Lithium Toxicity Triggered by NSAID, Thiazide, and Dehydration
A 57-year-old woman with bipolar I disorder takes lithium carbonate 900 mg at bedtime; her most recent level was 0.82 mmol/L two months ago. She also takes hydrochlorothiazide 25 mg daily for hypertension and started ibuprofen 400 mg three times daily 10 days ago for low back pain. She presents with 2 days of vomiting and diarrhea, coarse tremor, unsteady gait, confusion, and slurred speech. Blood pressure is 104/66 mmHg, heart rate 96/min, and temperature 37.8°C. Labs show lithium 1.9 mmol/L, sodium 132 mmol/L, potassium 3.4 mmol/L, creatinine 150 μmol/L (baseline 80), and eGFR 38 mL/min/1.73 m². She is not suicidal and has no focal neurologic deficit. The pharmacy is 20 minutes from the nearest emergency department; her daughter is with her. She asks if she can take another lithium dose and something for nausea.
1. Explain the pharmacokinetic and clinical reasons for her lithium toxicity, including the role of each contributing factor.
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Lithium is eliminated almost entirely by the kidney and has a narrow therapeutic index. Ibuprofen inhibits renal prostaglandin synthesis, reducing glomerular filtration and lithium clearance. Hydrochlorothiazide causes sodium and water depletion; the proximal tubule then reabsorbs more sodium and lithium. Vomiting and diarrhea add volume depletion and further reduce clearance. The result is a lithium level of 1.9 mmol/L with tremor, ataxia, confusion, and slurred speech-clinical toxicity. Her creatinine has risen from 80 to 150 μmol/L, confirming kidney injury. The combination of NSAID, thiazide, and dehydration is the key explanation; age and any baseline renal impairment increase risk.
2. What immediate action and triage plan is required?
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Hold the next lithium dose and arrange urgent transfer to the emergency department; do not send her home to watch. She needs IV fluids, electrolyte correction, and serial lithium and renal function measurements. Do not give another lithium dose. Stop ibuprofen and hydrochlorothiazide now. If she is unable to walk safely or has worsening confusion, call emergency services rather than having her daughter drive. In hospital, severe toxicity may require hemodialysis. Give the emergency team the medication list, last lithium level, renal function, and timing of the last dose.
3. Recommend alternatives for pain and hypertension and the counseling you would provide.
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For pain, use acetaminophen and non-drug measures; avoid NSAIDs. For hypertension, discuss amlodipine or another agent with the prescriber, because thiazides increase lithium reabsorption. Counsel on maintaining hydration, avoiding salt restriction or dehydration, and checking with the pharmacy before starting OTC NSAIDs. After recovery, lithium may be restarted at a lower dose with a level 5–7 days later. Document the interaction and provide a medication alert. Follow up renal function and lithium level.