Therapeutic Study Evaluating the Efficacy of Noradrenaline in the Prevention of Hypotension Related to Intubation for Cardiac or Thoracic Surgery (EPITUBE-HEART)

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

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.

Study Overview

• Status: Completed
• Conditions: Hypotension; Cardiac Disorder
• Intervention / Treatment: Drug: noradrenaline

• Study Type: Interventional
• Enrollment (Actual): 211
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Nantes, France
    • CHU de Nantes

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Noradrenaline; 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; noradrenaline
No Intervention: Standard care; 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

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Investigators: Principal Investigator: Mickael VOURC'H, MD, Nantes University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2022
• Primary Completion (Actual): December 12, 2023
• Study Completion (Actual): December 12, 2023

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: April 12, 2022
• First Posted (Actual): April 20, 2022

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: cardiac surgery; general anesthesia; intubation; hypotension; noradrenaline
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Heart Diseases; Hypotension; 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: RC21_0144

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