American Journal of Emergency Medicine 36 (2018) 2044–2049

Contents lists available at ScienceDirect

American Journal of Emergency Medicine

journal homepage: www.elsevier.com/locate/ajem

Original Contribution

Association of fentanyl use in rapid sequence intubation with post-

intubation hypotension
Jin Takahashi, MD a,⁎, Tadahiro Goto, MD, MPH b, Hiroshi Okamoto, MD c, Yusuke Hagiwara, MD, MPH d,
Hiroko Watase, MD, MPH e, Takashi Shiga, MD, MPH a,f, Kohei Hasegawa, MD, MPH b,g, on behalf of the
Japanese Emergency Medicine Network Investigators
a
Department of Emergency and Critical Care Medicine, Tokyo Bay Urayasu Ichikawa Medical Center, 3-4-32 Todaijima, Urayasu, Chiba 279-0001, Japan
b
Department of Emergency Medicine, Massachusetts General Hospital, 125 Nashua Street Boston, Suite 920, Boston, MA 02114, USA
c
Center for Clinical Epidemiology, St. Luke's International University, 3-6 Tsukiji, Chuo, Tokyo 104-0045, Japan
d
Department of Pediatric Emergency and Critical Care Medicine, Tokyo Metropolitan Children's Medical Center, 2-8-29 Musashidai, Fuchu, Tokyo 183-8561, Japan
e
Department of Radiology, University of Washington, 850 Republican Street Seattle, WA 98006, USA
f
Department of Emergency Medicine, International University of Health and Welfare, 1-4-3 Mita, Minato, Tokyo 108-8329, Japan
g
Harvard Medical School, Boston, MA, USA

a r t i c l e i n f o a b s t r a c t

Article history: Background: The anesthesia literature has reported that pre-intubation fentanyl use is associated with post-intu-
Received 31 October 2017 bation hypotension which is a risk factor of poor post-emergency department (ED) prognosis. However, little is
Received in revised form 11 March 2018 known about the relations between fentanyl use for intubation and post-intubation hypotension in the ED. We
Accepted 13 March 2018 aimed to determine whether pretreatment with fentanyl was associated with a higher risk of post-intubation hy-
potension in the ED.
Keywords:
Methods: We conducted a secondary analysis of data of ED airway management collected from a multicenter pro-
Fentanyl
Adverse events
spective study of 14 Japanese EDs from February 2012 through November 2016. We included all adult non-car-
Post-intubation hypotension diac-arrest patients who underwent rapid sequence intubation for medical indication. Patients were divided into
Rapid sequence intubation fentanyl and non-fentanyl groups. The primary outcome was post-intubation hypotension (systolic blood pres-
Emergency department sure ≤90 mm Hg) in the ED.
Results: Of 1263 eligible patients, 466 (37%) patients underwent pretreatment with fentanyl. The fentanyl group
had a higher risk of post-intubation hypotension (17% vs. 6%; unadjusted OR, 1.73; 95%CI, 1.01–2.97; P = 0.048)
compared to the non-fentanyl group. In the multivariable analysis adjusting for age, sex, weight, principal indi-
cation, sedatives, intubator's specialty, number of intubation attempts, and patient clustering within EDs, the fen-
tanyl group had a higher risk of post-intubation hypotension (adjusted OR, 1.87; 95%CI, 1.05–3.34; P = 0.03)
compared to the non-fentanyl group. In the sensitivity analysis using propensity score matching, this association
remained significant (OR, 3.17; 95%CI, 1.96–5.14; P b 0.01).
Conclusion: In this prospective multicenter study of ED airway management, pretreatment with fentanyl in rapid
sequence intubation was associated with higher risks of post-intubation hypotension.
© 2018 Elsevier Inc. All rights reserved.

1. Introduction been used as a pretreatment medication to mitigate the catecholamine

Rapid sequence intubation (RSI) is a standard tracheal intubation
approach in the emergency department (ED) [1-3]. In the U.S., approx-
imately 70% of ED intubations are performed with rapid sequence intu-
bation (RSI) [3]. In RSI, ultrashort-acting opioids, such as fentanyl, have
Abbreviations: JEAN-2, second Japanese Emergency Airway Network; JEMNet,
Japanese Emergency Medicine Network.
⁎ Corresponding author.
E-mail address: jint@jadecom.jp. (J. Takahashi).
release related to laryngoscopy and intubation in patients with cardio-
vascular diseases and those with elevated intracranial pressure [4-6].
However, in the operating room setting, the anesthesia literature has
reported that the use of fentanyl as pretreatment medication is associ-
ated with an increased risk of adverse events during intubation, such
as post-intubation hypotension [7,8]. Post-intubation hypotension is
known to be a risk factor for higher in-hospital mortality and longer in-
tensive care length-of-stay [9-11]. Despite the direct relevance to ED
airway management practice, there is a dearth of research that exam-
ines the relation between fentanyl use as a pretreatment agent for intu-
bation and post-intubation hypotension in the ED.

