Effect of Dobutamine on Hepatic Blood Flow During Goal-directed Hemodynamic Therapy (DOBU whipple)

Maintaining adequate perfusion pressure and oxygen supply is essential for organ survival. Splanchnic hypoperfusion during the perioperative period in abdominal surgery may result in mucosal ischemia with increased permeability of the gut barrier. Additionally, the liver is also sensitive for hypoxemia and hypoperfusion, especially during liver surgery.

Anesthetics (such as propofol or sevoflurane) have a cardiovascular depressant effect, resulting in a reduction of cardiac output (CO). Dobutamine is used to counteract myocardial depressant effect of anesthetics. Additionally, dobutamine is frequently used during abdominal surgery to maintain splanchnic perfusion.

Dobutamine could increase hepatic blood flow (HBF) indirectly by increasing cardiac output or directly by stimulating adrenergic receptors in the splanchnic circulation. The hepatic circulation has a large number of alpha and beta adrenergic receptors and could be sensitive for adrenergic stimulation such as dobutamine. Hence, dobutamine could have a direct effect on the hepatic vasculature.

The aim of the study is to evaluate the effect of dobutamine on hepatic blood flow during goal directed hemodynamic therapy and to distinguish between potential direct and indirect effects.

Study Overview

• Status: Completed
• Conditions: General Anesthesia
• Intervention / Treatment: Drug: Dobutamine Hydrochloride

Detailed Description

All patients receive standardized anesthesia care for pancreaticoduodenectomy according to the existing departmental protocol for these interventions.

All patients receive individualized goal-directed hemodynamic therapy based on the transpulmonary thermodilution technique.

At designated times, hemodynamic variables will be recorded. These include :

• Heart rate (bpm)
• Central venous pressure (mmHg)
• Systolic arterial pressure (mmHg)
• Diastolic arterial pressure (mmHg)
• Mean arterial pressure (mmHg)
• Cardiac index (L/min/m2)
• Pulse pressure variation (PPV)
• Stroke volume variation (SVV)

Measurements of hepatic flow and pressure will be performed by the surgeon :

• Hepatic flow : in the hepatic artery (arterial HBF) and portal vein (portal HBF).
• Pressure measurements : in portal vein (PPorta) and caval vein (PCava)

Measurements will be done :

• without inotropic support
• with infusion of dobutamine 2mcg/kg/min
• with infusion of dobutamine 5mcg/kg/min

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jurgen Van Limmen, MD; Phone Number: 09/332 32 81; Email: Jurgen.vanlimmen@Ugent.be
• Study Contact Backup: Name: Ann De Bruyne; Phone Number: 09/332 59 33; Email: ann.debruyne@Ugent.be

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Ghent University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult ≥ 18 years ≤ 80 years (female or male).
• ASA I - II - III.
• Able to comprehend, sign and date the written informed consent document to participate in the clinical trial.
• Patient is scheduled for pancreaticoduodenectomy (Whipple's procedure).

Exclusion Criteria:

• Allergy to the medication dobutamine.
• Renal insufficiency (SCr > 2 mg/dL).
• Severe heart failure (EF < 25%).
• Hemodynamic unstable patients.
• Atrial fibrillation.
• Sinus tachycardia > 100 bpm on pre-operative electrocardiogram.
• Sepsis.
• BMI > 40.
• Severe coagulopathy (INR > 2).
• Thrombocytopenia (< 80 x 103 /mcL).
• End stage liver disease and/or portal hypertension.
• Pregnancy and breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dobutamine; dobutamine infusion will be started at 2mcg/kg/min after min 10 minutes dobutamine infusion will be raised to 5mcg/kg/min	Drug: Dobutamine Hydrochloride; dobutamine infusion will be started at 2mcg/kg/min after min 10 minutes dobutamine infusion will be raised to 5mcg/kg/min

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in portal and arterial hepatic blood flow during goal-directed hemodynamic therapy with dobutamine	flow measurements with echo probe	from start anesthesia until end of anesthesia, up to a maximum of 11 hours
Changes in portal vein and caval vein pressures before and after dobutamine infusion	pressure measurements with 25gauge needle	from start anesthesia until end of anesthesia, up to a maximum of 11 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in systemic hemodynamic measurements :cardiac index, during goal-directed hemodynamic therapy with dobutamine	change in cardiac index (measurements with PiCCO catheter)	from start anesthesia until end of anesthesia, up to a maximum of 11 hours
change in systemic vascular resistance (SVR), during goal-directed hemodynamic therapy with dobutamine	change in systemic vascular resistance (SVR)	from start anesthesia until end of anesthesia, up to a maximum of 11 hours
change in portal venous resistance (PVR), during goal-directed hemodynamic therapy with dobutamine	change in portal venous resistance (PVR)	from start anesthesia until end of anesthesia, up to a maximum of 11 hours
change in systemic hemodynamic measurements :heart rate, during goal-directed hemodynamic therapy with dobutamine	change in heart rate (measurements with PiCCO catheter)	from start anesthesia until end of anesthesia, up to a maximum of 11 hours
change in systemic hemodynamic measurements :blood pressure, during goal-directed hemodynamic therapy with dobutamine	change in blood pressure (measurements with PiCCO catheter)	from start anesthesia until end of anesthesia, up to a maximum of 11 hours
change in systemic hemodynamic measurements :central venous pressure, during goal-directed hemodynamic therapy with dobutamine	change in cardiac index (measurements with central line)	from start anesthesia until end of anesthesia, up to a maximum of 11 hours
change in systemic hemodynamic measurements :pulse pressure variation, during goal-directed hemodynamic therapy with dobutamine	change in pulse pressure variation (measurements with PiCCO catheter)	from start anesthesia until end of anesthesia, up to a maximum of 11 hours
change in systemic hemodynamic measurements :stroke volume variation, during goal-directed hemodynamic therapy with dobutamine	change in stroke volume variation (measurements with PiCCO catheter)	from start anesthesia until end of anesthesia, up to a maximum of 11 hours
change in systemic hemodynamic measurements : Systemic Vascular Resistance Index (SVRI), during goal-directed hemodynamic therapy with dobutamine	change in Systemic Vascular Resistance Index (SVRI) (measurements with PiCCO catheter)	from start anesthesia until end of anesthesia, up to a maximum of 11 hours
change in systemic hemodynamic measurements : Left Ventricular contractility (dPmx), during goal-directed hemodynamic therapy with dobutamine	change in Left Ventricular contractility (dPmx) (measurements with PiCCO catheter)	from start anesthesia until end of anesthesia, up to a maximum of 11 hours

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Jurgen Van Limmen, MD, UZ Ghent

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2021
• Primary Completion (Actual): July 24, 2023
• Study Completion (Actual): July 25, 2023

Study Registration Dates

• First Submitted: April 30, 2021
• First Submitted That Met QC Criteria: May 12, 2021
• First Posted (Actual): May 19, 2021

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 31, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: dobutamine; hepatic blood flow; hepatic vascular pressure
• Additional Relevant MeSH Terms: 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: BC-08919

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