Circulation: Cardiovascular Quality and Outcomes

ORIGINAL ARTICLE

Hospital Variation in the Utilization and

Implementation of Targeted Temperature
Management in Out-of-Hospital Cardiac Arrest

BACKGROUND: Targeted temperature management (TTM) for out-of- Rohan Khera, MD

hospital cardiac arrest is associated with improved functional survival and Andrew Humbert, MS
is a class I recommendation in resuscitation guidelines. However, patterns Brian Leroux, PhD
of utilization of TTM and adherence to recommended TTM guidelines in Graham Nichol, MD
contemporary practice are unknown. Peter Kudenchuk, MD
Damon Scales, MD
METHODS AND RESULTS: In a multicenter, prospective cohort of Andrew Baker, MD
consecutive adults with non-traumatic out-of-hospital cardiac arrest in the Mike Austin, MD
Resuscitation Outcomes Consortium in 2012 to 2015, we identified all Craig D. Newgard, MD,
adults (≥18 years) who were potential candidates for TTM. Of 37 898 out- MPH
of-hospital cardiac arrest patients at 186 hospitals across 10 Resuscitation Ryan Radecki, MD, MS
Outcomes Consortium sites, 8313 survived for ≥4 hours after hospital Gary M. Vilke, MD
arrival, of which, 2878 (34.6%) received TTM. Mean age was 61.5 years Kelly N. Sawyer, MD
Downloaded from http://ahajournals.org by rohan.khera@utsouthwestern.edu on November 9, 2018

George Sopko, MD
and 36.3% were women. Median hospital rate of TTM use was 27%
Ahamed H. Idris, MD
(interquartile range [IQR]: 14%, 45%), with an over 2-fold difference
Henry Wang, MD, MS
across sites after accounting for differences in presentation characteristics Paul S. Chan, MD, MSc
(median odds ratio, 2.10 [1.83–2.26]). Notably, TTM utilization decreased Michael C. Kurz, MD, MS
during the study period (57.5% [2012] to 26.5% [2015], P<0.001) for the Resuscitation
including among shockable out-of-hospital cardiac arrest (73.4% to Outcomes Consortium
46.3%, P<0.001). When administered, the median rate of deviation from Investigators
one or more recommended practices was 60% (IQR: 40%, 78%). The
median rate for delayed onset of TTM was 13% (IQR: 0%, 25%), varying
by 70% for identical patients across 2 randomly chosen hospitals (median
odds ratio 1.70 [1.39–1.97]). Similarly, the median rate for TTM <24 hours
was 20% (IQR: 0%, 34%) and for achieved temperature <32°C was 18%
(IQR: 0%, 39%), with marked variation across sites (median odds ratios of
1.44 [1.18–1.64] and 1.98 [1.62–2.31], respectively).
CONCLUSIONS: There has been a substantial decline in the utilization of
TTM with significant variation in its real-world implementation. Further
standardization of contemporary post-resuscitation practices, like TTM, is
critical to ensure that their potential survival benefit is realized.

Key Words: hospitals ◼ resuscitation

◼ odds ratio ◼ out-of-hospital cardiac
arrest ◼ temperature

© 2018 American Heart Association, Inc.

https://www.ahajournals.org/journal/
circoutcomes

Circ Cardiovasc Qual Outcomes. 2018;11:e004829. DOI: 10.1161/CIRCOUTCOMES.118.004829 November 2018 1