https://doi.org/10.1016/j.ajem.2018.03.026
0735-6757/© 2018 Elsevier Inc. All rights reserved.
 J. Takahashi et al. / American Journal of Emergency Medicine 36 (2018) 2044–2049
To address the knowledge gap in the literature, by using the multi-
center prospective study data of emergency airway management, we
tested the hypothesis whether a pretreatment with fentanyl is associ-
ated with a higher risk of post-intubation hypotension in the ED.
2. Materials and methods
2.1. Study design and setting
We conducted a secondary analysis of multicenter prospective ob-
servational study of ED patients who underwent emergency airway
management — the second Japanese Emergency Airway Network
(JEAN-2) study. The study design, setting, methods of measurement,
and measured variables have been reported previously [12-15]. In
brief, the JEAN-2 study started in February 2012 as a consortium of 14
academic and community EDs from different geographic regions across
Japan. The participating EDs consisted of 11 level I and three level II
equivalent trauma centers. These EDs had a median ED census of
28,000 patient visits per year (range, 14,000–66,000). All EDs were affil-
iated with emergency medicine residency training programs and staffed
by attending emergency physicians. Transitional-year residents (post-
graduate years 1 and 2) also rotated through all of the EDs and partici-
pated in airway management. Each hospital maintained individual
protocols about the policy and procedures for ED airway management.
Intubations were performed by attending physicians or resident physi-
cians at the discretion of the attending physician. The institutional re-
view board of each participating hospital approved the protocol with
waiver of informed consent.
2.2. Selection of participants
In this analysis, we included all adult patients (aged ≥18 years) who
underwent RSI for non-cardiac-arrest medical indications during a 58-
month period (from February 2012 through November 2016). We ex-
cluded 1) patients with pre-intubation systolic blood pressure (SBP) of
b90 mm Hg, 2) those who received pretreatment medications other
than fentanyl (e.g., lidocaine, morphine, nicardipine, and pentazocine),
3) those who received sedatives other than ketamine, midazolam, or
propofol, which were rarely used in this study (i.e., diazepam and thio-
pental that consisted of 7% of RSI) [16], 4) those who received two or
more types of sedatives, 5) those who received paralytics other than
rocuronium, succinylcholine, or vecuronium, which were also rarely
used in this study (i.e., pancuronium that was used in b1% of RSI), and
6) those with missing data on age, weight, pre-intubation SBP, sedative,
intubation device, or specialty of intubator.
2.3. Data collection and processing
Immediately after each intubation, the intubator completed a stan-
dardized data collection form that included the patient demographics
(age, sex, estimated height, and weight), primary indication for intuba-
tion, methods of intubation, all medications and devises used to facili-
tate intubation, level of training, specialty of the intubator, number of
attempts, success or failure, intubation-related adverse events, and
vital signs (blood pressure, heart rate, arterial oxygen saturation) mea-
sured immediately before, immediately after, and 30 min after the intu-
bation. The JEMNet (Japanese Emergency Medicine Network)
coordinating center and site investigator at each ED reviewed the data
forms. If the form had any missing data, it was returned to the intubator
for completion. If information on the form contained inconsistencies,
the investigator interviewed the intubator for clarification. We moni-
tored compliance continuously by reviewing professional billing codes
and cross-referencing our findings with the intubation data forms. If
an intubation was identified without a data form, the investigator
interviewed the intubator within two weeks to maximize the capture
rate. An intubation “attempt” was defined as a single insertion of the
2045
laryngoscope (or other device) past the teeth. An attempt was success-
ful if it resulted in a tracheal tube being placed through the vocal cords
with confirmation by a quantitative or colorimetric end-tidal carbon di-
oxide monitor.
2.4. Outcome measure
The outcome measure of interest was post-intubation hypotension,
defined by post-intubation hypotension as any recorded SBP of
≤90 mm Hg during the 30-minute period following intubation in the
ED [3,17,18].
2.5. Statistical analysis
In this analysis, the patients were dichotomized into the fentanyl
group and non-fentanyl group. To investigate the association between
fentanyl use and risks of post-intubation hypotension, we constructed
an unadjusted and adjusted two-level hierarchical models with bino-
mial response using random intercepts for the EDs to account for pa-
tient clustering within the EDs. The multivariable models adjusted for
age, sex, weight, principal indication for intubation, sedatives (midazo-
lam, ketamine, or propofol), specialty of the intubator, and number of
intubation attempts. These covariates were selected based on the clini-
cal plausibility and a priori knowledge [7,17-19]. Age and weight were
dealt with as continuous variables [17]. Indication for intubation was
classified into three categories, respiratory failure, shock, and others
(airway obstruction, altered mental status, other medical indications)
[19]. Specialty of the intubator was dichotomized into transitional-
year resident and others including emergency medicine resident, emer-
gency physician, and other specialties. The number of intubation at-
tempts was dichotomized into two groups — ≤2 and ≥3 attempts
[18,20].
To determine the robustness of our inference, we performed a series
of sensitivity analyses. First, to address the potential effects of a regular
use medication that potentially affect the blood pressure (e.g., antihy-
pertensive), we repeated the analysis limiting to the patients aged 18–
54 years, who had a low possibility of using antihypertensive medica-
tions [21]. Second, we conducted an additional analysis to examine
the dose-response on the risk of post-intubation hypotension using
the fentanyl dose/body weight (μg/kg) as a continuous variable. We
also modeled the fentanyl dose as a categorical variable (tertile) because
it has an advantage that the model does not impose a linear relationship
between the exposure and outcome. Third, to address the selection bias
for fentanyl use, we performed following stratified analyses by indica-
tion for altered mental status or seizure [22], pre-intubation SBP (90–
119 mm Hg, 120–139 mm Hg, and ≥140 mm Hg), and sedative (midazo-
lam, ketamine, or propofol). Lastly, we conducted propensity score (PS)
matching analyses to further investigate the association of interest. First,
we computed the PS using the logistic regression model in which fenta-
nyl use was the dependent variable on the basis of the covariates in the
primary models except for the number of intubation attempts. The
number of attempts was not used for computing the PS as this variable
was not measured at baseline. Next, we performed one-to-one
matching of patients between the fentanyl and non-fentanyl groups
with the closest estimated PS within a caliper (≤0.20 of the pooled stan-
dard deviation of estimated logits) using the nearest neighbor method
without replacement [23]. We examined the standard differences to
evaluate the matching of the baseline characteristics between the
groups. A standard difference of N10% was regarded as imbalanced.
Lastly, we performed logistic regression analysis to examine the associ-
ation between fentanyl use and risks of post-intubation hypotension in
the PS-matched patients. The threshold for significance was P b 0.05.
Analyses were performed with the use of STATA 14.1 (StataCorp, Col-
lege Station, TX) and JMP 12.2.0 (SAS Institute, Inc., Cary, NC).
2046 J. Takahashi et al. / American Journal of Emergency Medicine 36 (2018) 2044–2049

