Research

JAMA | Original Investigation

Effect of Rocuronium vs Succinylcholine on Endotracheal Intubation

Success Rate Among Patients Undergoing Out-of-Hospital
Rapid Sequence Intubation
A Randomized Clinical Trial
Bertrand Guihard, MD; Charlotte Chollet-Xémard, MD; Philippe Lakhnati, MD; Benoit Vivien, MD, PhD;
Claire Broche, MD; Dominique Savary, MD; Agnes Ricard-Hibon, MD; Pierre-Jean Marianne dit Cassou, MD;
Frédéric Adnet, MD, PhD; Eric Wiel, MD, PhD; Juliette Deutsch, MD; Cindy Tissier, MD; Thomas Loeb, MD;
Vincent Bounes, MD, PhD; Emmanuel Rousseau, MD; Patricia Jabre, MD, PhD; Laetitia Huiart, MD, PhD;
Cyril Ferdynus, PhD; Xavier Combes, MD, PhD

Visual Abstract
IMPORTANCE Rocuronium and succinylcholine are often used for rapid sequence intubation, Supplemental content
although the comparative efficacy of these paralytic agents for achieving successful
intubation in an emergency setting has not been evaluated in clinical trials. Succinylcholine
use has been associated with several adverse events not reported with rocuronium.

OBJECTIVE To assess the noninferiority of rocuronium vs succinylcholine for tracheal

intubation in out-of-hospital emergency situations.

DESIGN, SETTING AND PARTICIPANTS Multicenter, single-blind, noninferiority randomized

clinical trial comparing rocuronium (1.2 mg/kg) with succinylcholine (1 mg/kg) for rapid
sequence intubation in 1248 adult patients needing out-of-hospital tracheal intubation.
Enrollment occurred from January 2014 to August 2016 in 17 French out-of-hospital
emergency medical units. The date of final follow-up was August 31, 2016.

INTERVENTIONS Patients were randomly assigned to undergo tracheal intubation facilitated

by rocuronium (n = 624) or succinylcholine (n = 624).

MAIN OUTCOMES AND MEASURES The primary outcome was the intubation success rate on
first attempt. A noninferiority margin of 7% was chosen. A per-protocol analysis was
prespecified as the primary analysis.

RESULTS Among 1248 patients who were randomized (mean age, 56 years; 501 [40.1%]
women), 1230 (98.6%) completed the trial and 1226 (98.2%) were included in the
per-protocol analysis. The number of patients with successful first-attempt intubation was
455 of 610 (74.6%) in the rocuronium group vs 489 of 616 (79.4%) in the succinylcholine
group, with a between-group difference of −4.8% (1-sided 97.5% CI, −9% to ⬁), which did not
meet criteria for noninferiority. The most common intubation-related adverse events were
hypoxemia (55 of 610 patients [9.0%]) and hypotension (39 of 610 patients [6.4%]) in the
rocuronium group and hypoxemia (61 of 616 [9.9%]) and hypotension (62 of 616 patients
[10.1%]) in the succinylcholine group.

CONCLUSIONS AND RELEVANCE Among patients undergoing endotracheal intubation in an

out-of-hospital emergency setting, rocuronium, compared with succinylcholine, failed to
demonstrate noninferiority with regard to first-attempt intubation success rate.

TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02000674

Author Affiliations: Author

affiliations are listed at the end of this
article.
Corresponding Author: Xavier
Combes, MD, PhD, Department of
Emergency, CHU de la Réunion,
Université de la Réunion, Allée des
Topazes, Saint Denis, 97400,
Réunion, France (x.combes.samu974
JAMA. 2019;322(23):2303-2312. doi:10.1001/jama.2019.18254 @chu-reunion.fr).

(Reprinted) 2303
© 2019 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a University Paris 5 Descartes User on 12/17/2019

 Research Original Investigation Effect of Rocuronium vs Succinylcholine on Successful Out-of-Hospital Rapid Sequence Intubation
T
racheal intubation is one of the most critical interven-
tions in emergency settings.1 Several clinical studies
have reported that sedation greatly improves ease and
safety of this emergency procedure.2,3 Rapid sequence intu-
bation (RSI) is therefore the most widely recommended seda-
tion technique for patients requiring emergency tracheal
intubation.4 RSI involves administration of rapid-onset drugs,
including a hypnotic and a paralytic agent. Use of a neuromus-
cular blocking agent improves the overall intubating condi-
tions and first-attempt intubation success rate, regardless of
the choice of induction agent.5,6 Succinylcholine has tradi-
tionally been the preferred neuromuscular blocking agent, ex-
cept when contraindicated.7 Rocuronium, introduced more re-
cently for use in emergency situations, has been proposed as
a good alternative to succinylcholine because of its pharma-
cokinetic characteristics. When used at a dose of 1.2 mg/kg,
rocuronium has a similar onset time to succinylcholine.8 Be-
cause succinylcholine has several clinical contraindications and
rocuronium has no contraindications (except for hypersensi-
tivity to the agent), debate about the paralytic agent of choice
for RSI has persisted for several years. Moreover, succinylcho-
line use has been associated with several adverse events not
reported with rocuronium, including hyperkalemia and in-
crease in oxygen consumption leading to rapid desaturation.9,10
Numerous reviews have concluded that succinylcholine
provides better intubating conditions than rocuronium, but
other observational studies have reported that when rocuronium
is used at a dose higher than 1 mg/kg, intubation is as success-
ful as with succinylcholine.11-13 Consequently, surveys have re-
ported a marked increase in rocuronium use in emergency
settings.11,14 To our knowledge, no randomized study has com-
pared these paralytic agents in emergency settings.15
Given these conflicting results and the lack of high-
quality evidence, a randomized clinical trial was conducted to
compare rocuronium vs succinylcholine use in emergency out-
of-hospital intubation situations. It was hypothesized that
rocuronium would be noninferior to succinylcholine for fa-
cilitating tracheal intubation.
Methods
Study Design
The Succinylcholine vs Rocuronium for Out-of-Hospital Emer-
gency Intubation (CURASMUR) trial was a nationwide, single-
blind, randomized, noninferiority clinical trial conducted from
January 2014 through August 2016 at 17 out-of-hospital emer-
gency medical units in France. The study patients were blinded
to intervention assignment, but the physicians conducting the
intubation procedures were not blinded. The Comité de Pro-
tection des Personnes Sud-Ouest et Outre-Mer ethics commit-
tee approved the trial protocol (ref 2013-001438-16), which is
available in Supplement 1. Patients undergoing out-of-
hospital emergency intubation are most often not able to pro-
vide informed consent. In accordance with French laws on
emergency medical research, if a patient's relative was present
when the medical team had to intubate, written consent from
the relative of the patient to be included in the clinical study
2304 JAMA December 17, 2019 Volume 322, Number 23 (Reprinted)
© 2019 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ by a University Paris 5 Descartes User on 12/17/2019
Key Points
Question Is rocuronium noninferior to succinylcholine with
regard to first-attempt endotracheal intubation success among
patients undergoing rapid sequence intubation in an
out-of-hospital emergency setting?
Findings In this randomized clinical trial that included 1248
patients, the number of patients with successful first-attempt
intubation was 455 of 610 (74.6%) in the rocuronium group vs
489 of 616 (79.4%) in the succinylcholine group, a difference of
−4.8% (1-sided 97.5% CI, −9% to ⬁), which did not meet criteria
for noninferiority.
Meaning The study findings failed to demonstrate noninferiority
of rocuronium compared with succinylcholine with regard to
first-attempt endotracheal intubation success rate.
was required. If no relatives were present at the time of intu-
bation, an information letter offering the opportunity to pro-
vide consent or to opt out of inclusion in the study was sys-
tematically sent to the patient if he or she survived and left the
hospital or to a relative if the patient died at the hospital. Ad-
ditional information on the methods for obtaining consent is
available in Supplement 2.
The emergency medical service system in France is a cen-
trally based, 2-tiered system. The first level is composed of ba-
sic life support fire department ambulances based at fire sta-
tions. The second level comprises advanced life support
physician-staffed ambulances. These mobile intensive care units
are distributed throughout each region. The physician-staffed
ambulances have a minimum team of a trained ambulance
driver, a nurse (or a nurse anesthesiologist), a senior physician
specializing in either emergency medicine (in more than 90%
of cases) or anesthesiology, and, sometimes, a medical stu-
dent on board. All physicians have at least 2 years of practice
and are emergency physicians or anesthesiologists. Tracheal in-
tubation is only performed by advanced life support units.
Patient Population
Patients were recruited between January 2014 and August 2016.
The study included all consecutive out-of-hospital adult pa-
tients requiring emergency tracheal intubation as assessed by
the emergency physician. Patients with all conditions (trauma,
dyspnea, coma, overdoses, and shock), except cardiac arrest,
were included. Patients who met any of the following criteria
were excluded from the study: younger than 18 years; preg-
nant women; contraindication to rocuronium (known allergy
to rocuronium), succinylcholine (personal or family history of
known malignant hyperthermia, known allergy to succinylcho-
line, congenital muscular dystrophy, myasthenia, specific hy-
perkalemia, recent open eye surgery, known congenital deficit
in plasma pseudocholinesterases), or sugammadex (the selec-
tive paralytic binding agent for rocuronium reversal); under
guardianship; and no health insurance.
Randomization
Patients were randomized in a 1:1 ratio to the rocuronium or
the succinylcholine group (Figure 1). A statistician at the meth-
odological unit of the La Réunion University Hospital Center,
jama.com
 Effect of Rocuronium vs Succinylcholine on Successful Out-of-Hospital Rapid Sequence Intubation Original Investigation Research

