Delaying Defibrillation to Give Basic Cardiopulmonary Resuscitation to Patients with Out-Of-Hospital Ventricular Fibrillation a Randomized Trial

ORIGINAL CONTRIBUTION

Delaying Defibrillation to Give Basic Cardiopulmonary Resuscitation to Patients With Out-of-Hospital Ventricular Fibrillation A Randomized Trial

Lars Wik, MD, PhD Context Defibrillation as soon as possible is standard treatment for patients with ven- Trond Boye Hansen tricular fibrillation. A nonrandomized study indicates that after a few minutes of ven- Frode Fylling tricular fibrillation, delaying defibrillation to give cardiopulmonary resuscitation (CPR) first might improve the outcome. Thorbjørn Steen, MD Objective To determine the effects of CPR before defibrillation on outcome in pa- Per Vaagenes, MD, PhD tients with ventricular fibrillation and with response times either up to or longer than Bjørn H. Auestad, PhD 5 minutes. Design, Setting, and Patients Randomized trial of 200 patients with out-of- Petter Andreas Steen, MD, PhD hospital ventricular fibrillation in Oslo, Norway, between June 1998 and May 2001. ARLY DEFIBRILLATION IS CRITICAL Patients received either standard care with immediate defibrillation (n=96) or CPR first for 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 brillation. The survival rate de- before additional defibrillation attempts compared with 3 minutes in the CPR first group. creases by 3% to 4% or 6% to 10%E per minute depending on whether Main Outcome Measure Primary end point was survival to hospital discharge. Sec- ondary end points were hospital admission with return of spontaneous circulation (ROSC), basic cardiopulmonary resuscitation 1,2 1-year survival, and neurological outcome. A prespecified analysis examined sub- (CPR) is performed. Another major fac- groups with response times either up to or longer than 5 minutes. tor known to influence survival in patients with ventricular fibrillation is Results In the standard group, 14 (15%) of 96 patients survived to hospital discharge vs 23 (22%) of 104 in the CPR first group (P=.17). There were no differences whether CPR is performed prior to when in ROSC rates between the standard group (56% [58/104]) and the CPR first group 1 a defibrillator is available. It has been as- (46% [44/96]; P=.16); or in 1-year survival (20% [21/104] and 15% [14/96], re- sumed that the blood flow generated by spectively; P=.30). In subgroup analysis for patients with ambulance response times CPR decreases the rate of deterioration of either up to 5 minutes or shorter, there were no differences in any outcome vari- of the heart and brain cells,3 butisin- 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 sues. If tissue perfusion could be im- in the CPR first group (58% [37/64]) compared with the standard group (38% [21/ proved, withholding defibrillation for a 55]; odds ratio [OR], 2.22; 95% confidence interval [CI], 1.06-4.63; P=.04); survival to hospital discharge (22% [14/64] vs 4% [2/55]; OR, 7.42; 95% CI, 1.61-34.3; P=.006); short period while administering CPR and 1-year survival (20% [13/64] vs 4% [2/55]; OR, 6.76; 95% CI, 1.42-31.4; P=.01). might improve the results for patients Thirty-three (89%) of 37 patients who survived to hospital discharge had no or minor with depleted myocardial levels of high- 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 defibrillation or for patients with ambulance response times shorter than 5 minutes. How- lation success.5,6 ever, the patients with ventricular fibrillation and ambulance response intervals longer In an experimental study, defibrilla- than 5 minutes had better outcomes with CPR first before defibrillation was at- tion was more successful following ba- tempted. These results require confirmation in additional randomized trials. sic CPR and high-dose epinephrine than JAMA. 2003;289:1389-1395 www.jama.com immediate defibrillation in dogs with

Author Affiliations are listed at the end of this PhD, Institute for Experimental Medical Research, Ul- For editorial comment see p 1434. article. leval University Hospital, N-0407 Oslo, Norway (e-mail: Corresponding Author and Reprints: Lars Wik, MD, [email protected]).