3. Results immediate after intubation, and 130 mm Hg (IQR, 110–152 mm Hg)

During the 58-month period, the JEAN-2 study recorded a total of
7570 patients with emergency airway management in the 14 EDs
(capture rate, 97%). Of these 1263 patients were eligible for the cur-
rent analysis (Fig. 1). Overall, the median age was 68 years (Inter-
quartile range (IQR), 54–78 years) and 67% were male. Fentanyl
was used as a pretreatment medication of RSI in 466 patients
(37%). The baseline characteristics of the fentanyl and non-fentanyl
groups are summarized in Table 1. The patients who received fenta-
nyl were less likely to be intubated for respiratory failure and more
likely to be intubated with rocuronium as paralytics and by a video
laryngoscope, compared to those who did not receive fentanyl (all
P b 0.05). In addition, the fentanyl group was more likely to be
intubated by emergency medicine resident and had a higher intuba-
tion success rate at the first attempt when compared to the non-fen-
tanyl group (81% vs. 72%; P b 0.05).
The heart rate and SBP of the fentanyl and non-fentanyl groups are
summarized in Supplemental Figs. 1 and 2 In the fentanyl group, the
median SBP was 132 mm Hg (IQR, 111–156 mm Hg) at pre-intubation,
127 mm Hg (IQR, 102–160 mm Hg) at immediate after intubation, and
126 mm Hg (IQR, 107–150 mm Hg) at 30 min after intubation. In the
non-fentanyl group, the median SBP was 140 mm Hg (IQR, 119–
170 mm Hg) at pre-intubation, 139 mm Hg (IQR, 110–168 mm Hg) at
at 30 min after intubation (Supplemental Fig. 2).
Overall, 125 patients (10%) experienced post-intubation hypoten-
sion (i.e., SBP of ≤90 mm Hg) during their ED course. Patients who re-
ceived fentanyl had a higher risk of post-intubation hypotension
compared to those who did not receive fentanyl (17% vs. 6%). The use
of fentanyl was associated with a significantly higher risk of post-intu-
bation hypotension in both univariate model (odds ratio [OR], 1.73;
95% CI, 1.01–2.97; P = 0.048; Table 2) and multivariable model
adjusting for seven potential confounders and patient clustering within
the EDs (adjusted OR, 1.87; 95% CI, 1.05–3.34; P = 0.03).
In the sensitivity analysis, in patients aged 18–54 years, while the
statistical power is limited, the association of fentanyl use with post-in-
tubation hypotension remained significant (1.6% vs. 4.2%; unadjusted
OR = 1.73 [95%CI 1.01–2.97] P = 0.048; adjusted OR = 6.33 [95%CI
1.15–34.99] P = 0.03). In the additional analysis that examines the
dose-response on the risk of post-intubation hypotension, while there
was no significant linear dose-response relationship, the association
remained significant with the use of tertiles (Supplemental Table 1).
In the sensitivity analyses with stratification by indication, pre-SBP,
and sedative, the associations between fentanyl use and post-intubation
hypotension were consistent across all strata (Supplemental Table 3).
Finally, in the analysis using one-to-one PS matching, the baseline char-
acteristics of 402 matched pairs were successfully balanced between the