Figure 1. Flow of Participants in CURASMUR, a Study of the Effect of Rocuronium vs Succinylcholine

on Endotracheal Intubation Success Rate Among Patients Undergoing Out-of-Hospital Intubation

1326 Patients assessed for eligibility

78 Excluded
26 Reason not provided
20 Did not meet inclusion criteria
7 No health insurance
6 With cardiac arrest
4 Age <18 years
2 Contraindications to succinylcholine
1 Under guardianship
12 Physician declined to participate
11 Improvement in clinical condition
9 Declined to participate

1248 Patients randomized

624 Randomized to the 624 Randomized to the

rocuronium group succinylcholine group
613 Received intervention 617 Received intervention
as randomized as randomized
11 Did not receive intervention 7 Did not receive intervention
as randomized as randomized
5 Withdrew consent 2 Under guardianship
3 No health insurance 2 Withdrew consent
1 Age <18 years 2 No health insurance
1 Under guardianship 1 Age <18 years
1 Pregnant

613 Included in the randomized 617 Included in the randomized

group analysis group analysis
2 No intubation attempted 1 Received rocuronium
1 Received succinylcholine

610 Included in the per-protocol 616 Included in the per-protocol

analysis analysis

not involved in patient recruitment, generated randomiza-
tion sequences. The sequences were generated using the PROC
PLAN procedure from SAS, version 9.4 (SAS Institute). Bal-
anced and stratified by center, randomization lists were gen-
erated using randomly permuted blocks of 4, 6, and 8 pa-
tients. Numbered and sealed opaque envelopes were then
generated from those lists and used by emergency physicians
in each ambulance to assign patients to the rocuronium or suc-
cinylcholine group. The emergency physicians conducting the
intubation procedures were blinded to the contents of the en-
velope at the time of assigning an individual patient.
Study Intervention
In both groups, sedation induction was performed after pre-
oxygenation. Emergency physicians were asked to follow the
French guidelines for sedation and analgesia in emergency
departments.4 Two hypnotics were recommended. Etomi-
date (0.3 mg/kg) or ketamine (2 mg/kg), with dosage based
on estimated patient weight, was injected followed immedi-
ately by an intravenous bolus injection of either succinylcho-
line (1 mg/kg) or rocuronium (1.2 mg/kg), with dosage based
on estimated patient weight. The use of another hypnotic
(propofol or thiopenthal) was allowed, according to the phy-
sician's preference. The Sellick maneuver was recommended
but optional, according to the physician's preference. It was
recommended to perform intubation 60 seconds after
administration of the paralytic agent. Single-use Macintosh
metallic laryngoscope blades (size 3 and 4) were used. The
standard intubation procedure did not include use of a stylet;
stylet use was considered an alternative airway procedure.
When standard laryngoscopy-assisted intubation was not
possible, an alternative procedure was recommended in
accordance with the French Society of Anesthesia and Resus-
citation guidelines on difficult airway management, includ-
ing gum elastic bougie, intubating laryngeal mask airway
(ILMA), or cricothyrotomy.16 If the patient was randomized to
the rocuronium group, the physician could subsequently
choose to antagonize the action of the rocuronium with
sugammadex, a procedure recommended for patients impos-
sible to intubate under direct laryngoscopy and who could
neither be intubated nor ventilated by alternative techniques
for difficult intubation. These airway practices were in accor-
dance with the French Society of Anesthesia and Resuscita-
tion consensus guidelines on difficult airway management.16
Aside from the randomization for paralytic agent used
for the induction of sedation, there was no change from usual
practices. In particular, hypotension was managed via fluid
resuscitation with crystalloids and ephedrine and prolonged

jama.com (Reprinted) JAMA December 17, 2019 Volume 322, Number 23 2305

© 2019 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a University Paris 5 Descartes User on 12/17/2019

 Research Original Investigation Effect of Rocuronium vs Succinylcholine on Successful Out-of-Hospital Rapid Sequence Intubation
hypotension was managed with continuous catecholamine
administration. Maintenance sedation after intubation was
performed according to the French Society of Anesthesia and
Resuscitation recommendations and included administration
of benzodiazepine or propofol and opioids. Doses of these
agents were adapted by the physician to the patient's clinical
status and the objectives of sedation, which vary according to
the pathology and the indication for mechanical ventilation.
Each physician completed a paper case report form on-
site. Later, to ensure the quality and completeness of the study
data, a clinical research associate at each center verified the
case report form data from the source medical file on-site and
recorded the data to a centralized database. Patients were fol-
lowed up until hospital admission.
Outcomes
The primary outcome measure was the percentage of pa-
tients with successful first-attempt orotracheal intubation as-
sessed by the physician and confirmed by a capnography curve
consistent over 3 respiratory cycles. A noninferiority margin
of 7% was selected.
Secondary prespecified outcomes were (1) the Cormack-
Lehane grade of glottis visibility obtained by direct laryngos-
copy (range, 1-4; 1 indicates full view of glottis; 2, partial view
of glottis; 3, only epiglottis seen; and 4, neither glottis nor
epiglottis seen)17; (2) the overall difficulty of the intubation
process, measured by the Intubation Difficulty Scale score
(range, 0 to infinite; score >5 indicates difficult intubation)18;
(3) intubation conditions, assessed by the Copenhagen score
(poor, good, or excellent conditions)19; (4) the percentage of
patients intubated by alternative techniques (stylet, gum
elastic bougie, ILMA [eg, Fastrach], or cricothyrotomy); and
(5) intubation-related complications in the first 15 minutes
after intubation (cardiac arrest, arterial hypotension [systolic
blood pressure <90 mm Hg], hypoxemia [occurrence of new
oxygen desaturation <90%], physician-reported aspiration,
severe arrhythmia [ventricular tachycardia, ventricular fibril-
lation], or allergic reaction).
Post hoc exploratory outcomes were the number of intu-
bation attempts, the number of intubation failures under di-
rect laryngoscopy, the time of out-of-hospital care, the num-
ber of deaths during out-of-hospital care, the number of
unintentional extubations, and the amount of sedative drugs
and vasopressors used after intubation.
Sample Size
The sample size was calculated from the previous literature,
with an expected percentage of successful first-attempt oro-
tracheal intubation of 75% for patients in the succinylcho-
line group.3,20,21 After assuming a noninferiority margin of
7% based on out-of-hospital studies that focused on emer-
gency intubation using the same main outcome, with a type
I error of 5% and type II error of 20%, it was determined that
602 patients were needed in each group (1204 overall).20-23
We set targeted enrollment at 1300 patients to take into
account risks of protocol deviations in this emergency ran-
domization context. Thus, we planned to include 650
patients in each group.
2306 JAMA December 17, 2019 Volume 322, Number 23 (Reprinted)
© 2019 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ by a University Paris 5 Descartes User on 12/17/2019
Statistical Analysis
Characteristics at baseline were described by their frequency
and percentages for categorical variables and by means and SDs
or medians and interquartile ranges for quantitative vari-
ables. To take the randomization stratification factor (ie, the
center) into account, a generalized estimating equations model
with an identity link function was used to compare the groups
for the percentage of patients with a successful first-attempt
orotracheal intubation. Therefore, the center was included as
the clustering factor and an exchangeable correlation matrix
was specified. Based on this model, noninferiority was as-
sessed for the primary outcome by the 1-sided 97.5% CI of the
absolute difference. As recommended for noninferiority stud-
ies, a per-protocol analysis was conducted first.24,25 Patients
who received allocated treatment and for whom intubation was
attempted were included in this analysis. An additional analy-
sis was conducted that analyzed patients according to their ran-
domized group and included all patients who were random-
ized and completed the trial.
In an exploratory post hoc analysis, we performed 2 sub-
group analyses to investigate the treatment effect of the pri-
mary outcome based on patients’ conditions; 1 analysis was
stratified on reason for intubation and the other on patient po-
sition at the time of intubation. Analyses included treat-
ment × subgroup interaction and the subgroup as covariates
in a generalized estimating equations model defined for analy-
ses of the primary outcome. The absolute difference between
treatment groups and 1-sided 97.5% CIs were then estimated
from these models.
We compared secondary outcomes using generalized es-
timating equations models with an identity link function. To
take into account potential nonindependence of patients in the
same center, the center was included as the clustering factor
and an exchangeable correlation matrix was specified. Abso-
lute differences and their 2-sided 95% CIs were derived from
these models. All tests for secondary outcomes were per-
formed at a 2-tailed type I error of 5%, with a superiority hy-
pothesis. Because of the potential for type I error due to mul-
tiple comparisons, findings for analyses of secondary end
points should be interpreted as exploratory.
The amount of missing data in this study was low. Analy-
ses were performed on complete cases and no assumptions
were made for the patterns of missing data. All analyses were
performed used SAS version 9.4 (SAS Institute). The statisti-
cal analysis plan is available in Supplement 3.
Results
Baseline Characteristics
A total of 1248 patients were enrolled in the study. Patients
were recruited between January 2014 and August 2016, with
final follow-up on August 31, 2016. Of the 1326 patients
assessed for eligibility, 1248 were randomized (mean age, 56
years; 501 [40.1%] women). Of the randomized patients, 1230
(98.6%) completed the trial and 1226 (98.2%) were included
in the per-protocol analysis (Figure 1). Patient characteristics
and clinical indications for intubation are reported in Table 1
jama.com
 Effect of Rocuronium vs Succinylcholine on Successful Out-of-Hospital Rapid Sequence Intubation Original Investigation Research

Table 1. Baseline Patient Data in a Study of the Effect of Rocuronium Table 1. Baseline Patient Data in a Study of the Effect of Rocuronium
vs Succinylcholine on Out-of-Hospital Endotracheal Intubation Success vs Succinylcholine on Out-of-Hospital Endotracheal Intubation Success
(continued)
No. (%)
Rocuronium Succinylcholine No. (%)
Characteristic (n = 610) (n = 616) Rocuronium Succinylcholine
Age, mean (SD), y 57.2 (18.7) 54.6 (19.1) Characteristic (n = 610) (n = 616)
Sex Patient position during intubation
Men 370 (60.7) 366 (59.3) Lying on a stretcher 324 (53.1) 307 (49.8)
Women 240 (39.3) 250 (40.7) Lying on the ground 161 (26.4) 187 (30.4)
BMI, mean (SD) 25.5 (5.4) 25.8 (5.1) Lying on a bed 112 (18.4) 110 (17.9)
Medical history Other 13 (2.1) 12 (1.9)
Hypertension 208 (35.9) 178 (30.1) Abbreviations: BMI, body mass index (calculated as weight in kilograms divided
(n = 580) (n = 592) by height in meters squared); IQR, interquartile range.
Smoking 151 (26.4) 127 (21.9) a
Coded by the emergency physician.
(n = 572) (n = 580)
b
Range, 3 (deep coma) to 15 (normal consciousness).
Alcoholism 112 (19.4) 107 (18.2)
(n = 576) (n = 589)
Cancer 55 (9.4) 42 (7.1)
(n = 582) (n = 593)
Coronary heart disease 51 (8.8) 42 (7.1)
(n = 580) (n = 592) and eFigure in Supplement 2 (74 patients with missing data).
Chronic obstructive 50 (8.6) 34 (5.7) Coma was the leading reason for intubation.
pulmonary disease (n = 578) (n = 592)
Heart failure 50 (8.6) 29 (4.9)
(n = 579) (n = 591) Primary Outcome
Chronic kidney failure 19 (3.3) 20 (3.4) The number of patients with successful first-attempt intuba-
(n = 580) (n = 591)
tion was 455 of 610 (74.6%) in the rocuronium group vs 489
Reason for intubationa
of 616 (79.4%) in the succinylcholine group, a difference of
Coma due to neurological disease 313 (51.3) 304 (49.4)
−4.8% (1-sided 97.5% CI, −9% to ⬁), which did not meet crite-
Coma due to self-poisoning 107 (17.5) 124 (20.1)
ria for noninferiority (margin of 7%; Figure 2). Additional analy-
Acute respiratory failure 101 (16.6) 71 (11.5) sis of patients according to their randomized group that in-
Trauma 51 (8.4) 52 (8.4) cluded all patients who were randomized and completed the
Shock 8 (1.3) 9 (1.5) trial is presented in the eTable 1 in Supplement 2. Subgroup
Other 30 (4.9) 56 (9.1) analyses for the primary outcome are reported in eTable 2 in
Characteristics at enrollment Supplement 2.
Glasgow Coma Scale score, 6.0 (3.0-8.0) 6.0 (3.0-8.0)
median (IQR)b
Heart rate, mean (SD), beats/min 99.4 (28.4) 95.6 (27.2) Secondary Outcomes
Among the secondary end points assessing tracheal intuba-
Respiratory rate, mean (SD), 21.4 (9.7) 21.1 (9.5)
breaths/min tion difficulty, there was no statistically significant between-
Arterial systolic pressure, mm Hg group difference for the mean (SD) Intubation Difficulty Scale
<90 47 (7.7) 37 (6.0) score (4.2 [2.9] for the rocuronium group vs 4.1 [2.4] for the
>140 258 (42.3) 227 (36.9) succinylcholine group; difference, 0.1 [95% CI, −0.2 to 0.4]).
Arterial diastolic pressure, mm Hg There was also no statistically significant difference in the
<50 43 (7.0) 35 (5.7) Copenhagen score between the groups; 327 of 580 (56.4%)
>90 193 (31.6) 168 (27.3) patients in the rocuronium group vs 313 of 584 (53.6%) in the
Peripheral oxygen saturation, 95.4 (6.8) 95.4 (7.5)
succinylcholine group had excellent intubation conditions
mean (SD), % (difference, 2.8 [95% CI, −0.5 to 6.4]) and 206 of 580 (35.5%)
Sedation given for intubation patients in the rocuronium group vs 222 of 584 (38.0%) in
Etomidate 536 (87.9) 543 (88.1) the succinylcholine group had good intubation conditions
Total dose, median (IQR), mg 30 (20-40) 30 (20-40) (difference, −2.5 [95% CI, −6.1 to 0.5]).
Ketamine 38 (6.2) 34 (5.5) There was no significant difference between the 2 groups
(n = 609) in the use of alternative intubation techniques, such as stylet
Total dose, median (IQR), mg 150 (67-190) 200 (125-250)
or gum elastic bougie, although significantly more patients in
Pentothal 21 (3.4) 19 (3.1) the rocuronium group had use of the ILMA, and 1 patient
(n = 609) (n = 615)
in the succinylcholine group underwent cricothyrotomy.
Total dose, median (IQR), mg 350 (200-400) 325 (250-400)
Intubation-related complications reported within 15 minutes
Propofol 21 (3.4) 21 (3.4)
after intubation were observed more frequently in patients in
Total dose, median (IQR), mg 60 (40-150) 150 (80-160)
the succinylcholine group than the rocuronium group (143 of
Combined administration, No. 6 1
616 [23.2%] vs 111 of 610 [18.2%]; absolute difference, −5%
(continued) [95% CI, −9.8% to −0.03%]; P = .04; Table 2).

