ACUTE PULMONARY EDEMA SECONDARY TO HYDROCLOROTHIAZIDE ADMINISTRATION

Abstract

Objective: To describe the clinical presentation and evolution of a severe and rare adverse reaction to hydroclorothiazide. Design and method: We present the case of a 74-year-old woman with a personal history of permanent atrial fibrillation under treatment with acenocumarol, pacemaker carrier, rheumatic valvular heart disease (moderate aortic stenosis and mitral mechanical prosthesis), chronic heapitis B viral infection and autoimmune hypothyroidism. She had previous severe adverse reactions with antihypertensive combined drugs in two ocasions: with hydroclorothiazide/valsartan and amilorid/ hydroclorothiazide. The patient was derivated to the emergency room from the Allergy Day Hospital. While perfoming an allergy provocation test with hydroclorothiazide (HCTZ) she rapidly developed hypotension (60/40 mmHg), fever (37.8 °C), dyspnea and desaturation with congestive symptoms. The patient required intensive care management with not invasive mechanical ventilation and vasoactive support. Results: The patient evolved favorably with rapid improvement of the congestive symptoms after supportive management and diuretics. Blood analyses revealed transient leukopenia 700/μL (Neutrophils 300/ μL; Lymphocytes 300/ μL), eosinophilia was not observed. Hemoglobin and platelets were whithin normal range and no renal, hepatic or ionic alterations were observed. Troponin levels were normal. C-reactive protein and Nt-proBNP were mild elevates (5.4 mg/dL and 2686 ng/L respectively). No changes were observed in the electrocardiogram. Chest X-ray showed bilateral pleural effusion and vascular redistribution. An echocardiogram was performed, without changes in the left ejection fraction, valvulopathies or contractility compared to the previous one performed a few months earlier. Blood and urine cultures and the patch test for HCTZ was negative. The leukopenia resolved and Nt-proBNP normalized in about 48 hours. Conclusions: There have been sporadic reports of hydroclorothiazid causing noncardiogenic pulmonary edema as an idiosyncratic reaction. The onset of symptoms typically occurs quickly after ingesting the medication (often within an hour). Due to the rare incidence of this reaction (less than 50 cases described in the literature), the diagnosis of HCTZ-induced pulmonary edema is often made only on re-exposure to the medication and may masquerade as septic shock and acute respiratory distress syndrome from a pneumonia. The possible mechanisms of the pulmonary edema still remain unknown.