7,804 patients who underwent emergency

tracheal intubation

7,570 recorded in the JEAN-2 study

6,307 patients excluded

3,153 cardiac arrests
2,257 non-rapid sequence
intubation
378 trauma
59 pediatric patients
249 pre-intubation systolic
blood pressure ӊ 90mmHg
47 other pretreatment used
59 other sedative used
22 multiple sedatives used
1,263 patients included in the current 1 other paralytics used
analysis 82 missing data

466 (37%) patients 797 (63%) patients

with the use of fentanyl without the use of fentanyl

Fig. 1. Patients receiving emergency airway management in the emergency department. During study period, the JEAN-2 study recorded a total of 7570 patients who underwent
emergency airway management at one of the 14 emergency departments (capture rate, 97%). Of these, 1263 patients were eligible for the current study.
 J. Takahashi et al. / American Journal of Emergency Medicine 36 (2018) 2044–2049 2047

Table 1 Table 2
Baseline characteristics, airway management characteristics, success rate, number of intu- Unadjusted and adjusted associations of fentanyl use as a pretreatment for intubation with
bation attempts, and post-intubation hypotension of patients who underwent rapid se- post-intubation hypotension in the emergency department.
quence intubation, according to fentanyl use.
Model and variable Odds ratio (95%CI) P-value
Fentanyl group (n Non-fentanyl group P-valueh
Unadjusted model
= 466, 37%) (n = 797, 63%)
Fentanyl use (vs no fentanyl use) 1.73 (1.01–2.97) 0.048
Patient characteristics
Age, median (IQR), years 67 (53–76) 69 (54–78) 0.21 Adjusted model
Male sex 301 (65) 547 (69) 0.14 Fentanyl use (vs no fentanyl use) 1.87 (1.05–3.34) 0.03
Weight, median (IQR), kg 60 (50–70) 60 (50–70) 0.21 Covariates
Primary indicationa Age (per each incremental year) 1.04 (1.02–1.06) b0.01
Respiratory failure 141 (30) 411 (52) b0.01 Female sex 0.88 (0.56–1.38) 0.56
Shock 101 (22) 92 (12) b0.01 Weight (per each incremental kg) 0.99 (0.97–1.01) 0.30
Othersb 224 (24) 294 (37) b0.01 Primary indication
Respiratory failure Reference
Airway management characteristics Shock 0.92 (0.53–1.61) 0.79
Sedativesa Othersa 0.37 (0.22–0.64) b0.01
Midazolam 284 (61) 493 (62) 0.75 Sedative
Propofol 105 (23) 190 (24) 0.60 Ketamine Reference
Ketamine 77 (17) 114 (14) 0.29 Midazolam 1.38 (0.74–2.55) 0.31
Paralyticsc Propofol 1.76 (0.82–3.78) 0.15
Rocuronium 433 (93) 676 (85) b0.01 Specialty of intubator
Succinylcholine 22 (5) 89 (11) b0.01 Othersb Reference
Vecuronium 18 (4) 33 (4) 0.81 Transitional year resident 1.02 (0.61–1.72) 0.93
Devicesa Multiple intubation attempts 1.32 (0.60–2.93) 0.49
Direct laryngoscope 85 (18) 655 (82) b0.01 a
Defined as airway obstruction, altered mental status, and other medical indications.
Video laryngoscope 380 (82) 127 (16) b0.01 b
d Defined as emergency medicine resident, emergency physician, surgeon, anesthesi-
Others 1 (b1) 15 (2) 0.01
ologist, pediatrician, and others.
Specialty of intubator
Transitional-year 69 (15) 431 (54) b0.01
residente
Emergency medicine 272 (58) 184 (23) b0.01 room settings [7,8]. For example, in a study of 2406 patients who
resident underwent intubation in the operating room, the use of fentanyl was a
Emergency physician 85 (18) 78 (10) b0.01
significant predictor for hypotension 0–10 min after anesthetic induc-
Others specialtiesf 40 (9) 104 (13) 0.02
Success rate at first 376 (81) 575 (72) b0.01
tion [7]. However, in the non-anesthesia settings, there has been no con-
attempt crete evidence of the relation of any intubation-related medications, let
Number of intubation 1 (1–1) 1 (1–2) b0.01 alone fentanyl, with post-intubation hypotension. For example, in the
attempts, median (IQR) intensive care unit settings, Green et al. reported that no conclusions
≥3 intubation attempts 25 (5) 73 (9) 0.02
can be drawn regarding the relation of any intubation-related media-
Post-intubation 81 (17) 44 (6) b0.01
hypotensiong tions with the risk of post-intubation hypotension [24]. In contrast,
