Clinical trial NCT04893655: Effect of Dobutamine on Hepatic Blood Flow During Goal-directed Hemodynamic Therapy
Official title: Effect of Dobutamine on Hepatic Blood Flow During Goal-directed Hemodynamic Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: General Anesthesia
Keywords: hepatic blood flow
dobutamine
hepatic vascular pressure
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
First posted: 2021-05-19
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.

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

Eligibility criteria: 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.

Primary outcomes:
measure: change in portal and arterial hepatic blood flow during goal-directed hemodynamic therapy with dobutamine
timeFrame: from start anesthesia until end of anesthesia, up to a maximum of 11 hours
measure: Changes in portal vein and caval vein pressures before and after dobutamine infusion
timeFrame: from start anesthesia until end of anesthesia, up to a maximum of 11 hours
Secondary outcomes:
measure: change in systemic hemodynamic measurements :cardiac index, during goal-directed hemodynamic therapy with dobutamine
timeFrame: from start anesthesia until end of anesthesia, up to a maximum of 11 hours
measure: change in systemic vascular resistance (SVR), during goal-directed hemodynamic therapy with dobutamine
timeFrame: from start anesthesia until end of anesthesia, up to a maximum of 11 hours
measure: change in portal venous resistance (PVR), during goal-directed hemodynamic therapy with dobutamine
timeFrame: from start anesthesia until end of anesthesia, up to a maximum of 11 hours
measure: change in systemic hemodynamic measurements :heart rate, during goal-directed hemodynamic therapy with dobutamine
timeFrame: from start anesthesia until end of anesthesia, up to a maximum of 11 hours
measure: change in systemic hemodynamic measurements :blood pressure, during goal-directed hemodynamic therapy with dobutamine
timeFrame: from start anesthesia until end of anesthesia, up to a maximum of 11 hours
measure: change in systemic hemodynamic measurements :central venous pressure, during goal-directed hemodynamic therapy with dobutamine
timeFrame: from start anesthesia until end of anesthesia, up to a maximum of 11 hours
measure: change in systemic hemodynamic measurements :pulse pressure variation, during goal-directed hemodynamic therapy with dobutamine
timeFrame: from start anesthesia until end of anesthesia, up to a maximum of 11 hours
measure: change in systemic hemodynamic measurements :stroke volume variation, during goal-directed hemodynamic therapy with dobutamine
timeFrame: from start anesthesia until end of anesthesia, up to a maximum of 11 hours
measure: change in systemic hemodynamic measurements : Systemic Vascular Resistance Index (SVRI), during goal-directed hemodynamic therapy with dobutamine
timeFrame: from start anesthesia until end of anesthesia, up to a maximum of 11 hours
measure: change in systemic hemodynamic measurements : Left Ventricular contractility (dPmx), during goal-directed hemodynamic therapy with dobutamine
timeFrame: from start anesthesia until end of anesthesia, up to a maximum of 11 hours
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Ghent University Hospital
Study officials:
affiliation: UZ Ghent
name: Jurgen Van Limmen, MD
role: PRINCIPAL_INVESTIGATOR
References: