Delaying Defibrillation to Give Basic Cardiopulmonary Resuscitation to Patients With Out-of-Hospital Ventricular Fibrillation A Randomized Trial Context Defibrillation as soon as possible is standard treatment for patients with ven-
tricular fibrillation. A nonrandomized study indicates that after a few minutes of ven-
tricular fibrillation, delaying defibrillation to give cardiopulmonary resuscitation (CPR)first might improve the outcome. Objective To determine the effects of CPR before defibrillation on outcome in pa-
tients with ventricular fibrillation and with response times either up to or longer than
Design, Setting, and Patients Randomized trial of 200 patients with out-of-
hospital ventricular fibrillation in Oslo, Norway, between June 1998 and May 2001.
Patients received either standard care with immediate defibrillation (n=96) or CPR first
ARLY DEFIBRILLATION IS CRITICALfor survival from ventricular fi-
with 3 minutes of basic CPR by ambulance personnel prior to defibrillation (n=104). If initial defibrillation was unsuccessful, the standard group received 1 minute of CPR
before additional defibrillation attempts compared with 3 minutes in the CPR first group. Main Outcome Measure Primary end point was survival to hospital discharge. Sec- ondary end points were hospital admission with return of spontaneous circulation (ROSC),
1-year survival, and neurological outcome. A prespecified analysis examined sub-
(CPR) is performed.1,2 Another major fac-
groups with response times either up to or longer than 5 minutes. Results In the standard group, 14 (15%) of 96 patients survived to hospital dis-
charge vs 23 (22%) of 104 in the CPR first group (P=.17). There were no differences
in ROSC rates between the standard group (56% [58/104]) and the CPR first group
a defibrillator is available.1 It has been as-
(46% [44/96]; P=.16); or in 1-year survival (20% [21/104] and 15% [14/96], re-
spectively; P=.30). In subgroup analysis for patients with ambulance response times
of either up to 5 minutes or shorter, there were no differences in any outcome vari-
of the heart and brain cells,3 but is in-
ables between the CPR first group (n=40) and the standard group (n=41). For pa-
sufficient to improve the state of the tis-
tients with response intervals of longer than 5 minutes, more patients achieved ROSC
in the CPR first group (58% [37/64]) compared with the standard group (38% [21/
55]; odds ratio [OR], 2.22; 95% confidence interval [CI], 1.06-4.63; P=.04); survivalto hospital discharge (22% [14/64] vs 4% [2/55]; OR, 7.42; 95% CI, 1.61-34.3; P=.006);
and 1-year survival (20% [13/64] vs 4% [2/55]; OR, 6.76; 95% CI, 1.42-31.4; P=.01).
Thirty-three (89%) of 37 patients who survived to hospital discharge had no or minor
reductions in neurological status with no difference between the groups.
energy phosphates,3 severe acidosis,4 and
Conclusions Compared with standard care for ventricular fibrillation, CPR first prior
a ventricular fibrillation frequency spec-
to defibrillation offered no advantage in improving outcomes for this entire study popu-
trum indicating a low chance of defibril-
lation or for patients with ambulance response times shorter than 5 minutes. How-
ever, the patients with ventricular fibrillation and ambulance response intervals longer
than 5 minutes had better outcomes with CPR first before defibrillation was at-
tempted. These results require confirmation in additional randomized trials. Author Affiliations are listed at the end of this
PhD, Institute for Experimental Medical Research, Ul-
leval University Hospital, N-0407 Oslo, Norway (e-mail:
For editorial comment see p 1434. Corresponding Author and Reprints: Lars Wik, MD, 2003 American Medical Association. All rights reserved.
(Reprinted) JAMA, March 19, 2003—Vol 289, No. 11 1389
not given before the first defibrillation
ences in survival were detected (PϽ.05),
were also included in the monitoring.
minutes prior to the first defibrillation
after, it was given for 3 minutes both for
ventricular fibrillation/ventricular tachy-
refractory ventricular fibrillation or re-
were identical on all units including the
ing to the guidelines of the European Re-
pressions and ventilation) prior to a de-
sent for inclusion in the study was waived
Utstein style.11 Out-of-hospital data were
Utstein data collection sheets. These data
men and 16% were older than 65 years.
culated from time of dispatch of the first
trolled trial involving patients older than
18 years with ventricular fibrillation or
ately. If unsuccessful, defibrillation was
witnessed the cardiac arrest. On-site ran-
domization after defibrillator electrocar-
diogram verification of ventricular fibril-
lance personnel to log the time of arrival
tal personnel were blinded, including the
physician not involved in the care of any
arrival at the patient’s location until direct
patients or in data collection. This phy-
sealed randomization list after 6, 18, and
synchronized with the other time points. 1390 JAMA, March 19, 2003—Vol 289, No. 11 (Reprinted) 2003 American Medical Association. All rights reserved. Figure 1. Flow Diagram of CPR First and
Inc) provided a power of 80 for ␣ of .05
1357 Patients Found Lifeless and Assessed for Eligibility
test. We calculated the odds ratios (ORs)
SPSS statistical software. PϽ.05 was
groups, a logistic regression analysis was
discharged alive was regressed on the in-
(Version 11.0, SPSS Inc, Chicago, Ill).