7.5 minutes of untreated ventricular fi- 30 months, and performed interim analy- not given before the first defibrillation brillation.7 In a nonrandomized hu- ses of outcome. If significant differ- attempt in either group due to the time man study, Cobb et al8 reported that 90 ences in survival were detected (PϽ.05), required before an intravenous line with seconds of CPR by ambulance person- the study would have been stopped. Sub- a continuous drip of 500 mL of Ringer nel before defibrillation improved sur- groups of patients with response times acetate could be established. vival to hospital discharge compared either up to or longer than 5 minutes The CPR first group was treated iden- with a historic control group. We there- were also included in the monitoring. tically except that CPR was given for 3 fore designed this clinical trial to de- minutes prior to the first defibrillation termine whether CPR prior to defibril- Treatment Protocol attempt, and if CPR was needed there- lation (CPR first) would improve The patients were attended by either 1 after, it was given for 3 minutes both for outcomes in patients with out-of- ambulance with an anesthesiologist and ventricular fibrillation/ventricular tachy- hospital ventricular fibrillation. 2 paramedics, or 2 ambulances with 2 cardia and nonventricular fibrillation/ ambulance personnel each and a mini- ventricular tachycardia. Countershock METHODS mum of 1 paramedic per ambulance. refractory ventricular fibrillation or re- Study Design The equipment, drugs, and procedures current ventricular fibrillation was The Regional Committee for Medical Re- were identical on all units including the treated according to the 1998 Euro- search Ethics, which is an independent physician-staffed unit. Advanced car- pean Resuscitation Council guide- but nationally coordinated committee of diac life support was provided accord- lines.10 A standard 100-mg dose of lido- members who are appointed by the Min- ing to the guidelines of the European Re- caine was given intravenously only after ister of Education, Research, and Church suscitation Council10 except for the 9 defibrillation attempts. Other antiar- Affairs based on recommendations from duration of CPR (defined as chest com- rhythmics, such as amiodarone, were the Research Council of Norway, ap- pressions and ventilation) prior to a de- not given. proved the study protocol. Informed con- fibrillation attempt, which was the in- sent for inclusion in the study was waived tervention studied. When the ambulance Data Collection as decided by this committee in accor- arrived, a monophasic automated defi- Data were collected according to the dance with paragraph 26 in the Hel- brillator (LIFEPAK 12, Medtronic Utstein style.11 Out-of-hospital data were sinki Declaration,9 but was required for Physio-Control, Redmond, Wash) was based on the digital dispatcher data- including 1-year follow-up data. immediately applied to the patient by 1 base, the ambulance records, and the The study was conducted in the Oslo EMS staff member and all patients with Utstein data collection sheets. These data emergency medical service (EMS) sys- ventricular fibrillation/pulseless ven- included the therapy administered, tem, which covers a land area of 427 km2 tricular tachycardia were included. The whether the cardiac arrest was wit- and a population of approximately other rescuer intubated the patient as nessed, application of bystander- 500000. Of this population, 48% were soon as possible without disturbing the initiated CPR, location of the cardiac men and 16% were older than 65 years. electrocardiographic analysis. arrest, and response-time intervals cal- The study was a randomized, con- In the standard group, a defibrillat- culated from time of dispatch of the first trolled trial involving patients older than ing shock of 200 J was given immedi- ambulance to arrival of the first ambu- 18 years with ventricular fibrillation or ately. If unsuccessful, defibrillation was lance as registered on-line by a central pulseless ventricular tachycardia in repeated once with 200 J, and if nec- computer system in the dispatch cen- whom the ambulance personnel had not essary once more with 360 J. If return ter. A computer board and screen in the witnessed the cardiac arrest. On-site ran- of spontaneous circulation (ROSC) was ambulance were connected to this cen- domization after defibrillator electrocar- not achieved, 1 minute of CPR was tral computer, and enabled the ambu- diogram verification of ventricular fibril- given for ventricular fibrillation/ lance personnel to log the time of arrival lation/ventricular tachycardia was ventricular tachycardia or 3 minutes for directly on this computer, which was the performed by opening a sealed study en- nonventricular fibrillation/ventricular same one that dispatched the ambu- velope that contained the treatment as- tachycardia before a new rhythm analy- lance, thus avoiding a time synchroni- signment. The ambulance personnel sis and the shock and CPR sequence zation problem. The time of patient col- could not be blinded thereafter. Hospi- was repeated as indicated with all lapse was estimated by the ambulance tal personnel were blinded, including the shocks at 360 J. All patients were ven- personnel based on the information they physicians responsible for assessing the tilated with 100% oxygen and given 1 received from bystanders, and manu- neurological outcome at hospital dis- mg of epinephrine intravenously ev- ally synchronized with the time on the charge. The study was monitored by a ery 3 minutes until ROSC or termina- computer screen. Time intervals from physician not involved in the care of any tion of the resuscitation attempt. Epi- arrival at the patient’s location until direct patients or in data collection. This phy- nephrine should be administered in the current shock and ROSC were taken from sician received all case records and the beginning of a chest compression- the defibrillator and did not need to be sealed randomization list after 6, 18, and ventilation interval, and was therefore synchronized with the other time points.

