowchart TD A[Lithium Toxicity Suspected]:::outcome --> B{Serum Li+ Level & Symptoms?}:::decision B -->|Mild: Level <1.5 mEq/L, asymptomatic| C[Supportive care, hydration, monitor]:::action B -->|Moderate: Level 1.5-2.5 mEq/L, mild symptoms| D[IV saline, loop diuretics, consider dialysis]:::action B -->|Severe: Level >2.5 mEq/L OR symptomatic| E[HEMODIALYSIS]:::urgent E --> F[Repeat dialysis if rebound occurs]:::action C --> G[Recheck level in 4-6 hours]:::action D --> H{Improving?}:::decision H -->|Yes| G H -->|No| E ``` ### Why Hemodialysis in This Case - **Serum level 2.8 mEq/L** = severe toxicity (>2.5 mEq/L) - **Symptomatic** with neurological signs (confusion, ataxia, tremor) - Lithium is water-soluble, small molecular weight (~7 Da), highly dialyzable - Removes 30–50% of body lithium per 4-hour session - **Rebound phenomenon:** Lithium redistributes from intracellular to extracellular compartment; repeat dialysis may be needed 6–8 hours later **High-Yield:** Lithium toxicity is one of the few psychiatric drug emergencies requiring dialysis. Do NOT delay for other interventions. ### Supportive Measures (Adjunctive) - IV normal saline: Enhances renal clearance (lithium reabsorbed in proximal tubule like sodium) - Loop diuretics: Increase urine flow (but avoid thiazides, which reduce lithium clearance) - Seizure precautions, cardiac monitoring - Discontinue lithium immediately **Clinical Pearl:** Thiazide diuretics and NSAIDs reduce lithium clearance and are common precipitants of toxicity in stable patients.