the current analysis using the data from a large multicenter prospective
Abbreviation: IQR, interquartile range.
Data are shown as n (%) unless otherwise specified. study with a high capture rate (97%) extends these prior studies by
a
Percentages may not equal 100 due to rounding. demonstrating the robust association between the use of fentanyl and
b
Defined as airway obstruction, altered mental status, other medical indications. the risk of post-intubation hypotension in the ED.
c
Percentage may not equal 100 because of the use of multiple paralytic use in eight cases. Fentanyl is an ultrashort acting opioid receptor agonist and is used to
d
Defined as flexible bronchoscope, a combination of a gum elastic bougie with a direct
blunt the potential elevation of blood pressure and intracranial pressure
laryngoscope or video laryngoscope.
e
Defined as post-graduate years 1 or 2. [4-6] in the setting of RSI. However, its effectiveness has not been con-
f
Defined as surgeon, anesthesiologist, pediatrician, and others. firmed in the ED population [25,26]. In addition, fentanyl also has an ef-
g
Any recorded systolic blood pressure of ≤90 mm Hg during the 30-minute period fect of attenuating the sympathetic nervous system which may result in
following intubation in the emergency department.
h
hypotension. Consequently, pretreatment with fentanyl is not viewed
t-test for continuous variables; chi-square test or Fisher's exact test for categorical
variables. as a nonessential step of RSI [25]. Further, the lack of difference in the
heart rate changes observed in the current study is also consistent
with the previous literature which did not show the preventive effects
fentanyl and non-fentanyl groups (all standardized differences of b10, of fentanyl on heart rate fluctuations following the use of fentanyl com-
Supplemental Table 3). Similar to the primary analysis, the patients pared to the use of lidocaine or lidocaine with fentanyl [27]. Our findings
with fentanyl use had a significantly higher risk of post-intubation hy- lend further support to the concept that the use of fentanyl as pretreat-
potension (17% vs. 6%), with a corresponding OR of 3.17 (95% CI, 1.96– ment of RSI should not be used routinely in the ED. Clinicians should
5.14; P b 0.01). weigh the potential risks and benefits of fentanyl use judiciously, partic-
ularly for patients at high risk for hemodynamic instability.
4. Discussion
4.1. Potential limitations
In this analysis of 1263 adult patients who underwent RSI in the ED,
we found that the use of fentanyl as pretreatment medication was asso- This study has several potential limitations. First, we did not mea-
ciated with a significantly higher risk of post-intubation hypotension. sure the post-ED outcomes, such as hospital length of stay and in-hospi-
This association remained significant across the different statistical as- tal mortality. While one may surmise that intubation-related
sumptions – in both multivariable hierarchical model and PS-matched hypotension is a transient adverse event, a body of evidence has indi-
model. To the best of our knowledge, this is the first study that has dem- cated that intubation-related hypotension is associated with higher in-
onstrated the association between the use of fentanyl and post-intuba- hospital mortality and longer hospital length-of-stay [9-11]. Second,
tion hypotension in the ED population. surveillance data introduce the potential of self-reporting bias, which
The anesthesia literature has shown that fentanyl administration is may lead to underestimation of the proportion of hypotension. How-
associated with the risk of post-intubation hypotension in the operating ever, we used the previously applied self-reporting systems with a
2048 J. Takahashi et al. / American Journal of Emergency Medicine 36 (2018) 2044–2049
standardized data form and high capture rate [12-18,28-31], and the in-
cidence of post-intubation hypotension in our study was comparable to
that was reported in a prior systematic review [32]. Third, as with any
