Therapeutic Study Evaluating the Efficacy of Noradrenaline in the Prevention of Hypotension Related to Intubation for Cardiac or Thoracic Surgery

Study Overview
=================
Brief Summary
-----------------
Arterial hypotension during general anaesthesia (GA) is a serious event. While hypotension can occur during surgery, it usually occurs following induction of GA (i.e. following the injection of drugs to enable intubation). This is due to the injection of large doses of anaesthetic drugs with a vasodilatory effect over a short period of time to induce a deep sleep to allow intubation to take place for artificial ventilation. The prevention of hypotension during surgery has been extensively studied. In contrast, the prevention of hypotension following GA induction has been the subject of only two randomised studies in the ICU and three non-randomised studies in the OR with small numbers of patients. The level of evidence for the use of noradrenaline in the operating theatre remains low. The hypothesis of the study is that noradrenaline initiated during preoxygenation can reduce the incidence of hypotension during induction of general anaesthesia.

Official Title
-----------------
Phase 3 Therapeutic Interventional Study Evaluating the Efficacy of Noradrenaline in the Prevention of Hypotension Related to Intubation for Cardiac or Thoracic Surgery - Single-centre Prospective Randomised Controlled Study With Blinded Assessment of the Primary Endpoint

Conditions
-----------------
Cardiac Disorder, Hypotension

Intervention / Treatment
-----------------
* Drug: noradrenaline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Requiring cardiac or thoracic surgery under general anaesthesia Requiring a blood pressure catheter prior to GA induction Exclusion Criteria: Hemodynamic instability on arrival in the operating room Hypotension on arrival in the operating theatre: Systolic blood pressure < 100 mmHg or Mean arterial pressure < 65 mmHg Hypertension on arrival at the operating theatre: Systolic blood pressure > 160 mmHg or Mean arterial pressure > 100 mmHg Adult under guardianship, curatorship or safeguard of justice Unable to give consent Pregnant or breastfeeding woman Emergency surgery (cannot be delayed by 24 hours) Current participation in an interventional protocol that interferes with the evaluation criteria of the study Not affiliated to or not benefiting from a social security scheme Lack of informed and written consent from the patient Patient with a dilated aorta with a risk of rupture (e.g. chronic dissection for example) Patient with severe aortic insufficiency Treated hypertensive history that may have hypersensitivity to noradrenaline and hypertensive flares hypertensive attacks