Survival and neurological status at A power analysis using Sigmastat sta- Figure 1. Flow Diagram of CPR First and hospital discharge were obtained from tistical software (Version 2.03, SPSS Standard Care the hospital record. Neurological sta- Inc) provided a power of 80 for ␣ of .05 tus was assessed according to the with 250 patients in each group for an 1357 Patients Found Lifeless and Assessed for Eligibility Glasgow-Pittsburgh outcomes, which increased survival from 15% for the 1157 Excluded consist of the cerebral performance cat- standard group to 25% for the CPR first 545 Did Not Meet egory (CPC) and the overall perfor- group. The survival of ventricular fi- Inclusion Criteria mance category (OPC) with CPC/OPC brillation patients has been 16% to 18% 576 CPR Not of 1 indicating a good cerebral/good in previous studies of standard ad- Started 36 Not Included overall performance; CPC/OPC of 2, vanced cardiac life support in this EMS by Mistake∗ moderate cerebral/moderate overall dis- system.13,14 ability; CPC/OPC of 3, severe cerebral/ Categorical data were analyzed by the 200 Randomized severe overall disability; CPC/OPC of 4, ␹2 (alternatively the Fisher-Irwin) test and coma/vegetative state; and CPC/OPC of numerical data by the Mann-Whitney U 104 Assigned to Receive 96 Assigned to Receive 5, brain death/death.12 One-year fol- test. We calculated the odds ratios (ORs) CPR First Standard Treatment low-up data were collected from a ques- and 95% confidence intervals (CIs) using 104 Included in Primary 96 Included in Primary tionnaire (available from the authors on SPSS statistical software. PϽ.05 was Analysis Analysis request) sent to patients or their rela- considered significant. 104 Included in Subgroup 96 Included in Subgroup tives during May 2002. To assess differences between the Analysis Analysis All data were stored in a database standard treatment and the CPR first 40 Response Time 41 Response Time ≤5 min ≤5 min (FileMaker Pro, Version 4.1, File- groups, a logistic regression analysis was 64 Response Time 55 Response Time Maker Inc, Santa Clara, Calif) and ana- performed. The dependent variable of >5 min >5 min lyzed using an SPSS statistical package discharged alive was regressed on the in- CPR indicates cardiopulmonary resuscitation. Aster- (Version 11.0, SPSS Inc, Chicago, Ill). dependent variables of group, age, sex, isk indicates emergency medical service personnel failed whether cardiac arrest was witnessed, to enroll patients even though they met study crite- Outcomes whether CPR was performed by a ria; the randomization envelope was missing for 2 patients. The primary outcome was survival to bystander, location of cardiac arrest, and hospital discharge. Secondary out- response time interval. The interaction comes were ROSC and survival to hos- term between group and response time The baseline characteristics of the pital, overall status scored as OPC and interval was also included. This term rep- 200 patients included in the study are neurological status scored as CPC at resents differences between the stan- shown in TABLE 1. There were no sig- discharge, and 1-year survival with neu- dard and the CPR first groups, with re- nificant differences between the study rological status. spect to probability of survival to hospital groups in terms of age, sex, EMS re- discharge as a function of response time, sponse times, location of the cardiac ar- Statistical Analysis and it may specifically be used to test the rest, proportion of cardiac arrests that Prior to analyzing the outcomes, we hypothesis generated by Cobb et al8 that were witnessed, or times CPR was per- postulated that any resultant survival a CPR first strategy only benefits pa- formed by a bystander. The physician- benefit would be most evident in cases tients with longer response times. manned ambulance was dispatched to with longer response intervals based on 25 (24%) of 104 patients in the CPR the report by Cobb et al,8 which was RESULTS first group and to 22 (23%) of 96 pa- published while our study was still on- Study Population tients in the standard treatment group. going. We decided prior to data analy- Between June 1998 and May 2001, 1357 There was no difference in the use of sis to analyze subgroups with re- patients were found lifeless and ad- epinephrine or lidocaine in the 2 sponse times either up to or longer than vanced CPR was started on 781 pa- groups. 5 minutes.13,14 Cobb et al8 used a re- tients; 466 had asystole and 55 had sponse interval of 4 minutes. These re- pulseless electrical activity. Of 260 car- Outcome sponse times are longer than those used diac arrests with ventricular fibrilla- There was no difference between the in Seattle,8 and we expected that we tion as the first documented rhythm, 24 CPR first group and the standard group would have too few patients in a group were witnessed by EMS personnel and in the survival rate to hospital dis- with response intervals shorter than 4 were therefore excluded. The random- charge (22% [23/104] vs 15% [14/ minutes. This decision was made by the ization envelope was missing in 2 cases. 96]; P=.17); ROSC rates (56% [58/ 2 main authors (L.W. and P.A.S.) alone Thirty-four patients were not included 104] vs 46% [44/96]; P=.16); or 1-year and communicated to the other au- in the study because EMS personnel survival (20% [21/104] vs 15% [14/ thors, but not to any other personnel failed to enroll them even though they 96]; P=.30) (TABLE 2). Of 37 patients involved in the study. met study criteria (FIGURE 1). discharged alive, 33 (89%) were re-

