Clinical trial NCT03965117: Effect of Norepinephrine Infusion on Hepatic Blood Flow During Goal-directed Haemodynamic Therapy.
Official title: Effect of Norepinephrine Infusion on Hepatic Blood Flow During Goal-directed Haemodynamic Therapy.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: General Anesthesia
Keywords: hepatic blood flow
Norepinephrine
hepatic vascular pressure
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
First posted: 2019-05-28
Enrollment: 49
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 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).

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

Primary outcomes:
measure: change in hepatic blood flow during goal-directed hemodynamic therapy with norepinphrine
timeFrame: From start anesthesia until end of anesthesia, up to a maximum of 11 hours
measure: change in hepatic blood pressures during goal-directed hemodynamic therapy with norepinphrine
timeFrame: From start anesthesia until end of anesthesia, up to a maximum of 11 hours
Secondary outcomes:
measure: change in systemic vascular resistance (SVR), during goal-directed hemodynamic therapy with norepinphrine
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 norepinphrine
timeFrame: From start anesthesia until end of anesthesia up to a maximum of 11 hours
measure: change in cardiac index during goal-directed hemodynamic therapy with norepinphrine
timeFrame: From start anesthesia until end of anesthesia, up to a maximum of 11 hours
measure: amount of blood loss
timeFrame: from start of surgery until end of surgery, up to a maximum of 10 hours
measure: amount of fluids given during surgery with goal-directed hemodynamic therapy with norepinphrine
timeFrame: from start of surgery until end of surgery up to a maximum of 10 hours
Other outcomes:
Locations:
city: Gent
country: Belgium
facility: University Hospital Ghent
state: Oost-Vlaanderen
Study officials:
affiliation: UZ Ghent
name: Jurgen Van Limmen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: van Limmen J, Iturriagagoitia X, Verougstraete M, Wyffels P, Berrevoet F, Abreu de Carvalho LF, De Hert S, De Baerdemaeker L. Effect of norepinephrine infusion on hepatic blood flow and its interaction with somatostatin: an observational cohort study. BMC Anesthesiol. 2022 Jul 2;22(1):202. doi: 10.1186/s12871-022-01741-2.