Francis Kim MD, Graham Nichol MD MPH, Charles Maynard PhD, Al Hallstrom PhD, Peter Kudenchuk MD, Thomas Rea MD,
Michael Copass MD, David Carlbom MDSteven Deem MD, WT Longstreth Jr MD, Michele Olsufka RN,
Leonard Cobb MD
University of WashingtonSeattle, WA
Randomized Clinical Trial of Pre-hospital Induction of Mild Hypothermia
in Out-of-Hospital Cardiac Arrest Patients Using a Rapid Infusion of 4oC
Normal Saline
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 AdultsReturn of pulseTracheal intubationIntravenous accessUnconsciousEsophageal temp probe
Exclusion CriteriaTraumatic cardiac arrestAge < 18Following commandsTemperature < 34ºC
Trial FlowField Cardiac Arrest
1364
N=583VF
Intervention292
Control291
5696
Eligible
Enrolled
2377
N=776Non-VF
Intervention396
Control380
Not Eligible (3319)
Not Enrolled (1013)
Outcomes: Survival at discharge/neurologic status
VF NON-VFIntervention
(n=292)Control(n=291)
Intervention(n=396)
Control(n=380)
Age 62.1 62.1 68.3 67.5Men (78%) (75%) (54%) (54%)
Witnessed cardiac arrest (78%) (74%) (53%) (52%)
CPR before EMS arrival (68%) (64%) (50%) (53%)
Time from call to randomization 32.9 32.5 34.4 35.2
Time from call to first responder
arrival5.3 5.2 5.4 5.2
Time from call to sustained ROSC 25 24 28 27
Baseline Characteristics
Temperature Effects
VF Non-VF
Intervention Control P value Intervention Control P value
Temperature at randomization
(95% CI) oC
36.1 (36.0-36.2)
(n=292)
36.0(35.9-36.1)
(n=290)0.16
36.0 (35.9-36.1)
(n=396)
35.9 (35.8-36.0)
(n=379)0.09
Temperature at hospital
arrival, oC
35.0(34.8-35.2)(n= 260)
35.9 (35.8-36.0)
(n=212)<0.0001
34.8 (34.6-35.0)
(n=350)
35.7 (35.6-35.8)
(n=248)<0.0001
Difference in temperature
between randomization
and arrival mean oC
-1.2 (-1.33- -1.07)
(n=260)
-0.1 (-0.19- -0.02)
(n=212)<0.0001
-1.3 (-1.4 - -1.2)
(n=350)
-0.1 (-0.19 --0.01)
(n=248)<0.0001
Outcomes-Survival
VF intervention n=292control n=291
Non-VF intervention n=396
control n=380
Outcomes-neurologic status at discharge
Secondary Outcomes- Days to achieve awakening
VF
Intervention Control P-value
Re-arrest after randomization 176 (26%) 138 (21%) 0.008
Pressors after randomization 62 (9%) 59 (9%) 0.82
Deaths in field 9 (1.3%) 11 (1.6%) 0.61Time from first
dispatch to hospital arrival
(min)
51+13 49+14 0.006
Safety- prehospital
Intervention Control P-value
Deaths in ED 88 (12.8%) 85 (12.7%) 0.95Pressors in the first 12 hours of
arrival374 (56%) 365 (56%) 0.93
Diuretics in the first 12 hours of
arrival119 (18%) 81 (12%) 0.009
Diuretics in 12-48 hours of arrival 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 edemaon 2nd chest x-ray 133 (27%) 123 (26%) 0.95
Safety- ED and hospital
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 trial
• Prehospital cooling with cold NS did not improve survival or neurologic outcomes in patients with out-of-hospital VF or non-VF
Implications
• Cold fluid has associated risks• Study findings do not support routine
initiation of hypothermia using cold fluid in the prehospital setting
Paramedics in Seattle and King CountyHospitals: 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
Acknowledgements
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 www.jama.com and also at mobile.jamanetwork.com
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