A 34-year-old woman with bipolar I disorder has been stable on lithium 900 mg daily for 2 years. She presents to the emergency department with confusion, coarse tremor, hyperreflexia, and rigidity. Serum lithium level is 2.8 mEq/L (therapeutic range 0.6–1.2 mEq/L). Serum creatinine is 1.8 mg/dL (baseline 0.9 mg/dL), and serum sodium is 128 mEq/L. What is the most appropriate immediate management?

Explanation

## Clinical Diagnosis: Lithium Toxicity with Acute Kidney Injury **Key Point:** This patient has severe lithium toxicity (level 2.8 mEq/L) manifesting as neurological symptoms (confusion, tremor, hyperreflexia, rigidity) and concurrent acute kidney injury (Cr 1.8 from baseline 0.9) with hyponatremia (Na 128). ### Pathophysiology of Lithium Toxicity Lithium has a narrow therapeutic window (0.6–1.2 mEq/L). Toxicity occurs when: 1. Renal clearance decreases (dehydration, NSAIDs, ACE inhibitors, renal disease) 2. Sodium depletion increases lithium reabsorption in the proximal tubule 3. Accumulation in the CNS causes neurotoxicity **High-Yield:** Hyponatremia worsens lithium toxicity because low extracellular Na^+^ increases proximal tubular reabsorption of lithium via the Na^+^-Li^+^ exchanger. ### Management Algorithm ```mermaid flowchart TD A["Lithium toxicity suspected<br/>(Level > 1.5 mEq/L + symptoms)"]:::outcome A --> B{"Severity & renal function?"}:::decision B -->|"Severe (>2.0) + AKI<br/>or CNS symptoms"|C["IV normal saline<br/>+ Hemodialysis"]:::action B -->|"Mild-moderate<br/>normal renal function"|D["IV hydration<br/>+ Hold lithium<br/>+ Monitor levels"]:::action C --> E["Lithium clearance<br/>via dialysis"]:::outcome D --> F["Renal clearance<br/>of lithium"]:::outcome ``` ### Why Normal Saline + Hemodialysis? | Intervention | Mechanism | Indication in This Case | |---|---|---| | **IV Normal Saline** | Expands intravascular volume → ↑ glomerular filtration → ↑ lithium clearance; replaces Na^+^ deficit | Hyponatremia (128) + AKI | | **Hemodialysis** | Removes lithium directly (not protein-bound); highly effective | Severe toxicity (level 2.8) + neurological symptoms + AKI | | **Peritoneal dialysis** | Slower clearance | Reserved if hemodialysis unavailable | **Clinical Pearl:** Lithium is NOT protein-bound and has low molecular weight (6.9 Da) — it dialyzes efficiently. In severe toxicity with neurological manifestations, hemodialysis is the standard of care. ### Why NOT the Other Options? **Hypertonic saline (3%):** While it corrects hyponatremia, it does NOT remove lithium. Correcting Na^+^ too rapidly can cause central pontine myelinolysis. Lithium must be actively removed first. **Reducing dose and monitoring:** With level 2.8 and acute kidney injury, the lithium already in the body is the problem. Dose reduction alone is insufficient; active removal is needed. **Switching to valproate:** Changing mood stabilizers does not address the acute toxicity crisis. Lithium must be removed emergently before considering alternative agents. **Key Point:** In severe lithium toxicity with AKI and neurological symptoms, the triad is: (1) IV hydration with normal saline, (2) hemodialysis for direct removal, (3) supportive care and monitoring of electrolytes.