observational study, the observed association between fentanyl use
and higher risk of post-intubation hypotension does not necessarily
prove causality and might be confounded by unmeasured factors, such
as physiological reserve of each patient, peri-intubation fluid resuscita-
tion, past history and related medications (e.g., anti-hypertensives), and
the use of vasopressors. Nevertheless, we excluded the patients with
pre-intubation SBP of b90 mm Hg — the population who potentially re-
quire these resuscitative measures. Furthermore, in the ED setting, there
is often very little information available to the clinicians who must make
rapid decisions on whether to use pretreatment (e.g., fentanyl) for intu-
bation. Therefore, our data represent the best available data and clini-
cally relevant in the real-world settings. Fourth, our observational
study does not have the information on the methods for measuring
blood pressure (e.g., non-invasive vs. invasive measurement), which
may be a source of measurement bias [33]. However, non-invasive
monitoring is well correlated with the invasive blood pressure [34]
and widely used in clinical settings. Fifth, there was a possibility of selec-
tion bias. Therefore, we conducted the main analysis with the variables
(i.e., age, principal indication for intubation, sedatives, specialty of the
intubator) which could be the rationales for selecting fentanyl. Addi-
tionally, to address the rationale behind fentanyl use for intubation,
we also conducted sensitivity analyses stratified by indication for intu-
bation, pre-SBP, and sedatives. Although the part of the results was
not statistically significant due to the limited number of events, the as-
sociations between fentanyl use and post-intubation hypotension were
also consistent with main analysis (Supplemental Table 2). Lastly, our
study population consisted of patients in academic EDs in Japan. Al-
though it is tempting to dismiss the broader generalizability, multiple
studies – despite differing patient populations and settings (e.g., anes-
thesia setting) – arrived at a similar conclusion.
5. Conclusion
Based on the data from a prospective multicenter study of ED airway
management, we found that fentanyl administration for pretreatment
of RSI was associated with a higher risk of post-intubation hypotension
in the ED. The significant association persisted across different statistical
assumptions. As post-intubation hypotension is related to worse post-
ED outcomes [9,10], our observations offer a caution to the use of fenta-
nyl as RSI pretreatment of ED. Furthermore, our data should facilitate
further investigation into the development of optimal airway manage-
ment in ED patients at high risk for hemodynamic instability and ele-
vated intracranial pressure, which will, in turn, improve the patient
outcomes.
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.ajem.2018.03.026.
Author contributions
J.T. takes responsibility for the paper as a whole. J.T., T.G., T.S., and K.
H. conceived the study. H.O., Y.H., H.W., and K.H. supervised the conduct
of the study. T.G., H.O., T.S., and K.H. provided statistical advice. J.T. and T.
G. analyzed the data. J.T. drafted the manuscript, and all authors contrib-
uted substantially to its revision.
Conflict of interest statement
The authors declare that there is no conflict of interest.
Funding
This work was supported by grants from St. Luke's Science Institute
(Tokyo, Japan). The study sponsor has no involvement in the study
deign, in the collection, analysis and interpretation of data, in the writ-
ing of the manuscript, and in the decision to submit the manuscript
for publication.
Acknowledgment
The authors acknowledge the following research personnel at the
study hospitals for their assistance with this project: Fukui University
Hospital (Hiroshi Morita, MD; Takahisa Kawano, MD; Yohei Kamikawa,
MD), Fukui Prefectural Hospital (Hideya Nagai, MD; Takashi
Matsumoto, MD; Suguru Nonami, MD; Yusuke Miyoshi, MD), Kameda
