Intraoperative Noradrenaline to Control Arterial Pressure (INPRESS Study) (INPRESS)

Effectiveness of Noradrenaline to Control Intraoperative Arterial Pressure in High-risk Surgical Patients: A Multicentre Prospective Randomized Controlled Trial

The purpose of this study is to evaluate whether a preventive strategy of intraoperative arterial hypotension using noradrenaline can reduce the incidence of postoperative organ failure.

Study Overview

• Status: Completed
• Conditions: Control of Arterial Blood Pressure
• Intervention / Treatment: Other: noradrenaline; Other: Ephedryne chorydrate

Detailed Description

The maintenance of arterial blood pressure is essential for organ perfusion pressure. Intraoperative hypotension is a frequent complication both after induction and during maintenance of anaesthesia, ranging from 5% to 75% depending on the chosen definition. Tissue hypoperfusion exposes to the occurrence of a systemic inflammatory response syndrome and is a key determinant of postoperative complications. Persistent intraoperative hypotension has been reported as an important prognostic factor of postoperative morbidity and mortality. Adequate treatment of arterial hypotension is therefore of particular importance during surgery, but optimal strategy of intraoperative blood pressure management remains undetermined, especially in high-risk patients. Target ranges for arterial pressure are not clearly defined, and hypotension is usually defined as a systolic pressure of less than 80 mmHg or a decrease of more than 40% from baseline.

Traditionally, management of intraoperative hypotension consisted primarily of fluid administration whereas vasoconstrictors, such as Ephedrine chlorhydrate, are often used as a second line therapy. This may, however, expose patients to prolonged hypotension and to excessive fluid administration, and each of them may alter tissue oxygenation.

Recent experimental data have shown that noradrenaline, which has - and -adrenergic effects, has no detrimental effects on microcirculatory blood flow and tissue oxygenation in the intestinal tract. Because of anaesthesia-induced vasodilatation, the use of a continuous infusion of noradrenaline to increase systemic vascular resistance could be useful to prevent detrimental effects of compromised tissue perfusion, especially in high-risk surgical patients.

The primary objective of the study is to compare two strategies of intraoperative blood pressure management in high-risk surgical patients: 1- Continuous infusion of noradrenaline to maintain arterial blood pressure of no more than 10% below its baseline value; 2- Conventional treatment of hypotension (defined as a blood pressure of below 80 mmHg or a decrease of more than 40% from baseline) using intravenous bolus of Ephedrine chorhydrate.

The investigators hypothesis is that maintenance of arterial blood pressure with noradrenaline could reduce postoperative organ dysfunction in high-risk surgical patients.

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • CHU Clermont-Ferrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 50 years
• ASA score ≥ 2
• Planned and unplanned surgical procedures
• Abdominal, orthopaedic and vascular surgery
• Expected duration ≥ 2 hours
• AKI risk index ≥ class 3

Exclusion Criteria:

• Severe preoperative hypertension (not controlled)
• Creatinine clearance < 30 ml/min or preoperative dialysis
• Acute cardiac failure
• Preoperative sepsis
• Preoperative hemodynamic failure (shock)
• Intraoperative use of locoregional anaesthesia (epidural and spinal)
• Patient refusal
• Pregnancy and/or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Noradrenaline; Continuous infusion of noradrenaline to maintain arterial blood pressure management in high-risk surgical patients	Other: noradrenaline; The primary objective of the study is to compare two strategies of intraoperative blood pressure management in high-risk surgical patients: 1- Continuous infusion of noradrenaline to maintain arterial blood pressure of no more than 10% below its baseline value; 2- Conventional treatment of hypotension (defined as a blood pressure of below 80 mmHg or a decrease of more than 40% from baseline) using intravenous bolus of Ephedrine chorhydrate.
Experimental: Ephedrine chorhydrate; Conventional treatment of hypotension (defined as a blood pressure of below 80 mmHg or a decrease of more than 40% from baseline)using intravenous bolus of Ephedrine chorhydrate	Other: Ephedryne chorydrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Composite endpoint of postoperative SIRS and at least one major organ dysfunction	day-7

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of intraoperative hypotension	at day 7
Incidence of intraoperative hypertension	at day 7
Incidence of intraoperative bradycardia	at day 7
Intraoperative volume of fluid perfused	at day 7
Intraoperative blood losses	at day 7
Need for intraoperative transfusion	at day 7
Postoperative organ failure	at day 7
Biologic criteria: plasma concentration of NGAL, creatinine, CRP, serum lactate, troponine)	at day 7

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: Aguettant laboratory

Publications and helpful links

General Publications

• Futier E, Lefrant JY, Guinot PG, Godet T, Lorne E, Cuvillon P, Bertran S, Leone M, Pastene B, Piriou V, Molliex S, Albanese J, Julia JM, Tavernier B, Imhoff E, Bazin JE, Constantin JM, Pereira B, Jaber S; INPRESS Study Group. Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial. JAMA. 2017 Oct 10;318(14):1346-1357. doi: 10.1001/jama.2017.14172.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): July 1, 2016
• Study Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: February 13, 2012
• First Submitted That Met QC Criteria: February 21, 2012
• First Posted (Estimate): February 22, 2012

Study Record Updates

• Last Update Posted (Estimate): October 3, 2016
• Last Update Submitted That Met QC Criteria: September 30, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Postoperative complications; Noradrenaline; Intraoperative hemodynamic; Arterial pressure; Intraoperative fluids
• 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: CHU-0111; 2011-004232-66 (EudraCT Number)