 Khera et al; TTM in Out-of-Hospital Cardiac Arrest
WHAT IS KNOWN
• Targeted temperature management (TTM) is asso-
ciated with improved patient outcomes after out-
of-hospital cardiac arrest.
• Resuscitation guidelines give TTM a class I recom-
mendation and suggest initiation of treatment
within 4 hours of return of spontaneous circula-
tion in all comatose survivors of out-of-hospital
cardiac arrest with lowering of core body temper-
atures to 32°C to 36°C for a period of 24 hours.
WHAT THE STUDY ADDS
• A median 27% of cardiac arrest patients at hos-
pitals participating in the Resuscitation Outcomes
Consortium potentially eligible for TTM actually
received the therapy, with over 2-fold variation in
treatment of similar patients across hospitals
• Their utilization of TTM decreased substantially
between 2012 and 2015 for both shockable and
non-shockable cardiac arrests.
• There was substantial practice variation in the
implementation of TTM across hospitals, with
wide variation in rates of timely initiation of ther-
apy, maintenance of appropriate temperatures,
and treatment for the recommended duration.
I
n the United States, nearly 350 000 people experience
out-of-hospital cardiac arrest (OHCA) each year with
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an average survival rate of roughly 10%,1 and fewer
survive without neurological disability.2,3 The low sur-
vival and high morbidity in patients who receive cardio-
pulmonary resuscitation (CPR) is a result of prolonged,
global ischemic insult during cardiac arrest compounded
by reperfusion injury after the return of spontaneous
circulation.4,5 Targeted temperature management (TTM)
is aimed at supporting patient recovery by a variety of
proposed mechanisms.5,6 Randomized trials have found
improved early and long-term survival with TTM be-
tween 32 and 36°C, initiated within 4 hours of return
of spontaneous circulation, and maintained for at least
24 hours after return of spontaneous circulation in co-
matose survivors of OHCA because of shockable cardiac
arrests.7,8 Observational studies suggest that TTM may
improve patient outcomes in non-shockable cardiac ar-
rest as well.9–14 Consequently, current evidence-based
clinical practice guidelines give TTM a class I recommen-
dation, regardless of the initial pulseless rhythm.15,16
Although >80% of all OHCA are comatose at hospital
presentation and temperature management has been rec-
ommended for the past decade,16–20 barriers may continue
to impede its implementation in routine practice.21–23 A
contemporary description of rates of TTM initiation in sur-
vivors of OHCA, and patterns of real-world implementa-
tion of TTM (eg, timeliness of initiating therapy, and ade-
quacy and duration of attained temperature), would allow
Circ Cardiovasc Qual Outcomes. 2018;11:e004829. DOI: 10.1161/CIRCOUTCOMES.118.004829
for a better understanding of whether this evidence-based
recommendation for OHCA patients has been broadly dis-
seminated and effectively practiced in post-arrest care.
Accordingly, in a large prospective clinical registry of
OHCA, the Resuscitation Outcomes Consortium (ROC)
Cardiac Arrest Epistry, we assessed the overall utilization
of TTM in comatose survivors of OHCA, as well as varia-
tion in actual implementation across different hospitals.
METHODS
Study Design
This investigation was a cohort study using data prospectively
collected by ROC. Approval was obtained from each institu-
tional review board or research ethics board at the respective
institutions within the participating communities. The authors
do not have ownership of the data, however, which can be
accessed with a limited data request from the ROC coordinat-
ing center. The analytic methods and study materials will be
made available to other researchers for purposes of reproduc-
ing the results upon request.
Data Source
The ROC is a network of 10 sites in North America that include
186 hospitals across the United States and Canada conduct-
ing research in cardiac arrest and severe traumatic injury.24 The
ROC Epistry is a prospective, multicenter, observational registry
of all OHCAs assessed by emergency medical services (EMS)
agencies in the participating geographic regions beginning in
the year 2005.24 The ROC Epistry was updated in May of 2012
to collect detailed information in the use of TTM in OHCA.
Briefly, all ROC sites use a multimodal approach to capture
consecutive cases, including automated identification from EMS
dispatch records, in-field defibrillator use, and CPR records,
along with manual review of both paper EMS charts and elec-
tronic EMS data by trained data abstracters.25 Data collection
in the ROC Epistry is standardized across sites with a uniform
case report form. These include standard Utstein data (age, sex,
witnessed, receipt of bystander CPR, public location, presenting
ECG rhythm, etc), EMS response characteristics, and in-hospital
management. In addition, data include detailed information on
whether TTM was initiated, duration of TTM, temperature mea-
surements during treatment, and survival to discharge. Data
from all sites are compiled by the data coordinating center at
the University of Washington, Seattle, where they are systemati-
cally assessed using internal logic checks, periodic reabstraction
of random subsets of data, and periodic site visits.25
Study Population
All adults (≥18 years of age) between May 2012 and October
2015 who had a nontraumatic OHCA, were presumed coma-
tose, and survived to 4 hours after presentation to the hospi-
tal were included in the study. As has been done previously,26
we used mechanical ventilation as a surrogate for identifica-
tion of comatose patients. Further, we restricted the analyses
to patients who survived to at least 4 hours of presentation
to exclude patients who may not be candidates for TTM (eg,
died or had care withdrawn soon after hospital presentation).
November 2018 2
 Khera et al; TTM in Out-of-Hospital Cardiac Arrest

Figure 1. Study flowsheet.

