Download Current Medication Practice and Tracheal Intubation Safety

Current Medication Practice and Tracheal
Intubation Safety Outcomes From a Prospective
Multicenter Observational Cohort Study*
Keiko M. Tarquinio, MD1; Joy D. Howell, MD2; Vicki Montgomery, MD3; David A. Turner, MD4;
Deyin D. Hsing, MD2; Margaret M. Parker, MD5; Calvin A. Brown III, MD6; Ron M. Walls, MD6;
Vinay M. Nadkarni, MD, MS7; Akira Nishisaki, MD, MSCE7; for the National Emergency Airway
Registry for Children and Pediatric Acute Lung Injury and Sepsis Investigators Network
*See also p. 290.
Department of Pediatrics, Pediatric Critical Care Medicine, Hasbro
Children’s Hospital, Rhode Island Hospital, The Warren Alpert Medical
School of Brown University, Providence, RI.
1
Department of Pediatrics, Weill Cornell Medical College, New York, NY.
2
Pediatric Critical Care Medicine, University of Louisville, Louisville, KY.
3
Department of Pediatrics, Division of Pediatric Critical Care Medicine,
Duke Children’s Hospital, Duke University Medical Center, Durham, NC.
4
Department of Pediatrics, Pediatric Critical Care Medicine, Stony Brook
University School of Medicine, Stony Brook, NY.
5
Department of Emergency Medicine, Brigham and Women’s Hospital,
Harvard Medical School, Boston, MA.
6
Department of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA.
7
The members of the Pediatric Acute Lung Injury and Sepsis Investigators
Network are updated in http://vpicu.info/palisi.php.
Supported, in part, by grants 1R03HS021583-01 and 1 R18 HS022464-01
from the Agency for Healthcare Research and Quality.
Drs. Nadkarni and Nishisaki (Principal Investigator) received support from
the Endowed Chair, Critical Care Medicine, The Children’s Hospital of
Philadelphia, and Unrestricted Research fund from Laerdal Foundation
Acute Care Medicine. Dr. Nishisaki received support for article research
from the Agency for Healthcare Research and Quality (AHRQ). His institution received grant support from AHRQ R03 HS21583-01 (government
funded) and from Nihon Kohden America (for evaluation of noninvasive
capnography). Dr. Tarquinio is employed by the Lifespan Physicians Group
and received support for article research from the AHRQ. Her institution
received grant support from the National Institutes of Health (grant submitted, review pending). Dr. Howell received royalties from UpToDateOnline.
org (status asthmaticus review article) and received support for article
research from the AHRQ. Drs. Montgomery, Turner, Hsing, and Nadkarni
received support for article research from the AHRQ. Dr. Parker provided
expert testimony for Charles X. Connick, PLLC; and received support for
article research from the AHRQ. Dr. Brown III received support for article
research from the AHRQ. His institution received grant support (part
of AHRQ grant for compliance monitoring). Dr. Walls received support
for development of educational presentations from the Airway Management Education Center and received support for article research from the
AHRQ. His institution received grant support (part of AHRQ grant for
compliance monitoring).
For information regarding this article, E-mail: [email protected]
Copyright © 2015 by the Society of Critical Care Medicine and the World
Federation of Pediatric Intensive and Critical Care Societies
DOI: 10.1097/PCC.0000000000000319
210
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Objectives: Tracheal intubation in PICUs is often associated
with adverse tracheal intubation–associated events. There is a
paucity of data regarding medication selection for safe tracheal
intubations in PICUs. Our primary objective was to evaluate the
association of medication selection on specific tracheal intubation–associated events across PICUs.
Design: Prospective observational cohort study.
Setting: Nineteen PICUs in North America.
Subjects: Critically ill children requiring tracheal intubation.
Interventions: None.
Measurement and Main Results: Using the National Emergency
Airway Registry for Children, tracheal intubation quality improvement data were prospectively collected from July 2010 to March
2013. Patient, provider, and practice characteristics including
medications and dosages were collected. Adverse tracheal intubation–associated events were defined a priori. A total of 3,366
primary tracheal intubations were reported. Adverse tracheal intubation–associated events occurred in 593 tracheal intubations
(18%). Fentanyl and midazolam were the most commonly used
induction medications (64% and 58%, respectively). Neuromuscular blockade was used in 92% of tracheal intubation with the
majority using rocuronium (64%) followed by vecuronium (20%).
