Lithium toxicity after introduction of bendroflumethiazide

A 50-year-old woman presented to the emergency department with a 1-week history of coarse tremor, diarrhoea and confusion. Her family reported that she had become increasingly withdrawn and intermittently disoriented over the past 5 days. She had a background of bipolar affective disorder, for which she had been taking lithium carbonate 400 mg twice daily for 10 years. Eight weeks before admission, she was diagnosed with hypertension and started on bendroflumethiazide 5 mg once daily. She also took ibuprofen occasionally for headaches, but no other regular medications. She had not seen a doctor recently and had not had any blood tests since starting therapy. On examination, she was drowsy and disoriented to time and place. Her temperature was 37.8°C, pulse 110/min, blood pressure 100/70 mmHg, and she was clinically dehydrated. There was a coarse tremor in both hands, ataxia on heel-to-toe walking, and no focal neurological deficit. Initial investigations revealed serum lithium 2.8 mmol/L (therapeutic range 0.6-1.2 mmol/L), creatinine 180 µmol/L (baseline 80 µmol/L), and estimated glomerular filtration rate 28 mL/min/1.73 m². Her blood cultures were negative, and urine culture grew Escherichia coli without clinical features of urinary tract infection. A CT head showed no acute abnormality. Bendroflumethiazide was stopped, and she was given intravenous fluids. Lithium was withheld and her symptoms resolved over 72 hours, with serum lithium falling to 1.1 mmol/L. She was not rechallenged with bendroflumethiazide. Her cause of symptoms was thought to be lithium toxicity precipitated by the addition of a thiazide diuretic, although a superimposed infection could not be entirely excluded.