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Stem
A 74-year-old woman is brought to the emergency department by her daughter with a one-week history of worsening unsteadiness, slurred speech, a "shaking" of both hands, and increasing confusion. Her past history includes bipolar affective disorder (for which she has taken lithium carbonate 800 mg at night for 18 years) and hypertension. Six weeks ago her general practitioner started hydrochlorothiazide 25 mg daily for blood-pressure control, and she had an episode of diarrhoea and vomiting four days ago. She also takes ibuprofen for osteoarthritis.
On examination: temperature 37.2 °C, pulse 92/min, blood pressure 104/64 mmHg (postural drop 18 mmHg systolic), respiratory rate 18, oxygen saturation 97 per cent on air, GCS 14. She has a coarse tremor of both hands, muscle fasciculations, hyperreflexia, marked gait and limb ataxia, dysarthria, and nystagmus. She passes large volumes of dilute urine. 12-lead ECG shows T-wave flattening and a QTc of 480 ms. Serum lithium 2.9 mmol/L, sodium 131 mmol/L, potassium 3.3 mmol/L, calcium 2.78 mmol/L, creatinine 178 micromol/L (baseline 92), TSH 7.2 mIU/L (raised).
Questions
a) What is the diagnosis, and identify the FOUR precipitants in the stem? (2 marks)
Diagnosis: chronic lithium toxicity. The neurological ladder (coarse tremor, fasciculations, hyperreflexia, ataxia, dysarthria, nystagmus, confusion) plus nephrogenic diabetes insipidus is characteristic, and the level (2.9 mmol/L) is in the moderate-to-severe range — note that chronic accumulation is dangerous at LOWER serum levels because tissue is already saturated, so clinical correlation trumps the number. The four precipitants are: (1) hydrochlorothiazide (causes sodium/volume loss -> increased proximal lithium reabsorption — the classic exam precipitant); (2) dehydration from the recent diarrhoea and vomiting (reduces filtered load and enhances lithium reabsorption); (3) ibuprofen (NSAID) (reduces renal lithium clearance via prostaglandin inhibition); (4) age-related reduced renal clearance / AKI (creatinine 178). The thiazide, NSAID and dehydration together explain the accumulation.
b) Explain the renal mechanism by which lithium is excreted, and why the thiazide diuretic precipitated toxicity. (3 marks)
Lithium is a small monovalent cation handled by the kidney LIKE SODIUM. It is freely filtered at the glomerulus and then REABSORBED (60-80 per cent) in the proximal tubule through the same sodium-transport pathways as sodium (the sodium-hydrogen exchanger; and ENaC channels more distally). Almost all filtered lithium is excreted in urine — there is no other significant clearance route. A thiazide causes sodium and volume depletion, which makes the proximal tubule increase sodium reabsorption to conserve sodium; because lithium shares these transport pathways, MORE LITHIUM IS REABSORBED TOO, raising the serum level (often within days). Her dehydration and the NSAID compound this (reduced GFR and reduced renal lithium clearance). This is also why aggressive isotonic saline is the cornerstone of treatment — it restores euvolaemia and the filtered sodium load, ENHANCING RENAL LITHIUM EXCRETION.
c) Outline the stepwise management of this patient, with drug doses where applicable. (3 marks)
- Stop lithium AND the precipitants (hydrochlorothiazide, ibuprofen); secure airway, IV access, continuous cardiac monitoring, serial GCS.
- Aggressive isotonic saline (0.9% NaCl IV) — the cornerstone; restore euvolaemia then maintenance; monitor for fluid overload given her AKI.
- Treat seizures if they occur — lorazepam 4 mg IV (2 mg in the elderly) repeated, or diazepam/midazolam.
- Haemodialysis — she meets EXTRIP criteria for impaired renal function (AKI) with a level over 2.5-4.0 mmol/L and has significant symptoms; arrange urgent haemodialysis.
- Recheck the lithium level at 4-6 hours after dialysis for REBOUND; use SLED or CRRT as a follow-on to prevent rebound.
- Correct electrolytes cautiously — sodium (hyponatraemia worsens retention; the thiazide should now be stopped), potassium; manage nephrogenic DI fluids carefully (avoid hypernatraemia). Avoid activated charcoal, loop/thiazide diuretics, NSAIDs, ACE-i.
- ICU admission.
d) According to the EXTRIP Workgroup, state TWO situations in which extracorporeal treatment (haemodialysis) is RECOMMENDED for lithium poisoning, and state when the treatment should be stopped. (2 marks)
EXTRIP RECOMMENDED indications (Grade 1D) — any two: (1) impaired kidney function AND serum lithium OVER 4.0 mEq/L; (2) decreased level of consciousness, seizures, OR life-threatening dysrhythmia at ANY serum lithium level. (EXTRIP also SUGGESTS treatment if the level is over 5.0 mEq/L, there is significant confusion, or the expected time to reduce below 1.0 mEq/L exceeds 36 hours.) Extracorporeal treatment should be continued until clinical improvement is apparent OR the serum lithium is BELOW 1.0 mEq/L (and for a minimum of 6 hours if the level is not readily measurable).