AIRWAY/ORIGINAL RESEARCH

Hemodynamic Response After Rapid Sequence

Induction With Ketamine in Out-of-Hospital Patients
at Risk of Shock as Defined by the Shock Index
Matthew Miller, MSc (Hons), MBChB*; Natalie Kruit, MBBS (Hons); Charlotte Heldreich, MBChB (Bris), DipRTM;
Sandra Ware, BSc MSc (Med); Karel Habig, MBBS BSc, Dip RTM (Edin); Cliff Reid, BM; Brian Burns, MBBCh MSc
*Corresponding Author. E-mail: mattdotmiller@gmail.com.

Study objective: Ketamine is considered a stable induction agent for rapid sequence induction; however, hypotension
rates up to 24% are reported. The shock index (shock index¼pulse rate/systolic blood pressure [SBP]) may identify
patients at risk of adverse hemodynamic change. We investigate whether SBP and pulse rate response to ketamine
induction differ when patients are classified as being at risk of shock by their shock index.

Methods: We conducted a prospective observational study of electronically collected vital sign data from patients
undergoing rapid sequence induction with ketamine. Patients were grouped into low shock index (shock index <0.9) or
high shock index (shock index 0.9) preinduction. Pulse rate and SBP were compared between 3 minutes preinduction
and for 3 measurements postinduction (3-minute intervals) by repeated-measures ANOVA. Proportions of patients
developing hypotension or hypertension are also reported.

Results: One hundred twelve patients were enrolled (81 low shock index, 31 high shock index). Low shock index
patients had increased SBP after induction (16 mm Hg; 95% confidence interval [CI] 11 to 21 mm Hg), whereas high
shock index patients did not (2 mm Hg; 95% CI –4 to 7 mm Hg). Pulse rate in low shock index patients increased
after induction (20 beats/min; 95% CI 16 to 25 beats/min) and remained elevated, whereas in high shock index
patients a difference occurred at the second postinduction measurement only (15 beats/min; 95% CI 11 to 18
beats/min). More high shock index patients became hypotensive (26%; 95% CI 12% to 45%) than low shock index ones
(2%; 95% CI 0% to 9%), whereas more low shock index patients became hypertensive (40%; 95% CI 29% to 51%) than
high shock index ones (13%; 95% CI 4% to 30%).

Conclusion: After ketamine induction, high shock index patients exhibited blunted hypertensive responses and more
frequent hypotension, whereas low shock index patients had sustained increases in pulse rate and SBP. [Ann Emerg
Med. 2016;68:181-188.]

Please see page 182 for the Editor’s Capsule Summary of this article.

A feedback survey is available with each research article published on the Web at www.annemergmed.com.
A podcast for this article is available at www.annemergmed.com.
0196-0644/$-see front matter
Copyright © 2016 by the American College of Emergency Physicians.
http://dx.doi.org/10.1016/j.annemergmed.2016.03.041

INTRODUCTION report hypotension rates of 3.6% to 24%,8-12 which may

Background
Ketamine is considered a suitable drug for emergency
intubation because of a catecholamine-mediated
maintenance of blood pressure and pulse rate,1 in addition
to its analgesic, amnestic, and bronchodilation properties.
Whereas in normovolemic patients hypertension may
occur,2,3 early research in critically ill patients found
ketamine to be occasionally associated with a reduction in
mean arterial blood pressure and cardiac output,4-6 with
hypovolemic patients potentially most at risk.7 Recent
clinical studies of ketamine rapid sequence intubation
be harmful because a systolic blood pressure (SBP) less than
90 mm Hg is associated with increased morbidity and
mortality in trauma patients13 and an SBP less than 110
mm Hg has been advocated as hypotension in moderate
to severe isolated traumatic brain injury.14 Similarly, in
the setting of traumatic brain injury an SBP greater than
140,15 160,16 or 175 mm Hg17 is associated with worse
outcomes, although the relationship between cause and
effect is less clear.
The out-of-hospital identification of shock is an
ongoing challenge. Traditional vital signs perform poorly