Etomidate and succinylcholine were rarely used (1.6% and 0.7%,
respectively). Vagolytics were administered in 37% of tracheal
intubations (51% in infants; 28% in > 1 yr old; p < 0.001). Ketamine was used in 27% of tracheal intubations but more often
for tracheal intubations in patients with unstable hemodynamics
(39% vs 25%; p < 0.001). However, ketamine use was not associated with lower prevalence of new hypotension (ketamine 8% vs
no ketamine 14%; p = 0.08).
Conclusions: In this large, pediatric multicenter registry, fentanyl,
midazolam, and ketamine were the most commonly used induction agents, and the majority of tracheal intubations involved
neuromuscular blockade. Ketamine use was not associated with
lower prevalence of hypotension. (Pediatr Crit Care Med 2015;
16:210–218)
March 2015 • Volume 16 • Number 3
Feature Articles
Key Words: endotracheal intubation; narcotic; paralytic; pediatrics;
premedication; sedative
P
ediatric tracheal intubation (TI), when required by critically ill children, is hazardous and commonly associated
with recognized potential adverse outcomes in highrisk patients (1–12). Our National Emergency Airway Registry for Children (NEAR4KIDS) clinical research collaborators
reported the landscape of safety and process of care for this
procedure in diverse PICUs (1). We reported that adverse TIassociated events (TIAEs) are common, occurring in approximately 20% of TI attempts (1). We identified several patient
and provider factors associated with occurrence of TIAEs and
severe TIAEs; these include attempted laryngoscopy by pediatric residents (2), documented history of a difficult airway, and
acute oxygenation and ventilation failure or unstable hemodynamic conditions as the indication for TI.
A variety of medications are used to facilitate TIs in critically ill children with the goal of achieving an appropriate level
of sedation and muscle relaxation that will generate favorable intubating conditions while avoiding adverse physiologic
responses to TIs (e.g., pain, agitation, or reflex bradycardia
secondary to laryngoscopy). Favorable intubation conditions
reduce the time and number of attempts needed to accomplish
the intubation (13, 14) and minimize the potential for intubation-related airway trauma (15). The American Academy of
Pediatrics recommends use of premedication in neonates (16);
however, no recommendation has been offered for the wide
age and diagnostic range of the pediatric population except for
children with septic shock (17).
To minimize the occurrence of adverse TIAEs, specific sets
of medications are selected for children with specific TI risks.
Vagolytic (antimuscarinic) medications, such as atropine or
glycopyrrolate, are often used to prevent sinus bradycardia or
atrioventricular block associated with laryngoscopy, especially
in young children. Ketamine, a dissociative anesthetic, is known
to trigger the release of endogenous catecholamines by its central sympathomimetic effect, thereby supporting cardiac output
and blood pressure (18). For this reason, ketamine has historically been chosen to prevent hypotension during TI induction
in critically ill children with shock (19). Propofol is a hypnotic
agent frequently used for sedation and general anesthesia. There
is limited information regarding the use of propofol in patients
in PICUs as there is a Food and Drug Administration “blackbox”
warning against its use for prolonged sedation in PICUs (20–23).
Intubation medications are typically administered sequentially
with a vagolytic agent preceding a sedative/hypnotic or analgesic
agent. Neuromuscular blockade is typically administered either
simultaneously with sedative/hypnotic agent(s) in rapid sequence
intubation or after adequate bag-valve-mask ventilation is established in standard sequence intubation (24). Neuromuscular
blockade facilitates optimal TI conditions by improving visualization of glottic structures, but these agents potentially predispose the patient to the risk of hypoxia and hypercarbia when
both bag-valve-mask ventilation and TI prove to be difficult.
Pediatric Critical Care Medicine
In this article, we aim to describe the current medication practice across diverse PICUs. We hypothesized that
medication selection would impact the prevalence of TIAEs.
Specifically, we hypothesized that 1) the use of a vagolytic
agent as part of the TI induction regimen is associated with
a reduced prevalence of bradycardia in children with risks for
dysrhythmia (bradycardia or atrioventricular block), 2) the use
of ketamine as part of the TI induction regimen is associated
with a lower prevalence of hypotension as a result of TI in children with existing hemodynamic instability, and 3) the use of
propofol as an induction regimen is associated with hypotension in children undergoing elective TIs.
METHODS
The NEAR4KIDS quality improvement registry tool was developed by members of the Pediatric Acute Lung Injury and Sepsis
Investigators Network in conjunction with the National Emergency Airway Registry investigators (1, 2). A data collection form
was developed and piloted in a single tertiary-care PICU and
refined for the NEAR4KIDS investigators for this multicenter
project. Institutional Review Board approval was obtained at
each participating site. Each site project leader (Appendix 1)
developed a site-specific compliance plan to ensure more than
95% TI encounter capture rate and the highest accuracy of data.
