A 67 year old woman developed acute renal failure with serum potassium 9.4 mmol/l requiring emergency dialysis after seven days of diarrhoea while taking an ACE inhibitor for vascular disease. Review of the literature, the British National Formulary, and the patient information leaflets for each of the 11 ACE inhibitors currently marketed in the UK suggests that this potentially life threatening complication of ACE inhibition is not yet widely recognised.
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ACE inhibitors are prescribed for diabetes, hypertension, and cardiovascular disease on account of their cardiac and reno-protective properties. Gastroenteritis is one of the commonest minor illnesses affecting an estimated million people in the UK each year. It is usually viral in origin, self limiting, and only rarely life threatening. Inevitably, some patients will develop gastroenteritis while they are taking ACE inhibitors and when this happens the resulting volume depletion may precipitate acute renal failure as a result of the known actions of ACE inhibitors on the renal vasculature.1 We have recently conducted a survey of emergency medical admissions and shown that a hospital with a catchment population of 150 000 might expect to see one case of acute renal failure occurring as a result of diarrhoea during ACE inhibition each month.2 All cases of acute renal failure in this series resolved without the need for dialysis, after temporary withdrawal of the ACE inhibitor and large volumes of intravenous fluid. We now wish to report another complication of diarrhoea during ACE inhibition namely that of life threatening hyperkalaemia.
A 67 year old woman was admitted as an emergency unresponsive with Glasgow coma scale 6/15. Her presenting complaint was seven days of diarrhoea on a background of widespread vascular disease for which she was taking enalapril, bisoprolol, bumetanide, and isosorbide mononitrate. She was profoundly bradycardic at 20 beats per minute with systolic blood pressure 40 mm Hg and an undetectable diastolic pressure. Electrocardiography showed a broad QRS complex with absent P waves. She was paced as an emergency. Biochemistry then showed serum potassium 9.4 mmol/l, serum bicarbonate 9 mmol/l, blood urea 42.6 mmol/l, and serum creatinine 598 μmol/l. The high concentration of serum potassium was confirmed on a second specimen. Three weeks previously serum potassium had been 5.1 mmol/l with urea 15.3 mmol/l and creatinine 135 μmol/l. After treatment with calcium chloride, insulin/dextrose, and emergency dialysis, heart rate and blood pressure were restored to normal values and serum potassium decreased to 4.4 mmol/l. Rehydration with large volumes of intravenous fluid led to return of urine output. No further dialysis was required. Stool culture was sterile and her diarrhoea settled spontaneously. This patient’s ACE inhibitor and other medications were re-introduced before discharge from hospital. Serum potassium at clinic review two months later was 4.3 mmol/l with urea 9.7 mmol/l and creatinine 81 μmol/l.
Both hyperkalaemia and acute renal failure are recognised complications of ACE inhibition.3 Hyperkalaemia occurs partly because ACE inhibitors lower plasma aldosterone values and partly as a result of acute renal failure (ARF). Hyperkalaemia is more common in elderly patients, those with pre-existing renal impairment, and in patients who are also taking potassium supplements, potassium sparing diuretics, non-steroidal anti-inflammatory drugs, or β blockers.4,5 ARF is a consequence of the failure of renal autoregulation because of loss of angiotensin II mediated efferent arteriolar vasoconstriction, leading to a reduction in glomerular capillary pressure when renal perfusion pressure falls: commonly because of volume depletion, hypotension, co-prescription of a non-steroidal anti-inflammatory drug or bilateral renovascular disease.1
Our patient presented with life threatening hyperkalaemia and acute renal failure when she developed diarrhoea while taking enalapril on a background of widespread vascular disease. Her loop diuretic will probably have protected against hyperkalaemia while increasing the risk of uraemia, whereas her β blocker may have had the opposite effects.1 No other causes of hyperkalaemia or ARF were apparent. Her ACE inhibitor was successfully reintroduced after renal function returned to normal after dialysis and resolution of her diarrhoea.
We2 and others6,7 have previously reported cases of ARF attributable to diarrhoea during ACE inhibition and have argued that affected patients may present in this way in part because vagal stimulation by the ACE inhibitor blocks the tachycardia response to volume depletion that would normally alert a patient to the fact that they were unwell.8,9 There were of course other explanations for the profound bradycardia in our patient’s case, namely her severe hyperkalaemia and her β blocker. We suspect that these complications of ACE inhibitor treatment will be recognised by most hospital doctors but perhaps less so by general practitioners.10 Neither the British National Formulary nor the patient information leaflets for each of the 11 ACE inhibitors currently marketed in the UK make any reference to the threat posed by diarrhoea during ACE inhibition, persuading us that these potentially life threatening complications of ACE inhibition are not as well publicised as they deserve to be.
What advice should be given to the patient who develops acute diarrhoea while taking an ACE inhibitor? Temporary withdrawal of diuretic or ACE inhibitor, or both, while maintaining a high oral fluid intake, is likely to be successful in mild cases. For those who develop ARF, admission to hospital for intravenous fluid will be required. Temporary dialysis will be needed occasionally and perhaps particularly if the ARF is complicated by life threatening hyperkalaemia as in the case reported here. Similar advice is likely to be appropriate for any patient taking an ACE inhibitor, angiotensin receptor blocker, or non-steroidal anti-inflammatory drug, whose circulation is compromised for any other reason during an acute illness, for example, by septic or cardiogenic shock. Failure of renal function to recover after dialysis and restoration of extra cellular fluid volume is rare.11 In the longer term there is evidence that angiotensin receptor blockers are less likely to cause hyperkalaemia than ACE inhibitors, which may make these the drugs of preference when re-instituting cardioprotective treatment.12
Patients with diarrhoea or vomiting, or both, while taking an ACE inhibitor may develop acute renal failure with life threatening hyperkalaemia.
Conflicts of interest: none declared.