Ataxia, Confusion, and a Creatinine That Doubled: Deconstructing a Lithium Toxicity
J.T., 58, has bipolar I disorder maintained on lithium 900 mg nightly; her level three months ago was 0.82 mmol/L. Lisinopril 10 mg daily was started four weeks ago for hypertension. For two weeks she has taken ibuprofen 600 mg three times daily for knee osteoarthritis. After two days of vomiting and diarrhea following a family gathering, she presents with coarse tremor, slurred speech, unsteady gait, and confusion. Vitals: BP 102/64, HR 108, afebrile. Labs: lithium 1.94 mmol/L, sodium 131 mmol/L, creatinine 1.5 mg/dL (baseline 0.9), eGFR 38 mL/min/1.73 m^2, TSH within normal limits. She lives alone and drove herself to the clinic.
1. What is your immediate disposition and treatment plan, and what are the indications for extracorporeal removal?
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This is severe lithium toxicity with neurotoxicity and acute kidney injury - she needs emergency department care now, not an outpatient adjustment.
- She should not drive herself; arrange ambulance transport.
Immediate management:
- Stop lithium, lisinopril, and ibuprofen.
- IV 0.9% sodium chloride to restore volume and enhance renal lithium clearance; monitor urine output.
- Continuous cardiac monitoring and ECG (T-wave changes, QT, bradyarrhythmias); check calcium, magnesium, and a full neuro exam.
- Serial lithium levels every 2–4 hours - levels can continue to rise after presentation because of ongoing absorption and declining clearance.
- Avoid thiazides, NSAIDs, and any further nephrotoxins. Do not use forced diuresis or loops as monotherapy for lithium elimination without nephrology input.
- Involve nephrology early and psychiatry for the underlying disorder.
Indications for hemodialysis:
- Level generally >2.5 mmol/L, or >2.0 mmol/L with significant neurologic or cardiac symptoms (as here), or any level with renal failure or life-threatening features.
- Lithium is small, water-soluble, and poorly protein-bound, so it is well dialyzed, but it has a large volume of distribution - expect rebound and recheck levels 6–12 hours after each session, with repeat dialysis if levels rebound.
Her clinical picture (confusion, ataxia, dysarthria) plus eGFR 38 puts her in the dialyze-early discussion group even before a repeat level returns.
2. Explain mechanistically why this happened now, attributing the effect of each new factor.
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Three hits converged on the same final pathway: increased proximal tubular lithium reabsorption and reduced GFR.
| Factor | Mechanism |
|---|---|
| Lisinopril (4 weeks) | ACE inhibition reduces angiotensin II–driven efferent arteriolar tone and causes natriuresis/volume depletion. In the proximal tubule, sodium depletion increases lithium reabsorption proportionally to sodium - lithium clearance falls even at stable doses. Onset over weeks fits perfectly. |
| Ibuprofen (2 weeks) | NSAIDs inhibit vasodilatory prostaglandins, reducing renal blood flow and GFR; reduced distal sodium delivery increases proximal lithium reabsorption. NSAIDs are among the classic precipitants of lithium toxicity. |
| Vomiting/diarrhea (2 days) | Volume and sodium depletion activates the RAAS, maximizing proximal sodium (and lithium) reabsorption and causing prerenal AKI. This is the acute decompensation. |
The creatinine rise from 0.9 to 1.5 reflects both prerenal injury and possibly chronic lithium nephropathy; the AKI itself further reduces lithium elimination, creating a self-reinforcing cycle that explains why levels can keep climbing after the vomiting stops.
Teaching point: the sodium–lithium counter-transport in the proximal tubule is why any sodium-depleting state - diet, diuretics, ACEi/ARB, NSAIDs, GI losses - is a lithium toxicity risk, and why "sick day" rules matter.
3. Assume she recovers with a creatinine of 0.95 and a lithium level of 0.4 after dialysis. Design the medication plan for the next three months.
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Restart deliberately, not automatically.
- Wait until she is eating and drinking normally, off the NSAID, and renal function is stable.
- Restart lithium at a lower dose (~600 mg/day) and recheck a trough level (12 hours post-dose) in 5–7 days; target 0.6–0.8 mmol/L given her age and renal risk. Do not re-challenge with 900 mg.
- Do not restart lisinopril without thought. If an ACEi/ARB is needed for her hypertension, lithium can be continued, but only with closer level monitoring after initiation and dose changes. Alternative antihypertensives (e.g., amlodipine) avoid this interaction.
- Permanent NSAID avoidance: written and verbal. For her knee OA, offer topical NSAID (low systemic exposure), acetaminophen, exercise/PT, intra-articular corticosteroid, or duloxetine - and note that topical diclofenac still warrants a level check if used long-term.
- Sick-day plan: explicit instructions to hold lithium and call during vomiting, diarrhea, fever, or poor oral intake; hydrate with sodium-containing fluids, not free water.
- Education for her and a contact person: tremor, unsteadiness, confusion, and vomiting are warning signs. She lives alone - consider a medication blister pack or a check-in call.
- Monitoring schedule: lithium level, creatinine/eGFR, TSH, calcium, and weight at baseline, 1 week, then every 3–6 months; more often after any new drug or illness.
- Reassess whether lithium remains the right agent given her AKI; if it is, document the shared decision explicitly.