Two centralized compliance officers reviewed and approved the
compliance plan for each site. Data collection was then initiated
for each PICU TI at each center. The inclusion criteria for this
study were 1) TI encounters physically took place within PICUs
and 2) patient age younger than 18 years.
Outcome Measures
Adverse events were defined as TIAEs with two categories: nonsevere TIAEs and severe TIAEs (1). Briefly, nonsevere TIAEs
included mainstem bronchial intubation, esophageal intubation with immediate recognition, emesis without aspiration,
hypertension requiring therapy, epistaxis, lip trauma, medication error, dysrhythmia, and pain and/or agitation requiring
additional medication thus causing delay in intubation. The
NEAR4KIDS operational definition of dysrhythmia included
sinus bradycardia. Mainstem bronchial intubation was considered only when it was confirmed on chest radiograph or recognized after the clinical team secured the tracheal tube.
Severe TIAEs included cardiac arrest, esophageal intubation
with delayed recognition, emesis with witnessed aspiration,
hypotension requiring intervention (fluid and/or vasopressors), laryngospasm, malignant hyperthermia, pneumothorax/
pneumomediastinum, or dental trauma. Three airway management events, “encounter,” “course,” and “attempt,” were explicitly defined a priori and periodically reinforced on bimonthly
conference calls, as described previously (3). Briefly, encounter was defined as one episode of completed advanced airway
management intervention, including TI. Course was defined
as one method or approach to secure an airway (e.g., oral vs
nasal, awake vs sedated, and standard vs rapid sequence) and
one set of medications including premedication and induction. If an additional dose of medication was given as prepared,
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Tarquinio et al
it was considered as a part of the initial course. An attempt was
defined as a single advanced airway maneuver (e.g., beginning
with the insertion of the device, such as laryngoscope/laryngeal
mask into patient’s mouth or nose, and ending when the device
was removed). In the current study, the first course of each TI
encounter was included for analysis to eliminate the effect of
medication from multiple courses within a one TI encounter.
Statistical Methods
Statistical analysis was performed using STATA 11.2 (Stata Corp,
College Station, TX). Sample size calculation was not performed
for each hypothesis described in introductory text, as this study
was considered as a pilot study to provide information regarding the effect size for future investigation. Summary statistics
were described with means and sd for parametric variables and
median with interquartile range (IQR) for nonparametric variables. For categorical variables with a dichotomous outcome, a
contingency table method was used with Fisher exact test analysis, as appropriate. Multivariate logistic regression models were
developed to evaluate an association between each medication
use as an exposure variable and specific adverse TIAEs or process variable as an outcome variable (e.g., all TIAEs, hypotension, dysrhythmia, and multiple attempts) while adjusting for a
priori–identified covariates. Results were reported in odds ratio
(OR) with 95% CI. A p value of less than 0.05 was considered
significant for all hypotheses.
RESULTS
Demographics
There were 3,366 primary TI courses reported across the 19
centers (Fig. 1). The median patient age was 1 year (IQR, 0–7).
The most common diagnostic categories were respiratory
(41%) and neurological (17%) followed by cardiac condition
(13%). Common indications for TI include oxygenation failure
(38%), ventilation failure (38%), and unstable hemodynamics
(11%). Eighteen percent of TIs were for elective procedures.
History of difficult airway was reported in 14% (Table 1).
Attending level providers were present at 89% of TIs; however,
we were not able to delineate the differences among disciplines
(e.g., PICU attending vs anesthesiology attending).
Medication Choice for TI
Table 2 presents the commonly used medications. Vagolytics were
used in 37%. Fentanyl and midazolam were the most commonly
used TI induction medications (64% and 58%, respectively). Ketamine was used in 27%. Propofol was used in 14% of TIs with a
wide variance in use (range, 0–85% across sites). Etomidate was
rarely used (2%). Neuromuscular blockade was used in 92%
(range, 75–96% across sites) with
rocuronium the most commonly
used paralytic (64%) and succinylcholine rarely used (0.7%).
Concomitant use of sedative/
narcotic/hypnotic medications
was common. When midazolam
was used, the adjunct medications for TI included fentanyl
(73%), ketamine (21%), and
propofol (7%). When fentanyl
was used, the adjunct medications for TI included midazolam
(67%), ketamine (13%), and
propofol (10%). When ketamine
was used, the adjunct medications for TI included midazolam
(45%), fentanyl (31%), and propofol (2%). When propofol was
used, the adjunct medications
for TI included fentanyl (42%),
midazolam (28%), and ketamine (4%).