Medical Center (Sho Segawa, MD; Kitai Yuya, MD; Kenzo Tanaka,
MD), Kishiwada Tokushukai Hospital (Hiromasa Yakushiji, MD), Kura-
shiki Central Hospital (Hiroshi Okamoto, MD), Nagoya Ekisaikai Hospi-
tal (Yukari Goto, MD), Nigata City General Hospital (Nobuhiro Sato, MD,
MPH), Okinawa Chubu Prefectural Hospital (Koichiro Gibo, MD;
Masashi Okubo, MD; Yukiko Nakayama, MD), Otowa Hospital
(Nobuhiro Miyamae, MD), Shonankamakura General Hospital (Hirose
Kaoru, MD; Taichi Imamura, MD; Azusa Uendan, MD), St. Marianna Uni-
versity School of Medicine Hospital (Yasuaki Koyama, MD), Tokyo Bay
Urayasu Ichikawa Medical Center (Hiroshi Kamura, MD; Nakashima
Yoshiyuki, MD), University Hospital, Kyoto Prefectural University of
Medicine (Jin Irie, MD), and Yokohama Rosai Hospital (Seiro Oya,
MD), Hyogo Emergency Medical Center (Akihiko Inoue, MD), and our
many emergency physicians and residents for their perseverance in
pursuing new knowledge about this vital resuscitative procedure.
References
[1] Sakles JC, Laurin EG, Rantapaa AA, Panacek EA. Airway management in the emer-
gency department: a one-year study of 610 tracheal intubations. Ann Emerg Med
1998;31:325–32.
[2] Sagarin MJ, Barton ED, Chng YM, Walls RM, National Emergency Airway Registry
Investigators. Airway management by US and Canadian emergency medicine resi-
dents: a multicenter analysis of more than 6,000 endotracheal intubation attempts.
Ann Emerg Med 2005;46:328–36.
[3] Walls RM, Brown 3rd CA, Bair AE, Pallin DJ, NEAR II Investigators. Emergency airway
management: a multi-center report of 8937 emergency department intubation. J
Emerg Med 2011;41:347–54.
[4] Cork RC, Weiss JL, Hameroff SR, Bentley J. Fentanyl preloading for rapid-sequence in-
duction of anesthesia. Anesth Analg 1984;63:60–4.
[5] Kautto UM. Attenuation of the circulatory response to laryngoscopy and intubation
by fentanyl. Acta Anaesthesiol Scand 1982;26:217–21.
[6] Helfman SM, Gold MI, DeLisser EA, Herrington CA. Which drug prevents tachycardia
and hypertension associated with tracheal intubation: lidocaine, fentanyl, or
esmolol? Anesth Analg 1991;72:482–6.
[7] Reich DL, Hossain S, Krol M, Baez B, Patel P, Bernstein A, et al. Predictors of hypoten-
sion after induction of general anesthesia. Anesth Analg 2005;101:622–8.
[8] Billard V, Moulla F, Bourgain JL, Megnigbeto A, Stanski DR. Hemodynamic response
to induction and intubation. Propofol/fentanyl interaction. Anesthesiology 1994;
81:1384–93.
[9] Heffner AC, Swords D, Kline JA, Jones AE. The frequency and significance of post-in-
tubation hypotension during emergency airway management. J Crit Care 2012;27
(417):e9–13.
[10] Green RS, Edwards J, Sabri E, Fergusson D. Evaluation of the incidence, risk factors,
and impact on patient outcomes of postintubation hemodynamic instability. Can J
Emerg Med 2012;14:74–82.
[11] Smischney NJ, Demirci O, Diedrich DA, Barbara DW, Sandefur BJ, Trivedi S, et al. In-
cidence of and risk factors for post-intubation hypotension in the critical ill. Med Sci
Mnit 2016;22:346–55.
[12] Hagiwara Y, Watase H, Okamoto H, Goto T, Hasegawa K, Japanese Emergency
Medicine Network Investigators. Prospective validation of the modified LEMON
criteria to predict difficult intubation in the ED. Am J Emerg Med 2015;33:1492–6.
[13] Goto T, Gibo K, Hagiwara Y, Morita H, Brown DF, Brown IIICA, et al. Multiple failed
intubation attempts are associated with decreased success rates on the first rescue
intubation in the emergency department: a retrospective analysis of multicentre ob-
servational data. Scand J Trauma Resusc Emerg Med 2015;16 [23:5].
[14] Nakao S, Hagiwara Y, Kimura A, Hasegawa K, Japanese Emergency Medicine
Network Investigators. Trauma airway management in emergency depart-
ments: a multicenter, prospective, observational study in Japan. BMJ Open
2015;5:e006623.
[15] Goto T, Gibo K, Hagiwara Y, Okubo M, Brown FM, Brown III CA, et al. Factors associ-
ated with first-pass success in pediatric intubation in the emergency department.
West J Emerg Med 2016;17:129–34.