Volume 68, no. 2 : August 2016 Annals of Emergency Medicine 181

Ketamine Induction in Patients With Shock
Editor’s Capsule Summary
What is already known on this topic
Although sympathomimetic, ketamine can produce
hypotension in patients with depleted catecholamine
stores.
What question this study addressed
When ketamine is used for rapid sequence
intubation, how do the resulting hemodynamics
differ when patients with or without risk of shock are
compared (as estimated by the shock index)?
What this study adds to our knowledge
In this observational comparison of 112 out-of-
hospital adults, those without apparent shock
generally exhibited the expected increases in blood
pressure and pulse. These effects were blunted in
patients with a high shock index, with 8 of these 31
experiencing hypotension.
How this is relevant to clinical practice
When ketamine is used for rapid sequence induction,
hypotension and blunted sympathomimetic
responses are more common when initial
hemodynamics suggest possible shock.
in predicting blood loss.18,19 The shock index is an
alternative measure and is calculated by dividing pulse rate
by blood pressure. A shock index greater than 0.9 in the
emergency department (ED) predicts increased mortality in
trauma patients and the need for blood transfusion,20-22 as
well as prolonged vasopressor use early in sepsis.23,24 The
exact cutoff for shock index varies between studies;
however, a shock index of less than 0.7 is considered
normal and values greater than 0.9 are associated with
increasing risk of morbidity and mortality.21,25 One of the
advantages of the shock index is that it identifies individuals
at risk whose blood pressure would be considered normal
by other measures.26 A shock index of greater than 0.9 had
been shown elsewhere to identify patients at risk of
hypotension27 and cardiac arrest28 postinduction in the
ED, with etomidate as the induction drug.
Importance
It would be useful to identify patients at risk of
hypotension or hypertension when ketamine is used as an
induction agent, as well as the frequency of these events.
Consideration can then be made to reduce the dose of
ketamine if the patient is at risk of hypotension, or add
additional opiate if hypertension is likely to occur.
182 Annals of Emergency Medicine
Miller et al
Goals of This Investigation
We performed a prospective observational study to
investigate the hemodynamic response to out-of-hospital
induction with ketamine in our patients. Our goals were to
investigate the pattern of SBP and pulse rate change, as well
as the proportion of patients developing hypotension and
hypertension, and whether this differed in patient groups
when divided by the shock index. Our primary outcome
measure was the change in SBP and pulse rate between
preinduction and 3 measurements after induction (taken at
3-minute intervals) in these groups, with the proportion
of hypotension and hypertension in these groups as
secondary outcomes.
MATERIALS AND METHODS
Study Design and Setting
This prospective observational study was conducted
between June 2014 and July 2015 at the Greater Sydney
Area Helicopter Emergency Medical Service, New South
Wales, Australia. This service provides a physician-
paramedic team for out-of-hospital response. Ethical
approval and consent waiver were granted by the Sydney
Local Health District Human Ethics Committee.
Selection of Participants
We included patients undergoing out-of-hospital
intubation when ketamine was used as the induction agent
and excluded those younger than 15 years and those in
cardiac arrest before intubation. The choice and dose of
induction drug is physician preference, in discussion with
the paramedic, guided by a standard operating procedure.
Ketamine is our most commonly used induction drug.
Methods of Measurement
During each patient encounter, vital signs (pulse rate,
noninvasive blood pressure, SpO2, and end tidal CO2) are
recorded on a Lifepak-15 monitor (Physio Control,
Redmond, WA) every 3 minutes, and physicians are
requested to record the induction and intubation time.
Each month, one investigator (M.M.) extracted
demographic and clinical data from the encounter database.
Three investigators (M.M., N.K., and C.H.) independently
extracted SBP and pulse rate data. All 3 pulse rates (if
available) were recorded and a final pulse rate was
determined according to agreement between modalities or
in the order ECG, SpO2, and noninvasive blood pressure if
there was disagreement. If the SBP or pulse rate at a specific
point differed between investigators, then the vital signs
printout was reviewed until agreement was reached. If no
pulse rate or SBP data were available in the predefined
Volume 68, no. 2 : August 2016
Miller et al Ketamine Induction in Patients With Shock