jama.com (Reprinted) JAMA December 17, 2019 Volume 322, Number 23 2307

© 2019 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a University Paris 5 Descartes User on 12/17/2019

 Research Original Investigation
Figure 2. Difference in Successful First-Attempt Intubation Rate Between Patients Given Rocuronium vs Succinylcholine While Undergoing
Out-of-Hospital Rapid Sequence Intubation
No. of Patients/Total No. (%)
Rocuronium
Group
Randomized group analysis 456/613 (74.4)
Per-protocol analysis 455/610 (74.6)
The dashed line represents the noninferiority margin of 7%. Because the CI lines go above the prespecified noninferiority margin of 7%, the null hypothesis that
succinylcholine is superior cannot be rejected.
Post Hoc Exploratory Outcomes
Significantly more intubation attempts were required in
the rocuronium group than in the succinylcholine group
(Table 2). Six patients in the rocuronium group and 3 in the
succinylcholine group died during out-of-hospital care. No
deaths were attributed to difficult intubation. In the succinyl-
choline group, 100 of 606 (16.5%) patients were treated with
norepinephrine during the immediate postintubation period,
compared with 60 of 604 (9.9%) in the rocuronium group
(difference, −6.6% [95% CI, −10.8% to −1.9%]; P < .001;
Table 3). Fifteen patients could not be intubated under direct
laryngoscopy in the out-of-hospital care period. Among
them, 6 were intubated blindly through a laryngeal intuba-
tion mask. Six more were effectively ventilated by ILMA and
were intubated at the hospital. One patient had a cricothy-
rotomy and 2 patients were ventilated with a face mask until
arrival at the hospital (Table 2). Eleven of these 15 patients
were assigned to receive rocuronium. Two patients received
sugammadex to antagonize rocuronium. Airway control was
obtained for 1 of these 2 patients by application of the recom-
mended algorithm; an intubating laryngeal mask was put in
place and enabled effective mechanical ventilation until
arrival at the hospital. For the second patient, sugammadex
was injected after only 1 intubation attempt failure under
direct laryngoscopy, without attempting any alternative tech-
nique. That is, this physician did not follow the recom-
mended algorithm for difficult intubation for this patient.
The patient awoke 45 minutes later, and the final diagnosis
was status epilepticus.
Discussion
This randomized clinical trial failed to demonstrate noninfe-
riority for the success rate of rocuronium compared with suc-
cinylcholine for first-attempt intubation in adult patients re-
ceiving emergency intubation at a noninferiority margin of 7%.
To our knowledge, this study is the first randomized clini-
cal trial comparing rocuronium and succinylcholine in emer-
gency settings, even though reports indicate that emergency
physicians are adopting rocuronium as a standard practice, with
some departments using this drug more often than
succinylcholine.26,27 Most of the published trials comparing
these neuromuscular-blocking agents have examined operat-
2308 JAMA December 17, 2019 Volume 322, Number 23 (Reprinted)
© 2019 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ by a University Paris 5 Descartes User on 12/17/2019
Effect of Rocuronium vs Succinylcholine on Successful Out-of-Hospital Rapid Sequence Intubation
Succinylcholine Absolute Difference Favors Favors
Group (1-Sided 97.5% CI), % Rocuronium Succinylcholine
489/617 (79.2) –4.8 (–9.1 to ∞)
489/616 (79.4) –4.8 (–9.0 to ∞)
–15 –10 –5 0 5 10
Between-Group Difference in First-Attempt
Intubation Rate (1-Sided 97.5% CI), %
ing room settings.28,29 To our knowledge only 1 randomized trial
has examined the intensive care setting, and none have exam-
ined emergency departments or out-of-hospital settings.30
Accordingly, the systematic reviews of this comparison essen-
tially analyze operating room studies only.12,29,31
For many years, succinylcholine has been the principal
paralytic agent recommended for facilitating tracheal intuba-
tion in patients needing out-of-hospital tracheal intubation.
One of the main characteristics of succinylcholine is its very
quick onset, which enables optimal intubation conditions to
be obtained in less than a minute after intravenous adminis-
tration. Rocuronium, a nondepolarizing paralytic agent, has
pharmacokinetic characteristics that provide optimal intuba-
tion conditions in almost the same time as succinylcholine, as
long as the dose administered is at least 1 mg/kg. For this rea-
son, it has been proposed as an alternative paralytic agent when
RSI is indicated.32
The primary end point chosen for this trial was the first-
attempt intubation success rate. This criterion is often used in
clinical studies assessing tracheal intubation in the emergency
setting context because several studies of emergency intuba-
tions report that the complication rate related to airway con-
trol increases with the number of intubation attempts.33-36 It ap-
pears to be a more relevant and direct criterion than intubation
condition, measured by scores that take into account many ele-
ments that may be difficult to accurately assess in the emer-
gency context, which was assessed here only as a secondary out-
come and did not differ significantly between the groups.
Nonetheless, none of the published meta-analyses that com-
pared succinylcholine with rocuronium used this primary end
point. Instead, all used intubation conditions considered to be
good or excellent as their primary outcome.
Design of a noninferiority study seemed necessary be-
cause succinylcholine has a tolerance profile that appears to
be lower than that of rocuronium. The choice of a margin of
noninferiority is a major element when performing a nonin-
feriority study. For this study, determination of this value was
not straightforward because very little data have been pub-
lished on this topic. No randomized trials have been con-
ducted in an emergency setting to compare succinylcholine and
rocuronium. All randomized trials were conducted in a hos-
pital setting, primarily in the operating room, and the pri-
mary end point of these trials was the intubation conditions
assessment and not the first-attempt intubation success rate.
jama.com
 Effect of Rocuronium vs Succinylcholine on Successful Out-of-Hospital Rapid Sequence Intubation Original Investigation Research