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Further, given the limited reliability of estimates for low- used to derive an estimate for a median odds ratio (OR),
volume hospitals, hospitals with fewer than 5 cardiac arrest which quantifies the odds that OHCA patients would differ
cases meeting the above criteria during the study period were in TTM treatment at 2 randomly selected ROC hospitals. For
excluded from hospital-level analyses (Figure 1). example, a median OR of 1.5 for delayed initiation of TTM

Statistical Analysis
Among study patients, yearly trends in utilization of TTM as a
proportion of total cardiac arrest cases were examined, both
overall and by initial rhythm—shockable (ventricular fibrilla-
tion or ventricular tachycardia]) versus non-shockable (pulse-
less electrical activity, asystole, or other undetermined rhythm
in pulseless arrest). Next, we compared baseline characteris-
tics between those who were and were not treated with TTM,
including sex, age, shockable rhythm, location of arrest, if the
arrest was witness and if bystander CPR was delivered. We
also compared differences in EMS response time and time to
initiation of advanced life support.
Next, we evaluated the quality of TTM implementation
in routine practice among treated patients. Specifically, we
examined TTM implementation that differed from recom-
mended practice: (1) delayed initiation of TTM >4 hours
from arrival to the hospital, (2) administering TTM for <24
hours, and (3) achieved temperatures below 32°C. For
each of these 3, we constructed a hierarchical model with
hospital site as a random effect, and patient factors (age, Figure 2. Time trends in the utilization of targeted temperature man-
agement (TTM) in out-of-hospital cardiac arrest, overall, and based on
sex, cardiac arrest type [shockable or non-shockable], and cardiac arrest rhythm at presentation—shockable (ventricular tachy-
calendar-year) as fixed effects. The pooled hospital-level cardia [VT]/ventricular fibrillation [VF]) and non-shockable (pulseless
intercept obtained from this multilevel model was then electrical activity/asystole/others).

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 Khera et al; TTM in Out-of-Hospital Cardiac Arrest

suggests that, on average, a patient has 50% higher odds
of having TTM initiated >4 hours from hospital admission
at 1 randomly selected hospital compared with a second
randomly selected hospital.26–28
Finally, to understand if the utilization and quality of TTM
at hospitals varied based on their experience with OHCAs, we
assessed for the correlation between a hospital’s volume of
cardiac arrest cases and their utilization of TTM and quality
of its implementation using Spearman rank correlation test.
All analyses were conducted using R 3.4.2 for Windows (R
Foundation, Vienna, Austria) and SAS 9.4 (SAS Institute, Cary,
NC). All statistical tests were 2-sided and level of significance
was set at an α of 0.05.
RESULTS
Trends in TTM Utilization
During the study period, a total of 37 898 patients
had an OHCA of which 20 992 survived to present
at 1 of 186 ROC affiliated hospitals. A total of 8313
were intubated and survived ≥4 hours, forming the
study cohort (Figure  1). Of these, 2878 (34.6%)
received TTM. The rate of TTM utilization decreased
during the study period, both overall (57.5% in
2012 to 26.5% in 2015, P<0.001), and in shockable
(73.4% in 2012 to 46.3% in 2015, P<0.001) and
non-shockable (49.3% in 2012 to 14.1% in 2015,
P<0.001) cardiac arrests (Figure 2).
Characteristics of TTM
Patients receiving TTM differed substantially from
those who did not receive this therapy (Table 1). TTM
recipients were more frequently men (70.0% versus
60.3%) and had a cardiac arrest that was shockable
(58.1% versus 23.7%), in a public location (26.7%
versus 18.3%), and managed with bystander CPR
(58.3% versus 55.4%). There were no significant dif-

