Examining the “Repletion Reflex”: The Association between Serum Potassium and Outcomes in Hospitalized Patients with Heart Failure

Potassium Repletion

We evaluated whether patients received potassium during the exposure window (defined as any supplemental potassium order during the hospital stay) and the total number of days the patient was eligible for repletion (defined as a serum potassium result that was <4.0 mEq/L). We then recorded the total number of days repletion was given (using medication orders). We also calculated the ratio of days that repletion was received to the days that the patient was eligible for repletion. We also recorded all instances in which serum potassium values were <3.5 mEq/L at any time during the exposure window

Analysis

We evaluated the differences in patient characteristics across serum potassium categories. Categorical variables are presented as frequencies and percentages, whereas continuous variables are presented as means and standard deviations. For binary outcomes, we used generalized estimating equations (with a binomial family and logit link and clustering by hospital) to estimate incidence and calculate unadjusted and adjusted odds ratios (ORs) and 95% confidence intervals (CIs). For LOS, we estimated the median and 95% CIs using quantile regression with clustered standard errors.²⁴ We calculated all models using both a binary exposure (<4.0 versus ≥4.0 mEq/L) and a three-level categorization (<4.0, 4.0-4.5, and >4.5 mEq/L) to explore the effects at the highest potassium level. We adjusted all models for age, race, LAPS-2 score, and combined comorbidity score. We conducted two sensitivity analyses. First, we restricted our sample to those who never received potassium during the exposure window, as these patients may be different than patients who required potassium repletion. Second, we stratified our findings by the presence or absence of acute or chronic renal insufficiency (defined as an admission creatinine >1 or the presence of a diagnostic code for renal insufficiency, as defined by Elixhauser et al.).^19,21 Statistical significance was set at an alpha of 0.05. Analysis was completed using Stata v15.1, StataCorp LP, College Station, Texas.

Cohort Description

We identified patients from 56 geographically diverse US hospitals, although most were located in either the northeast (n = 21; 38%) or south (n = 18; 32%). A total of 59% of the hospitals were teaching hospitals, and nearly 95% were in an urban setting. We identified 13,163 patients with HF, of which 4,995 (38.0%) met the inclusion criteria. We excluded 3,744 (28.4%) patients with LOS < 72 hours, 2,210 (16.8%) with admission potassium values outside of the defined range, and 896 (6.8%) with fewer than three potassium values during the exposure window. Of the patients who met the inclusion criteria, 2,080 (41.6%), 2,326 (46.6%), and 589 (11.8%) were categorized in the <4.0, 4.0-4.5, and >4.5 mEq/L groups, respectively (Table 1). The groups were clinically similar in terms of age, sex, illness severity (LAPS-2), and comorbidity score. Compared with other racial groups, black patients had higher potassium values. While the <4.0 and 4.0-4.5 mEq/L groups were relatively similar, the group with mean potassium >4.5 mEq/L had higher admission creatinine and a greater prevalence of chronic kidney disease, deficiency anemias, and chronic obstructive pulmonary disease (Table 1).