[16] Goto Y, Goto T, Hagiwara Y, Tsugawa Y, Watase H, Okamoto H, et al. Techniques and
outcomes of emergency airway management in Japan: an analysis of two multicen-
ter prospective observational studies, 2010–2016. Resuscitation 2017;114:14–20.
 J. Takahashi et al. / American Journal of Emergency Medicine 36 (2018) 2044–2049
[17] Hasegawa K, Hagiwara Y, Imamura T, Chiba T, Watase H, Brown III CA, et al. In-
creased incidence of hypotension in elderly patients who underwent emergency air-
way management: an analysis of a multi-centre prospective observational study. Int
J Emerg Med 2013;6(12).
[18] Hasegawa K, Shigemitsu K, Hagiwara Y, Chiba T, Watase H, Brown IIICA, et al. Asso-
ciation between repeated intubation attempts and adverse events in emergency de-
partments: an analysis of a multicenter prospective observational study. Ann Emerg
Med 2012;60 [749–54.e2].
[19] Franklin C, Samuel J, Hu TC. Life-threatening hypotension associated with emer-
gency intubation and the initiation of mechanical ventilation. Am J Emerg Med
1994;12:425–8.
[20] Mort TC. Emergency tracheal intubation: complications associated with repeated
laryngoscopic attempts. Anesth Analg 2004;99:607–13.
[21] Centers for Disease Control and Prevention. Self-reported hypertension and use of
antihypertensive medication among adults - United States, 2005–2009. MMWR
Morb Mortal Wkly Rep 2013;62:237–44.
[22] Gabor AJ, Brooks AG, Scobey RP, Parsons GH. Intracranial pressure during epileptic
seizures. Electroencephalogr Clin Neurophysiol 1984;57:497–506.
[23] Austin PC. An introduction to propensity score methods for reducing the effects of
cofounding in observational studies. Multivar Behav Res 2011;46:399–424.
[24] Green RS, Turgeon AF, McIntyre LA, Fox-Robichaud AE, Fergusson DA, Doucette S,
et al. Postintubation hypotension in intensive care unit patients: a multicenter co-
hort study. J Crit Care 2015;30:1055–60.
[25] Overbeck MC. Airway management of respiratory failure. Emerg Med Clin North Am
2016;34:97–127.
[26] Schofer JM. Premedication during rapid sequence intubation: a necessity or waste of
valuable time? Cal J Emerg Med 2006;7:75–9.
2049
[27] Hashemian AM, Zamani Moghadam Doloo H, Saadatfar M, Moallem R, Moradifar M,
Faramarzi R, et al. Effects of intravenous administration of fentanyl and lidocaine on
hemodynamic responses following endotracheal intubation. Am J Emerg Med 2018;
36:197–201.
[28] Hasegawa K, Hagiwara Y, Chiba T, Watase H, Walls RM, Brown DF, et al. Emergency
airway management in Japan: interim analysis of a multi-center prospective obser-
vational study. Resuscitation 2012;83:428–33.
[29] Imamura T, Brown III CA, Ofuchi H, Yamagami H, Branch J, Hagiwara Y, et al. Emer-
gency airway management in geriatric and younger patients: analysis of a
multicentre prospective observational study. Am J Emerg Med 2013;31:190–6.
[30] Goto Y, Watase H, Brown III CA, Tsuboi S, Kondo T, Brown DF, et al. Emergency air-
way management by resident physicians in Japan: an analysis of multicentre pro-
spective observational study. Acute Med Surg 2014;1:214–21.
[31] Goto T, Watase H, Morita H, Nagai H, Brown IIICA, Brown DF, et al. Repeated tracheal
intubation attempts by a single intubator associated with decreased success rates in
emergency departments: an analysis of multicentre prospective observational study.
Emerg Med J 2015;32:781–6.
[32] Green R, Hutton B, Lorette J, Bleskie D, Mcintyre L, Fergusson D. Incidence of
postintubation hemodynamic instability associated with emergent intubations per-
formed outside the operating room: a systemic review. Can J Emerg Med 2014;16:
69–79.
[33] Lehman LH, Saeed M, Talmor D, Mark R, Malhotra A. Methods of blood pressure
measurement in the ICU. Crit Care Med 2013;41:34–40.
[34] Liu B, Qiu P, Chen H, Li Q. Comparison of simultaneous invasive and non-invasive
measurements of blood pressure based upon MIMIC II database. Artery Res 2015;
8:209–13.
Reproduced with permission of copyright owner. Further reproduction
prohibited without permission.