Association of stress biomarkers with 30-day unplanned readmission and death
BACKGROUND
The theory that posthospitalization stress might increase the risk of postdischarge complications has never been investigated.
OBJECTIVE
To assess whether serum levels of stress biomarkers at discharge are associated with readmission and death after an acute-care hospitalization.
DESIGN
We prospectively included 346 patients aged ≥50 years admitted to the department of general internal medicine at a large community hospital between April 8, 2013 and September 23, 2013. We measured the serum levels of several biomarkers at discharge: midregional pro-adrenomedullin, copeptin, cortisol, and prolactin. All patients were followed for up to 90 days after discharge (none was lost to follow-up). The main outcome was first unplanned readmission or death within 30 days after hospital discharge. We assessed the additional value of biomarkers to 2 validated readmission prediction scores: the LACE index (Length of stay, Admission Acuity, Charlson Comorbidity Index, and number of Emergency department visits within preceding 6 months) and the HOSPITAL score (Hemoglobin level at discharge, discharge from Oncology service, Sodium level at discharge, any Procedure performed during index hospitalization, Index admission Type, number of Admissions within preceding 12 months, and Length of stay).
RESULTS
Forty patients (11.6%) had a 30-day unplanned readmission or death. High serum copeptin and cortisol levels were associated with an increase in the odds of unplanned readmission or death (odds ratios [95% confidence interval] 2.69 [1.29-5.64] and 3.43 [1.36, 8.65], respectively). We found no significant association with midregional pro-adrenomedullin or prolactin. Furthermore, these stress biomarkers increased the performance of two readmission prediction scores (LACE index and HOSPITAL score).
CONCLUSION
High serum levels of copeptin and cortisol at discharge were independently associated with 30-day unplanned readmission or death, supporting a possible negative effect of hospitalization stress during the postdischarge period. Stress biomarkers improved the performance of prediction models and therefore could help better identify high-risk patients. Journal of Hospital Medicine 2017;12:523-529. © 2017 Society of Hospital Medicine
© 2017 Society of Hospital Medicine
It has been theorized that the physiologic stress that hospitalized patients experience accounts for their transient vulnerability after discharge, or posthospital syndrome.1 Their acute illness and life-habit changes during hospitalization result in continued impairment of physiologic systems after discharge, and this impairment might leave them more susceptible to new health threats.1 However, the theory that the stress experienced after a hospitalization might be associated with readmission has never been investigated.
Four biomarkers of the hypothalamic-pituitary-adrenal (HPA) axis may help quantify posthospitalization stress: (1) midregional pro-adrenomedullin (ADM), a precursor reflecting adrenomedullin activity2; (2) copeptin (the C-terminal part of prepro-vasopressin, produced by the hypothalamus in response to stress3,4), the level of which closely correlates to the vasopressin level but is more stable and lacks circadian rhythm fluctuations5-7; (3) cortisol, released by the adrenal cortex in response to stress; and (4) prolactin, an indicator of HPA axis activity. These 4 stress biomarkers have been related to the severity, complications, or mortality of several diseases.3,5,8-17 Besides explaining the hypothetical association between posthospitalization stress and readmission and death, these biomarkers might be valuable in predicting which patients are at higher risk for readmission. Indeed, many prediction models have been developed to identify those patients, but most of these models underperform, target only very specific populations, or have not been externally validated.18
We hypothesized that the hospitalization stress measured by biomarkers is associated with readmission or death after discharge. In a prospective cohort study, we evaluated the association between 4 stress biomarkers (ADM, copeptin, cortisol, prolactin) and 30-day unplanned readmissions and deaths after an acute-care medical hospitalization, and assessed their additive value to validated readmission prediction scores.
METHODS
Study Design and Population
Our prospective cohort study included all consecutive patients aged ≥50 years and admitted to the department of general internal medicine at Fribourg Cantonal Hospital in Switzerland between April 8, 2013 and September 23, 2013. Exclusion criteria were discharge on day of admission; death before discharge; discharge to another division, another acute-care hospital, a rehabilitation clinic, or a palliative-care clinic; and refusal or inability to give informed consent. In this hypothesis-generating observational study, we collected data on a convenience sample of patients and did not calculate sample size before data collection. The study was approved by the local ethics committee, and all patients gave informed consent.
