Randomized Clinical Trial of Prehospital Induction of Mild Hypothermia
in Out-of-Hospital Cardiac Arrest
Patients Using a Rapid Infusion of 4oC
Normal Saline
Francis Kim MD, Graham Nichol MD MPH, Charles Maynard PhD,
Al Hallstrom PhD, Peter Kudenchuk MD, Thomas Rea MD,
Michael Copass MD, David Carlbom MD
Steven Deem MD, WT Longstreth Jr MD, Michele Olsufka RN,
Leonard Cobb MD
University of Washington
Seattle, WA
Background
• Hospital cooling (32-34oC) improves
neurologic outcome after out-of-hospital
ventricular fibrillation (VF)
• Pre-hospital cooling may result in better
outcomes compared to hospital alone
• Pre-hospital infusion of cold fluid to
reduce temperature
• Determine whether prehospital cooling
improves outcomes from cardiac arrest
with VF or non-VF
Trial Setting/Design
• Emergency medical services (EMS)
agencies in Seattle and surrounding
King County
• Individual subjects randomized to
– Intervention-Rapid infusion of 2 liters of
4oC NS after ROSC, sedation, skeletal
muscle relaxation
– Control-standard care
• Randomization stratified by
– Receipt of hospital cooling
– First recorded rhythm
Eligibility
Inclusion Criteria
Adults
Return of pulse
Tracheal intubation
Intravenous access
Unconscious
Esophageal temp probe
Exclusion Criteria
Traumatic cardiac arrest
Age < 18
Following commands
Temperature < 34ºC
Trial Flow
Field Cardiac Arrest
5696
Not Eligible (3319)
Eligible
2377
Not Enrolled (1013)
1364
Enrolled
N=776
Non-VF
N=583
VF
Intervention
292
Control
291
Intervention
396
Control
380
Outcomes: Survival at discharge/neurologic status
Baseline Characteristics
VF
Age
Men
Witnessed cardiac
arrest
CPR before EMS
arrival
Time from call to
randomization
Time from call to
first responder
arrival
Time from call to
sustained ROSC
NON-VF
Intervention
(n=292)
Control
(n=291)
Intervention
(n=396)
Control
(n=380)
62.1
(78%)
(78%)
(68%)
32.9
5.3
25
62.1
(75%)
(74%)
(64%)
32.5
5.2
24
68.3
(54%)
(53%)
(50%)
34.4
5.4
28
67.5
(54%)
(52%)
(53%)
35.2
5.2
27
Temperature Effects
VF
Temperature at
randomization
(95% CI) oC
Temperature at
hospital
arrival, oC
Difference in
temperature
between
randomization
and arrival
mean oC
Intervention
Control
36.1
36.0
(36.0-36.2)
(n=292)
(35.9-36.1)
(n=290)
35.0
35.9
(34.8-35.2)
(n= 260)
(35.8-36.0)
(n=212)
-1.2
-0.1
(-1.33- -1.07)
(n=260)
(-0.19- -0.02)
(n=212)
Non-VF
P value
0.16
<0.0001
<0.0001
Intervention
Control
36.0
35.9
(35.9-36.1)
(n=396)
(35.8-36.0)
(n=379)
34.8
35.7
(34.6-35.0)
(n=350)
(35.6-35.8)
(n=248)
-1.3
-0.1
(-1.4 - -1.2)
(n=350)
(-0.19 --0.01)
(n=248)
P value
0.09
<0.0001
<0.0001
Outcomes-Survival
VF
intervention n=292
control n=291
Non-VF
intervention n=396
control n=380
Outcomes-neurologic status at discharge
Secondary OutcomesDays to achieve awakening
VF
Non-VF
Safety- prehospital
Intervention
Re-arrest after
randomization
Control
176 (26%) 138 (21%)
P-value
0.008
Pressors after
randomization
62 (9%)
59 (9%)
0.82
Deaths in field
9 (1.3%)
11 (1.6%)
0.61
Time from first
dispatch to
hospital arrival
(min)
51+13
49+14
0.006
Safety- ED and hospital
Intervention
Control
P-value
88 (12.8%)
85 (12.7%)
0.95
374 (56%)
365 (56%)
0.93
119 (18%)
81 (12%)
0.009
151 (23%)
109 (17%)
0.011
pH
7.16+0.23
7.20+0.29
0.005
PaO2 (mmHg)
189+135
218+144
<0.0001
Pulmonary edema
on 1st chest x-ray
256 (41%)
184 (30%)
<0.0001
Pulmonary edema
on 2nd chest x-ray
133 (27%)
123 (26%)
0.95
Deaths in ED
Pressors in the
first 12 hours of
arrival
Diuretics in the
first 12 hours of
arrival
Diuretics in 12-48
hours of arrival
Summary of prehospital cooling
Conclusions
• Cold NS reduced core temperature by
hospital arrival
• Use of cold NS associated with increased
re-arrest during transport and increased
transient pulmonary edema
• Lack of benefit of prehospital cooling
consistent with previous smaller trials
• Prehospital cooling with cold NS did not
improve survival or neurologic outcomes in
patients with out-of-hospital VF or non-VF
Implications
• Prehospital cooling does not add benefit
to hospital-initiated cooling
• Cold fluid has associated risks
• Study findings do not support routine
initiation of hypothermia using cold fluid
in the prehospital setting
Acknowledgements
Paramedics in Seattle and King County
Hospitals: Harborview Medical Center, Swedish Medical Center, Virginia
Mason Hospital, UWMC, Northwest Hospital, Overlake Hospital, Valley Medical
Center, Auburn General Hospital, St. Francis Hospital, Stevens Hospital.
DSMB:
Chair: Kyra Becker, MD. Members: Margaret Neff,
MD, Tina Chang, MD, Karl B. Kern, MD, Nancy Temkin, PhD,
Ralph D’Agostino, PhD, Chief Earl Sodeman, Seattle Fire
Department, Thomas Hearne, Michele Plorde, King County
Public Health, Emergency Medical Services Division.
Study Nurses: Dianne K. Staloch, Karen Dong, Sue
Scruggs, Alana C. Clark, Jane Edelson, Debi Solberg, Sally
Ragsdale, Kathleen Fair, Barbara Ricker
Funding: NIH/NHLBI
F Kim and coauthors
Effect of Prehospital Induction of Mild
Hypothermia on Survival and
Neurological Status Among Adults With
Cardiac Arrest: A Randomized Clinical
Trial
Published online November 17, 2013
Available at
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