CPR indicates cardiopulmonary resuscitation. Aster-isk indicates emergency medical service personnel failed
to enroll patients even though they met study crite-
ria; the randomization envelope was missing for 2patients.
bystander, location of cardiac arrest, and
interval was also included. This term rep-
shown in TABLE 1. There were no sig-
spect to probability of survival to hospital
discharge as a function of response time,
sponse times, location of the cardiac ar-
and it may specifically be used to test the
tients in the standard treatment group.
pulseless electrical activity. Of 260 car-
ization envelope was missing in 2 cases.
96]; P = .17); ROSC rates (56% [58/
104] vs 46% [44/96]; P=.16); or 1-year
96]; P = .30) (TABLE 2). Of 37 patients
met study criteria (FIGURE 1). 2003 American Medical Association. All rights reserved.
(Reprinted) JAMA, March 19, 2003—Vol 289, No. 11 1391
had been in the interval of Յ5 minutes).
tients in the CPR first group than in the
[37/64] vs 38% [21/55]; P = .04); sur-
(TABLE 3). As of May 2002, 29 pa-
64] vs 4% [2/55]; P = .006); and 1-year
tients were still alive and 27 patients or
In logistic regression analysis, both for-
Table 1. Baseline Characteristics of Patients
with the predictor variables of age (OR,0.97; 95% CI, 0.94-0.99), CPR per-
CPR First Standard P Characteristic
present (OR, 1.41; 95% CI, 1.03-1.94).
significant (P = .03). The term group is
results. FIGURE 2 shows the estimated
charge plotted against response time.
Abbreviations: CI, confidence interval; CPR, cardiopulmonary resuscitation; ROSC, restoration of spontaneous circu-
shapes of the curves are significantly dif-
ferent. The estimated survival with CPRfirst vs standard therapy is a functionof the response time interval formula
Table 2. Rates of Discharge From Hospital, ROSC, and 1-Year Survival* CPR First Standard P OR (95% CI)† Value‡
In this study, there were no overall dif-
prior to defibrillation. However, for pa-
Abbreviations: CI, confidence interval; CPR, cardiopulmonary resuscitation; OR, odds ratio; ROSC, return of sponta-
*Patients received ventricular fibrillation posthospitalization and 3 minutes of CPR before defibrillation vs standard treat-
†ORs and 95% CIs were calculated by logistic regression.
pital discharge and 1-year survival rates
‡Calculated from the Fisher exact test. 1392 JAMA, March 19, 2003—Vol 289, No. 11 (Reprinted) 2003 American Medical Association. All rights reserved. Table 3. Overall Performance Categories and Cerebral Performance Categories of Patients at Hospital Discharge and at 1-Year Survival No. Received Treatment, No. Received Treatment, No. Received Treatment, All Patients CPR First Standard CPR First Standard CPR First Standard Discharge Discharge Discharge Year* Discharge Discharge Discharge
Abbreviation: CPR, cardiopulmonary resuscitation. *There are no differences between the groups when comparing patients surviving (overall performance category and cerebral performance category 1 through 4) to either hospital
discharge or 1 year after cardiac arrest. In both the CPR first and the standard treatment group, 1 patient with response time of 5 minutes or less failed to answer the question-naire. The other patients with unknown scores lived longer than 1 year, but died before the questionnaire was sent out in May 2002.
of defibrillation first was questioned as
Figure 2. Estimated Probability of Survival
tricular fibrillation demonstrate that CPR
rate.7,17,18 In dogs with 7.5 minutes of ini-
response times of 4 minutes or longer.
