Original article
Safety of furosemide administration in an elderly woman recovered from thiazide-induced hyponatremia

https://doi.org/10.1016/j.ejim.2008.04.006Get rights and content

Abstract

Background

Elderly women are at risk to develop severe hyponatremia after thiazide but not loop diuretic administration. In patients with previous thiazide-induced hyponatremia, the risk for recurrent hyponatremia after furosemide has not been established.

Methods

In order to determine how both diuretics affect water metabolism, we here compare the effects of a rechallenge with either amiloride-hydrochlorothiazide fixed association (AmHTZ; amiloride chlorhydrate 5 mg + hydrochlorothiazide 50 mg; Moduretic™) or furosemide (F; 40 mg; Lasix™) on water excretion in a 79 year old woman who was previously admitted for severe symptomatic hyponatremia secondary to a 5 days course of AmHTZ for systolic hypertension. After correction of initial hydromineral disturbances, a standard oral water load (WL; 20 mL per kg body weight) was administered before, during and after AmHTZ or F challenges.

Results

Hyponatremia developed after AmHTZ but not after F challenge. A negative free water clearance (CH2O) was only observed during AmHTZ (− 0.39 mL/min), while maximal CH2O during F was 3.17 mL/min. Based on the results obtained during WL, the calculated maximal daily electrolyte free water clearance ability was only 888 mL after AmHTZ but 10,166 mL after F therapy. Taking into account a measured mean daily water intake of 1830 mL, severe hyponatremia could be predicted to occur after a few days treatment with AmHTZ. In comparison, F appears to be safer, without risk of hyponatremia, during an equivalent period of time.

Conclusions

We here showed that F may be administered to a patient with previous AmHTZ induced hyponatremia without risk for recurrent hyponatremia.

Introduction

Hyponatremia is a well known complication of diuretic therapy [1]. In most instances, the offending drugs have been thiazides or related molecules [2] which induced both sodium depletion and inappropriate water retention.

Indeed, contraction of extracellular compartment secondary to diuretics induced volume depletion decreases fluid delivery to the diluting segment of the nephron and increases water reabsorption due to the stimulation of vasopressin release by non-osmotic stimuli ; both factors are responsible for a decrease in free water excretion, increasing the risk for the development of hyponatremia. Interestingly, furosemide, which is a more potent natriuretic drug has been only exceptionally involved in diuretic-induced hyponatremia [2], [3]. All these data suggest that the intrinsic molecular properties of the thiazide diuretics and related molecules may be directly instrumental in the occurrence of hyponatremia at least in part though an increase of the permeability to water of the collecting tubule as reported for indapamide [2]. Conversely specific properties of loop diuretic may protect for the development of hypoosmolar syndromes as exemplified by their use in the treatment of inappropriate antidiuresis [4]. We thus hypothesized that furosemide could be a safer diuretic in patients with an history of thiazide-induced hyponatremia. In the present study, we prospectively compare the effects of furosemide and AmHTZ on renal water excretion in one patient recovered from a hyponatremic episode related to AmHTZ treatment.

Section snippets

Case report

A 79-year-old woman was admitted with anorexia, nausea, and recent loss of memory. Her past medical history included systolic hypertension treated with one AmHTZ tablet a day, during the 5 days preceding the hospitalization. On admission, she was stuporous; physical examination was otherwise normal. Pertinent initial serum blood values were as follow: urea 57 mg/dl; creatinine 0.80 mg/dl; K+ 4.5 mEq/L; Na+ 119 mEq/L; Cl 77 mEq/L; HCO3 23 mEq/L; blood and urine osmolality were respectively 242

Evolution of SNa+ (Fig. 1)

After recovering, the patient was on a free water intake averaging 1830 mL a day, during the whole admission period. SNa remained above 135 mEq/L during that period even after the first water loading test. After AmHTZ administration followed by the second water load, serum Na+ falls significantly from 133 to 128 mEq/L. In contrast during administration of furosemide, no significant decrease in serum Na+ was noted. During the first 3 days, serum potassium fluctuated between 4.5 mEq/L and

Discussion

Elderly hypertensive women are at risk to develop severe hyponatremia when treated by thiazide diuretics or related molecules [1], [2], [11]. Although several pathogenic mechanisms responsible for the occurrence of hyponatremia have been proposed, inappropriate water retention appears to be the major pathogenic factor as suggested by Friedman et al [12]. Arguments favoring the role of a thiazide-induced decrease in urinary diluting capacity as the major cause of hyponatremia are the positive

Learning points

  • The occurrence of hyponatremia after thiazide administration identifies patients at risk for recurrent hyponatremic episodes after rechallenge with the offending drug

  • If confirmed by larger studies, Furosemide would be a safest diuretic alternative for patients with a previous thiazide-induced hyponatremic episode

  • Evaluating the ability to electrolyte free water by a standard oral water loading test performed during thiazide rechallenge helps to predict the occurrence of future hyponatremia.

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