The age category, presence
of cardiac diagnosis, and indication for vagolytic, ketamine,
and propofol use were collected
(Table 3). In infants, a vagolytic
was used more often, whereas
Figure 1. Tracheal intubation (TI) courses. Note only the first courses of each TI encounter were included in
analysis. See Methods section.
ketamine and propofol were
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March 2015 • Volume 16 • Number 3
Feature Articles
Table 1. Patient and Practice
Characteristics (Total n = 3,366)
Characteristics
Table 2. Medication Use for the First Tracheal
Intubation Course (Total n = 3,366)
Counts (%)
Medication
Patient age
< 1 yr
1,393 (41.4)
Vagolytic
1–7 yr
1,218 (36.2)
Atropine
% of Medication
Use (Range
per Site, %)
31 (0–80)
≥ 8 yr
755 (22.4)
Glycopyrrolate
7 (0–21)
Weight, kg (median, interquartile range)
10.0 (5.2–22.2)
Any vagolytic
37 (0–80)
Diagnostic category
Respiratory
Dose
(IQR, per kg)
0.02 mg (0.02–0.03)
5 μg (4.2–7.1)
Not applicable
Sedative/narcotic/hypnotic
1,391 (41.3)
Fentanyl
64 (25–90)
1.9 μg (1.0–2.3)
Neurological
575 (17.1)
Midazolam
58 (7–82)
0.1 mg (0.09–0.13)
Cardiac
431 (12.8)
Ketamine
27 (3–68)
1.9 mg (1.1–2.1)
Sepsis/shock
215 (6.4)
Propofol
14 (0–85)
2.8 mg (1.9–4.2)
Trauma (includes traumatic brain injury)
87 (2.6)
Etomidate
2 (0–13)
0.3 mg (0.26–0.31)
Other
491 (14.6)
Neuromuscular blockade
Missing
176 (5.2)
Rocuronium
64 (0–88)
1.0 mg (1.0–1.2)
Indicationa
Vecuronium
20 (0–91)
0.1 mg (0.1–0.2)
Ventilation failure
1,282 (38.1)
Pancuronium
0.5 (0–8)
0.2 mg (0.1–0.3)
Oxygenation failure
1,264 (37.6)
Succinylcholine
0.7 (0–8)
1.4 mg (1.0–1.9)
Elective procedure
607 (18.0)
Upper airway obstruction
407 (12.1)
Unstable hemodynamics
375 (11.1)
Impaired airway reflex
228 (6.7)
Pulmonary toilet
178 (5.3)
Neuromuscular weakness
106 (3.2)
Therapeutic hyperventilation
History of difficult airway
88 (2.6)
464 (13.8)
Device
Laryngoscope
Indirect laryngoscope
3,205 (95.2)
112 (3.3)
Laryngeal mask
26 (0.8)
Bronchoscope
17 (0.5)
Laryngeal mask + bronchoscope
1 (0.0)
Light wand
1 (0.0)
Missing
4 (0.1)
One tracheal intubation encounter may have more than one indication.
a
used less often. A vagolytic was also used more often in patients
with a cardiac diagnosis (cardiac 43% vs noncardiac 36%;
p = 0.002), whereas propofol was used significantly less often
in this population (cardiac 3% vs noncardiac 16%; p < 0.001).
Ketamine was used more often in patients with hemodynamic instability (39% vs 25%; p < 0.001), whereas propofol
was less often used in this population (2% vs 16%; p < 0.001).
Pediatric Critical Care Medicine
Any neuromuscular 92 (75–96)
blockade
Lidocaine
4 (0–7)
Not applicable
1.0 mg (1.0–1.1)
IQR = interquartile range.
Propofol was used preferentially in patients undergoing TI for
an elective procedure (48% vs 7%; p < 0.001). A vagolytic agent
was administered in 48% of TIs involving ketamine. A paralytic agent was used less frequently in patients with history of
difficult airway (86%) compared with those without history of
difficult airway (93%; p < 0.001). Similarly, a paralytic agent
was used less frequently in patients with hemodynamic instability (87%) compared with those without history of hemodynamic instability (92%; p < 0.001).
Medication Use and Adverse TIAEs
Adverse TIAEs were reported in 17.6% of the primary TI courses
(Table 4). Use of vagolytic agents were associated with an
increased prevalence of dysrhythmia in univariate analysis (2.4%
vs 0.9%; unadjusted OR, 2.55; 95% CI, 1.45–4.48; p = 0.0017) and
in multivariate analysis after adjusting for cardiac diagnostic and
age (adjusted OR, 2.63; 95% CI, 1.46–4.72; p = 0.001) (Table 5).
