Effect of Norepinephrine Infusion on Hepatic Blood Flow During Goal-directed Haemodynamic Therapy.

Study Overview
=================
Brief Summary
-----------------
Maintaining adequate blood pressure is important for survival of organs. Recent studies have demonstrated that higher blood pressures were necessary for prevention of acute kidney injury and myocardial injury after non-cardiac surgery. Hypotension after induction and maintenance of anesthesia is common. For maintaining adequate blood pressure in a euvolemic patient, vasopressor therapy is required. Norepinephrine (NOR) is commonly used to treat anesthesia-related hypotension. The hepatic circulation has a large number of alpha and beta adrenergic receptors and is very sensitive for adrenergic stimulation such as norepinephrine infusion. Animal studies (Hiltebrand et al.) suggest that NOR has only minimal effect on hepatic blood flow however the effect of NOR on hepatic blood flow in clinical surgical patients remains unclear. The aim of the study is to evaluate the effect of NOR on hepatic blood flow during. goal directed haemodynamic therapy.

Detailed Description
-----------------
All patients receive standardized anesthesia care for pancreas surgery according to the existing departmental protocol for these interventions. All patients receive individualized goal-directed haemodynamic therapy based on the transpulmonary thermodilution technique. At designated times, hemodynamic variables will be recorded. These include: Heart rate (bpm) Central venous pressure (mmHg) Mean arterial pressure (mmHg) Cardiac index (L/min/m2) Pulse pressure variation (PPV) Blood flow and pressure measurements performed by the surgeon : Hepatic flow : hepatic artery (HAF) and portal vein (PVF) Pressure measurements in portal vein (PPorta) and caval vein (PCava) Both flow and pressure will be simultaneously recorded. To minimize the effect of ventilation on pressure, these measurements will be obtained during apnea. Between each flow measurement there will be a minimum of 5 minutes. NOR will be started at 0,1 mcg/kg/min and titrated according to its haemodynamic effect. After baseline MAP (which is > 60 mmHg), NOR is targeted according baseline MAP. At T2, MAP is between 10 - 20 % above baseline (T1), at T3 MAP is between 20 - 30 % above baseline (T1).

Official Title
-----------------
Effect of Norepinephrine Infusion on Hepatic Blood Flow During Goal-directed Haemodynamic Therapy.

Conditions
-----------------
General Anesthesia

Intervention / Treatment
-----------------
* Drug: Norepinephrine


Participation Criteria
=================
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 pancreatic surgery. Exclusion Criteria: Allergy to the medication. Renal insufficiency (SCr > 2 mg/dL). Severe heart failure (EF < 25%). Hemodynamic instable patients. Atrial fibrillation. Sepsis. BMI > 40. Severe coagulopathy (INR > 2). Thrombocytopenia (< 80 x 103 /mcL). End stage liver disease. Pregnancy and breastfeeding women

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: norepinephrine<br>norepinephrine will be started at 0,1 mcg/kg/min and titrated according to its haemodynamic effect. | Drug: Norepinephrine<br>* norepinephrine will be started at 0,1 mcg/kg/min and titrated according to its haemodynamic effect. After baseline MAP (which is > 60 mmHg), norepinephrine is targeted according baseline MAP. At T2, MAP is between 10 - 20 % above baseline (T1), at T3 MAP is between 20 - 30 % above baseline (T1).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in hepatic blood flow during goal-directed hemodynamic therapy with norepinphrine | flow measurements with echo probe | From start anesthesia until end of anesthesia, up to a maximum of 11 hours | 
| change in hepatic blood pressures during goal-directed hemodynamic therapy with norepinphrine | pressure measurements with 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 vascular resistance (SVR), during goal-directed hemodynamic therapy with norepinphrine | 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 norepinphrine | change in portal venous resistance (PVR) | From start anesthesia until end of anesthesia up to a maximum of 11 hours | 
| change in cardiac index during goal-directed hemodynamic therapy with norepinphrine | change in cardiac index | From start anesthesia until end of anesthesia, up to a maximum of 11 hours | 
| amount of blood loss | amount of blood loss at end of surgery | from start of surgery until end of surgery, up to a maximum of 10 hours | 
| amount of fluids given during surgery with goal-directed hemodynamic therapy with norepinphrine | total amount of cristalloids and colloids given during surgery | from start of surgery until end of surgery up to a maximum of 10 hours | 

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