Treating Intraoperative Bradycardia in Non-cardiac Surgery Patients With Atropine at Heart Rates Below 60 Versus 30 Beats Per Minute and Norepinephrine Requirements (RAPID)

Treating Intraoperative Bradycardia in Non-cardiac Surgery Patients With Atropine at Heart Rates Below 60 Versus 30 Beats Per Minute and Norepinephrine Requirements: the Randomized RAPID Trial

The RAPID trial is a randomized, single-center trial investigating whether giving atropine at heart rates below 60 beats per minute versus giving atropine only at heart rates below 30 beats per minute reduces the amount of norepinephrine needed to keep MAP above 65 mmHg in non-cardiac surgery patients with intraoperative bradycardia.

Study Overview

• Status: Completed
• Conditions: Intraoperative Bradycardia
• Intervention / Treatment: Drug: Giving atropine at heart rates below 60 beats per minute; Drug: Giving atropine at heart rates below 30 beats per minute

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Hamburg, Germany, 20246
    • University Medical Center Hamburg-Eppendorf

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: Consenting patients ≥50 years scheduled for elective non-cardiac surgery with general anesthesia that is expected to last ≥60 minutes with at least two of the following risk criteria for developing acute kidney injury:

• Age ≥65 years
• American Society of Anesthesiologists physical status III or IV
• Chronic arterial hypertension
• Diabetes mellitus requiring medication
• Intraabdominal surgery
• Preoperative renal insufficiency (serum creatinine ≥1.2 mg/dL)

Exclusion Criteria:

Patients with the following exclusion criteria: contraindication for atropine administration (e.g., myasthenia gravis, high-grade aortic stenosis, high-grade coronary artery disease, glaucoma, paralytic ileus, prostatic hypertrophy); renal replacement therapy within the previous 3 months; chronic kidney disease with an estimated glomerular filtration rate <20 mL/min/1.73 m2; pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Giving atropine at heart rates below 60 beats per minute	Drug: Giving atropine at heart rates below 60 beats per minute; In patients assigned to the atropine therapy at heart rates below 60 beats per minute, atropine will be given at a dose of 0.5 mg when heart rate is below 60 beats per minute for one continuous minute. A second and third atropine dose of 0.5 mg will be given if heart rate remains or again drops below 60 beats per minute for one continuous minute. Patients will not be given more than 1.5 mg atropine.
Active Comparator: Giving atropine at heart rates below 30 beats per minute	Drug: Giving atropine at heart rates below 30 beats per minute; In patients assigned to atropine therapy at heart rates below 30 beats per minute, atropine will be given at a dose of 0.5 mg when heart rate is below 30 beats per minute for one continuous minute. A second and third atropine dose of 0.5 mg will be given if heart rate remains or again drops below 30 beats per minute for one continuous minute. Patients will not be given more than 1.5 mg atropine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average norepinephrine infusion rate	Average norepinephrine infusion rate in μg per kg actual body weight per minute (μg kg-1 min-1) needed to keep MAP above 65 mmHg from anesthetic induction until the end of surgery (continuous outcome)	Perioperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-weighted average MAP <65 mmHg	From anesthetic induction until the end of surgery	Perioperative
Time-weighted average heart rate <60 bpm	From anesthetic induction until the end of surgery	Perioperative
Time-weighted average MAP >110 mmHg	From anesthetic induction until the end of surgery	Perioperative
Time-weighted average heart rate >100 bpm	From anesthetic induction until the end of surgery	Perioperative

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of acute kidney injury	Acute kidney injury (binary outcome) will be defined as an increase in postoperative creatinine of ≥50 % from baseline.	Within the first 3 postoperative days
Incidence of delirium	Delirium (binary outcome) will be assessed twice daily within the first three postoperative days using the 3-Minute Diagnostic Confusion Assessment Method for patients on normal wards and the Confusion Assessment Method for Intensive Care Unit for patients in intensive care units.	Within the first 3 postoperative days
Incidence of urinary retention	Urinary retention (binary outcome) will be assessed by reviewing the diagnoses documented in the patients' medical records within the first 3 postoperative days.	Within the first 3 postoperative days
Incidence of central anticholinergic syndrome	Central anticholinergic syndrome (binary outcome) will be assessed by reviewing the diagnoses documented in the patients' medical records within the first 3 postoperative days.	Within the first 3 postoperative days
Incidence of acute angle-closure glaucoma	Acute angle-closure glaucoma (binary outcome) will be assessed by reviewing the diagnoses documented in the patients' medical records within the first 3 postoperative days.	Within the first 3 postoperative days

Collaborators and Investigators

• Sponsor: University of Hamburg-Eppendorf
• Investigators: Principal Investigator: Alina Bergholz, MD, University Medical Centre Hamburg-Eppendorf

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2025
• Primary Completion (Actual): November 11, 2025
• Study Completion (Actual): December 16, 2025

Study Registration Dates

• First Submitted: March 23, 2025
• First Submitted That Met QC Criteria: April 9, 2025
• First Posted (Actual): April 10, 2025

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Bradycardia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Anti-Arrhythmia Agents; Adjuvants, Anesthesia; Respiratory System Agents; Anti-Asthmatic Agents; Bronchodilator Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Parasympatholytics; Mydriatics; Atropine
• Other Study ID Numbers: 2025-101426-BO-ff

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No