Esophageal intubation was observed in 290 TI courses
(8.6%) and was not associated with paralytic use (prevalence
of esophageal intubation, 8.7% with paralytic vs 7.6% without
paralytic; p = 0.65).
Ketamine use in patients with existing hemodynamic instability was not associated with a significantly lower prevalence of
new hypotension when compared with sedative/hypnotic regimens without ketamine (prevalence of new hypotension, 8.1%
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Tarquinio et al
Table 3.
Factors Associated With Vagolytic, Ketamine, and Propofol Use
Medication Type
Vagolytic
(%, Range per Site),
1,258/3,366 (37%)
pa
Ketamine
(%, Range per Site),
894/3,366 (27%)
p
Propofol
(%, Range per Site),
484/3,366 (14%)
p
Age
Infant
705/1,393
(51, 0–96)
324/1,393
(23, 0–79)
Child (1–7 yr)
410/1,218
(34, 0–68)
Older child (≥ 8 yr)
143/755
(19, 0–34)
216/755
(29, 0–48)
151/755
(20, 0–71)
Cardiac
185/431
(43, 0–86)
125/431
(29, 0–100)
15/431
(3, 0–29)
Noncardiac
993/2,759
(36, 0–78)
Missing
80/176
(45, 0–100)
< 0.001
354/1,218
(29, 0–73)
82/1,393
(6, 0–78)
0.001
251/1,218
(21, 0–100)
< 0.001
Diagnostic category
0.002
711/2,759
(26, 4–69)
0.05
58/176
(33, 0–100)
437/2,759
(16, 0–85)
< 0.001
32/176
(18, 0–100)
Indication for tracheal intubationb
Respiratoryc
42
Nonrespiratory
30
Hemodynamicd
32
Nonhemodynamic
38
Elective
30
Nonelective
39
< 0.001
0.03
< 0.001
31
19
39
25
19
28
< 0.001
< 0.001
< 0.001
7
29
2
16
48
7
< 0.001
< 0.001
< 0.001
All analyses were performed with Fisher exact test.
Proportion of the drug use. For example, 42% of tracheal intubation with respiratory failure as an indication used a vagolytic, whereas 30% of tracheal intubation
without respiratory failure used a vagolytic.
c
Respiratory indication includes upper airway obstruction, oxygenation, and ventilation failure.
d
Hemodynamic indication includes shock and cardiac arrest.
a
b
vs 14.1%; unadjusted OR, 0.54; 95% CI, 0.27–1.07; p = 0.08).
The dose of ketamine was lower in patients with existing hemodynamic instability (existing hemodynamic instability: median,
1.6 mg/kg; IQR, 1.0–2.0; vs no hemodynamic instability: 2.0 mg/
kg; IQR, 1.1–2.1; p < 0.001). In patients undergoing elective TI
(e.g., TIs for invasive or noninvasive procedural sedation purposes), the use of propofol was not associated with higher prevalence of new hypotension (0.7% vs 2.2%; unadjusted OR, 0.31;
95% CI, 0–1.31; p = 0.18). The use of neuromuscular blockade
was not associated with an increased prevalence of TIAEs (17%
vs 22%; unadjusted OR, 0.75; 95% CI, 0.56–1.03; p = 0.08). This
remained the case even when adjusting for patient age and history of difficult airway (Table 5). The use of neuromuscular
blockade was not associated with an increased prevalence of
multiple attempts, defined a priori as more than two attempts
(15% vs 15%; unadjusted OR, 0.97; 95% CI, 0.68–1.37; p = 0.86).
DISCUSSION
There is remarkably little evidence-based guidance with
respect to medications that can be used to facilitate pediatric
TI outside of the neonatal and pediatric anesthesia literature.
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Though the basic pharmacology of the different medications
may be consistent across a wide age range, the illnesses and
injuries encountered in PICUs are distinctly different from
those in the neonatal population. The circumstances surrounding TIs are far less controlled, and patients are in general
more unstable than TIs performed in the operating suites. Our
report is one of the few that evaluate the impact of medications
used to facilitate TIs in PICU settings and is based on the largest reported cohort of patients to date.
We identified that the use of a vagolytic agent was more
common in infants and in the cardiac population, similar to a
previously published single-center study (25). Ketamine was
preferentially used for patients with hemodynamic instability,
whereas propofol was used for the lower risk TIs for procedure.
Neuromuscular blockade use was common, similar to previously published single-center data (8). Although providers chose
specific medications to avoid adverse events during TIs, our
results were not able to support their reported protective effects.