Table 1.  Patient Characteristics

Received Hypothermia No Hypothermia All Patients

(N=2878) (N=5435) (N=8313)
Age, y, mean (SD) (N=2870; 5420; 8290) 61.8 (15.6) 61.4 (19.3) 61.5 (18.1)
Male, n (%) (N=2878; 5428; 8306) 2015 (70.0%) 3274 (60.3%) 5289 (63.7%)
Public location, n (%) (N=2877; 5429; 8306) 767 (26.7%) 992 (18.3%) 1759 (21.2%)
Witness status, n (%) (N=2806; 5310; 8116)
 EMS witnessed 81 (2.9%) 1033 (19.5%) 1114 (13.7%)
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 Bystander witnessed 1759 (62.7%) 2373 (44.7%) 4132 (50.9%)

Bystander CPR, n (%) (N=2751; 4252; 7003) 1603 (58.3%) 2355 (55.4%) 3958 (56.5%)
Initial rhythm, n (%) (N=2811; 5053; 7864)
 VF/VT 1632 (58.1%) 1199 (23.7%) 2831 (36.0%)
 PEA 513 (18.2%) 1885 (37.3%) 2398 (30.5%)
 Asystole 614 (21.8%) 1817 (36.0%) 2431 (30.9%)
 Other non-shockable 52 (1.8%) 152 (3.0%) 204 (2.6%)
Call time to first EMS arrival (min), mean 5.7 (2.4) 5.9 (4.2) 5.8 (3.7)
(SD) (N=2873; 5367; 8240)
Call time to first ALS arrival (min), mean 8.5 (4.7) 8.9 (7.7) 8.7 (6.8)
(SD) (N=2860; 5326; 8186)
Site, n (%) (N=2878; 5435; 8313)
 A 59 (2.1%) 112 (2.1%) 171 (2.1%)
 B 350 (12.2%) 1080 (19,9%) 1430 (17.2%)
 C 200 (6.9%) 250 (4.6%) 450 (5.4%)
 D 117 (4.1%) 201 (3.7%) 318 (3.8%)
 E 27 (0.9%) 101 (1.9%) 128 (1.5%)
 F 187 (6.5%) 509 (9.4%) 696 (8.4%)
 G 89 (3.1%) 386 (7.2%) 475 (5.7%)
 H 619 (21.5%) 1123 (20.7%) 1742 (21.0%)
 I 770 (26.8%) 882 (16.2%) 1652 (19.9%)
 J 460 (16.0%) 791 (14.6%) 1251 (15.0%)

Values represent numbers (percentage of total) unless otherwise specified.

ALS indicates advanced life support; CPR, cardiopulmonary resuscitation; EMS, emergency medical services; VF,
ventricular fibrillation; and VT, ventricular tachycardia

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 Khera et al; TTM in Out-of-Hospital Cardiac Arrest

