Intraoperative Noradrenaline to Control Arterial Pressure (INPRESS Study)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Control of Arterial Blood Pressure

Intervention / Treatment
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* Other: noradrenaline
* Other: Ephedryne chorydrate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Noradrenaline<br>Continuous infusion of noradrenaline to maintain arterial blood pressure management in high-risk surgical patients | Other: noradrenaline<br>* 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.<br>|
| Experimental: Ephedrine chorhydrate<br>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<br> <br> |

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intraoperative hemodynamic, Arterial pressure, Postoperative complications, Intraoperative fluids, Noradrenaline