Contrary to our hypothesis, dysrhythmia (including bradycardia)
was observed more often in TIs with vagolytic use. The use of ketamine for hemodynamically unstable patients was not associated
March 2015 • Volume 16 • Number 3
Feature Articles
Table 4. Prevalence of Adverse Tracheal Intubation–Associated Events Among Primary
Tracheal Intubation Courses
Incidence of any TIAEsa, %
17.6
Incidence of any severe TIAEs, %
5.5
Severe TIAEs, %
Incidence of any nonsevere TIAEs, %
13.6
Nonsevere TIAEs, %
Cardiac arrest with ROSC
1.1
Mainstem bronchial intubation
3.1
Cardiac arrest without ROSC
0.3
Esophageal intubation with immediate recognition
8.3
Esophageal intubation without immediate recognition
0.4
Emesis without aspiration
0.6
Emesis with aspiration
0.7
Dysrhythmia (includes sinus bradycardia)
1.5
Hypotension requiring treatment
2.7
Hypertension requiring treatment
0.2
Laryngospasm
0.3
Epistaxis
0.3
Malignant hyperthermia
0
Lip trauma
0.5
Pneumothorax/pneumomediastinum
0.1
Medication error
0.1
Dental trauma
0.2
Pain/agitation requiring additional medication with
delay in tracheal intubation
0.5
TIAE = tracheal intubation–associated events, ROSC = return of spontaneous circulation > 20 min.
a
Note that each tracheal intubation encounter may experience more than one adverse TIAE.
Total number of tracheal intubations, n = 3,366.
Table 5.
Specific Adverse Tracheal Intubation–Associated Events With Medications
Medication
Patient Population
Adverse Events
Vagolytic
All
Dysrhythmia
Ketamine
Patients with
hemodynamic instability
Hypotension
Propofol
Paralytics
Cardiac arrest
Univariate Analysis
Multivariate Analysis
OR
95% CI
OR
95% CI
2.55a
1.45–4.48
2.63b,c
1.46–4.72
0.54
0.27–1.07
0.18–0.92
NA
0.58e
0.24–1.42
All
Hypotension
0.41d
Patients with elective
tracheal intubation
Hypotension
0.31
0–1.31
All
All tracheal intubation–
associated events
0.75
0.56–1.03
0.78f
0.57–1.06
All
Multiple attempts
(> 2 attempts)
0.97
0.68–1.37
1.02g
0.72–1.45
NA
OR = odds ratio, NA = not applicable.
a
p = 0.0017.
b
Adjusted for cardiac diagnosis and age (infant vs noninfant).
c
p = 0.001.
d
p = 0.033.
e
Adjusted for indications (elective tracheal intubation and unstable hemodynamics).
f
Adjusted for a history of difficult airway, age (infant vs noninfant).
g
Adjusted for a history of difficult airway.
with lower prevalence of new hypotension. Propofol use was relatively common in PICUs, preferentially in patients requiring elective TIs for procedural sedation. Paralytic use was less common
in patients with history of difficult airway (86%) compared with
those without history of difficult airway (93%; p < 0.001), suggesting that providers often chose to maintain spontaneous ventilation of patients in an anticipated difficult airway. Paralytic use
was also less common in patients with hemodynamic instability
Pediatric Critical Care Medicine
(85%) compared with those without history of hemodynamic
instability (93%; p < 0.001) including cardiac arrest.
As previously mentioned, the majority of studies involving
medication selection for TIs outside the operating suites focus
on the neonatal population and suggest tremendous variation
in practice. A French neonatal study showed a wide unit-level
variation in TI premedication practice (26). Among all TIs,
premedication was employed in only 56% of TIs. Among those
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Tarquinio et al
with premedication administration, opioids were the most
commonly used drugs (67%). One recent Australian/New
Zealand study employing a web-based survey of 28 neonatal
ICUs similarly reported varying use of premedication (27).
Several investigators have evaluated the protective effect of
atropine on preventing dysrhythmia in the pediatric and neonatal populations (25, 28–31). Jones et al (29) evaluated the
effect of atropine in relation to new onset dysrhythmia in the
peri-intubation period during transport and in PICU settings.
Atropine use was associated with an increase in heart rate (lowest heart rate, 109 ± 41/min in the no-atropine group vs 149 ± 37/
min in the atropine group). Dysrhythmia was more commonly
observed in the no-atropine group (45/170) compared with the
atropine group (7/152) (25). Observed dysrhythmia was predominantly junctional rhythm and atrial extrasystole. Their
data also suggested that atropine reduced the occurrence of dysrhythmia by increasing heart rate nadir during TI procedure.