3-minute period or agreement could not be reached, then

no data were entered for that period.
We defined the period of 3 minutes preinduction up to
induction as pre–rapid sequence induction, and the periods
0 to 3 minutes, 3 to 6 minutes, and 6 to 9 minutes after
induction, respectively, as first, second, and third SBP or
pulse rate measurement post–rapid sequence induction.
Shock index was derived by dividing pulse rate by SBP.
We divided patients into low and high shock index groups
if one shock index measurement in 6 to 3 minutes or 3
to 0 minutes preinduction was less than 0.9 (low shock
index) or greater than or equal to 0.9 (high shock index),
consistent with previous research.20,27,29 A hypotensive
response was defined as an SBP greater than 90 mm Hg
preinduction and SBP less than 90 mm Hg at any
measurement after induction. A hypertensive response was
defined as SBP less than 160 mm Hg preinduction and
SBP greater than 160 mm Hg at any measurement after Figure 1. Selection of participants for data analysis. RSI, rapid
induction. sequence induction; LSI, low shock index; HSI, high shock
index.
Primary Data Analysis
We analyzed our data with R statistical software (version 0 to 0.4 mg/kg), whereas the total ketamine dose
3.2; R Core Team, Vienna) and the Post-Hoc Interaction (preinduction plus induction) was similar (mean difference
Analysis package version 0.2-1.30 We contrasted the 0.3 mg/kg; 95% CI –0.2 to 0.9 to mg/kg). Other
hemodynamic response between high and low shock index intubation characteristics were similar between groups.
groups with repeated-measures ANOVA. If sphericity
assumptions were violated according to Mauchly tests, we
applied the Greenhouse-Geisser correction. Confidence Table 1. Demographic data for low and high shock index patients
intervals (CIs) for the ANOVA effect sizes were calculated and those with missing data.*
with the method described by Hollands and Jarmasz.31 Demographic Data LSI (SI <0.9) HSI (SI ‡0.9) Missing Data
We calculated our sample size with G*Power 3 (version n 81 31 64
3.1.9.2; Heinrich-Heine University, Dusseldorf) according Age, median (25–75 36 (28) 32 (25–55) 38 (26–51)
to a preinduction to postinduction decrease in SBP of 20 quantiles), y
Sex, male (%) 64 (80) 19 (61) 51 (79)
mm Hg (SD 30 mm Hg; significance level 0.05, power of
Estimated weight, mean 80.2 (16.8) 76.2 (12.7) 82.0 (18)
0.8), which we considered clinically significant because it (SD), kg
would represent a critically ill head-injured patient with an GCS category (%)
SBP of 110 mm Hg becoming hypotensive after induction. No HI 6 (7) 3 (10) 6 (9)
Mild (GCS score 13–14) 7 (9) 2 (6) 5 (8)
Assuming a dropout rate of 10%, this resulted in a sample size Moderate (GCS score 24 (30) 9 (29) 20 (31)
of 96 participants (48 patients in each shock index group). 8–12)
Severe (GCS score <8) 44 (54) 17 (55) 33 (52)
Trauma (%) 76 (94) 25 (80) 62 (95)
RESULTS Intubation reason (%)
HI with threatened airway 51 (63) 17 (55) 40 (61)
Characteristics of Study Subjects Combative 13 (16) 5 (16) 8 (13)
Patient flow is shown in Figure 1. Most of the 112 Other neurologic 5 (6) 2 (6) 3 (5)
subjects were intubated for either severe head injuries or condition
Respiratory or cardiac 4 (5) 4 (13) 4 (6)
combativeness, with demographic characteristics similar arrest/failure
between groups (Table 1). Shock 3 (4) 3 (10) 6 (9)
Most patients were intubated within 2 minutes and first- Burns/inhalation 3 (4) 0 3 (5)
Face/neck trauma 2 (2) 0 0
pass laryngoscopy success was high (Table 2). The mean
ketamine induction dose was slightly higher in the low SI, Shock index; GCS, Glasgow Coma Scale; HI, head injury.
*Data are number of patients (%) unless otherwise indicated.
shock index group (mean difference 0.2 mg/kg; 95% CI

Volume 68, no. 2 : August 2016 Annals of Emergency Medicine 183

Ketamine Induction in Patients With Shock Miller et al

Table 2. Intubation data for low and high shock index patients and patients with missing data.*
Intubation Data LSI (<0.9) HSI (‡0.9) Missing Data
n 81 31 64
Painful procedures, No. (%)
None 67 (83) 25 (81) 53 (82)
Thoracostomy 5 (6) 4 (12) 9 (14)
Pelvic binder 7 (9) 1 (3) 3 (5)
Limb splint 2 (2) 1 (3) 0
Laryngoscopy attempts, %
1 90 97 86
2 9 3 11
3 1 0 2
Cricoid pressure, number of patients 2 0 2
Time from induction to intubation, min 1 (1–2) 1 (1–2) 1 (1–2)
Preinduction medications
Fentanyl IV, No. (%) 3 (3) 1 (3) 1 (2)
Fentanyl IV dose, mg/kg 1.5 1.4 1.6
Fentanyl IN, No. (%) 3 (3) 1 (3) 1 (2)
Fentanyl IN dose, median, mg/kg 1.5 1.25 3
Morphine, No. (%) 14 (17) 4 (13) 12 (19)
Morphine dose, median, mg/kg 0.11 (0.07–0.13) 0.13 (0.10–0.18) 0.13 (0.11–0.18)
Midazolam, No. (%) 13 (16) 6 (19) 11 (17)
Midazolam dose, mg/kg 0.04 (0.01–0.05) 0.08 (0.05–0.14) 0.06 (0.03–0.07)
Ketamine, No. (%) 50 (60) 15 (48) 38 (58)
Ketamine dose, mg/kg 0.5 (0.3–0.8) 0.4 (0.2–0.6) 0.5 (0.3–0.9)
Induction medications
Induction fentanyl (%) 9 (11) 0 5 (8)
Induction fentanyl dose, mg/kg 1.1 (1.0–1.6) 0 1.9 (1.5)
Ketamine induction dose, mean (SD), mg/kg 1.4 (0.4) 1.2 (0.5) 1.1 (0.5)
Total ketamine dose, mean (SD), mg/kg 2.0 (0.5) 1.7 (0.9) 1.9 (1.1)
Rocuronium (%) 71 (88) 24 (77) 47 (72)
Suxamethonium (%) 10 (12) 7 (23) 18 (28)
Rocuronium dose, mg/kg 1.4 (1.3–1.5) 1.4 (1.4–1.5) 1.3 (1.1–1.5)
Suxamethonium dose, mg/kg 1.6 (1.4–1.8) 1.9 (1.5–2.2) 1.5 (1.3–1.9)
Metaraminol, No. of patients (%) 1 0 1
IV, Intravenous; IN, intranasal.
*Data are median (IQR) unless otherwise indicated. Percentages may not add to 100% because of rounding. Total ketamine dose¼preinduction doseþinduction dose.