Table 2. Intubation Characteristics and Outcomes of Patients in a Study of the Effect of Rocuronium
vs Succinylcholine on Out-of-Hospital Endotracheal Intubation Success

No./Total No. (%)

Absolute Difference
Rocuronium Group Succinylcholine Group (95% CI), %a P Valueb
Primary Outcome
(Successful First-Attempt
Intubation)
Per-protocol analysis 455/610 (74.6) 489/616 (79.4) −4.8 (1-sided 97.5% CI,
−9.0 to ⬁)c
Randomized group analysis 456/613 (74.4) 489/617 (79.2) −4.8 (1-sided 97.5% CI,
−9.1 to ⬁)c
Secondary Outcomes
Prespecified analyses
Cormack-Lehane graded
I (best view) 375/609 (61.6) 346/616 (56.2) 5.4 (−0.3 to 10.9) .06
II 125/609 (20.5) 173/616 (28.1) −7.6 (−11.5 to −3.7) <.001 Abbreviation: IQR, interquartile
III 81/609 (13.3) 72/616 (11.7) 1.6 (−2.9 to 6.2) .49 range.
a
The estimated difference between
IV (worst view) 28/609 (4.6) 25/616 (4.0) 0.6 (−1.5 to 2.6) .60
the groups was calculated with a
Intubation Difficulty 4.2 (2.9) 4.1 (2.4) 0.1 (−0.2 to 0.4) .52 2-sided 95% CI using a generalized
Scale score, mean (SD)e
estimated equation model, in which
Intubation Difficulty 138/605 (22.8) 130/614 (21.2) 1.6 (−3.5 to 6.8) .53 center was specified as the
Scale score >5 clustering factor.
Copenhagen score b
(reflecting intubation Not corrected for multiple
conditions)f comparisons.
c
Excellent 327/580 (56.4) 313/584 (53.6) 2.8 (−0.5 to 6.4) .09 The estimated difference between
the groups was calculated with a
Good 206/580 (35.5) 222/584 (38.0) −2.5 (−6.1 to 0.5) .10
1-sided 97.5% CI using a generalized
Poor 47/580 (8.1) 49/584 (8.4) −0.3 (−3.0 to 2.6) .87 estimated equation model, in which
Need for alternative center was specified as the
intubation techniques clustering factor. The margin for
Stylet 55/610 (9.0) 51/616 (8.3) 0.7 (−1.9 to 2.0) .97 noninferiority was set at −7%. A
lower bound of the CI that did not
Gum elastic bougie 114/610 (18.7) 107/616 (17.4) 1.3 (−1.2 to 3.8) .31
exceed this margin indicated
Intubating laryngeal 10/610 (1.6) 2/616 (0.3) 1.3 (0.5 to 2.4) .003 noninferiority.
mask airway d
Reflects glottis visualization. Range,
Cricothyrotomy 0/610 (0.0) 1/616 (0.2) −0.2 (−0.5 to 0.2)
1-4; higher scores indicate less
Early intubation-related .04 glottis visualization.
complications e
Range, 0 (intubation without
Patients with at least 111/610 (18.2) 143/616 (23.2) −5 (−9.8 to −0.03) difficulty) to infinity; a value greater
1 complication
than 5 indicates difficult intubation.
Hypoxemia episodesg 55/610 (9.0) 61/616 (9.9) −0.9 (−4.4 to 2.6) f
The Copenhagen score is composed
Severe arrhythmiah 12/610 (2.0) 26/616 (4.2) −2.2 (−3.8 to −0.7) of 5 items with responses coded as
Cardiac arrest 22/609 (3.6) 13/615 (2.1) 1.5 (−0.1 to 3.3) “excellent,” “good,” or “poor”:
laryngoscopy (easy, fair, difficult),
Pulmonary aspirationi 19/610 (3.1) 21/616 (3.4) −0.3 (−1.7 to 1.1)
vocal cords position (abducted,
Hypotension episodesj 39/610 (6.4) 62/615 (10.1) −3.7 (−6.8 to −0.3) intermediate, closed), vocal cords
Exploratory analysesk movement (none, moving, closing),
movements of the tube during
No. of intubation 1.4 (0.8) 1.3 (0.6) 0.1 (0.05 − 0.2) <.001
attempts, mean (SD) insertion (none, slight, vigorous),
and coughing during tracheal tube
2 110/609 (18.1) 96/615 (15.6) 2.5 (−2.2 to 6.9) .31
insertion (none, diaphragm,
3 34/609 (5.6) 27/615 (4.4) 1.2 (−0.8 to 3.2) .23 sustained); intubation conditions
≥4 10/609 (1.6) 3/615 (0.5) 1.1 (0.2 to 2.0) .01 are defined as excellent if all items
are excellent, good if all items are
Intubation failure 11/610 (1.8) 4/616 (0.7) 1.1 (0.3 − 2.3) .01
under direct excellent or good, and poor if a
laryngoscopy single item is poor.
g
Time of prehospital care, 55 (38 to 78) 55 (39 to 80) −2.2 (−6.9 to 2.5) .35 Defined as any oxygen saturation
median (IQR), min reading of less than 90%.
Death during 6/608 (1.0) 3/615 (0.5) 0.5 (−0.4 to 1.3) .26 h
Ventricular tachycardia and
prehospital care
ventricular fibrillation.
Complications i
Visually detected by the physician
No. of complications 0 0 −0.09 (−0.17 to −0.08) .03 during laryngoscopy.
per patient, j
median (IQR) Defined as a new episode of
arterial systolic pressure of less
≥1 severe complication 115/608 (18.9) 150/615 (24.4) −5.5 (−10.8 to −0.05) .04
than 90 mm Hg.
Unintentional extubation 1/609 (0.2) 4/615 (0.6) 0.4 (−1.0 to 0.03) .06 k
Post hoc outcomes.

jama.com (Reprinted) JAMA December 17, 2019 Volume 322, Number 23 2309

© 2019 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a University Paris 5 Descartes User on 12/17/2019

 Research Original Investigation Effect of Rocuronium vs Succinylcholine on Successful Out-of-Hospital Rapid Sequence Intubation

Table 3. Sedative and Vasopressor Use During the Postintubation Period in a Study of the Effect of Rocuronium
vs Succinylcholine on Out-of-Hospital Endotracheal Intubation Success

