Liberal Versus Restrictive Use of Dobutamine in Cardiac Surgery (DOBUTACS)

Liberal Versus Restrictive Dobutamine in Cardiac Surgery (DOBUTACS): a Prospective Randomized Non-inferiority Clinical Trial

Inotropic agents are usually administered in the postoperative period after cardiac surgery. In most cases, dobutamine is administered routinely, for the probable occurrence of myocardial dysfunction after cardiopulmonary bypass or a low cardiac output with minimal evidence of altered tissue perfusion.

Recent data show that inotropic agents are used in 35-52% of cardiac surgeries in the perioperative period. However, the use of inotropic agents may be associated with adverse events, including myocardial ischemia, by elevation in myocardial oxygen consumption and the imbalance between supply and consumption, and tachyarrhythmias (atrial fibrillation, sinus tachycardia, ventricular tachyarrhythmias), primarily due to the β1-adrenergic effect.

This study is a non-inferiority clinical randomized study aiming to compare the use of dobutamine in a liberal strategy (in all patients at the time of withdrawal of CPB) with a restrictive strategy (based on clinical and hemodynamic evidence of low cardiac output syndrome associated with altered tissue perfusion). Our primary hypothesis is that the restrictive use of dobutamine is as safe and effective as the liberal one.

Study Overview

• Status: Completed
• Conditions: Coronary Disease; Cardiac Output, Low
• Intervention / Treatment: Drug: Liberal dobutamine protocol; Drug: Restrictive dobutamine protocol

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 05403000
      • Heart Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients undergoing cardiac surgery of coronary artery bypass graft (CABG) with cardiopulmonary bypass;
• Age equal or greater than 18 years;
• Written informed consent.

Exclusion Criteria:

• Previous ventricular dysfunction (ejection fraction lower than 50%)
• Sustained supraventricular or ventricular arrhythmias;
• Cardiogenic shock or need for inotropes before surgery;
• Immediate need of ventricular assist device or intraaortic balloon after CPB;
• Combined procedure;
• Pregnancy;
• Participation in another study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Liberal dobutamine group; All patients will receive dobutamine at the cardiopulmonary bypass weaning	Drug: Liberal dobutamine protocol; All patients will receive dobutamine at the cardiopulmonary bypass weaning.
Active Comparator: Restrictive dobutamine group; Patients will only receive dobutamine if they present clinical signs of cardiogenic shock	Drug: Restrictive dobutamine protocol; Patients will receive dobutamine during the first 8 hours after cardiopulmonary bypass weaning only if they have a cardiac index of ≤ 2.5L/min/m2 and at least one sign of tissue hypoperfusion: ScvO2 ≤ 70% and / or urine output < 2 mL/Kg/h despite adequate fluid replacement.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Combined endpoint of arrhythmias (ventricular and supraventricular), acute myocardial infarction, stroke or transient ischemic attack, low-output syndrome, cardiogenic shock and death from all causes within 30 days after cardiac surgery	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality rate	We will compare the mortality rate between groups within 30 days after randomization	30 days
Acute myocardial infarction incidence	We will compare the incidence of acute myocardial infarction between groups within 30 days after randomization	30 days
Stroke incidence	We will compare the incidence of stroke between groups within 30 days after randomization	30 days
Low cardiac output syndrome	We will compare the incidence of low cardiac output syndrome between groups within 30 days after randomization	30 days
Cardiogenic shock	We will compare the incidence of cardiogenic shock between groups within 30 days after randomization	30 days
Cardiac arrhythmias	We will compare the incidence of ventricular and supraventricular arrhythmias between groups within 30 days after randomization	30 days
ICU and hospital length of stay		30 days
Days free of mechanical ventilation	We will compare the number of days free of mechanical ventilation between groups within 30 days after randomization	30 days
Severe sepsis and septic shock	We will compare the incidence of severe sepsis and septic shock between groups within 30 days after randomization	30 days
SOFA score within 72 hours	We will compare the SOFA score between groups 72 hours after randomization	72 hours

Collaborators and Investigators

• Sponsor: University of Sao Paulo

Publications and helpful links

General Publications

• Franco RA, de Almeida JP, Landoni G, Scheeren TWL, Galas FRBG, Fukushima JT, Zefferino S, Nardelli P, de Albuquerque Piccioni M, Arita ECTC, Park CHL, Cunha LCC, de Oliveira GQ, Costa IBSDS, Kalil Filho R, Jatene FB, Hajjar LA. Dobutamine-sparing versus dobutamine-to-all strategy in cardiac surgery: a randomized noninferiority trial. Ann Intensive Care. 2021 Jan 26;11(1):15. doi: 10.1186/s13613-021-00808-6.

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: February 2, 2015
• First Submitted That Met QC Criteria: February 6, 2015
• First Posted (Estimate): February 12, 2015

Study Record Updates

• Last Update Posted (Actual): March 16, 2022
• Last Update Submitted That Met QC Criteria: March 14, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: cardiac surgery; dobutamine
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Coronary Disease; Cardiac Output, Low; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Adrenergic Agonists; Cardiotonic Agents; Adrenergic beta-Agonists; Sympathomimetics; Adrenergic beta-1 Receptor Agonists; Dobutamine
• Other Study ID Numbers: DOBUTACS