The median SBP was similar between 6 and 3 minutes
preinduction for both the low shock index group
(difference 2 mm Hg; 95% CI –2 to 2 mm Hg) and high
shock index group (difference 1 mm Hg; 95% CI –5 to 13
mm Hg). Likewise, the median pulse rate between 6 and 3
minutes preinduction was similar for both the low shock
index group (difference 1 beat/min; 95% CI –2 to 4 beats/
min) and high shock index group (difference 3 beats/min;
95% CI –5 to 9 beats/min) groups.
Main Results
We found that low shock index patients exhibited
significantly greater mean SBPs than high shock index
patients at each interval (Table 3). For low shock index
patients, the SBP increased for the first measurement and
remained elevated for the second and third measurements
(Table 3, Figure 2). For high shock index patients, the SBP
remained similar at all points. The SBP increased the most
from preinduction to the first measurement postinduction
in low shock index patients (difference 15 mm Hg; 95% CI
11 to 19 mm Hg).
We observed hypotension in 9% of the entire sample
(95% CI 4% to 16%), with 26% (95% CI 12% to 45%)
in the high shock index group (n¼8) versus 2% (95%
CI 0% to 9%) in the low shock index group (n¼2). Two
of these patients received thoracostomies postinduction;
in one patient the SBP improved to 98 mm Hg, and in the
other it remained less than 90 mm Hg. We observed
hypertension in 40% of the low shock index group (95%
CI 29% to 51%; n¼32) versus 13% (95% CI 4% to 30%)
in the high shock index group (n¼4).
We found that high shock index patients had
significantly higher pulse rate at each interval compared with
low shock index patients (Table 4). For low shock index
patients, the pulse rate increased for the first measurement
and remained elevated for the second and third
measurements (Table 4, Figure 3). For high shock index
patients, the only significant difference was contrasting the

184 Annals of Emergency Medicine Volume 68, no. 2 : August 2016

Miller et al Ketamine Induction in Patients With Shock

Table 3. SBP data for 3 minutes preinduction to 9 minutes postinduction for low and high shock index patients.*
Measurements
Patient Group Preinduction First Postinduction Second Postinduction Third Postinduction
LSI group SBP, mean (SD) 140 (21) 157 (24) 155 (25) 147 (29)
Difference, mean (95% CI) 16 (11 to 21) 2 (–3 to 7) 5 (0 to 10)
HSI group SBP, mean (SD) 115 (22) 117 (25) 118 (26) 116 (31)
Difference, mean (95% CI) 2 (–4 to 7) 1 (–4 to 6) –2 (–3 to 7)
Difference between LSI and HSI, mean (95% CI) 25 (20 to 30) 40 (35 to 45) 37 (32 to 42) 33 (29 to 38)
*Difference describes the difference in means (effect size) for adjacent measurements. All values are in millimeters of mercury. LSI¼SI <0.9; HSI¼SI 0.9.