No. Who Received Some of the Agent/No. With Available Data (%)
Absolute Difference
Drug Rocuronium (n = 610) Succinylcholine (n = 616) (95% CI), %a,b
Hypnotics
Midazolam 521/610 (85.4) 546/616 (88.6) −3.2 (−5.9 to 0.4)
Total dose, 5.0 (4.0 to 10.0) 8.0 (5.0 to 13.0) −3.0 (−4.3 to −2.3)
median (IQR), mgc
No. of boluses, 1.3 (0.7) 1.5 (0.9) −0.2 (−0.3 to −0.02)
mean (SD)
Propofol 34/608 (5.6) 40/613 (6.5) −0.9 (−2.5 to 0.2)
Total dose, 133.0 (50.0 to 200.0) 200.0 (100.0 to 250.0) −52.3 (−98.9 to −6.0)
median (IQR), mgc
No. of boluses, 1.0 (1.0) 1.5 (1.4) −0.5 (−1.1 to 0.04)
mean (SD)
Analgesics
Fentanyl 50/610 (8.2) 48/614 (7.8) 0.4 (−0.1 to 1.8)
Total dose, 100.0 (50.0 to 200.0) 100.0 (67.5 to 200.0) −13.5 (−59.2 to 32.4)
median (IQR), μgc
No. of boluses, 0.9 (0.8) 1.4 (1.0) −0.3 (−0.4 to −0.2)
mean (SD)
Abbreviation: IQR, interquartile
Sufentanyl 491/610 (80.5) 513/616 (83.3) −2.8 (−6.3 to 0.7)
range.
Total dose, 15.0 (10.0 to 25.0) 20.0 (10.0 to 34.0) −8.0 (−12.0 to −4.0) a
The estimated difference between
median (IQR), μgc
the groups was calculated with a
No. of boluses, 1.2 (0.5) 1.5 (0.8) −0.3 (−0.4 to −0.2) 2-sided 95% CI using a generalized
mean (SD)
estimated equation model, in which
Vasopressors center was specified as the
Epinephrine 26/605 (4.3) 26/605 (4.3) 0.0 (−4.1 to 4.1) clustering factor.
b
Norepinephrine 60/604 (9.9) 100/606 (16.5) − 6.6 (−10.8 to −1.9) Not corrected for multiple
comparisons.
Dopamine 1/604 (0.2) 0/605 (0.0) 0.2 (−0.2 to 0.5)
c
Calculated only from patients who
≥1 vasopressor 77/604 (12.7) 121/608 (19.9) −7.2 (−11.0 to −2.8)
received the agent.

Some observational studies conducted in an emergency situ-
ation compared the first-attempt intubation rate between pa-
tients who did vs patients who did not receive a paralytic agent,
such as succinylcholine. The difference in first-attempt intu-
bation rate varies in these observational studies between 20%
and 17%, in favor of succinylcholine use.20,23 Therefore, in the
present study the standard comparator was succinylcholine
and the new agent was rocuronium. As suggested for nonin-
feriority trials, the margin of noninferiority was set to less than
half of the difference previously reported for the first-
attempt intubation rate, depending on whether succinylcho-
line was used.25
While the results of the primary outcome analysis showed
that rocuronium cannot be considered noninferior to succi-
nylcholine in terms of ease of intubation, fewer complica-
tions were observed with rocuronium. These results must be
interpreted cautiously. Cardiovascular complications, such as
hypotension or cardiac arrhythmia, were more frequent after
succinylcholine use. However, it should be noted that more
deaths were recorded during the prehospital period of care in
the rocuronium group, although this difference was not sta-
tistically significant. Nearly all patients in both groups re-
ceived postintubation sedation, usually a hypnotic agent (gen-
erally midazolam) and an opioid analgesic (most commonly
sufentanil). The total doses of opioids and midazolam admin-
istered were greater in the succinylcholine group, which might
have contributed to the higher frequency of hemodynamic dis-
orders in that group. Continuous sedation began as soon as tra-
cheal intubation was in place. The total dose of hypnotic ad-
ministered during the out-of-hospital period differed between
the groups because of more frequent bolus administration of
sedative agents in the succinylcholine group. It appears likely
that in patients with frequent hemodynamic instability, using
a longer-acting paralytic agent might reduce the likelihood of
the patient fighting the ventilator, which may lead emer-
gency physicians to administer a bolus of midazolam or an opi-
oid to avoid adverse respiratory events.37
Limitations
This study has several limitations. First, this trial was not
double-blinded, and the physician might have been influ-
enced by knowledge of which drug was administered. In emer-
gency situations, it would have been extremely difficult to mask
the fasciculations observed in more than 90% of individuals
who receive succinylcholine. Moreover, the time between the
injection of the paralytic agent and the first tracheal intuba-
tion attempt was not recorded. It is possible that patients in
the rocuronium group might have been intubated before the
recommended 60-second delay with incomplete paralysis,
whereas the fasciculations most often indicated to physi-
cians the effectiveness of paralysis after succinylcholine ad-
ministration before the intubation attempt.
Second, these results were obtained in a specific physician-
staffed out-of-hospital emergency medical system and may
not be generalizable to a paramedical-based care system.
Third, awareness phenomena was not evaluated. Nevertheless,

2310 JAMA December 17, 2019 Volume 322, Number 23 (Reprinted) jama.com

© 2019 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a University Paris 5 Descartes User on 12/17/2019

 Effect of Rocuronium vs Succinylcholine on Successful Out-of-Hospital Rapid Sequence Intubation Original Investigation Research

all patients were sedated according to recommendations, most
often with a combination of an opioid and a benzodiazepine.
Fourth, only the early intubation-related complications dur-
ing the out-of-hospital period were collected and later hospi-
tal complications were not evaluated. Fifth, although a recom-
mended dose of 1 mg/kg of succinylcholine was used, a higher
dose may have been given to patients, as suggested by some
clinical studies that have reported higher intubation success
rates with administration of 1.5 mg/kg of succinylcholine.38
Sixth, because patients were intubated without use of a sty-
let or video laryngoscope and with only Macintosh metallic
blades, this limits the generalization of the results to other out-
of-hospital systems where these practices are widespread. Sev-
enth, the number of intubations performed per year and per
physician and the number of years of practice for each physi-
cian who participated in this study were not reported. Eighth,
the sample size calculation was carried out starting from a hy-
pothesis of a first-attempt intubation success rate of 75% with
succinylcholine, whereas in the present study, a success rate
close to 80% was observed in the succinylcholine group. Ninth,
the noninferiority margin of 7% that was selected was based
in part on an expert opinion, which can be considered as a
methodological limitation.
Conclusions
Among patients undergoing endotracheal intubation in a
medical-based out-of-hospital emergency care system,
rocuronium, compared with succinylcholine, failed to dem-
onstrate noninferiority with regard to first-attempt intuba-
tion success rate.

