Markers of diuretic resistance in emergency department patients with acute heart failure

Abstract

BackgroundLoop diuretics are common therapy for emergency department (ED) patients with acute heart failure (AHF). Diuretic resistance (DR) is a term used to describe blunted natriuretic response to loop diuretics. It would be important to detect DR prior to it becoming clinically apparent, so early interventions can be initiated. However, several definitions have been proposed, and it is not clear if they identify similar patients. We compared these definitions and described the clinical characteristics of patients who fulfilled them.MethodsTo qualify for this secondary analysis of 1033 ED patients with AHF, all patients needed to receive intravenous diuretics in the ED and have urine available within 24 h of their ED evaluation. A poor diuretic response, suggesting DR, was characterized by (1) a fractional sodium excretion (FeNa) of less than 0.2%; (2) spot urinary sodium of less than 50 meq/L; and (3) a urinary Na/K ratio <1.0. McNemar’s test was used to compare the different cohorts identified by the three definitions. Secondary analyses evaluated associations between each DR definition and hospital length of stay (LOS), ED revisits and rehospitalizations for AHF, and mortality using the Wilcoxon rank-sum tests and linear regression or Pearson chi-square test and logistic regression, as appropriate.ResultsThe median age of the 187 patients was 64, and 50% were African-American. There were 5.9% of patients with a FeNa less than 0.2%, 17.1% had urinary sodium less than 50 meq/L, and 10.7% had a urinary Na/K ratio <1.0. The three definitions identified significantly different patients with very little overlap (p < 0.02 for all comparisons). There were 37 (19.8%) patients who were readmitted to the ED or hospital or died within 30 days of ED evaluation. Patients with spot urinary sodium less than 50 meq/L were more likely to be readmitted (p = 0.03).ConclusionsThe patient proportion with poor natriuresis and DR varies depending on the definition used. Early ED therapy would be impacted at different rates if clinical decisions are made based on these definitions. These findings need to be further explored in a prospective ED-based study.Trial registrationClinicalTrials.gov, NCT00508638 Electronic supplementary materialThe online version of this article (doi:10.1186/s12245-017-0143-x) contains supplementary material, which is available to authorized users.

Role of electrolyte concentrations and renin‐angiotensin‐aldosterone activation in the staging of canine heart disease

“…Stage D dogs made up 21% of the CHF population in our study. This percentage is similar to reports of people with CHF that show diuretic resistance, but we do not know if all (or any) of these dogs had diuretic resistance . Laboratory variables, including FE Na, uNa, uNa:uK, and uNa:Fur, have been proposed as markers of diuretic resistance, associated with refractory CHF, in people.…”

“…Diuretic resistance is identified in up to 17% of people with CHF and also is suspected to occur in dogs . Although reports of diuretic resistance are lacking in veterinary medicine, the American College of Veterinary Internal Medicine (ACVIM) considers a role for diuretic failure in the description of refractory heart disease (HD), termed Stage D .…”

“…Potential causes of suboptimal diuretic responsiveness include inadequate gastrointestinal drug absorption, decreased renal tubular transport, loop of Henle cell hypertrophy, and RAAS activation . In humans, diuretic resistance is defined as persistent CHF despite an appropriate furosemide dosage; fractional excretion of sodium (FE Na) <0.2%; failure of adequate natriuresis after furosemide administration; or urine sodium:urine potassium ratio (uNa:uK) <1.0 . Some studies in people with CHF also have associated poor diuretic response with deceased spot urine sodium concentration (uNa), hypochloremia, and low urine sodium:urine furosemide ratio (uNa:uFur), the latter indicating pharmacodynamic unresponsiveness to the diuretic .…”

Early urine electrolyte patterns in patients with acute heart failure

“…15 Evaluating natriuresis and diuresis within 1 h of diuretic administration could identify patients within 2-3 h of ED presentation who may need early treatment intensification. In contrast to prior studies that were conducted in the inpatient setting after admission and initial therapy, we followed up patients in the ED and documented urine output in the first 6 h as a measure of acute diuretic response.…”

“…Our previous study also suggested a relationship between urinary sodium and hospital LOS. 15 Evaluating natriuresis and diuresis within 1 h of diuretic administration could identify patients within 2-3 h of ED presentation who may need early treatment intensification. Other markers of response to diuretic therapy, such as weight loss and fluid excretion, have been used and have been inconsistent markers of decongestion and treatment endpoints.…”