β-Blockers are used widely in the outpatient care of chronic disease, but less is known about how to restart chronic therapy during and after hospitalization for septic shock [1, 2]. We sought to characterize the epidemiology of β-blocker treatment during and after septic shock among patients administered chronic β-blocker therapy in the year prior to hospitalization [3].

We studied patients who received outpatient β-blocker therapy in the 12 months prior to hospitalization at 12 UPMC hospitals from 2010 to 2014 with follow up through 2019. Eligible patients were adults (age ≥ 18 years) with septic shock, defined as suspected infection and sequential organ failure assessment (SOFA) score ≥ 2 within 24 h of admission and receiving vasopressor therapy [4]. Demographics, biomarkers, outpatient and inpatient β-blocker and vasopressor administration were abstracted from outpatient records (EPIC Inc.) for each admission day up to 14 days (CERNER Inc.). Patients were stratified as: (i) those who were administered β-blockers each hospital day (“continued”), (ii) those with cessation of chronic therapy for more than 24 h with or without restart during the hospital stay (“held”), and (iii) those who never received β-blockers (“discontinued”). Descriptive data were compared across groups using the Kruskal–Wallis test and χ² test with a Bonferroni adjusted (2-sided) significance level of P < 0.05, as appropriate. All analyses used Stata, version 18.0 (StataCorp).

Of 22,208 patients, 3748 were hospitalized with septic shock and received chronic β-blockers (mean age 67 ± 14 years, 56% male, 87% White, median SOFA score 9.0 (IQR: 6.0–11.0) (Fig. 1A). Of those who received chronic therapy, 405 (11%) continued, 2,025 (54%) held, and 1,317 (35%) discontinued chronic β-blocker therapy during intensive care. Patients in whom β-blockers were discontinued presented with greater SOFA score (“continued,” median SOFA 8.0 (IQR: 6.0–11.0); “held,” 8.0 (IQR: 6.0–11.0; “discontinued,” 10.0 (IQR: 7.0–12.0); p < 0.001), while first-measured biomarkers, such as serum lactate, troponin, and platelets, were similar across groups.

Patient characteristics and prescribing patterns. A Patient characteristics of adults with septic shock who received chronic β-blocker therapy prior to hospitalization. Abbreviations include: d, days; ICU, intensive care unit; INR, international normalized ratio; IQR, interquartile range; no, number; SD, standard deviation; SIRS, systemic inflammatory response syndrome; SOFA, sequential organ failure assessment; y, years. SI conversion factors: To convert serum creatinine to micromole per liter, multiply by 88.4; platelet count to × 10^9/L, multiply by 1.0; and total bilirubin to micromoles per liter, multiply by 17.104. ^aDerived from UPMC registration system data using fixed categories similar to the Centers for Medicare & Medicaid Services electronic health record meaningful use data set. “Other” includes Chinese, Filipino, Hawaiian, American Indian/Alaskan Native, Asian, Hawaiian/other Pacific Islander, Middle Eastern, Native American, not specified, or Pacific Islander. ^bA method of categorizing comorbidities of patients based on the International Classification of Diseases, Ninth Revision diagnosis codes found in administrative data. Scores range from 0 to 31. ^cA measure of acute organ dysfunction, assessed across 6 organs, with scores ranging from 0 to 24, maximum score reached within 6 h of sepsis episode. ^dA measure of systemic inflammation, ranging from 0 to 4, maximum score reached within 6 h of sepsis episode. ^eFor 43 of 3,119 patient days (1.4%), beta blocker data was missing. ^fAt any time during hospitalization. ^gMissing 5-year mortality for remaining patients. B Heatmap of variable inpatient prescribing among 100 randomly selected patients by hospital day

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Among 33,384 total patient-days, 12,613 (38%) had β-blockers alone, 9317 (28%) vasopressors alone, 2085 (6%) both vasopressors and β-blockers, and 9369 (28%) neither (Fig. 1B). During hospitalization, 92% of patients with β-blockers held restarted therapy, and the median time to restart from admission was 4 days (IQR: 2–6 days).

In-hospital mortality was highest if β-blockers were discontinued (“continued”, 17%; “held”, 16%; “discontinued”, 41%; p < 0.001). Among 1,908 patients who survived 6 months after septic shock, 89% were administered outpatient β-blockers, most often those with inpatient β-blockers continued (95%) or held (94%) versus discontinued (74%; p < 0.001).

In a multicenter cohort of septic shock patients who received chronic β-blocker therapy, most patients had therapy discontinued or held during hospitalization. Among those with chronic β-blockers held, inpatient prescribing was variable, and resumed, on average, four days after presentation. Nearly all restarted β-blocker therapy in the 6 months following hospitalization. Study limitations include that medication data was censored after 14 days of hospitalization, and that practice patterns may have changed since cohort inception. However, with an increasing use of β-blockade in chronic disease management, variable inpatient prescribing during septic shock suggests an important opportunity and duty to optimize adrenergic regulation during resuscitation and recovery to improve clinical outcomes.

Data will be made available from the corresponding author for researchers whose proposed use has been approved either with investigator support, after approval of a proposal, or with a signed data access agreement.

SOFA:

Sequential organ failure assessment

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The work was funded in part by the National Institutes of Health (Seymour, R35GM119519). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Authors and Affiliations

1. Department of Critical Care Medicine, University of Pittsburgh, 3550 Terrace St, Pittsburgh, PA, 15213, USA

   Stuthi Iyer, Jason N. Kennedy & Christopher W. Seymour

2. Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

   Peter C. Nauka

3. Division of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

   Mourad H. Senussi

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Contributions

C.W.S. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design were created by S.I., C.W.S., and J.N.K. Acquisition, analysis, or interpretation of the data were conducted by S.I., C.W.S., J.N.K., and M.H.S. Drafting of the manuscript was completed by S.I. and C.W.S. All authors provided critical revision of the manuscript for important intellectual content. Administrative, technical, or material support were provided by J.N.K., P.C.N., and C.W.S.

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Correspondence to Stuthi Iyer.

Ethics approval and consent to participate

The University of Pittsburgh institutional review board approved this minimal risk study with a waiver of informed consent.

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Consent for publication was obtained from study participants.

Competing interests

Dr. Seymour reports grants from the NIH and personal fees from Inotrem, Beckman Coulter, and Octapharma outside the submitted work. Ms. Iyer, Mr. Kennedy, Dr. Nauka, and Dr. Senussi report no disclosures.

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Iyer, S., Kennedy, J.N., Nauka, P.C. et al. Epidemiology of β-blocker use among critically iII patients during and after septic shock. Crit Care 28, 364 (2024). https://doi.org/10.1186/s13054-024-05145-1

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• Received: 14 October 2024

• Accepted: 22 October 2024

• Published: 11 November 2024

• DOI: https://doi.org/10.1186/s13054-024-05145-1

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