Lithium toxicity during Ramadan with NSAID use
A 68-year-old woman with bipolar I disorder, stable on lithium carbonate 900 mg at night for 12 years, presents to the emergency department in Nizwa during Ramadan with three days of vomiting and confusion. She has been fasting from dawn to sunset. A week ago she began ibuprofen 400 mg three times daily for knee pain. Her daughter says she has been tremulous, unsteady and "not herself", and a neighbour found her on the floor at home. On examination she is drowsy and dysarthric, with a coarse tremor and ataxia, and cannot cooperate with cognitive testing. Pulse 104/min, BP 96/60 mmHg, temperature 37.4 °C. Lithium 2.7 mmol/L, creatinine 156 µmol/L (baseline 76), sodium 132 mmol/L, potassium 4.6 mmol/L, TSH and calcium normal. ECG shows flattened T waves and a QT of 430 ms. She lives alone.
1. Explain the factors that produced this toxicity and justify why this is not simply "a high lithium level".
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Lithium is a small, unbound cation cleared almost entirely by the kidney, and its handling mirrors sodium. Three factors converged here. First, fasting from dawn to sunset reduces fluid and sodium intake, causing mild volume depletion and increased proximal tubular reabsorption of both sodium and lithium. Second, vomiting causes further volume and sodium loss and reduces oral intake. Third, ibuprofen inhibits renal prostaglandin synthesis, reducing renal blood flow and glomerular filtration and further increasing lithium reabsorption. Age-related decline in GFR magnifies all three.
The serum creatinine of 156 µmol/L against a baseline of 76 indicates acute kidney injury, so clearance has fallen sharply while her dose stayed the same. The clinical picture - coarse tremor, ataxia, dysarthria, confusion and vomiting - is the syndrome of moderate to severe toxicity, and the level must be interpreted alongside it. Lithium distributes slowly into tissue, so a single level can underestimate total body burden, and levels may continue to rise or rebound after dialysis as tissue stores re-equilibrate. The management decision therefore rests on the clinical state, renal function and trajectory, not on the number alone. Neurotoxicity can persist or become irreversible, which is the real reason this is an emergency.
2. Set out your acute management and the thresholds at which you would involve nephrology for haemodialysis.
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Stop lithium immediately. Establish IV access and give 0.9% sodium chloride to restore volume, guided by blood pressure, urine output and repeat electrolytes; avoid dextrose-containing fluids as the primary resuscitation fluid because they do not correct the sodium deficit, and avoid diuretics. Treat vomiting, monitor fluid balance and daily weight, and nurse in a monitored bed with continuous cardiac monitoring.
Measure lithium, urea, electrolytes and creatinine every 6–12 hours initially, with ECG monitoring for QT and bradyarrhythmia and a low threshold for checking magnesium and phosphate. Examine neurologically at each review, since worsening confusion, seizures or reduced consciousness indicates severe toxicity. Avoid all nephrotoxins, including further NSAIDs, ACE inhibitors and thiazides.
Involve nephrology for haemodialysis if there is severe neurotoxicity (confusion, seizures, coma), a lithium level above 2.5–4.0 mmol/L depending on symptoms and renal function, renal failure with oliguria, or a level that is not falling despite adequate fluids. Dialysis should continue until the level is below about 1.0 mmol/L and she is clinically improved, because of rebound from tissue stores, and she needs observation after the last session. This patient meets the threshold for discussion now, given confusion, ataxia and acute kidney injury at 2.7 mmol/L.
3. Plan her management after recovery, including restarting lithium, fasting advice and monitoring.
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Do not restart lithium until renal function has returned to baseline and she is eating and drinking normally. Then restart at a lower dose, approximately 600 mg at night, since her clearance is unlikely to return fully to its previous level, and check a trough level 12 hours after the dose five to seven days later; target 0.4–0.6 mmol/L in an older adult rather than the 0.6–0.8 mmol/L range used in younger patients. Recheck creatinine, electrolytes and TSH at baseline, after any dose change, and then every six months.
Counsel her and her daughter explicitly: avoid ibuprofen and other NSAIDs, using paracetamol for knee pain instead; during Ramadan, discuss the fast with her psychiatrist beforehand, keep fluid intake up between sunset and dawn, and hold lithium and seek advice if vomiting or diarrhoea occurs or intake falls. Give written sick-day rules. Once-daily dosing at night reduces renal exposure and is already her regimen, so continue it.
Because she lives alone, arrange a family or neighbour support plan, a medication review, and follow-up within one to two weeks with both psychiatry and her primary care physician. Discuss safer alternatives for her knee pain and consider whether her bipolar disorder remains stable on the lower target level.