Clinical trial NCT03960801: Assessment of Remifentanil for Rapid Sequence Induction and Intubation in Full Stomach Patient Compared to Muscle Relaxant
Official title: Assessment of Remifentanil for Rapid Sequence Induction and Intubation in Full Stomach Patient Compared to Muscle Relaxant. A Non-inferiority Simple Blind Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Intra-tracheal Intubation
Keywords: Intubation
Remifentanil
neuromuscular blockade
succinylcholine
Rocuronium
emergency anesthesia
rapid sequence induction
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
First posted: 2019-05-23
Enrollment: 1150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial in 2 parallel groups assigned to tested drug in intervention group and to reference treatment for control group.
Primary purpose: SUPPORTIVE_CARE

Brief summary: REMICrush is a French multicentric non inferiority simple blind randomized clinical trial that will compare the use of Remifentanil to muscle relaxant (reference treatment) for anesthetic rapid sequence intubation in terms of major complications (difficult intubation, gastric liquid aspiration, desaturation, hemodynamics reaction, ventricular arrhythmia, anaphylactic reaction).

Detailed description: BACKGROUND: Rapid sequence intubation is the reference anaesthetic procedure for patient at risk of pulmonary aspiration of gastric contents (for example emergency procedure, bowel obstruction, obese patients, gastroesophageal reflux ...) or difficult airway management. Nowadays the use of Succinylcholine (CELOCURINE), a neuromuscular blockade with a short duration of action, is recommended in this indication. However, several adverse events are frequently reported, especially anaphylactic reaction, restraining its use for rapid sequence intubation. Other adverse effects such as extended neuromuscular block, malignant hyperthermia or severe hyperkaliemia prohibit its use. In this case the use of another neuromuscular blockade, Rocuronium (ESMERON), is an alternative solution. Unfortunately, this other molecule causes as many anaphylactic event as Succinylcholine (1 anaphylactic event for 3000 uses) and produce a long duration of neuromuscular block. Incidence of anaphylactic reaction is increasing in France and mostly severe reactions. Its utilization is therefore reduced to 31 to 55% of crush induction despite the recommendations. Remifentanil is an opioid agent with very shorts delay and duration of action. Several study have shown similar intubation conditions in planned surgery with the use of Remifentanil instead of neuromuscular blockade and less hemodynamic reactions. Remifentanil is already approved for anesthetic induction and recognized as an alternative to neuromuscular blockade for the intubation of children. Use of remifentanil has shown satisfying intubation conditions for adults but its incidence of major complications compared to succinylcholine remains unknown.

Study hypothesis: The investigators thus hypothesized that Remifentanil is non inferior to neuromuscular blockade in terms of major complications after a crush induction.

Methods: A multicenter simple blind randomized controlled trial. 11 centers will participate in this project.

Experimental treatment arm: During anesthetic induction remifentanil will be injected immediately after hypnotic drug through bolus intravenous injection by a peripheral or verified central venous access, at 3 to 4 µg/kg. Orotracheal intubation will be performed 30 to 60 seconds later by a graduated anesthesiologist or a resident with 4 validated semesters.

Control arm treatment: A neuromuscular blockade will be injected right after the hypnotic drug. Whether succinylcholine (CELOCURINE) at 1mg/kg or Rocuronium (ESMERON) at 1mg/kg in a bolus intravenous injection by a peripheral or verified central venous access. Orotracheal intubation will be performed after occurring of fasciculations with succinylcholine or 30 to 60 seconds after injection of Rocuronium by a graduated anesthesiologist or a resident with 4 validated semesters.

Objective and judgment criteria: The primary objective is to demonstrate non inferiority of Remifentanil compared to neuromuscular blockade in terms of major complications after a crush induction. Primary endpoint is the rate of tracheal intubation without major complications as defined by 1/ tracheal intubation with less than 2 laryngoscopies 2/ no aspiration during the 10 minutes after induction 3/ no desaturation under 95% during the 10 minutes after induction 4/ no hypo or hypertension as defined by a Median blood pressure\<50 mmHg or \>110 mmHg 5/ NO ventricular arrhythmia involving an emergency treatment or cardiac arrest during the 10 minutes after induction 6/ No grade III or IV anaphylactic reaction after the 10 minutes after induction.