We find an unexpected association between vagolytic use and a
higher prevalence of dysrhythmia. Our NEAR4KIDS database
does not gather sufficient data to account for all possible variables necessary to explain this variation or to infer causation.
For example, it is plausible that atropine or glycopyrrolate was
administered in some cases to treat bradycardia that occurred
during TI induction or upper airway instrumentation, rather
than as a preventative. The study population receiving atropine
was also substantially older (median age, 22 mo; IQR, 5–91)
than that studied by Jones et al (29). Future studies with inclusive of monitor waveform analysis and event logs with medication administration may be able to address this question.
With regard to ketamine, it not only provides anesthesia and
analgesia but also increases endogenous catecholamine release
leading to increased heart rate, systemic vascular resistance, and
cardiac output. However, it is important to note that ketamine
itself is a direct myocardial depressant due to neuronal catecholamine uptake inhibition in the failing heart (32–34). Our
results indicate that ketamine was used in a quarter of all intubations across a wide variety of PICUs and was chosen more
commonly in patients undergoing intubation for unstable
hemodynamics. However, ketamine use was not associated with
a reduced prevalence of hypotension as compared with other
sedative regimens. This result might be due to the possibility
that 1) the current subgroup analysis was underpowered, as the
true protective effect of ketamine against hypotension is mild
in patients with existing hemodynamic instability; or 2) in children with existing hemodynamic instability, who perhaps were
catecholamine depleted, the direct myocardial depressant effect
could not be overcome by ketamine-induced endogenous catecholamine release; or 3) the protective effect of ketamine may
have been weakened by concurrent administration of a second
induction agent. Our findings need to be re-evaluated with a
larger study with more precise hemodynamic data.
The decision to employ neuromuscular blockade as part of the
TI medication regimen requires sound clinical judgment. Use of
neuromuscular blockade may be discouraged in patients who are
at high risk for difficult bag-valve-mask ventilation and/or difficult to perform TI (35). However, withholding neuromuscular
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blockade may result in more difficult TI conditions, which may
lead to longer apnea time, multiple attempts, or traumatic intubation (36). This issue is particularly important in the PICU population as many patients lack the physiological reserve to tolerate
a long apnea time and/or profound hypoxemia. Our data demonstrate that neuromuscular blockade is used in the overwhelming
majority of PICUs to facilitate TI, although with much variability
in practice among centers. Use of neuromuscular blockade was
not associated with an untoward frequency of TIAEs. It is noteworthy that succinylcholine is rarely used in PICUs, despite being
the preferred agent by anesthesiologists or emergency medicine
physicians for rapid sequence intubation in children due to rapid
onset of action and short half-life of medication (12, 37). This
difference in practice may be due to perceived risks associated
with succinylcholine (38). Regardless, studies have demonstrated
that rocuronium 0.9–1.0 mg/kg provides similar intubation conditions to succinylcholine of 1.0–1.5 mg/kg during anesthesia
induction when combined with a hypnotic agent at hypnotic
doses (39, 40). Succinylcholine, however, has a much shorter
duration of action than rocuronium.
Our current study is based on a large cohort of pediatric TIs
reported from multiple PICUs for the quality improvement
purposes. Nonetheless, important limitations must be noted.
Our data collection tool captures dysrhythmia and hypotension, among other adverse TIAEs based on self-reporting by the
bedside providers. Clinicians and data coordinators at participating centers are trained and guided by operational definitions
with the intent of optimizing consistency; however, we have no
means of verifying those reports with an independent chart
review, video-recording of TI events, or downloads of bedside
monitor records. The current methodology might have led to
underreporting of TIAE events. Furthermore, we were not
able to clarify the time sequence of medication administration
relative to the development of TIAEs (e.g., timing of vagolytic
administration and occurrence of bradycardia, dose of sedatives
given before the occurrence of hypotension). We are considering
revising the data collection tool to capture the time sequences
of medication administration (including doses) and intubation
procedures. Future studies inclusive of monitor analysis, event
logs, and potentially, video monitoring with medication administration may be able to address this challenge.
Also each site developed a site-specific data compliance plan
to ensure capture of all TIs; albeit small, there is a possibility that
some sites missed some portion of TIs. It is unclear how these
potential reporting biases could have affected our results, especially the association between medication use and specific TIAEs.
CONCLUSIONs
In this large database of over 3,000 intubations, substantial differences in medication use for TI induction were observed across
participating PICUs. Fentanyl and midazolam were employed in
a majority of TIs. Although vagolytic use was associated with
increased prevalence of dysrhythmia, we are not able to draw
any causative inference. Ketamine use in patients with hemodynamic instability did not show significant association with
reduced prevalence of hypotension. Propofol has been and can
March 2015 • Volume 16 • Number 3
Feature Articles
be safely used in the PICU population for elective and perhaps
nonelective intubations without an untoward risk of hemodynamic instability. Further study is warranted to establish the best
medication practices for specific patient populations.