tially untreated ventricular fibrillation,
the defibrillation success was higher af-
brillation.7 The same laboratory later re-
fibrillation than CPR first in swine with
Average fraction of surviving patients for each 2-minute
5 minutes of initially untreated ventricu-
interval. Lines indicate logistic regression models withtime as independent variable fitted separately for each
lar fibrillation.19 In a study of dogs, im-
these rates along with the fact that car-
episodes of fibrillation if it was limited
we did not find a higher survival rate with
patients below which defibrillation first
search15) is unlikely to specifically affect
this could be due to a type II error, and
average cut-off time for CPR first vs de-
2003 American Medical Association. All rights reserved.
(Reprinted) JAMA, March 19, 2003—Vol 289, No. 11 1393
fibrillation first is therefore not pres-
tients with ventricular fibrillation, with
vorably with previous research.8,26 In the
outcome (PϽ.11) in the group who re-
(Figure 2), but the fall-off rate with time
studies have indicated that the effects of
guidelines for reporting results after car-
this study, the findings are based on non-
on the quality.25 In a study from Oslo,13
pital discharge, and the accuracy of this
quire confimation in future clinical trials.
of life later after discharge has been chal-
a CPC score of 1 at hospital discharge had
factor for survival.1,23,24 In those stud-
a sensitivity of 78% and a specificity of
ies, defibrillation was attempted as soon
43% for predicting that quality of life at
a later date was the same as or better than
evaluated. Also, the response time in the
ration of the cardiac arrest and the qual-
defibrillation was an important factor for
ity of CPR performed by a bystander.
survival, but the analysis indicates that
physicians appear to be inaccurate judges
performed defibrillation prior to CPR.
of patient function.27 In the present study,
The delay before defibrillation is still im-
we are reporting 1-year follow-up and the
basis of the scores is the patient or rela-
fibrillation is better with response times
tive’s own evaluation of function, mood,
of 3 minutes than of 7 or 10 minutes.
prior to cardiac arrest. In May 2002 when
the follow-up questionnaire was sent out,
judged from spectral analysis of the elec-
trocardiogram appears to deteriorate rap-
seven patients or their relatives answered
troshock of prolonged ventricular fibril-
ventricular fibrillation to a more resus-
citation-refractory rhythm, such as asys-
tion6 seems related to the relatively high
1394 JAMA, March 19, 2003—Vol 289, No. 11 (Reprinted) 2003 American Medical Association. All rights reserved.
termine the optimal duration of CPR first
tion of current resuscitation guidelines,
in patients with ventricular fibrillation. Author Affiliations: Norwegian Competence Center
and our data, signal the need for reevalu-
for Emergency Medicine, Institute for Experimental
Medical Research (Dr Wik), Division of Surgery (DrsT. Steen and P. A. Steen, and Messrs Hansen and
Fylling), Ulleval University Hospital, Oslo, Norway; Nor-
wegian Defense Research Establishment Division ofProtection and Material, Kjeller, Norway (Dr Vaa-
treatment of ventricular fibrillation. An
genes); and Department of Technology and Natural
While defibrillation is the essential in-
Science, Stavanger University College, Stavanger, Nor-way (Dr Auestad).
tervention in ventricular fibrillation, de-
Author Contributions: Study concept and design: Wik, Acquisition of data: Wik, T. Steen, Vaagenes. Analysis and interpretation of data: Wik, Vaagenes,
Drafting of the manuscript: Wik, Hansen, Fylling,Auestad. Critical revision of the manuscript for important in-
yond the factors of the local ischemia. tellectual content: Wik, T. Steen, Vaagenes, Auestad,
shock for ventricular fibrillation is not
P. A. Steen. Statistical expertise: Wik, Vaagenes, Auestad, P. A.
sidered useful to apply CPR to “coarsen
Obtained funding: Wik, P. A. Steen. Administrative, technical, or material support: Wik,
ventricular fibrillation.” However, that
been several minutes’ delay before defi-
Study supervision: Vaagenes, P. A. Steen. Funding/Support: This study was supported by grants
brillation as soon as possible for all pa-
from the Norwegian Air Ambulance and Laerdal Foun-
tients with ventricular fibrillation.30,31
with out-of-hospital ventricular fibrilla-
tion. Further trials are needed to evalu-
Acknowledgment: We thank the paramedics, Mona Monsen, and the physicians of Oslo EMS for their work
ate this resuscitation strategy and to de-
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Nicholas Sitar Nick Sitar received his undergraduate degree in Geological Engineering from the University of Windsor in Windsor, Ontario in 1973, and his Ph.D. in Geotechnical Engineering from Stanford University in 1979. After receiving his Ph.D., he spent two years teaching in the Geological Engineering Program at the University of British Columbia in Vancouver, B.C. He joined the
September MIMS Monthly Medicine Update NEW PRODUCTS Priligy (dapoxetine hydrochloride) Zaltrap (aflibercept (rch)) is a Erivedge (vismodegib) is a low severe chronic neutropenia (SCN); and in endothelial growth factor (VEGF) receptor (1 and 2) extracellular domains fused to HIV therapy. Zarzio is contraindicated in ejaculatory latency time (IELT) of less than patients with kn