pulse rate preinduction and at the second measurement
(difference 15 beats/min; 95% CI 11 to 18 beats/min).
Individual patient changes are depicted in Figures E1
and E2 (available online at http://www.annemergmed.
com). Relative changes in vital signs are summarized in
Tables E1 and E2 (available online at http://www.
annemergmed.com).
LIMITATIONS
Our principal limitation is that our study was
observational and not randomized. Additionally, patient
weight was estimated and not measured in accordance with
actual practice. We relied on noninvasive blood pressure, not
invasive blood pressure, which can be inaccurate, especially
in patients with shock.32 However, invasive blood pressure
is rarely used in the out-of-hospital environment. We had
a number of patients with incomplete data who could not
be studied.
We attempted to account for other potential causes of
altered peri-intubation hemodynamics. Laryngoscopy was
complete within 2 minutes for most patients, and thus
associated baroreceptor response would be expected to
diminish by the second period (6 minutes).33,34 Similarly,
first-pass success rate was high, suggesting little prolonged
laryngoscopy. One patient likely became hypotensive
because of tension pneumothorax postinduction because
the SBP recovered post-thoracostomy.
Finally, although uneven sample sizes are not desirable,
to achieve the same power as the original sample size
calculation, the high shock index group of 31 required a
low shock index sample size of 76, which is 5 patients fewer
than our final sample size.
DISCUSSION
We set out to investigate whether the pattern of
hemodynamic change in patients intubated with ketamine
differed in patients without shock and those potentially
with shock, as defined by the shock index. Although the
overall rate of hypotension was low, we found that patients
with a shock index greater than 0.9 had less overall change
in SBP up to 9 minutes after intubation, but more episodes
of hypotension, whereas those with a shock index of less
than 0.9 had larger sustained changes in SBP.
Our findings are similar to those of 2 previous studies
investigating the relationship between the shock index and
the risk of peri-intubation hypotension conducted in the
ICU and ED. Trivedi et al29 used a single episode of shock
index greater than 0.9 in 60 minutes preintubation to

Figure 2. Box plots of SBP at 4 intervals for low shock index patients (A) and high shock index patients (B). The overlaid line plots
represent the data of individual participants.

Volume 68, no. 2 : August 2016 Annals of Emergency Medicine 185

Ketamine Induction in Patients With Shock Miller et al

Table 4. Pulse rate data for 3 minutes preinduction to 9 minutes postinduction for low and high shock index patients.*
Measurements
Patient Group Preinduction First Postinduction Second Postinduction Third Postinduction
LSI group pulse rate, mean (SD) 88 (20) 108 (26) 114 (23) 112 (23)
Difference, mean (95% CI) 20 (16 to 25) 5 (0 to 9) –2 (–6 to 2)
HSI group pulse rate, mean (SD) 115 (20) 124 (27) 130 (25) 127 (24)
Difference, mean (95% CI) 9 (–1 to 19) 6 (–3 to 16) –4 (–13 to 6)
Difference between LSI and HSI, mean (95% CI) 27 (22 to 32) 16 (11 to 21) 16 (11 to 21) 15 (9 to 20)
*All values are beats per minute. Difference describes the difference in means (effect size) for adjacent measurements. LSI¼SI <0.9; HSI¼SI 0.9.

identify their high shock index ICU patients and found an
increased rate of postintubation hypotension (odds ratio
2.13; 95% CI 1.07 to 4.35) and mortality for shock index
greater than 0.9. Heffner et al27 studied ED patients and
found increased risk of hypotension within 60 minutes of
onset of intubation and ventilation for their high shock
index group (odds ratio 55; 95% CI 13 to 232), also
comprising patients with a shock index greater than 0.9.
Both these studies used etomidate and propofol as their
induction agents. As far as we are aware, ours is the first
study to investigate the association of the shock index to
out-of-hospital induction or in association with ketamine.
In vitro, ketamine is negatively inotropic when applied
directly to cardiac muscle35; however, in vivo it is
sympathomimetic in patients with an intact autonomic
nervous system, acting to release centrally mediated
catecholamines and inhibit their reuptake. This mechanism
accounts for the hemodynamic stability of ketamine.35,36
The hypotension observed in the high shock index group
could be explained by these patients having depleted
their catecholamines, allowing less substrate on which
ketamine could act to maintain hemodynamic stability.
The delayed and limited compensatory tachycardia in the
high shock index group compared with the low shock index
group could again be a reflection of limited sympathetic
reserve. This is supported by a study by Waxman et al,6
who investigated 12 critically ill patients comparing
hemodynamic variables preketamine and 5 minutes
postketamine-only induction (average dose 70 mg). One
patient developed severe bradycardia, 4 demonstrated
decreased cardiac output and mean arterial pressure, and
6 had decreases in ventricular contractility. Lippmann et al7
repeated these measurements at 2-minute intervals up to
15 minutes postinduction in 22 critically ill patients.
They reported that although myocardial performance was
improved in the majority of patients, the response was
not uniform, and hypovolemic patients or those with
prolonged preoperative stress were most at risk of reduced
cardiac output. An alternative explanation, given that
postintubation hypotension is also reported after propofol
and etomidate9,29 induction, is that this is not solely a
pharmacologic effect but occurs as an interaction between
the hypovolemic state of the patient, onset of positive-
pressure ventilation, and a subsequent reduction in venous
return.37,38 If this were the case, then our results would
suggest that the median dose of ketamine used in high
shock index patients in this study (up to 1.7 mg/kg) is not
protective of this effect.