ACKNOWLEDGMENTS
We acknowledge Jessica Leffelman for her tireless work as a
multicenter coordinator. We also acknowledge Stephanie Tuttle for her administrative support.
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Appendix 1.
List of National Emergency Airway Registry for Children Investigators
Michelle Adu-Darko, MD
[email protected]
Department of Pediatrics, University of Virginia Children’s Hospital
Michael Apkon, MBA, MD, [email protected]
PhD
President and Chief Executive Officer, The Hospital for Sick
Children, Canada
Katherine Biagas, MD
[email protected]
Division of Pediatric Critical Care Medicine, New York Presbyterian
Hospital
Kris G. Bysani, MD
[email protected]
Critical Care Medicine, Medical City Children’s Hospital
Ira M. Cheifetz, MD, FCCM [email protected]
Department of Pediatrics, Division of Pediatric Critical Care, Duke
Children’s Hospital
Kathleen Culver, DNP, RN, kathleen.culver@
CPNP
stonybrookmedicine.edu
Department of Pediatrics, Tony Brook Long Island Children’s
Hospital
Ashley Derbyshire, MSN,
RN, CRNP
[email protected]
Division of Critical Care Medicine, Penn State Children’s Hospital
Guillaume Emeriaud
guillaume.emeriaud@
umontreal.ca
Soins intensifs pédiatriques, CHU Sainte-Justine, Université de
Montréal (Dr. Emeriaud was supported by Young investigator
award of the Respiratory Health Network of the Fonds de la
Recherche du Québec, Santé)
John S. Giuliano Jr, MD
[email protected]
Critical Care Medicine, Department of Pediatrics, Yale New Haven
Children’s Hospital
Ana Lia Graciano, MD
[email protected] Pediatric Critical Care Medicine, Children’s Hospital Central California
Glenda Hefley, RN
[email protected]
Department of Pediatrics, Section of Critical Care, Arkansas
Children’s Hospital
J. Dean Jarvis, MBA, BSN [email protected]
Department of Pediatrics, Dartmouth-Hitchcock Medical Center
Pradip Kamat, MD, MBA
[email protected]
Department of Pediatrics, Emory University School of Medicine,
Children’s Hospital of Atlanta
Anthony Lee, MD
anthony.lee@
nationwidechildrens.org
Critical Care Medicine, Nationwide Children’s Hospital, Ohio State
University
Simon Li, MD, MPH
[email protected]
Critical Care Medicine, Maria Fareri Children’s Hospital
Keith Meyer, MD
[email protected]
Critical Care Medicine, Miami Children’s Hospital
Tracey Monjure, RN
[email protected]
Critical Care Medicine, Medical City Children’s Hospital
Natalie Napolitano,
RRT-NPS, MPH
[email protected]
Department of Respiratory Care, The Children’s Hospital of
Philadelphia
Sholeen Nett, MD, PhD
[email protected]
Department of Pediatrics, Dartmouth-Hitchcock Medical Center
Gabrielle Nuthall, MD
[email protected]
Paediatric Intensive Care, Starship Children’s Hospital, New Zealand
Matthew Pinto, MD
[email protected]
Critical Care Medicine, Maria Fareri Children’s Hospital
Kyle J. Rehder, MD
[email protected]
Department of Pediatrics, Division of Pediatric Critical Care, Duke
Children’s Hospital
Jackie Rubottom, RCP
jrubottom@childrenscentralcal.
org
Respiratory Care Services, Children’s Hospital Central California
Ronald Sanders, MD
[email protected]
Department of Pediatrics, Section of Critical Care, Arkansas
Children’s Hospital
Michael Shepard, MD
[email protected]
Paediatric Intensive Care, Starship Children’s Hospital, New Zealand
Darlene Simas, RN, MSN
[email protected]
Department of Pediatrics, Division of Pediatric Critical Care, Rhode
Island/Hasbro Children’s Hospital
Debra Spear, RN
[email protected]
Division of Critical Care Medicine, Penn State Children’s Hospital
Janice E. Sullivan, MD
[email protected]
Department of Pediatrics, Division of Pediatric Critical Care,
University of Louisville, Kosair Children’s Hospital
Robert Tamburro, MD
[email protected]
Division of Critical Care Medicine, Penn State Children’s Hospital
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March 2015 • Volume 16 • Number 3