Statistical analyses:

A 80% incidence of intubation without major complication was hypothesized. Non inferiority has been set under a superior limit of 7% for the primary endpoint 95% of the proportions difference between intervention and control group. In order to achieve 80 power with a 5% alpha risk, 1150 patients (575 for each arms) are to be included.

Eligibility criteria: Inclusion Criteria:

* - male or female
* aged from 18 to 80 years old
* surgery requiring general anaesthesia with tracheal with oro-tracheal intubation
* Rapid sequence intubation indication
* aspiration risk defined as : fasting \< 6h00, digestive occlusion, functional ileus, vomiting \< 12h00, orthopaedic trauma \< 12h00, severe gastric reflux, gastroparesis and/or dysautonomia and or gastro-oesophagus surgery
* signed informed consent sheet ; or emergency procedure if impossible

Exclusion Criteria:

* planned impossible intubation
* suspected/known allergy to neuromuscular blockade or remifentanil
* Neuromuscular disease forbidding neuromuscular blockade use
* Prolonged neuromuscular block former episode
* Malignant hyperthermia former episode
* Pre-operative respiratory failure (spO2\< 95%)
* Pre-operative hemodynamic failure (use of vasopressor)
* cardiac arrest
* A woman of childbearing age who has an active pregnancy and/or clinical signs suggestive of an active pregnancy and/or does not have a contraceptive or contraceptive method and has had unprotected sex within 15 days of the last menstrual period.
* Patients under justice protection
* Use of etomidate for anesthetic induction

Primary outcomes:
measure: Rate of tracheal intubation without major complication
timeFrame: Day 7 from randomization
Secondary outcomes:
measure: quality of intubation: score IDS3
timeFrame: At Day 7
measure: level of intubation difficulty
timeFrame: within 10 minutes
measure: Intubation difficulty evaluated by Percentage of opening of the gluteal opening
timeFrame: within 10 minutes
measure: use of alternative technic
timeFrame: within 10 minutes
measure: induction-intubation delay
timeFrame: Within 7 days
measure: desaturation
timeFrame: within 10 minutes
measure: severe hemodynamic reaction
timeFrame: within 10 minutes
measure: teeth/ tracheal trauma
timeFrame: At day 7
measure: Allergies
timeFrame: within 10 minutes
measure: postoperative sore throat
timeFrame: 1 hour after extubation
measure: post operative pneumonia
timeFrame: At day 7
measure: Proportion of patients with post-operative respiratory distress
timeFrame: At day 7
measure: In hospital mortality
timeFrame: At day 7
Other outcomes:
Locations:
city: Angers
country: France
facility: University Hospital
city: Brest
country: France
facility: Military Hospital
city: Brest
country: France
facility: University Hospital
city: Grenoble
country: France
facility: University Hospital
city: La Roche-sur-Yon
country: France
facility: CHD Vendée
city: Le Mans
country: France
facility: Hospital
city: Lille
country: France
facility: University hospital (SALENGRO hospital)
city: Lille
country: France
facility: University Hospital
city: Lyon
country: France
facility: University Hospital Lyon Sud
city: Nantes
country: France
facility: Le Confluent
city: Nantes
country: France
facility: University Hospital
city: Toulouse
country: France
facility: Toulouse University Hospital
city: Valenciennes
country: France
facility: Hospital
Study officials:
References:
citation: Grillot N, Garot M, Lasocki S, Huet O, Bouzat P, Le Moal C, Oudot M, Chatel-Josse N, El Amine Y, Danguy des Deserts M, Bruneau N, Cinotti R, David JS, Langeron O, Minville V, Tching-Sin M, Faurel-Paul E, Lerebourg C, Flattres-Duchaussoy D, Jobert A, Asehnoune K, Feuillet F, Roquilly A. Assessment of remifentanil for rapid sequence induction and intubation in patients at risk of pulmonary aspiration of gastric contents compared to rapid-onset paralytic agents: study protocol for a non-inferiority simple blind randomized controlled trial (the REMICRUSH study). Trials. 2021 Mar 30;22(1):237. doi: 10.1186/s13063-021-05192-x.