Figure 3. Box plots of pulse rate at 4 time intervals for low shock index patients (A) and high shock index patients (B). The overlaid
line plots represent the data of individual participants.

186 Annals of Emergency Medicine Volume 68, no. 2 : August 2016

Miller et al
Of the low shock index patients, 40% developed
hypertension 9 minutes postinduction. This may be the
result of a combination of the sympathomimetic effect of
ketamine and laryngoscopy because ketamine does not
attenuate the baroreceptor response to intubation. White39
found ketamine at 1.5 mg/kg increased mean arterial
pressure by 10% when used for rapid sequence induction
in emergency anesthesia, whereas a reduced dose of 0.75
mg/kg ketamine in combination with midazolam at 0.15
mg/kg resulted in no changes to mean arterial pressure.
Provision of an opiate such as fentanyl at induction is
common to obtund the hemodynamic response to
laryngoscopy; however, few of the low shock index patients
and none of the high shock index patients received fentanyl
at induction. When fentanyl was administered, it was at a
relatively low dose (1 mg/kg), given that 5 mg/kg of fentanyl
is required to obviate the laryngoscopic response.40 Lyon
et al41 found that fentanyl at 3 mg/kg in out-of-hospital
patients without shock limited the percentage of change in
SBP within 5 minutes of induction, and this may be a
reasonable compromise between modifying the response to
intubation and excessive sympatholysis. Alternatively, 20 to
40 mg/kg of alfentanil in combination with 1 mg/kg of
ketamine has been shown to obtund the hemodynamic
response to intubation in elective surgery patients.3
In conclusion, ketamine offers favorable hemodynamics
as an induction drug. Overall, in our study the rate of
hypotension postintubation was at the lower margins of
that of previous studies, but in some vulnerable patients the
risk of hypotension may be higher. In our study, patients
who were identified as having a high shock index by a
shock index greater than or equal to 0.9 appeared to be at
risk. A prospective trial using fentanyl at a higher dose than
we currently use in low shock index patients and using no
fentanyl in high shock index patients, with consideration to
reduce the ketamine dose, would be useful to support our
findings.
The authors would like to acknowledge the paramedics and
physicians of Greater Sydney Area HEMS for annotating vital
signs printouts to aid data collection, and Kait Luker for here
help providing monthly intubation reports.
Supervising editor: Steven M. Green, MD
Author affiliations: From the Aeromedical and Retrieval Service,
Ambulance Service, New South Wales, Sydney, Australia (Miller,
Ware, Habig, Reid, Burns); the Kent Surry Sussex Air Ambulance,
Marden, Kent, United Kingdom (Miller); the Department of
Anaesthesia, Westmead Hospital, Sydney, Australia (Kruit); the
Department of Anaesthesia, Austin Hospital, Melbourne, Australia
(Heldreich); the School of Molecular Bioscience, University of
Volume 68, no. 2 : August 2016
Ketamine Induction in Patients With Shock
Sydney, New South Wales, Australia (Ware); and the Sydney
Medical School, Sydney University, New South Wales, Australia
(Habig, Reid, Burns).
Author contributions: MM, NK, CH, SW, CR, and BB conceived and
planned the study. MM, NK, and SW designed the study and
analysis. KH contributed to data collection. MM was responsible
for ethical and site-specific approvals. MM and SW provided
statistical analysis. MM drafted the article, and all authors
contributed to its revision. MM takes responsibility for the paper as
a whole.
Funding and support: By Annals policy, all authors are required to
disclose any and all commercial, financial, and other relationships
in any way related to the subject of this article as per ICMJE conflict
of interest guidelines (see www.icmje.org). The authors have stated
that no such relationships exist.
Publication dates: Received for publication December 26, 2015.
Revisions received February 28, 2016; March 10, 2016; and
March 21, 2016. Accepted for publication March 24, 2016.
Available online April 27, 2016.
REFERENCES
1. Marland S, Ellerton J, Andolfatto G, et al. Ketamine: use in anesthesia.
CNS Neurosci Ther. 2013;19:381-389.
2. Marlow R, Reich DL, Neustein S, et al. Haemodynamic response to
induction of anaesthesia with ketamine/midazolam. Can J Anesth.
1991;38:844-848.
3. Katz RI, Levy A, Slepian B, et al. Haemodynamic stability and ketamine-
