Effect of Remifentanil vs Neuromuscular Blockers During Rapid Sequence Intubation on Successful Intubation Without Major Complications Among Patients at Risk of Aspiration
Nicolas Grillot
(1, 2)
,
Gilles Lebuffe
(3, 4)
,
Olivier Huet
(5, 6)
,
Sigismond Lasocki
(7)
,
Xavier Pichon
(8, 9)
,
Mathieu Oudot
(10)
,
Nathalie Bruneau
(4)
,
Jean-Stéphane David
(11, 12)
,
Pierre Bouzat
(13, 14)
,
Alexandra Jobert
(15, 16, 17)
,
Martine Tching-Sin
(16, 18)
,
Fanny Feuillet
(15, 16, 17)
,
Raphael Cinotti
(15, 16)
,
Karim Asehnoune
(1, 2)
,
Antoine Roquilly
(2, 1)
,
Pascal Incagnoli
(19)
,
Anne Li
(20)
,
Xavier Pichon
(8, 9)
,
Amazigh Aguersif
(8)
,
Vincent Minville
(21, 22)
,
Martin Dupuis
(23)
,
Matthias Garot
(24)
,
Florence Lallemant
(4)
,
Christine Ducam
,
Aurélien Rohn
(4)
,
Alexis Duchalais
(10)
,
Clément Starck
(25)
,
Maxime Lecourtois Du Manoir
,
Paul Rooze
(1)
,
Amelie Trichot
,
Romain Deransy
(1, 2)
,
Benoit Plaud
(26)
,
Denis Frasca
(15, 27)
,
Laura Leo
1
Service d'anesthésie et réanimation chirurgicale [Nantes]
2 CIC 0004 - Nantes - Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique
3 GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365
4 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
5 CHRU Brest - Centre Hospitalier Régional Universitaire de Brest
6 UBO - Université de Brest
7 CHU Angers - Centre Hospitalier Universitaire d'Angers
8 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
9 UT3 - Université Toulouse III - Paul Sabatier
10 CHD Vendée - Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon
11 RESHAPE - Inserm U1290 - UCBL1 - Research on Healthcare Performance
12 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
13 UGA - Université Grenoble Alpes
14 GIN - [GIN] Grenoble Institut des Neurosciences
15 SPHERE - MethodS in Patients-centered outcomes and HEalth ResEarch
16 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
17 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
18 Nantes Univ - Nantes Université
19 HCL - Hospices Civils de Lyon
20 UNIROUEN UFR Santé - UNIROUEN - UFR Santé
21 Pôle Anesthésie Réanimation [CHU de Toulouse]
22 RESTORE - Geroscience and rejuvenation research center
23 UGA UFRM - Université Grenoble Alpes - UFR Médecine
24 Hôpital Claude Huriez [Lille]
25 CHU - BREST - DAR - CHRU Brest - Département d'Anesthésie Réanimation
26 AP-HP - Hopital Saint-Louis [AP-HP]
27 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
2 CIC 0004 - Nantes - Centre d'investigation clinique (CIC) de Nantes -CIC Plurithématique
3 GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365
4 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
5 CHRU Brest - Centre Hospitalier Régional Universitaire de Brest
6 UBO - Université de Brest
7 CHU Angers - Centre Hospitalier Universitaire d'Angers
8 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
9 UT3 - Université Toulouse III - Paul Sabatier
10 CHD Vendée - Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon
11 RESHAPE - Inserm U1290 - UCBL1 - Research on Healthcare Performance
12 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
13 UGA - Université Grenoble Alpes
14 GIN - [GIN] Grenoble Institut des Neurosciences
15 SPHERE - MethodS in Patients-centered outcomes and HEalth ResEarch
16 CHU Nantes - Centre Hospitalier Universitaire de Nantes = Nantes University Hospital
17 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
18 Nantes Univ - Nantes Université
19 HCL - Hospices Civils de Lyon
20 UNIROUEN UFR Santé - UNIROUEN - UFR Santé
21 Pôle Anesthésie Réanimation [CHU de Toulouse]
22 RESTORE - Geroscience and rejuvenation research center
23 UGA UFRM - Université Grenoble Alpes - UFR Médecine
24 Hôpital Claude Huriez [Lille]
25 CHU - BREST - DAR - CHRU Brest - Département d'Anesthésie Réanimation
26 AP-HP - Hopital Saint-Louis [AP-HP]
