Omeprazole and refractory hypomagnesaemia

Hypomagnesaemia is common in hospital patients and is often accompanied by other electrolyte abnormalities, such as hypocalcaemia, hypokalaemia, and hypophosphataemia, that may remain refractory to treatment until the underlying magnesium deficiency is corrected.1 We present two patients with refractory chronic hypokalaemia and hypocalcaemia secondary to hypomagnesaemia that resolved after withdrawal of the proton pump inhibitor omeprazole.

A 78 year old woman was admitted to hospital after an exacerbation of chronic obstructive pulmonary disease accompanied by diarrhoea and vomiting. Her medical history included breast cancer, ischaemic heart disease, myocardial infarction, osteoporosis, and spinal stenosis. A several year history of paraesthesia, numbness, and weakness in her limbs had been attributed to spinal stenosis, but surgery had been ruled out because anaesthesia was risky. Seven years earlier she had been investigated for postprandial pain, early satiety, nausea, and weight loss. Non-erosive duodenitis, diverticular disease, and a hiatus hernia had been diagnosed. She had been prescribed omeprazole (40 mg/day) and her symptoms improved slightly. In addition, she was receiving spironolactone, bumetanide, furosemide, gabapentin, co-codamol, hyoscine butylbromide, glyceryl trinitrate, losartan, aspirin, atorvastatin, ipratropium bromide, and salmeterol.

She was hypokalaemic on admission (table 1⇓), and this failed to respond to withdrawal of diuretics and intravenous and oral potassium replacement. On day 4 she developed hallucinations and became agitated: muscular excitability was noted but Chvostek’s sign was absent. She remained markedly hypokalaemic and was also hypocalcaemic and hypomagnesaemic: retrospective analysis of samples from the day of her admission showed that magnesium and calcium concentrationshad been low then.She was also hypophosphataemic. Her symptoms resolved after treatment with intravenous magnesium sulphate, calcium gluconate, and continued potassium. Magnesium concentration was normal while she received intravenous replacement, but when it was stopped magnesium fell again. She was discharged after 10 days and was taking oral magnesium glycerophosphate and a phosphate supplement; her diuretics were withheld even though she had some ankle oedema.

At outpatient follow-up, serum magnesium and calcium concentrations remained low, and her history was reviewed for potential causes of magnesium loss. She had had no further diarrhoea and denied using laxatives or alcohol. Measurement of urinary calcium and magnesium concentrations suggested appropriate renal conservation (table 1⇑). In light of a report of two cases of hypomagnesaemic hypoparathyroidism associated with omeprazole,2 we discontinued omeprazole and prescribed the H₂ receptor antagonist ranitidine. Electrolyte status improved dramatically and was maintained even after her magnesium supplements were stopped (table 1⇑). The patient remains well and reported an improved appetite after omeprazole was withdrawn.

An 81 year old man who lived independently was admitted to hospital after presenting to his general practitioner with dizziness and nausea that had been ongoing for three months but had worsened in the previous two days. He had vomitedafter meals but had had no diarrhoea; he had also had urinary incontinence for two days and reported polyuria over the previous month.

His medical history included hypertension, ischaemic heart disease, benign prostatic hyperplasia, and diabetes controlled by diet. He was taking omeprazole (40 mg/day), isosorbide mononitrate, atenolol, atorvastatin, lisinopril, quinine, amlodipine, olmesartan, and aspirin. He had no history of alcohol misuse.

He had muscle cramps and paraesthesia, with pins and needles in his hands; Trousseau’s sign was elicited at venepuncture. He was very unsteady, falling to both sides, and had an irregular heartbeat. Hypokalaemia, hypocalcaemia, and hypomagnesaemia were seen, and his symptoms were attributed to these. Parathyroid hormone concentration was subsequently reported as within the reference range but inappropriate for his degree of hypocalcaemia (table 2⇓). His incontinence and raised C reactive protein were attributed to a urinary tract infection, which was treated with trimethoprim.

With oral potassium and intravenous calcium gluconate and magnesium glycerophosphate replacement his calcium and potassium concentrations gradually normalised and his dizziness and paraesthesia improved, but he developed hypomagnesaemia whenever the supplements were stopped. While in hospital he developed bradycardia (pulse 48 beats/min) and hypotension (blood pressure 90/55 mm Hg), and it was suggested that this might account for his dizzy episodes. His antihypertensive drug was stopped. An electrocardiogram showed atrial flutter and long (4 second) pauses. As his hypomagnesaemia was thought to be contributing to the abnormal electrocardiogram, we considered that the hypomagnesaemia should be corrected before fitting a pacemaker.

Drug review raised the possibility that omeprazole was causing his electrolyte disturbances, and it was stopped. Within a few days the patient “felt great.” Normal electrolytes were maintained without supplementation. He was discharged with outpatient follow-up.