Predicting Early Circulatory Deterioration After Short-Acting Beta-Blocker Treatment in Intensive Care Patients

NCT07846995 | Completed

• 1 other identifier: B2026-484-BBlocker
• Study Type: observational
• Target: 2,541
• Locations: 1 country
• Sites: 1

Brief Summary

This retrospective observational study used existing intensive care records to examine whether heart rate and blood pressure measured before short-acting beta-blocker treatment could help predict early signs of worsening circulation recorded after treatment. The study included patients who had received intravenous esmolol or landiolol during routine care. Researchers did not assign treatment or change patient care. The main analysis used records from Zhongshan Hospital, Fudan University. Additional intensive care databases were used to evaluate whether a prediction model developed at this hospital could be applied to other patient populations. The main questions were whether pretreatment heart rate and blood pressure could predict recorded circulatory changes, whether combining these measurements improved prediction over simpler blood pressure measures, and whether differences in blood pressure monitoring affected the findings. The main outcome combined a recorded fall in blood pressure, initiation or escalation of norepinephrine (a medicine used to support blood pressure), or early discontinuation of the same beta-blocker. Blood pressure and norepinephrine changes were assessed during the first three hours after the treatment index, and drug discontinuation during the first hour. External database analyses focused on recorded low blood pressure during the first three hours. The study evaluated prediction among patients who had already received treatment. It was not designed to determine whether beta-blockers caused these events or whether a patient should receive a beta-blocker. Data collection and the analyses described here were completed before registration.

Conditions

Critical Illness

Keywords

Short-Acting Beta-Blockers; Intensive Care; Hemodynamics; Prediction Model

Outcome Measures

Primary Outcomes (1)

• Percentage of ICCA Patients With Recorded Early Haemodynamic Deterioration

  Percentage of eligible ICCA patients with at least one recorded component of the composite outcome: (1) new mean arterial pressure (MAP) below 65 mmHg during (0,180\] minutes after the treatment index; (2) documented norepinephrine initiation, a within-source change from zero to a positive rate, or a greater than 20% increase from a positive pre-index rate during (0,180\] minutes; or (3) an explicit stop record for the same study beta-blocker during (0,60\] minutes. Norepinephrine changes were compared only within the same data source and measurement unit. Eligible patients had a last MAP of at least 65 mmHg during \[-30,0) minutes, post-index MAP observation, and ICU presence through 180 minutes. Patients meeting these observation requirements without a qualifying recorded signal were classified as having no recorded composite event. This outcome does not establish drug causality, and early stopping does not necessarily indicate intolerance. This composite was assessed in ICCA only.

  From the documented treatment start to 180 minutes afterward; same-drug discontinuation assessed within the first 60 minutes.

Secondary Outcomes (1)

• Percentage of Patients With Newly Recorded Hypotension

  Within 180 minutes after the database-specific treatment index

Study Arms (1)

ICU Patients Receiving Short-Acting Intravenous Beta-Blockers

Patients receiving intravenous esmolol or landiolol during routine intensive care, identified retrospectively from six data sources. ICCA at Zhongshan Hospital, Fudan University, provided 1,354 esmolol- or landiolol-treated patients for model development and internal validation. External esmolol cohorts comprised MIMIC-IV (625), eICU (191), AmsterdamUMCdb (56), HiRID (88), and SICdb (227). The first eligible treatment index per patient was selected within each source. Eligibility required baseline MAP of at least 65 mmHg, complete pretreatment predictors, post-index MAP observation, and ICU presence through 180 minutes. ICCA assessed the recorded composite outcome; external cohorts evaluated the frozen MAP-only model without refitting, with AmsterdamUMCdb limited to descriptive evaluation. Treatment was not assigned by the study. Esmolol and landiolol were alternative recorded exposures, not a required combination.

Drug: Esmolol; Drug: Landiolol

Interventions

Esmolol DRUG

Intravenous esmolol administered during routine intensive care, as documented in existing medication records. Treatment selection, dose, and duration were determined by treating clinicians. Esmolol exposure was identified retrospectively; no treatment was assigned or modified by the study.

ICU Patients Receiving Short-Acting Intravenous Beta-Blockers

Landiolol DRUG

Intravenous landiolol administered during routine intensive care, as documented in existing medication records. Treatment selection, dose, and duration were determined by treating clinicians. Landiolol exposure was identified retrospectively; no treatment was assigned or modified by the study.

ICU Patients Receiving Short-Acting Intravenous Beta-Blockers

Eligibility Criteria

• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients receiving intravenous short-acting beta-blockers during routine intensive care, identified retrospectively from electronic health records. The development population comprised patients treated with esmolol or landiolol at Zhongshan Hospital, Fudan University, identified through ICCA. External validation populations comprised esmolol-treated patients in MIMIC-IV, eICU, AmsterdamUMCdb, HiRID, and SICdb. Analyses used the first qualifying treatment index per patient and required preserved baseline mean arterial pressure, available pretreatment predictors, post-index blood pressure monitoring, and documented ICU presence through 180 minutes. Treatment was determined by clinical care, not assigned by the study.

You may qualify if:

• ICU patients with routinely collected medication and physiological records in ICCA at Zhongshan Hospital, Fudan University, or in MIMIC-IV, eICU, AmsterdamUMCdb, HiRID, or SICdb.
• Documented intravenous esmolol or landiolol treatment in ICCA, or documented intravenous esmolol treatment in the external validation cohorts.
• An identifiable treatment index according to database-specific medication-record rules. ICCA required a timestamp-verified treatment start. In eICU, the index was the first documented positive-rate infusion record rather than a verified initiation time.
• The last recorded mean arterial pressure within 30 minutes before the treatment index was at least 65 mmHg.
• At least one mean arterial pressure measurement was recorded after the treatment index and within 180 minutes.
• Documented ICU presence extended through 180 minutes after the treatment index.
• Pretreatment heart rate, diastolic blood pressure, and pulse pressure were available to calculate the model predictors within the 120 minutes before the treatment index.

You may not qualify if:

• Medication records that could not be mapped unambiguously to the patient, ICU stay, study drug, or treatment index.
• In ICCA, candidate starts with a conflicting same-time stop or an unresolved continuation or restart.
• No qualifying baseline mean arterial pressure measurement, or a last baseline mean arterial pressure below 65 mmHg.
• No mean arterial pressure measurement in the 180-minute post-index window.
• Insufficient documented ICU presence through 180 minutes after the treatment index.
• Missing pretreatment measurements required to calculate the model predictors.
• Record-selection rules:
• The first accepted treatment index per patient was selected before assessing outcome completeness in each cohort; later courses were not substituted when this first index failed eligibility requirements.
• Duplicate medication records at the same patient, stay, drug, and timestamp were collapsed.
• Physiological measurements recorded exactly at the treatment index were excluded because their temporal order relative to drug administration was uncertain.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

Study Sites (1)

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Critical Illness

Interventions

esmolol; landiolol

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2026
• First Posted: September 29, 2026
• Study Start: August 1, 2026
• Primary Completion: September 20, 2026
• Study Completion: September 22, 2026
• Last Updated: September 29, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)