27 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
Pierre Bouzat
- Fonction : Auteur
- PersonId : 917326
- IdHAL : pierre-bouzat
Fanny Feuillet
- Fonction : Auteur
- PersonId : 745334
- IdHAL : fanny-feuillet
- ORCID : 0000-0001-5804-5269
- IdRef : 193094401
Raphael Cinotti
- Fonction : Auteur
- PersonId : 1444396
- IdHAL : raphael-cinotti
- ORCID : 0000-0001-9217-8532
- IdRef : 140188363
Christine Ducam
- Fonction : Auteur
Maxime Lecourtois Du Manoir
- Fonction : Auteur
Amelie Trichot
- Fonction : Auteur
Romain Deransy
- Fonction : Auteur
- PersonId : 1069960
- IdRef : 155990500
Denis Frasca
- Fonction : Auteur
- PersonId : 760285
- ORCID : 0000-0003-1230-715X
- IdRef : 121567761
Laura Leo
- Fonction : Auteur
Résumé
Importance It is uncertain whether a rapid-onset opioid is noninferior to a rapid-onset neuromuscular blocker during rapid sequence intubation when used in conjunction with a hypnotic agent. Objective To determine whether remifentanil is noninferior to rapid-onset neuromuscular blockers for rapid sequence intubation. Design, Setting, and Participants Multicenter, randomized, open-label, noninferiority trial among 1150 adults at risk of aspiration (fasting for <6 hours, bowel occlusion, recent trauma, or severe gastroesophageal reflux) who underwent tracheal intubation in the operating room at 15 hospitals in France from October 2019 to April 2021. Follow-up was completed on May 15, 2021. Interventions Patients were randomized to receive neuromuscular blockers (1 mg/kg of succinylcholine or rocuronium; n = 575) or remifentanil (3 to 4 μg/kg; n = 575) immediately after injection of a hypnotic. Main Outcomes and Measures The primary outcome was assessed in all randomized patients (as-randomized population) and in all eligible patients who received assigned treatment (per-protocol population). The primary outcome was successful tracheal intubation on the first attempt without major complications, defined as lung aspiration of digestive content, oxygen desaturation, major hemodynamic instability, sustained arrhythmia, cardiac arrest, and severe anaphylactic reaction. The prespecified noninferiority margin was 7.0%. Results Among 1150 randomized patients (mean age, 50.7 [SD, 17.4] years; 573 [50%] women), 1130 (98.3%) completed the trial. In the as-randomized population, tracheal intubation on the first attempt without major complications occurred in 374 of 575 patients (66.1%) in the remifentanil group and 408 of 575 (71.6%) in the neuromuscular blocker group (between-group difference adjusted for randomization strata and center, –6.1%; 95% CI, –11.6% to –0.5%; P = .37 for noninferiority), demonstrating inferiority. In the per-protocol population, 374 of 565 patients (66.2%) in the remifentanil group and 403 of 565 (71.3%) in the neuromuscular blocker group had successful intubation without major complications (adjusted difference, –5.7%; 2-sided 95% CI, –11.3% to –0.1%; P = .32 for noninferiority). An adverse event of hemodynamic instability was recorded in 19 of 575 patients (3.3%) with remifentanil and 3 of 575 (0.5%) with neuromuscular blockers (adjusted difference, 2.8%; 95% CI, 1.2%-4.4%). Conclusions and Relevance Among adults at risk of aspiration during rapid sequence intubation in the operating room, remifentanil, compared with neuromuscular blockers, did not meet the criterion for noninferiority with regard to successful intubation on first attempt without major complications. Although remifentanil was statistically inferior to neuromuscular blockers, the wide confidence interval around the effect estimate remains compatible with noninferiority and limits conclusions about the clinical relevance of the difference. Trial Registration ClinicalTrials.gov Identifier: NCT03960801