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

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.

Study Overview

• Status: Completed
• Conditions: General Anesthesia
• Intervention / Treatment: Drug: Norepinephrine

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).

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 4

Contacts and Locations

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

Study Locations

• Belgium
  • Oost-Vlaanderen
    • Gent, Oost-Vlaanderen, Belgium, 9000
      • University Hospital Ghent

Participation Criteria

Eligibility Criteria

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

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 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

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: norepinephrine; norepinephrine will be started at 0,1 mcg/kg/min and titrated according to its haemodynamic effect.	Drug: Norepinephrine; 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).

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

Collaborators and Investigators

• Sponsor: University Hospital, Ghent

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2019
• Primary Completion (Actual): October 22, 2020
• Study Completion (Actual): October 14, 2022

Study Registration Dates

• First Submitted: May 20, 2019
• First Submitted That Met QC Criteria: May 24, 2019
• First Posted (Actual): May 28, 2019

Study Record Updates

• Last Update Posted (Estimate): December 9, 2022
• Last Update Submitted That Met QC Criteria: December 8, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Norepinephrine; 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; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine
• Other Study ID Numbers: 2019/0395

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