Tremor, ataxia and confusion in a long-term lithium user: three prescriptions and a vomiting illness
Mrs K, 64, has bipolar I disorder and has taken lithium carbonate 300 mg three times daily for 12 years, with a stable serum level of 0.7 mmol/L. Three weeks ago her physician added hydrochlorothiazide 25 mg daily for hypertension, and for the past two days she has taken ibuprofen 400 mg three times daily for knee pain. She now has vomiting, a coarse tremor of both hands, unsteady gait, slurred speech, and is disoriented to time and place. Her daughter says she has eaten little and drunk less because of nausea. Observations: pulse 112/min, BP 98/64 mmHg, temperature 37.9 °C, respiratory rate 22/min, urine output 20 mL/hour, weight 54 kg (usual 58 kg). Her next lithium dose is due in one hour and the ward nurse has already prepared it. The medical officer is at an emergency call and will be free in about 45 minutes.
1. What is happening, and how does each factor in the history contribute? Explain the mechanism rather than listing the drugs.
Read the worked answer
This is lithium toxicity, probably moderate to severe. The features that separate toxicity from therapeutic effect are the coarse tremor (therapeutic lithium causes a fine tremor), ataxia, dysarthria, vomiting and disorientation. Serum level will confirm, but treatment must not wait for it.
Three insults have converged:
- Hydrochlorothiazide causes sodium and water depletion. The proximal tubule responds by increasing sodium reabsorption, and lithium is handled as a sodium analogue, so it is reabsorbed too. Thiazides can raise lithium levels by roughly a quarter to a half within days.
- Ibuprofen inhibits renal prostaglandin synthesis, reducing glomerular filtration and therefore lithium clearance - a second hit in the same direction.
- Vomiting with reduced intake produces volume depletion, which again increases proximal sodium and lithium reabsorption, at the same time as the vomiting is itself an early symptom of toxicity.
Age 64 means a lower baseline GFR, and the 4 kg weight loss shows how dehydrated she has become. Note that all three triggers were iatrogenic or preventable, and that she is now in a loop: toxicity causes vomiting, vomiting worsens toxicity.
2. What will you do in the next hour, and what would you specifically avoid? Why is holding the dose and waiting 45 minutes not enough?
Read the worked answer
Immediate actions:
- Withhold the prepared dose. The prescription no longer fits the patient's condition; giving it would add to the burden. Record the omission and the reason.
- Escalate now rather than at 45 minutes: page the on-call physician or psychiatrist, and the medical officer again. A deteriorating patient with reduced consciousness and oliguria is not a routine call-back.
- Intravenous 0.9% sodium chloride for volume repletion, with strict hourly fluid balance and urine output.
- Continuous observation: neurological checks, seizure precautions, falls precautions, aspiration precautions, ECG for arrhythmia and QT change.
- Bloods: lithium level (repeat every 12 hours), urea and creatinine, sodium and potassium, calcium, thyroid function; consider a chest X-ray if aspiration is suspected.
- Stop the hydrochlorothiazide and ibuprofen and ask for a safe antihypertensive and analgesic.
Avoid: forced diuresis, sodium restriction, dextrose-only fluids, further nephrotoxic drugs, and any suggestion that she can go home.
Why waiting is not enough: lithium is a small ion distributed in total body water and cleared only by the kidney. With a GFR already reduced by dehydration, NSAIDs and a thiazide, the level is still rising; her conscious level and urine output are falling. Assess for dialysis criteria - level above 2.5 mmol/L, or above 1.5 mmol/L with renal impairment or severe symptoms.
3. Design the monitoring and the discharge counselling that would prevent a recurrence.
Read the worked answer
Monitoring until recovery: lithium level 12-hourly until clearly falling and symptoms resolving; renal function and electrolytes daily; fluid balance chart with hourly urine output; neurological observations; ECG; weight; and a documented record of tremor and gait, since these improve before the level normalises. Watch for rebound: once she rehydrates faster than the lithium is cleared, levels can shift unpredictably.
Counselling before discharge - make it concrete, not general:
- Lithium is cleared by the kidney, so fluid and salt matter. Do not go on a crash diet, do not restrict salt, and drink more in hot weather or during exercise.
- Vomiting, diarrhoea or fever means a call to the clinic the same day, because dehydration can push the level up within hours.
- Avoid over-the-counter NSAIDs such as ibuprofen. Paracetamol is the safer analgesic.
- Thiazide diuretics interact. Ask before any new medicine, including herbal products.
- Report a coarse tremor, unsteadiness, slurred speech, or vomiting - these are early warnings, not side effects to be tolerated.
- Keep a medical alert card or bracelet naming lithium, and keep lithium levels checked every 3 to 6 months and after any new drug is started.
- Involve the daughter in this teaching; she noticed the change first and is the practical safety net.