Effect of Dobutamine on Hepatic Blood Flow During Goal-directed Hemodynamic Therapy

Study Overview
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Brief Summary
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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
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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

Official Title
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Effect of Dobutamine on Hepatic Blood Flow During Goal-directed Hemodynamic Therapy

Conditions
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General Anesthesia

Intervention / Treatment
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* Drug: Dobutamine Hydrochloride


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dobutamine<br>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<br>* dobutamine infusion will be started at 2mcg/kg/min after min 10 minutes dobutamine infusion will be raised to 5mcg/kg/min<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatic blood flow, dobutamine, hepatic vascular pressure