alfentanil anaesthetic induction. Br J Anaesth. 1998;81:702-706.
4. Wong DH, Jenkins LC. The cardiovascular effects of ketamine in
hypotensive states. Can Anaesth Soc J. 1975;22:339-348.
5. Weiskopf RB, Bogetz MS, Roizen MF, et al. Cardiovascular and
metabolic sequelae of inducing anesthesia with ketamine or
thiopental in hypovolemic swine. Anesthesiology. 1984;60:214-219.
6. Waxman K, Shoemaker WC, Lippmann M. Cardiovascular effects of
anesthetic induction with ketamine. Anesth Analg. 1980;59:355-358.
7. Lippmann M, Appel PL, Mok MS, et al. Sequential cardiorespiratory
patterns of anesthetic induction with ketamine in critically ill patients.
Crit Care Med. 1983;11:730-734.
8. Jabre P, Avenel A, Combes X, et al. Morbidity related to emergency
endotracheal intubation—a substudy of the Ketamine Sedation trial.
Resuscitation. 2011;82:517-522.
9. Price B, Arthur AO, Brunko M, et al. Hemodynamic consequences of
ketamine vs etomidate for endotracheal intubation in the air medical
setting. Am J Emerg Med. 2013;31:1124-1132.
10. Sibley A, Mackenzie M, Bawden J, et al. A prospective review of the use of
ketamine to facilitate endotracheal intubation in the helicopter emergency
medical services (HEMS) setting. Emerg Med J. 2011;28:521-525.
11. Tarquinio KM, Howell JD, Montgomery V, et al. Current medication
practice and tracheal intubation safety outcomes from a prospective
multicenter observational cohort study. Pediatr Crit Care Med.
2015;16:210-218.
12. Ballow SL, Kaups KL, Anderson S, et al. A standardized rapid
sequence intubation protocol facilitates airway management in
critically injured patients. J Trauma Acute Care Surg. 2012;73:
1401-1405.
13. Franschman G, Peerdeman SM, Andriessen TMJC, et al. Effect of
secondary prehospital risk factors on outcome in severe traumatic
brain injury in the context of fast access to trauma care. J Trauma.
2011;71:826-832.
14. Berry C, Ley EJ, Bukur M, et al. Redefining hypotension in traumatic
brain injury. Injury. 2012;43:1833-1837.
Annals of Emergency Medicine 187
Ketamine Induction in Patients With Shock
15. Zafar SN, Millham FH, Chang Y, et al. Presenting blood pressure in
traumatic brain injury: a bimodal distribution of death. J Trauma.
2011;71:1179-1184.
16. Sellmann T, Miersch D, Kienbaum P, et al. The impact of arterial
hypertension on polytrauma and traumatic brain injury. Dtsch Arztebl
Int. 2012;109:849-856.
17. Reisner A, Chen X, Kumar K, et al. Prehospital heart rate and blood
pressure increase the positive predictive value of the Glasgow Coma
Scale for high-mortality traumatic brain injury. J Neurotrauma.
2014;31:906-913.
18. Mutschler M, Nienaber U, Münzberg M, et al. Assessment of
hypovolaemic shock at scene: is the PHTLS classification of
hypovolaemic shock really valid? Emerg Med J. 2013;31:35-40.
19. Little RA, Kirkman E, Driscoll P, et al. Preventable deaths after injury:
why are the traditional “vital” signs poor indicators of blood loss?
J Accid Emerg Med. 1995;12:1-14.
20. Vandromme MJ, Griffin RL, Kerby JD, et al. Identifying risk for massive
transfusion in the relatively normotensive patient: utility of the
prehospital shock index. J Trauma. 2011;70:384-390.
21. Cannon CM, Braxton CC, Kling-Smith M, et al. Utility of the shock index
in predicting mortality in traumatically injured patients. J Trauma.
2009;67:1426-1430.
22. Mutschler M, Nienaber U, Münzberg M, et al. The shock index
revisited—a fast guide to transfusion requirement? a retrospective
analysis on 21,853 patients derived from the TraumaRegister DGU.
Crit Care. 2013;17:R172.
23. Wira CR, Francis MW, Bhat S, et al. The shock index as a predictor of
vasopressor use in emergency department patients with severe
sepsis. West J Emerg Med. 2014;15:60-66.
24. Berger T, Green J, Horeczko T, et al. Shock index and early recognition
of sepsis in the emergency department: pilot study. West J Emerg Med.
2013;14:168-174.
25. Olaussen A, Blackburn T, Mitra B, et al. Review article: shock index for
prediction of critical bleeding post-trauma: a systematic review. Emerg
Med Australas. 2014;26:223-228.
26. Vandromme MJ, Griffin RL, Weinberg JA, et al. Identifying risk for
massive transfusion in the relatively normotensive patient: utility of the
prehospital shock index. J Trauma. 2011;70:384-390.
27. Heffner AC, Swords DS, Nussbaum ML, et al. Predictors of the
complication of postintubation hypotension during emergency airway
management. J Crit Care. 2012;27:587-593.