ferences in time to arrival of EMS from the time of
first call or the use of advanced cardiac life support
between those who did and did not receive TTM.
Patients receiving TTM more frequently survived to
hospital discharge (37.6% versus 15.3%, P<0.001 for
all comparisons).
Among those treated, TTM was initiated at a median
1.4 hours (interquartile range [IQR]: 0.4 to 3.1 hours)
from arrival to the hospital, administered for a median
of 33.0 hours (IQR: 24.1 to 38.0 hours), and with a
temperature measurement every 1.6 hours on average
(IQR: every 1.1 hour to every 1.9 hour). The median
average temperature during TTM therapy was 34.1°C
(IQR: 33.7 to 35.0°C). The nature of TTM therapy did
not differ substantially between those with a shock-
able arrest compared with those with a non-shockable
arrest (see Table 2).
Table 2.  Details of Targeted Temperature Management (TTM) Therapy,
Overall and Based on Cardiac Arrest Type by Presenting Rhythm
Shockable
TTM Therapy Overall Cardiac Arrest
Time from ROSC to TTM
 Mean (SD) 2.7 (4.5) 2.5 (2.7)
 <2 h 1337 (53.4%) 777 (53.3%)
 2–4 h 693 (27.7%) 423 (29.0%)
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Hospital Variation in TTM
Implementation
Of the 186 hospitals included in this analysis, 167 had 5
or more cases of cardiac arrest during the study period
with a total of 8303 cardiac arrests (99.8% of cases over-
all). The hospital-level rates of TTM utilization and adher-
ence to guideline-recommended practices are included
in Figures 3 through 6. The median cardiac arrest volume
at these hospitals during the study period was 33 (IQR:
8 to 69), and the median hospital rate of TTM utiliza-
tion was 25% (IQR: 8% to 43%). The median OR for
TTM utilization was 2.10 (95% CI, 1.83–2.36), which
suggests that there was greater than 2-fold variation, on
average, in the likelihood that identical patients present-
ing to 2 randomly ROC hospitals would receive TTM.
Among those treated with TTM, the hospital rate of
delayed initiation of TTM >4 hours was 13% (IQR: 0
to 25%). Notably, the median OR was 1.70 (95% CI,
1.39–1.97), suggesting that the likelihood of patients
having delayed initiation of TTM >4 hours from hospi-
Non- tal arrival at 2 randomly selected ROC hospitals varied
Shockable by 70%. Similarly, the median hospital rate for shorter
Cardiac
Arrest
than recommended TTM treatment (<24 hours) was
20% (IQR: 0%, 34%), with a median OR of median
OR of 1.44 (95% CI, 1.18–1.64). Lastly, the median
3.0 (6.4)
hospital rate for achieved temperatures below 32°C
529 (53.5%) was 18% (0%, 39%), with a median OR of 1.98 (95%
257 (26.0%) CI, 1.62–2.31), suggesting that overcooling with TTM

 >4 h 472 (18.9%) 258 (17.7%) 202 (20.4%) varied by as much as 2-fold across randomly chosen
Time from ED to hypothermia hospitals. Finally, the median hospital rate of at least
 Mean (SD) 2.3 (4.5) 2.2 (2.7) 2.6 (6.2)
1 deviation from the aforementioned 3 recommended
TTM practices was 60% (IQR: 40% to 78%). Finally,
 <2 h 1650 (59.9%) 932 (59.8%) 679 (60.0%)
hospital volume of cardiac arrest was strongly correlat-
 2–4 h 670 (24.3%) 400 (25.7%) 257 (22.7%)
ed to TTM utilization, with higher cardiac arrest volume
 >4 h 433 (15.7%) 226 (14.5%) 196 (17.3%) hospitals more likely to use TTM than low-volume hos-
Length of hypothermia pitals (Spearman r, 0.54; P value<0.001; Figure 7).
 Mean (SD) 30.3 (12.5) 31.1 (11.5) 29.0 (13.7)
 <6 h 161 (6.2%) 70 (4.6%) 89 (8.8%)
 6–12 h 148 (5.7%) 68 (4.5%) 75 (7.4%)
DISCUSSION
 12–24 h 336 (13.0%) 171 (11.3%) 154 (15.2%)
In this study assessing contemporary TTM treatment
in a large prospective registry of OHCA at 186 hospi-
 >24 h 1940 (75.0%) 1206 (79.6%) 696 (68.6%)
tals across 10 North American metropolitan areas, we
Minimum temperature
found a low and progressively declining rate of TTM use
 Mean (SD) 32.8 (1.5) 32.9 (1.5) 32.6 (1.4) between 2012 and 2015. Overall, TTM is used infre-
 <32°C 653 (25.5%) 355 (23.6%) 284 (28.3%) quently in OHCA, with only 35% of eligible patients
 32–34°C 1420 (55.4%) 832 (55.2%) 557 (55.6%) surviving to hospital presentation receiving this treat-
 34–36°C 432 (16.9%) 280 (18.6%) 143 (14.3%) ment. Moreover, there was wide variation in adher-
 >36°C 58 (2.3%) 39 (2.6%) 18 (1.8%)
ence to recommended practices for TTM. A majority
of patients at hospitals received TTM therapy with at
Average temperature, °C
least 1 deviation from recommended practices. Hos-
 Mean (SD) 34.4 (1.1) 34.5 (1.1) 34.2 (1.2)
pitals with higher volume of cardiac arrest cases more
Number of readings frequently used TTM and were less likely to be non-
 Mean (SD) 18.1 (10.8) 19.4 (10.3) 16.4 (11.2) adherent to recommended practices.
Values represent numbers (percentage of total) unless otherwise To our knowledge, our work represents the larg-
specified. ROSC indicates return of spontaneous circulation. est assessment of real-world application of TTM and its

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 Khera et al; TTM in Out-of-Hospital Cardiac Arrest

Figure 3. Variation in the rates of utilization of targeted temperature management (TTM).

