A 42-year-old man with bipolar disorder has been on lithium 1200 mg daily for 2 years. He presents to the emergency department with confusion, coarse tremor, hyperreflexia, and ataxia. Serum lithium level is 2.2 mEq/L (therapeutic range 0.6–1.2 mEq/L). Serum creatinine is 1.8 mg/dL (baseline 1.0 mg/dL). What is the most appropriate immediate next step?

Explanation

## Clinical Scenario: Severe Lithium Toxicity with AKI The patient has **severe/moderate-to-severe lithium toxicity** with: - **Neurological signs:** confusion, coarse tremor, hyperreflexia, ataxia — classic neurotoxicity triad - **Supratherapeutic serum level:** 2.2 mEq/L (>1.5 mEq/L = toxicity threshold) - **Acute kidney injury:** Creatinine 1.8 mg/dL (baseline 1.0 mg/dL) — a near-doubling indicating significant renal impairment ## Why Hemodialysis Is the Correct Answer **High-Yield:** According to current toxicology guidelines (EXTRIP Workgroup, 2015 — the definitive evidence-based guideline for lithium toxicity management), **hemodialysis is indicated** when ANY of the following are present: 1. **Decreased level of consciousness, seizures, or life-threatening dysrhythmias** — this patient has confusion (altered consciousness) 2. **Impaired renal function** — creatinine has nearly doubled (AKI), meaning the kidneys cannot clear lithium adequately 3. **Serum lithium ≥4.0 mEq/L** (regardless of symptoms), OR **≥2.5 mEq/L with significant neurological symptoms and renal impairment** This patient has **two independent indications**: (1) significant neurological symptoms (confusion, ataxia, hyperreflexia) AND (2) acute kidney injury. IV saline alone is insufficient because the kidneys are already compromised and cannot reliably clear lithium, risking further neurological deterioration or permanent sequelae. **Clinical Pearl:** The EXTRIP guidelines specifically state that hemodialysis should be performed when lithium toxicity is accompanied by impaired renal function AND neurological symptoms, even if the level is below 4.0 mEq/L. Waiting for IV fluids to work in the setting of AKI risks prolonged CNS exposure to toxic lithium levels. ## Pathophysiology Lithium is a small monovalent cation with a narrow therapeutic index. It is renally excreted and competes with Na⁺ for proximal tubule reabsorption. In AKI, GFR falls dramatically, lithium clearance drops, and toxic levels persist. Hemodialysis removes lithium efficiently (clearance ~170 mL/min vs. normal renal clearance ~25 mL/min). **Lithium rebounds** after HD due to redistribution from tissues, so repeat HD sessions may be needed. ## Why Other Options Are Incorrect | Option | Problem | |--------|---------| | **Sodium bicarbonate** | Does NOT meaningfully enhance lithium excretion. Lithium reabsorption is not significantly pH-dependent in the proximal tubule. Bicarbonate alkalinization is used for salicylate/barbiturate toxicity, not lithium. | | **IV normal saline + monitoring** | Appropriate for *mild* toxicity (level 1.5–2.0 mEq/L, no significant neuro signs, normal renal function). Insufficient here given AKI + significant neurological compromise. | | **Activated charcoal** | Lithium is an inorganic ion; activated charcoal does not adsorb it. Charcoal is effective only for organic molecules. | **Key Point (per KD Tripathi, Essentials of Medical Pharmacology, 8th ed.):** Hemodialysis is the treatment of choice for severe lithium toxicity, particularly when renal function is impaired, as it provides rapid and effective removal of lithium that cannot be achieved by supportive measures alone. **Reference:** Decker BS et al. EXTRIP Workgroup. Extracorporeal Treatment for Lithium Poisoning. *Clin J Am Soc Nephrol.* 2015;10(5):875-887.