A 52-year-old woman with bipolar I disorder has been on lithium carbonate 900 mg daily for 3 years with good mood stabilization. She presents to the emergency department with confusion, coarse tremor, ataxia, and slurred speech for 2 days. Her family reports she had gastroenteritis with vomiting and diarrhea for 3 days last week. Serum lithium level is 2.8 mEq/L (therapeutic range 0.6–1.2 mEq/L), serum creatinine 1.8 mg/dL (baseline 0.9 mg/dL), and serum sodium 128 mEq/L. What is the most appropriate immediate management?

Explanation

## Clinical Diagnosis: Acute Lithium Toxicity with Severe Hypernatremia ### Pathophysiology This patient has developed **acute lithium toxicity** secondary to volume depletion from gastroenteritis. Lithium is filtered freely by the glomerulus and reabsorbed in the proximal tubule via sodium channels. During dehydration, increased proximal tubular reabsorption of sodium leads to increased lithium reabsorption, raising serum levels into the toxic range. **Key Point:** Lithium toxicity is dose-dependent and correlates poorly with serum levels; clinical severity depends on acuity, renal function, and volume status. ### Clinical Features of Acute Toxicity (Serum Li⁺ > 2.0 mEq/L) The triad of **coarse tremor, ataxia, and confusion** indicates moderate-to-severe acute toxicity: - Coarse tremor (vs. fine tremor at therapeutic levels) - Ataxia, dysarthria, slurred speech - Confusion, disorientation - Nausea, vomiting, diarrhea - In severe cases: seizures, coma, cardiac arrhythmias ### Why Hemodialysis + Normal Saline? | Intervention | Rationale | |---|---| | **Stop lithium immediately** | Eliminate further absorption and accumulation | | **Normal saline IV** | Restore intravascular volume; increases glomerular filtration and lithium clearance (lithium clearance ∝ sodium clearance) | | **Hemodialysis** | Indicated when serum Li⁺ > 2.5 mEq/L, acute toxicity with CNS/cardiac signs, or renal impairment (Cr 1.8 here). Removes lithium more efficiently than renal clearance | **High-Yield:** Normal saline (not hypotonic fluid) is the fluid of choice because hyponatremia (Na⁺ = 128) and volume depletion coexist. Hypotonic fluids worsen hyponatremia and cerebral edema. ### Why NOT the Other Options? - **Option 1 (Dextrose 5% in water):** Hypotonic; worsens existing hyponatremia (128 mEq/L) and increases risk of cerebral edema and seizures. - **Option 3 (Continue lithium):** Contraindicated in acute toxicity; continued dosing perpetuates accumulation. - **Option 4 (Lithium-binding resin):** No such agent exists in clinical practice. Sodium polystyrene sulfonate (Kayexalate) is for potassium, not lithium. ### Monitoring During Treatment - Repeat serum lithium levels every 4–6 hours until < 1.0 mEq/L - Monitor serum sodium, potassium, creatinine, and fluid balance - ECG for arrhythmias - Neurological checks for improvement **Clinical Pearl:** Lithium has a narrow therapeutic index (0.6–1.2 mEq/L). Risk factors for toxicity include dehydration, NSAIDs, ACE inhibitors, thiazide diuretics, and renal disease — all reduce lithium clearance.