Clinical trial NCT01536470: Intraoperative Noradrenaline to Control Arterial Pressure (INPRESS Study)
Official title: Effectiveness of Noradrenaline to Control Intraoperative Arterial Pressure in High-risk Surgical Patients: A Multicentre Prospective Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Control of Arterial Blood Pressure
Keywords: Intraoperative hemodynamic
Arterial pressure
Postoperative complications
Intraoperative fluids
Noradrenaline
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
Collaborators: name: Aguettant laboratory
First posted: 2012-02-22
Enrollment: 300
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Composite endpoint of postoperative SIRS and at least one major organ dysfunction
timeFrame: day-7
Secondary outcomes:
measure: Incidence of intraoperative hypotension
timeFrame: at day 7
measure: Incidence of intraoperative hypertension
timeFrame: at day 7
measure: Incidence of intraoperative bradycardia
timeFrame: at day 7
measure: Intraoperative volume of fluid perfused
timeFrame: at day 7
measure: Intraoperative blood losses
timeFrame: at day 7
measure: Need for intraoperative transfusion
timeFrame: at day 7
measure: Postoperative organ failure
timeFrame: at day 7
measure: Biologic criteria: plasma concentration of NGAL, creatinine, CRP, serum lactate, troponine)
timeFrame: at day 7
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Emmanuel FUTIER
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.