ARTICLE INFORMATION
Accepted for Publication: October 16, 2019.
Author Affiliations: Department of Emergency,
CHU de la Réunion, Allée des Topazes, Saint Denis,
Réunion, France (Guihard); Groupe
Hospitalo-Universitaire Henri Mondor, SAMU 94,
Assistance Publique-Hôpitaux de Paris, Créteil,
France (Chollet-Xémard); SMUR 95, Centre
Hospitalier de Gonesse, Gonesse, France
(Lakhnati); Department of Anesthesia & Critical
Care - SAMU, Assistance Publique - Hôpitaux de
Paris, Hôpital Necker-Enfants Malades, Université
Paris Descartes, Paris, France (Vivien);
Département d'Anesthésie-Réanimation-SMUR,
Hôpital Universitaire Lariboisière, AP-HP, Paris,
France (Broche); Emergency Department, General
Hospital of Annecy, Annecy, France (Savary); SMUR
de l'hôpital Beaujon, Clichy, France (Ricard-Hibon);
Department of Emergency, CHU de la Réunion,
Réunion, France (Marianne dit Cassou); AP-HP,
Urgences-SAMU 93, Unité
Recherche-Enseignement-Qualité, Hôpital
Avicenne, Bobigny, France (Adnet); Univ Lille, EA
2694 - Santé Publique: Epidémiologie et Qualité
des Soins, Lille, France (Wiel); French National
Out-of-Hospital Cardiac Arrest Registry Research
Group - Registre électronique des Arrêts
Cardiaques, Lille, France (Wiel); Emergency
Medicine Department and SAMU 59, Lille
University Hospital, Lille, France (Wiel);
Department of Emergency Medicine, Groupe
Hospitalier Broca Cochin Hôtel-Dieu, Paris, France
(Deutsch); Department of Emergency Medicine,
University Hospital Dijon, Dijon, France (Tissier);
Raymond Poincaré Hospital (APHP), SAMU 92,
Paris, France (Loeb); Pôle Médecine d'Urgence,
Hôpital Universitaire de Purpan, Toulouse, France
(Bounes); INSERM UMR 1027, Université Paul
Sabatier, Toulouse, France (Bounes); Services de
Médecine d’Urgence et de Réanimation, Pôle
Urgence Réanimation, SAMU 77, Melun, France
(Rousseau); AP-HP, Service d'Aide Médicale
d'Urgence (SAMU) de Paris and Paris Sudden Death
Expertise Center, Université Paris Descartes, Paris,
France (Jabre); INSERM CIC 1410 Clinical and
Epidemiology/ CHU Réunion/Université de la
Réunion, Saint-Pierre, Reunion, France (Huiart);
Department of Population Health, Luxembourg
Institute of Health, Strassen, Luxembourg (Huiart);
Departement d'Informatique Clinique, Centre
Hospitalier Universitaire de La Réunion Site Félix
Guyon, Saint-Denis, France (Ferdynus); Department
of Emergency, CHU de la Réunion, Université de la
Réunion, Réunion, France (Combes).
Author Contributions: Dr Ferdynus had full access
to all of the data in the study and takes
responsibility for the integrity of the data and the
accuracy of the data analysis.
Concept and design: Guihard, Lakhnati,
Ricard-Hibon, Adnet, Deutsch, Jabre, Huiart,
Ferdynus, Combes.
Acquisition, analysis, or interpretation of data:
Guihard, Chollet-Xémard, Lakhnati, Vivien, Broche,
Savary, Ricard-Hibon, Marianne Dit Cassou, Wiel,
Tissier, Loeb, Bounes, Rousseau, Huiart, Ferdynus,
Combes.
Drafting of the manuscript: Ricard-Hibon, Marianne
Dit Cassou, Deutsch, Rousseau, Ferdynus, Combes.
Critical revision of the manuscript for important
intellectual content: Guihard, Chollet-Xémard,
Lakhnati, Vivien, Broche, Savary, Adnet, Wiel,
Tissier, Loeb, Bounes, Jabre, Huiart, Ferdynus,
Combes.
Statistical analysis: Huiart, Ferdynus.
Obtained funding: Lakhnati, Savary, Combes.
Administrative, technical, or material support:
Guihard, Vivien, Savary, Wiel, Bounes.
Supervision: Guihard, Lakhnati, Savary, Adnet,
Jabre, Huiart, Ferdynus, Combes.
Conflict of Interest Disclosures: Dr Huiart
reported receiving grants from the French Ministry
of Health during the conduct of the study and a
salary from University Hospital of La Réunion from
2011 to 2017, Luxembourg Institute of Health since
2017, and University of La Réunion from 2016 to
2017 outside the submitted work. Dr Ferdynus
reported receiving grants from the French Ministry
of Health during the conduct of the study.
Dr Combes reported receiving grants from French
Ministry of Health during the conduct of the study.
No other disclosures were reported.
Funding/Support: This study was supported by the
Programme Hospitalier de Recherche Clinique 2012
of the French Ministry of Health. The Centre
Hospitalier Universitaire de la Réunion is the key
sponsor of this study and by delegation the
Department of Clinical Research and Development
supervises all work in accordance with the French
public health code.
Role of the Funder/Sponsor: The funders had no
role in the design and conduct of the study;
collection, management, analysis, and
interpretation of the data; preparation, review, or
approval of the manuscript; and decision to submit
the manuscript for publication.
Data Sharing Statement: See Supplement 4.
REFERENCES
1. Jabre P, Avenel A, Combes X, et al. Morbidity
related to emergency endotracheal intubation—a
substudy of the KETAmine SEDation trial.
Resuscitation. 2011;82(5):517-522. doi:10.1016/j.
resuscitation.2011.01.015
2. Adnet F, Minadeo JP, Finot MA, et al A survey of
sedation protocols used for emergency
endotracheal intubation in poisoned patients in the
French prehospital medical system. Eur J Emerg Med.
1998;5(4):415-419.
3. Combes X, Jabre P, Jbeili C, et al. Prehospital
standardization of medical airway management:
incidence and risk factors of difficult airway. Acad
Emerg Med. 2006;13(8):828-834. doi:10.1197/j.
aem.2006.02.016
4. de La Coussaye JE, Adnet F; groupe d’experts
Sfar–SFMU. Sedation and analgesia in emergency
structure: which sedation and/or analgesia for
tracheal intubation? [article in French]. Ann Fr
Anesth Reanim. 2012;31(4):313-321. doi:10.1016/j.
annfar.2012.01.008
5. Bozeman WP, Kleiner DM, Huggett V.
A comparison of rapid-sequence intubation and
etomidate-only intubation in the prehospital air
medical setting. Prehosp Emerg Care. 2006;10(1):8-
13. doi:10.1080/10903120500366854
6. Okubo M, Gibo K, Hagiwara Y, Nakayama Y,
Hasegawa K; Japanese Emergency Medicine
Network Investigators. The effectiveness of rapid
sequence intubation (RSI) versus non-RSI in
emergency department: an analysis of multicenter
prospective observational study. Int J Emerg Med.
2017;10(1):1. doi:10.1186/s12245-017-0129-8
7. Sakles JC, Laurin EG, Rantapaa AA, Panacek EA.
Rocuronium for rapid sequence intubation of
emergency department patients. J Emerg Med.
1999;17(4):611-616. doi:10.1016/S0736-4679(99)
00046-3

jama.com (Reprinted) JAMA December 17, 2019 Volume 322, Number 23 2311

© 2019 American Medical Association. All rights reserved.

Downloaded From: https://jamanetwork.com/ by a University Paris 5 Descartes User on 12/17/2019