Variation observed across (A) hospitals and (B) Resuscitation Outcomes Consortium (ROC) sites.

associated clinical practices. Previous studies that have
assessed patterns of TTM use were based on adminis-
trative data,29–31 and are thus limited by challenges with
accurately identifying consecutive cardiac arrest cases32,33
and lack clinical and operational details of TTM imple-
mentation.29–31 Other studies predate contemporary TTM
guidelines or represent practice at single centers.9,34 Our
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observed 35% rate of TTM use among OHCA survivors
suggests poor translation of these guidelines into clinical
practice. Further, the wide variation in deviations from
recommended TTM practices across hospitals highlights
a dual challenge—getting hospital to initiate TTM and to
effectively implement TTM protocols.
While only few conventional resuscitation prac-

study extends these observations to a real-world setting
and identifies contemporary practices related to TTM use
across a large number of hospitals. While 80% of patients
with OHCA are comatose at hospital presentation and
international professional societies give the strongest
recommendation for TTM in these patients,17–20,35 the
tices have high-quality evidence supporting their use,
TTM was introduced into clinical practice after evalu-
ation in several clinical studies.6 Randomized clinical
trials support the efficacy of TTM therapy,7,8 as well
as appropriate TTM practices, including temperature
targets and duration of therapy.36–38 While the design

Figure 4. Variation in the rates of delayed initiation of targeted temperature management (TTM) > 4 hours after arrival to emergency department or hospital.
Variation observed across (A) hospitals and (B) Resuscitation Outcomes Consortium (ROC) sites.

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 Khera et al; TTM in Out-of-Hospital Cardiac Arrest

Figure 5. Variation in the rates of the use of targeted temperature management (TTM) for < 24 hours.
Variation observed across (A) hospitals and (B) Resuscitation Outcomes Consortium (ROC) sites.

of the clinical trials has been debated in the resuscita-
tion research community,16,39 and the utility of TTM
in non-shockable is not supported by high-quality
evidence,16,39 clinical guidelines continue to strongly
recommend the use TTM. However, despite these rec-
ommendations, we found that the rate of TTM use in
cardiac arrest has actually declined over time. Second,
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Several potential factors may explain the low utili-
zation of TTM. First, despite its cost-effectiveness at a
patient-level,40 the use of TTM is resource intensive for
health systems, requiring dedicated hypothermia deliv-
ery systems and dedicated nursing and physician sup-
port for which little cost recovery is possible unless the
patient survives.41,42 Further, since most hospitals observe

in addition to declining utilization, the actual imple-
mentation of TTM seems to be inconsistent and var-
ied across hospitals, with frequent long delays in the
initiation of therapy, early termination of treatment
before 24 hours, and cooling to potentially deleteri-
ous low temperatures.
a modest number of cardiac arrest annually, there may
be little impetus to streamline TTM delivery infrastruc-
ture in light of other, competing clinical priorities (ie,
sepsis management or heart failure readmissions). Our
observation that hospitals with higher cardiac arrest
volumes are more likely to use TTM supports that less

Figure 6. Variation in the rates of overcooling to temperatures below 32°C.

Variation observed across (A) hospitals and (B) Resuscitation Outcomes Consortium (ROC) sites.

