Examining the “Repletion Reflex”: The Association between Serum Potassium and Outcomes in Hospitalized Patients with Heart Failure
BACKGROUND: In patients hospitalized with heart failure (HF) exacerbations, physicians routinely supplement potassium to maintain levels ≥4.0 mEq/L. The evidence basis for this practice is relatively weak. We aimed to evaluate the association between serum potassium levels and outcomes in patients hospitalized with HF.
METHODS: We identified patients admitted with acute HF exacerbations to hospitals that contributed to an electronic health record-derived dataset. In a subset of patients with normal admission serum potassium (3.5-5.0 mEq/L), we averaged serum potassium values during a 72-hour exposure window and categorized as follows: <4.0 mEq/L (low normal), 4.0-4.5 mEq/L (medium normal), and >4.5 mEq/L (high normal). We created multivariable models examining associations between these categories and outcomes.
RESULTS: We included 4,995 patients: 2,080 (41.6%), 2,326 (46.6%), and 589 (11.8%) in the <4.0, 4.0-4.5, and >4.5 mEq/L cohorts, respectively. After adjustment for demographics, comorbidities, and presenting severity, we observed no difference in outcomes between the low and medium normal groups. Compared to patients with levels <4.0 mEq/L, patients with a potassium level of >4.5 mEq/L had a longer length of stay (median of 0.6 days; 95% CI: 0.1 to 1.0) but did not have statistically significant increases in mortality (OR [odds ratio] = 1.51; 95% CI: 0.97 to 2.36) or transfers to the intensive care unit (OR = 1.78; 95% CI: 0.98 to 3.26).
CONCLUSIONS: Inpatients with heart failure who had mean serum potassium levels of <4.0 showed similar outcomes to those with mean serum potassium values of 4.0-4.5. Compared with mean serum potassium level of <4.0, mean serum levels of >4.5 may be associated with increased risk of poor outcomes.
© 2019 Society of Hospital Medicine
We included patients who had a principal International Classification of Disease (ICD-9-CM) diagnosis of HF or a principal diagnosis of respiratory failure with secondary diagnosis of HF (ICD-9-CM codes for HF: 402.01, 402.11, 402.91, 404.01, 404.03, 404.11, 404.13, 404.91, 404.93, 428.xx16 and for respiratory failure: 518.81, 518.82, 518.84) and were 18 years or older. We ensured that patients were treated for acute decompensated HF during the hospitalization by restricting the cohort to patients in whom at least one HF therapy (eg, loop diuretics, metolazone, inotropes, and intra-aortic balloon pump) was initiated within the first two days of hospitalization. We excluded patients with a pediatric or psychiatric attending physician, those with elective admissions, and those who were transferred from or to another acute care facility because we could not accurately determine the onset or subsequent course of their illness.
Definition of Variables Describing Serum Potassium Levels
We limited the sample to patients hospitalized for longer than 72 hours in order to observe how initial potassium values influenced outcomes over the course of hospitalization. We chose an exposure window of 72 hours because this allowed, on average, three potential observations of serum potassium per patient. We further restricted the sample to those who had a normal potassium value (3.5-5.0 mEq/L) at admission (defined as 24 hours prior to admission through midnight of the day of admission) to ensure that the included patients did not have abnormal potassium values upon presentation. We identified the period of time from 24 hours prior to admission through 72 hours following admission as “the exposure window” (the time during which patients were eligible to be classified into average serum potassium levels of <4.0, 4.0-4.5, or >4.5 mEq/L). We excluded patients who, during this window, had fewer than three serum potassium levels drawn (“exposure” levels could be disproportionately influenced by a single value) or received sodium polystyrene (as this would indicate that the physicians felt the potassium was dangerously high). For patients with repeated hospitalizations, we randomly selected one visit for inclusion to reduce the risk of survivor bias. We calculated the mean of all serum potassium levels during the exposure window, including the admission value, and then evaluated two different categorizations of mean serum potassium, based on categories of risk previously reported in the literature:8,17,18: (1) <4.0, 4.0-4.5, or >4.5 mEq/L and (2) <4.0 versus ≥4.0 mEq/L.
Outcomes
We assessed three outcomes: in-hospital mortality, transfer to an intensive care unit (ICU), and length of stay (LOS). Admission to the ICU was defined as any evidence, after the exposure window, that the patient received care in the ICU. We excluded patients with ICU admissions during the exposure window from the analysis of this outcome. We calculated LOS as the difference between discharge date/time and the admission date/time.
Covariates and Comorbidity Adjustment
We obtained information on patient demographics (age and race) and identified the presence of comorbid conditions using previously derived and validated models.19,20 We then further quantified these conditions into a single combined score to adjust for differences in presenting illness severity (including kidney disease) and help reduce confounding.21 To account for presenting severity of illness, we calculated the Laboratory-based Acute Physiology Score (LAPS-2).22,23 LAPS-2 was developed for predicting mortality risk in general medical patients, but we previously externally validated it against other published clinical HF models in a cohort of patients hospitalized with acute decompensated HF.5