 Research Original Investigation
8. Magorian T, Flannery KB, Miller RD. Comparison
of rocuronium, succinylcholine, and vecuronium for
rapid-sequence induction of anesthesia in adult
patients. Anesthesiology. 1993;79(5):913-918. doi:
10.1097/00000542-199311000-00007
9. Tang L, Li S, Huang S, Ma H, Wang Z.
Desaturation following rapid sequence induction
using succinylcholine vs. rocuronium in overweight
patients. Acta Anaesthesiol Scand. 2011;55(2):203-
208. doi:10.1111/j.1399-6576.2010.02365.x
10. Taha SK, El-Khatib MF, Baraka AS, et al. Effect
of suxamethonium vs rocuronium on onset of
oxygen desaturation during apnoea following rapid
sequence induction. Anaesthesia. 2010;65(4):
358-361. doi:10.1111/j.1365-2044.2010.06243.x
11. Patanwala AE, Stahle SA, Sakles JC, Erstad BL.
Comparison of succinylcholine and rocuronium for
first-attempt intubation success in the emergency
department. Acad Emerg Med. 2011;18(1):10-14. doi:
10.1111/j.1553-2712.2010.00954.x
12. Tran DTT, Newton EK, Mount VAH, et al.
Rocuronium vs. succinylcholine for rapid sequence
intubation: a Cochrane systematic review.
Anaesthesia. 2017;72(6):765-777. doi:10.1111/anae.
13903
13. Mallon WK, Keim SM, Shoenberger JM,
Walls RM. Rocuronium vs. succinylcholine in the
emergency department: a critical appraisal. J Emerg
Med. 2009;37(2):183-188. doi:10.1016/j.jemermed.
2008.07.021
14. April MD, Arana A, Pallin DJ, et al; NEAR
Investigators. Emergency department intubation
success with succinylcholine versus rocuronium:
a National Emergency Airway Registry study. Ann
Emerg Med. 2018;72(6):645-653. doi:10.1016/j.
annemergmed.2018.03.042
15. Perry JJ, Lee JS, Sillberg VA, Wells GA.
Rocuronium versus succinylcholine for rapid
sequence induction intubation. Cochrane Database
Syst Rev. 2008;(2):CD002788. doi:10.1002/
14651858.CD002788.pub2
16. Langeron O, Bourgain JL, Laccoureye O, Legras
A, Orliaguet G. [Difficult airway algorithms and
management: question 5. Société Française
d’Anesthésie et de Réanimation]. Ann Fr Anesth
Reanim. 2008;27(1):41-45. doi:10.1016/j.annfar.2007.
10.025
17. Cormack RS, Lehane J. Difficult tracheal
intubation in obstetrics. Anaesthesia. 1984;39(11):
1105-1111. doi:10.1111/j.1365-2044.1984.tb08932.x
18. Adnet F, Borron SW, Racine SX, et al. The
Intubation Difficulty Scale (IDS): proposal and
evaluation of a new score characterizing the
complexity of endotracheal intubation.
2312 JAMA December 17, 2019 Volume 322, Number 23 (Reprinted)
© 2019 American Medical Association. All rights reserved.
Downloaded From: https://jamanetwork.com/ by a University Paris 5 Descartes User on 12/17/2019
Effect of Rocuronium vs Succinylcholine on Successful Out-of-Hospital Rapid Sequence Intubation
Anesthesiology. 1997;87(6):1290-1297. doi:10.1097/
00000542-199712000-00005
19. Viby-Mogensen J, Engbaek J, Eriksson LI, et al.
Good clinical research practice (GCRP) in
pharmacodynamic studies of neuromuscular
blocking agents. Acta Anaesthesiol Scand. 1996;40
(1):59-74. doi:10.1111/j.1399-6576.1996.tb04389.x
20. Ricard-Hibon A, Chollet C, Leroy C, Marty J.
Succinylcholine improves the time of performance
of a tracheal intubation in prehospital critical care
medicine. Eur J Anaesthesiol. 2002;19(5):361-367.
doi:10.1097/00003643-200205000-00008
21. Jabre P, Galinski M, Ricard-Hibon A, et al.
Out-of-hospital tracheal intubation with single-use
versus reusable metal laryngoscope blades:
a multicenter randomized controlled trial. Ann
Emerg Med. 2011;57(3):225-231. doi:10.1016/j.
annemergmed.2010.10.011
22. Jabre P, Leroux B, Brohon S, et al. A comparison
of plastic single-use with metallic reusable
laryngoscope blades for out-of-hospital tracheal
intubation. Ann Emerg Med. 2007;50(3):258-263.
doi:10.1016/j.annemergmed.2007.04.022
23. Kociszewski C, Thomas SH, Harrison T,
Wedel SK. Etomidate versus succinylcholine for
intubation in an air medical setting. Am J Emerg Med.
2000;18(7):757-763. doi:10.1053/ajem.2000.18033
24. Piaggio G, Elbourne DR, Pocock SJ, Evans SJ,
Altman DG; CONSORT Group. Reporting of
noninferiority and equivalence randomized trials:
extension of the CONSORT 2010 statement. JAMA.
2012;308(24):2594-2604. doi:10.1001/jama.2012.
87802
25. Jones B, Jarvis P, Lewis JA, Ebbutt AF. Trials to
assess equivalence: the importance of rigorous
methods. BMJ. 1996;313(7048):36-39. doi:10.1136/
bmj.313.7048.36
26. April MD, Schauer SG, Brown Rd CA, et al. A
12-month descriptive analysis of emergency
intubations at Brooke Army Medical Center:
a National Emergency Airway Registry study. US
Army Med Dep J. 2017(3-17):98-104.
27. Johnson EG, Meier A, Shirakbari A, Weant K,
Baker Justice S. Impact of rocuronium and
succinylcholine on sedation initiation after rapid
sequence intubation. J Emerg Med. 2015;49(1):43-
49. doi:10.1016/j.jemermed.2014.12.028
28. Sørensen MK, Bretlau C, Gätke MR, Sørensen
AM, Rasmussen LS. Rapid sequence induction and
intubation with rocuronium-sugammadex
compared with succinylcholine: a randomized trial.
Br J Anaesth. 2012;108(4):682-689. doi:10.1093/
bja/aer503
29. Tran DT, Newton EK, Mount VA, Lee JS, Wells
GA, Perry JJ. Rocuronium versus succinylcholine for
rapid sequence induction intubation. Cochrane
Database Syst Rev. 2015;(10):CD002788. doi:10.
1002/14651858.CD002788.pub3
30. Marsch SC, Steiner L, Bucher E, et al.
Succinylcholine versus rocuronium for rapid
sequence intubation in intensive care:
a prospective, randomized controlled trial. Crit Care.
2011;15(4):R199. doi:10.1186/cc10367
31. Herbstritt A, Amarakone K. Towards
evidence-based emergency medicine: best BETs
from the Manchester Royal Infirmary. BET 3: is
rocuronium as effective as succinylcholine at
facilitating laryngoscopy during rapid sequence
intubation? Emerg Med J. 2012;29(3):256-258. doi:
10.1136/emermed-2012-201100.4
32. Higgs A, McGrath BA, Goddard C, et al; Difficult
Airway Society; Intensive Care Society; Faculty of
Intensive Care Medicine; Royal College of
Anaesthetists. Guidelines for the management of
tracheal intubation in critically ill adults. Br J Anaesth.
2018;120(2):323-352. doi:10.1016/j.bja.2017.10.021
33. Wang HE, Yealy DM. How many attempts are
required to accomplish out-of-hospital
endotracheal intubation? Acad Emerg Med. 2006;
13(4):372-377. doi:10.1197/j.aem.2005.11.001
34. Mort TC. Emergency tracheal intubation:
complications associated with repeated
laryngoscopic attempts. Anesth Analg. 2004;
99(2):607-613. doi:10.1213/01.ANE.0000122825.
04923.15
35. Sakles JC, Chiu S, Mosier J, Walker C, Stolz U.
The importance of first pass success when
performing orotracheal intubation in the
emergency department. Acad Emerg Med. 2013;20
(1):71-78.
36. Hasegawa K, Shigemitsu K, Hagiwara Y, et al
Association between repeated intubation attempts
and adverse events in emergency departments: an
analysis of a multicenter prospective observational
study. Ann Emerg Med. 2012;60(6):749-754.
37. Jaffrelot M, Jendrin J, Floch Y, et al. Prevention
of awakening signs after rapid-sequence intubation:
a randomized study. Am J Emerg Med. 2007;25(5):
529-534. doi:10.1016/j.ajem.2006.09.016
38. Naguib M, Samarkandi AH, El-Din ME,
Abdullah K, Khaled M, Alharby SW. The dose of
succinylcholine required for excellent endotracheal
intubating conditions. Anesth Analg. 2006;102(1):
151-155. doi:10.1213/01.ANE.0000181320.88283.BE
jama.com