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 Khera et al; TTM in Out-of-Hospital Cardiac Arrest
frequent exposure to cardiac arrest management may
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be playing a role in the wide practice variation. The mul-
tidisciplinary nature of post-arrest care dilutes the train-
ing and education that would normally be championed
by professional societies. Second, the temporal decline
in TTM use suggests that recent studies on the appli-
cation of TTM may have been misinterpreted. Studies
that demonstrated similar outcomes between more lib-
eral (36°C) and conservative temperature targets (33°C)
in TTM, as well as those less supportive for TTM use
in the in-hospital cardiac arrest setting may have been
incorrectly assumed to suggest ineffectiveness of TTM in
OHCA,26,36,37 which itself is supported by evidence from
randomized clinical trials.7,8 However, we do not have
a sufficient period of data on utilization to specifically
evaluate whether there was a measurable change in
TTM use after the publication of these studies.
Furthermore, the low experience with TTM use may
further reflect in its clinical application, with wide varia-
tion in its use. For example, in this study, a median 7
cases of TTM at hospitals over a 3.5 year period sug-
gests that an average hospital used TTM once or twice
a year, thereby limiting a potential for developing expe-
rience with its use.43
Improvement in TTM use will likely require a multi-
pronged approach. First, guideline recommendations for
advanced therapies like the TTM will need to be incor-
porated in regular simulation training for cardiac arrest
Circ Cardiovasc Qual Outcomes. 2018;11:e004829. DOI: 10.1161/CIRCOUTCOMES.118.004829
Figure 7. Correlation plot for hospital
cardiac arrest volume and rate of use of
targeted temperature management (TTM).
care. Other interventions may include implementation of
teams that specialize in postcardiac arrest care or post-
arrest care in concert with a designated post-arrest care
center of excellence with more experience.44–48 Second,
resuscitation programs should limit changes to thera-
peutic protocols without appropriately vetting new evi-
dence. Third, implementation of performance measures
for OHCA, similar to the ones used by the American
Heart Association for in-hospital cardiac arrest,49 may be
a strategy to ensure that important interventions, like
the TTM, are used more uniformly. The adoption of qual-
ity metrics will drive compliance and set the stage for
improving reimbursement for this complex care. Finally,
there are several treatment protocols for initiating and
maintaining TTM,50–58 and more uniform recommenda-
tions on the protocols for TTM use may be useful.
The study has certain limitations. First, the present
study is based on data from EMS agencies and hospi-
tals in 10 metropolitan regions that participate in the
ROC Epistry and may not represent practices at nonpar-
ticipating hospitals. However, it is unlikely that practices
at institutions not participating in ROC, a consortium
designed to investigate therapies for OHCA, will be sub-
stantially better. Second, neurological status at hospital
presentation was non-routinely captured in ROC Epi-
stry;26 therefore, the use of mechanical ventilation was
used as a surrogate for comatose status. A recent sin-
gle-center study of 102 in-hospital cardiac arrests found
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 Khera et al; TTM in Out-of-Hospital Cardiac Arrest
that 22 (22%) of the mechanically ventilated patients
in the post-arrest setting were not comatose.59 Misclas-
sification rates of mechanically ventilated patients as
comatose would be expected to be lower for out-of-
hospital arrest given longer times from pulselessness to
initiation of CPR and would not be expected to differ
by year. Moreover, 80% of patients arriving at a hos-
pital after an OHCA are comatose,5 which is similar to
the proportion of patients requiring mechanical ventila-
tion at 4 hours from arrival to the hospital in our study
(8313 of 10 852 or 77%). Therefore, while the actual
TTM utilization may be modestly higher than the esti-
mates reported in our study, it would still be expected
to be low and we would not expect such misclassifica-
tion to affect our TTM trends analysis. Third, changes in
guideline recommendations for TTM, particularly TTM
duration, may overestimate the rate of short TTM ther-
apy (defined as TTM <24 hours), since earlier guidelines
from the year 2010, a period of 12 to 24 hours of TTM
was appropriate.60 However, these guidelines supported
