Answers

Short answers

1 The electrocardiogram shows PR interval prolongation, ST segment depression, QT interval prolongation, T wave flattening, and U waves.

2 The arterial blood gas shows metabolic alkalosis, with some respiratory compensation.

3 A urea and electrolytes blood test should be performed to assess concentrations of sodium (normal range 135-145 mmol/l), potassium (3.5-5.3 mmol/l), urea (2.5-7.5 mmol/l), and creatinine (53-100 µmol/l).

4 The diagnosis is profound iatrogenic hypokalaemia (potassium level 1.1 mmol/l) as a result of treatment with both a thiazide diuretic and a loop diuretic. The urea and electrolytes blood test revealed a sodium concentration of 126 mmol/l, a potassium concentration of 1.1 mmol/l, a urea concentration of 22 mmol/l, and a creatinine concentration of 102 µmol/l.

Long answers
1 Electrocardiogram abnormalities
Electrocardiographic features of hypokalaemia include broad, flat T waves; ST segment depression; QT interval prolongation; U waves, particularly in the presence of coexistent hypomagnesaemia; and ventricular arrhythmias (for example, premature ventricular contractions, torsades de pointes, ventricular tachycardia, and ventricular fibrillation).¹

2 Abnormalities on the arterial blood gas
The arterial blood gas shows marked metabolic alkalosis, with some respiratory compensation (hypoventilation, resulting in a rise in pCO₂ and fall in pO₂). The hypoxia was the result of hypoventilation owing to metabolic alkalosis and the fact that the patient was a lifelong smoker. In clinical practice, metabolic alkalosis is usually seen following vomiting (loss of hydrogen ions) or, as in this case, because of hypokalaemia. Metabolic alkalosis in hypokalaemia is the result of a shift of hydrogen ions into the intracellular space: as the extracellular potassium concentration decreases, potassium ions move out of the cells, and hydrogen ions move into the intracellular space to maintain neutrality.²

3 Further investigation
The urea and electrolytes blood test showed marked hypokalaemia, moderate hyponatraemia, and biochemical evidence of dehydration (urea disproportionately raised compared to creatinine). These results explain the electrocardiogram and arterial blood gas findings, both of which normalised following intravenous rehydration and potassium replacement. Magnesium and calcium concentrations were within normal limits.

4 Diagnosis
The unifying diagnosis was profound iatrogenic hypokalaemia secondary to treatment with both a thiazide diuretic and a loop diuretic (in this case, furosemide 40 mg once daily and bendroflumethiazide 2.5 mg once daily). Further investigation showed that the patient was on bendroflumethiazide for hypertension and furosemide for ankle swelling. The patient had no clinical features of congestive cardiac failure and a normal echocardiogram.

Conn’s syndrome should be considered as an alternative diagnosis in this patient in view of the severity of the hypokalaemia and the coexisting hypertension. Investigation of this possibility should be deferred until the patient has fully recovered and has been off diuretic treatment for some weeks.

Both thiazide diuretics and loop diuretics increase sodium delivery to the distal segment of the distal tubule. This increase in sodium concentration stimulates the aldosterone sensitive sodium pump to increase sodium reabsorption and consequently increase potassium and hydrogen ion excretion, resulting in hypokalaemia and metabolic alkalosis.³ This case highlights the dangers of using thiazide diuretics and loop diuretics in combination and the importance of close monitoring of electrolytes (usually under specialist supervision).

Outcome
The patient discontinued diuretic treatment. Following intravenous rehydration and potassium replacement, her hypokalaemia, symptoms, electrocardiogram abnormalities, and metabolic alkalosis resolved and she made a full recovery.

Cite this as: BMJ 2009;338:b1623