Suspension of disbelief - or the Bumetanide paradox

Figure 1A.

Localised interstitial streaks are present in both lungs. Pathology like this is more descriptive than conclusive in its nature but the possible relation with the use of bumetanide makes it exemplary in this case.

Figure 1B.

Situation after withdrawal of bumetanide.

Once in a while a clinician is confronted with a situation where his pharmaceutical intervention itself dominates a given clinical picture in a way that was not foreseen, and certainly not anticipated. Druginduced allergic alveolitis is a fine example of such a mishap and knowledge of its presentation and nature is particularly useful in a time where nurse practitioners and paramedics are more and more in control of the management of heart failure patients. In decisionmaking they heavily rely on guidelines and laboratory results, such as BNP, together with findings on physical examination. Basic roentgenology like a plain X-ray of the thorax is not routinely used for plausible reasons of patient care and cost-effectiveness. Nevertheless, roentgenology and analysis of arterial gasses are mandatory in unexplained dyspnoea or deterioration of a previously stable clinical picture.

A 79-year-old man with a history of limited myocardial infarction, mild aortic stenosis (peak gradient 45 mmHg) and renal insufficiency (creatinine 211 mmol), presented with dyspnoea and gradually increasing limitation in his exercise capacity. At that time he was on drug therapy, including bumetanide and prednisone for interstitial pulmonary disease or alveolitis, which presented with haemoptysis in its early stages and demonstrated a rather variable but distinct roentgenological pattern.

Retrospectively, the onset of pulmonary disease coincided with the use of bumetanide, prescribed one year earlier for signs of congestive heart failure. After replacing bumetanide with furosemide the clinical picture improved and the roentgenology gradually cleared. Only once before has a comparable case been reported in the literature.¹ Of course it should be stressed that there is no solid proof that bumetanide alone is responsible for the reported cascade of clinical effects. But then again, there is a bit more than circumstantial evidence alone. Although the proof of the pudding is in the eating, it did not seem very rational or ethical at the time to put an old and fragile patient to the test again.

Drug-induced allergic alveolitis itself is not an uncommon finding in daily clinical practice and can be associated with high morbidity and mortality. Amiodarone,² for instance, is well known for its potential pulmonary toxicity, but thalidomide³ (revisited as drug therapy for multiple myoma) and sulphasalazine⁴ (in rheumatoid arthritis) have also been related to lung toxicity and respiratory insufficiency.

Of the anti-inflammatory agents, acetylsalicylic acid can produce several different airway and parenchymal complications, including aggravation of asthma, noncardiac pulmonary oedema and a pseudosepsis syndrome.⁵ Apparently, even bumetanide, which is widely used for the relief of dyspnoea, should be added to a short list of pharmaceutical agents with a potentially deleterious effect on pulmonary function, and at the same time exerting a paradoxically enhancing effect on that very dyspnoea as the specific symptom involved. So once more, one should argue for a prudential approach when confronted with a situation where ‘freshly’ installed drug therapy leads to an adverse reaction such as ‘new’ dyspnoea. A proactive attitude is then warranted despite possible disbelief or a lack of supportive evidence at that moment. A situation like this also stresses the need for an accurate drug history especially in patients with unexplained symptoms.