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Noradrenaline<br>Noradrenaline diluted to 16µg/ml infused at 0.06g/kg/min by peripheral venous line from the start of peripheral venous line from the start of preoxygenation | Drug: noradrenaline<br>* noradrenaline<br>|
| No Intervention: Standard care<br>standard care | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intubation-related hypotension | Occurrence of at least one episode of arterial hypotension defined by a Mean Arterial Pressure below 55 mmHg with Mean Blood Pressure = (Systolic Blood pressure + 2xDiastolic Blood Pressure)/3 | Within 20 minutes of the start of general anesthesia (induction) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of complications | Occurrence (yes/no) of complications related to the intubation: Desaturation < 80%, Severe hypotension (defined as hypotension with systolic blood pressure < 80mmHg), Cardiac arrest, Death during intubation, Difficult intubation (more than two laryngoscopies and/or the use of an alternative technique after optimization of head position, with or without external laryngeal manipulation), Heart rhythm disorder (ventricular extrasystole, ventricular fibrillation, ventricular tachycardia) Esophageal intubation, Regurgitation/inhalation, Tooth breakage | Within 20 minutes of the start of the intubation | 
| Total dose of vasopressor | Total dose of vasopressors (noradrenaline, ephedrine, neosynephrine) | Within 20 minutes of the start of the intubation | 
| Duration of episodes of hypotension | Cumulative duration of episodes of hypotension < 55mmHg | Within 20 minutes of the start of the intubation | 
| Hypotension event | At least one Mean Arterial Pressure measurement < 65 mmHg | Within 20 minutes of the start of the intubation | 
| Hypertension event | At least one Systolic Blood Pressure measurement > 160 mmHg or Mean Arterial Pressure > 100mmHg | Within 20 minutes of the start of the intubation | 
| ECC Cardiac Output | Extra Corporeal Circulation generated Cardiac Output frequency in bpm (beat per minute) | Within 20 minutes of the start of the intubation | 
| ECC Arterial Line Pressure | Extra Corporeal Circulation generated Arterial Line Pressure in mmHg | Within 20 minutes of the start of the intubation | 
| ECC Arterial Line Temperature | Extra Corporeal Circulation generated Arterial Line Temperature in degree Celcius | Within 20 minutes of the start of the intubation | 
| ECC Mean Arterial Pressure | Extra Corporeal Circulation generated Mean Arterial Pressure in mmHg | Within 20 minutes of the start of the intubation | 
| ECC VO2 | Extra Corporeal Circulation generated VO2 (Volume O2) in Liter per Minute | Within 20 minutes of the start of the intubation | 
| ECC duration | Extra Corporeal Circulation duration in minutes | Within 20 minutes of the start of the intubation | 
| ECC SaO2 | Extra Corporeal Circulation generated SaO2 (Arterial Saturation in O2) in percentage | Within 20 minutes of the start of the intubation | 
| ECC SvO2 | Extra Corporeal Circulation generated SvO2 (Venous Saturation in O2) in percentage | Within 20 minutes of the start of the intubation | 
| ECC PaO2 | Extra Corporeal Circulation generated PaO2 (Arterial Pressure in O2) in kPa | Within 20 minutes of the start of the intubation | 
| ECC PaCO2 | Extra Corporeal Circulation generated PaCO2 (Arterial Pressure in CO2) in kPa | Within 20 minutes of the start of the intubation | 
| Delirium score | At least episode with ICDSC (Intensive Care Delirium Screening Checklist) score of 4 or more (0 to 8, binary interpretation with scores from 0 to 4 excluding the presence of delirium and scores greater than or equal to 4 indicating the presence of delirium, the highest scores are not related with greater intensity of delirium) | After extubation within 48 hours postoperatively | 
| Duration of Noradrenaline and Dobutamine treatments | Duration of treatment with Noradrenaline (in hours) and Dobutamine (in hours) | Within 28 days after surgery | 
| PaO2/FiO2 | Lowest value of PaO2/FiO2 (Arterial Pressure of O2 / Fraction inspired in Oxygen) measured | In the 5 post-operative days | 
| Dialysis | Use of dialysis in intensive care (Yes/No) | Within 28 days after surgery | 
| Hemolysis index | Maximum hemolysis index (0 to 10000, with higher scores being more pejorative) | In the 5 post-operative days | 
| Acute renal failure | Occurrence of acute renal failure. This criterion will be assessed using the KDIGO (Kidney Disease: Improving Global Outcomes) scale (stage 1 to 3 with higher stages being more pejorative). Any renal attack defined as at least stage I according to this classification (1.5 to 1.9 times the base rate) will be considered as acute renal failure. The urinary output assessment component of the KDIGO scale will not be used because of the frequency of use of diuretics in cardiac surgery. | In the 5 post-operative days | 
| CVA | Occurrence of a CVA (cerebrovascular accident) | In the 5 post-operative days | 
| Postoperative invasive ventilation duration | Duration of postoperative invasive ventilation in hours: this duration is defined by the duration of mechanical ventilation between arrival in intensive care and extubation | Until 28 days after surgery | 
| Stay in intensive care duration | Length of stay in intensive care in days: this duration is evaluated between the day of arrival in intensive care and the date on which the patient is considered to have left intensive care (no longer subject to monitoring in intensive care). | Until 28 days after surgery | 
| Hospitalization duration | Length of hospitalization in days | Until 28 days after surgery | 
| Mortality | Death of the patient | Until 28 days after surgery | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
general anesthesia, intubation, cardiac surgery, hypotension, noradrenaline