the use of 24 hours of TTM therapy, and most contem-
porary guidelines have consistently recommended ≥24
of TTM.16,35 Further, in sensitivity analyses restricted to
the most recent year of the data, the observed variation
in short TTM therapy was similar to the primary analy-
ses (data not shown). Fourth, cardiac arrest characteris-
tics captured in ROC had varying rates of missingness,
with substantial missingness for certain characteristics.
For example, the use of bystander CPR was missing for
Downloaded from http://ahajournals.org by rohan.khera@utsouthwestern.edu on November 9, 2018
nearly 16% of all patients. Given the descriptive nature
of our study, we chose to not pursue imputation of
missing values. However, to ensure transparency, we
have reported missingness of all included care charac-
teristics in Table 1. Fifth, given the low volume of TTM
use at hospitals, it is possible that some of the observed
hospital-level differences in adherence to TTM practices
represent random variation. Finally, we did not have
reliable information on the location of TTM initiation
(prehospital, emergency room or the intensive care unit)
or complications arising from its use. These questions
remain important issues in future investigation.
In conclusion, there has been a substantial decline
in the utilization of TTM with significant variation in
its real-world implementation. Further standardization
of contemporary practice is critical if potential survival
benefits of TTM are to be realized.
ARTICLE INFORMATION
Received April 27, 2018; accepted September 26, 2018.
This article was handled independently by Pamela N. Peterson, MD.
The Data Supplement is available at https://www.ahajournals.org/doi/
suppl/10.1161/CIRCOUTCOMES.118.004829.
Correspondence
Michael C. Kurz, MD, MS, Department of Emergency Medicine, University
of Alabama School of Medicine, 619 19th ST S, OHB 251, Birmingham, AL
35249–7013. Email mckurz@uabmc.edu
Circ Cardiovasc Qual Outcomes. 2018;11:e004829. DOI: 10.1161/CIRCOUTCOMES.118.004829
Affiliations
Division of Cardiology, UT Southwestern Medical Center, Dallas, TX (R.K.). Clini-
cal Trial Center, Department of Biostatistics (A.H., B.L.), Department of Medi-
cine (G.N., P.K.), University of Washington, Seattle. Department of Medicine,
University of Toronto, Ontario, Canada (D.S., A.B.). Department of Emergency
Medicine, University of Ottawa, Ontario, Canada (M.A.). Department of Emer-
gency Medicine, Oregon Health & Science University, Portland (C.D.N.). De-
partment of Emergency Medicine, Kaiser Permanente Northwest, Portland, OR
(R.R.). Department of Emergency Medicine, University of California San Diego,
CA (G.M.V.). Department of Emergency Medicine, University of Pittsburgh, PA
(K.N.S.). National Heart, Lung and Blood Institute, National Institutes of Health,
Bethesda, MA (G.S.). Departments of Emergency Medicine and Internal Medi-
cine, UT Southwestern Medical Center, Dallas, TX (A.H.I.). Department of Emer-
gency Medicine, University of Texas Health Sciences Center at Houston (H.W.).
Mid America Heart Institute, Kansas City and the University of Missouri-Kansas
City, MO (P.S.C.). Department of Emergency Medicine, University of Alabama
School of Medicine, Birmingham (M.C.K.).
Sources of Funding
The Resuscitation Outcomes Consortium is supported by a series of coopera-
tive agreements to 9 regional clinical centers and 1 Data Coordinating Cen-
ter (5U01 HL077863—University of Washington Data Coordinating Center,
HL077866—Medical College of Wisconsin, HL077867—University of Wash-
ington, HL077871—University of Pittsburgh, HL077872—St. Michael’s Hospi-
tal, HL077873—Oregon Health and Science University, HL077881—University
of Alabama at Birmingham, HL077885—Ottawa Hospital Research Institute,
HL077887—University of Texas SW Medical Ctr/Dallas, HL077908—University
of California San Diego) from the National Heart, Lung and Blood Institute in
partnership with the US Army Medical Research & Material Command, The
Canadian Institutes of Health Research (CIHR)—Institute of Circulatory and
Respiratory Health, Defence Research and Development Canada, the Heart,
Stroke Foundation of Canada and the American Heart Association. Dr Khera is
supported by the National Heart, Lung, and Blood Institute (5T32HL125247-02)
and the National Center for Advancing Translational Sciences (UL1TR001105)
of the National Institutes of Health. The content is solely the responsibility of
the authors and does not necessarily represent the official views of the National
Heart, Lung and Blood Institute or the National Institutes of Health.
Disclosures
None.
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