28. Heffner AC, Swords DS, Neale MN, et al. Incidence and factors
associated with cardiac arrest complicating emergency airway
management. Resuscitation. 2013;84:1500-1504.
CORRECTION
In the May 2011 issue, regarding the article by Mallory et al (“Emergency physician-administered propofol
sedation: a report on 25,433 sedations from the pediatric sedation research consortium,” pages 462-468)
as a part of a follow-up inquiry the authors discovered an error made in reporting information on one of two
patients found to have had aspiration. One of the patients was erroneously reported as having been 5 years
old when in fact he was 10 years old. The authors regret this error.
188 Annals of Emergency Medicine
Miller et al
29. Trivedi S, Demirci O, Arteaga G, et al. Evaluation of preintubation
shock index and modified shock index as predictors of postintubation
hypotension and other short-term outcomes. J Crit Care. 2015;30:861.
e1-7.
30. De Rosario-Martinez H. Phia: Post-Hoc Interaction Analysis. R package
version 0.2-0; 2015. Available at: http://CRAN.R-project.org/
package¼phia. Accessed December 12, 2015.
31. Hollands JG, Jarmasz J. Revisiting confidence intervals for repeated
measures designs. Psychon Bull Rev. 2010;17:135-138.
32. Lakhal K, Macq C, Ehrmann S, et al. Noninvasive monitoring of blood
pressure in the critically ill: reliability according to the cuff site (arm,
thigh, or ankle). Crit Care Med. 2012;40:1207-1213.
33. O’Hare R, McAtamney D, Mirakhur RK, et al. Bolus dose remifentanil
for control of haemodynamic response to tracheal intubation during
rapid sequence induction of anaesthesia. Br J Anaesth. 1999;82:
283-285.
34. Alanoglu Z, Ates Y, Yilmaz AA, et al. Is there an ideal approach for rapid-
sequence induction in hypertensive patients? J Clin Anesth. 2006;18:
34-40.
35. Gelissen HP, Epema AH, Henning RH, et al. Inotropic effects of
propofol, thiopental, midazolam, etomidate, and ketamine on isolated
human atrial muscle. Anesthesiology. 1996;84:397-403.
36. Morris C, Perris A, Klein J, et al. Anaesthesia in haemodynamically
compromised emergency patients: does ketamine represent
the best choice of induction agent? Anaesthesia. 2009;64:
532-539.
37. Shafi S, Gentilello L. Pre-hospital endotracheal intubation and
positive pressure ventilation is associated with hypotension and
decreased survival in hypovolemic trauma patients: an analysis
of the National Trauma Data Bank. J Trauma. 2005;59:
1140-1145.
38. Franklin C, Samuel J, Hu TC. Life-threatening hypotension associated
with emergency intubation and the initiation of mechanical ventilation.
Am J Emerg Med. 1994;12:425-428.
39. White PF. Comparative evaluation of intravenous agents for rapid
sequence induction—thiopental, ketamine, and midazolam.
Anesthesiology. 1982;57:279-284.
40. Hosalli V, Es A, Hulkund SY, et al. Comparative efficacy of different
doses of fentanyl on cardiovascular responses to laryngoscopy
and tracheal intubation. J Clin Diagn Res. 2014;8:GC01-GC03.
41. Lyon RM, Perkins ZB, Chatterjee D, et al. Significant modification
of traditional rapid sequence induction improves safety and
effectiveness of pre-hospital trauma anaesthesia. Crit Care. 2015;19:
134.
Volume 68, no. 2 : August 2016
Miller et al Ketamine Induction in Patients With Shock

Figure E1. Absolute SBP change for low and high shock index patients compared with baseline for first, second, and third SBP
postinduction.

Volume 68, no. 2 : August 2016 Annals of Emergency Medicine 188.e1

Ketamine Induction in Patients With Shock Miller et al

Figure E2. Absolute pulse rate change for low and high shock index patients compared with baseline for first, second, and third
pulse rate postinduction.

Table E1. Number and percentage of patients with a positive or Table E2. Number and percentage of patients with a positive or
negative change in SBP compared with preinduction SBP for each negative change in pulse rate compared with preinduction pulse
interval. rate for each interval.
Direction of SBP Change LSI HSI Direction of Pulse Rate Change LSI HSI
Positive change (%) Positive change (%)
First 63 (77) 16 (52) First 67 (83) 19 (61)
Second 58 (72) 20 (65) Second 75 (93) 24 (77)
Third 49 (60) 16 (52) Third 75 (93) 21 (68)
Negative change (%) Negative change (%)
First 17 (21) 14 (45) First 10 (12) 9 (29)
Second 21 (25) 11 (35) Second 6 (7) 7 (23)
Third 28 (35) 15 (48) Third 4 (5) 9 (29)

188.e2 Annals of Emergency Medicine Volume 68, no. 2 : August 2016