©2003 American Medical Association. All rights reserved. (Reprinted) JAMA, March 19, 2003—Vol 289, No. 11 1391 CPR PRIOR TO DEFIBRILLATION ported to have made a good neurolo- low-up survey. Two patients did not re- For the 119 patients with response gical recovery at hospital discharge spond (1 patient in each group; both times longer than 5 minutes, more pa- (CPC/OPC of 1 or 2) with no differ- had been in the interval of Յ5 minutes). tients in the CPR first group than in the ence between the groups at discharge For the 81 patients with ambulance standard group achieved ROSC (58% or when evaluated by the patient or a response times of 5 minutes or less, [37/64] vs 38% [21/55]; P=.04); sur- relative 1 year after cardiac arrest there were no differences in ROSC, survival to hospital discharge (22% [14/ (TABLE 3). As of May 2002, 29 pa- vival to hospital discharge, 1-year 64] vs 4% [2/55]; P=.006); and 1-year tients were still alive and 27 patients or survival, or neurological outcome of survival (20% [13/64] vs 4% [2/55]; their relatives responded to the fol- survivors (Table 2 and Table 3). P=.01) (Table 2). In logistic regression analysis, both for- ward and backward stepwise variable se- Table 1. Baseline Characteristics of Patients lection procedures resulted in a model No. (%) with the predictor variables of age (OR, 0.97; 95% CI, 0.94-0.99), CPR per- CPR First Standard P Characteristic (n = 104) (n = 96) Value formed by a bystander (OR, 3.75; 95% Age, median (range), y 71 (18-88) 70 (18-96) .57 CI, 1.49-9.42), response time (OR, 0.68; Men 88 (85) 85 (89) .42 95% CI, 0.52-0.90), and the interaction Cardiac arrest observed by others 95 (91) 90 (94) .52 term between group and response time Bystander performed CPR 64 (62) 54 (56) .41 present (OR, 1.41; 95% CI, 1.03-1.94). Location of cardiac arrest Specifically, the interaction term is Home 51 (49) 42 (44) significant (P=.03). The term group is Public place 36 (35) 42 (44) .39 also included since it is involved in a Other 17 (16) 12 (12) significant interaction. Leaving it out Time, mean (95% CI), min Collapse to ambulance arrival 12.0 (10.7-13.4) 11.7 (10.7-12.7) .76 implies only minor differences in the Arrival to first defibrillation attempt 3.8 (3.4-4.2) 1.9 (1.6-2.2) Ͻ.01 results. FIGURE 2 shows the estimated First defibrillation attempt to ROSC 12.9 (9.2-16.5) 14.4 (11.5-17.3) .22 probability of survival to hospital dis- Collapse to ROSC 26.9 (23.4-30.4) 26.7 (23.6-29.8) .74 charge plotted against response time. Dose of epinephrine, mean (95% CI), mg 5.3 (4.3-6.4) 5.0 (4.2-5.9) .74 The significant interactions between Lidocaine given intravenously 22 (21) 21 (22) Ͼ.99 group and response time means that the Abbreviations: CI, confidence interval; CPR, cardiopulmonary resuscitation; ROSC, restoration of spontaneous circu- shapes of the curves are significantly dif- lation. ferent. The estimated survival with CPR first vs standard therapy is a function * of the response time interval formula Table 2. Rates of Discharge From Hospital, ROSC, and 1-Year Survival ϫ No. (%) (−1.305+0.346 Time), indicating a higher chance of survival with CPR first CPR First Standard P for response time intervals longer than Group (n = 104) (n = 96) OR (95% CI)† Value‡ Total 4 minutes. Discharged from hospital 23 (22) 14 (15) 1.66 (0.80-3.46) .20 The calculated OR for survival with ROSC 58 (56) 44 (46) 1.49 (0.85-2.60) .20 CPR before defibrillation increased from 1-Year survival 21 (20) 14 (15) 1.48 (0.71-3.11) .35 0.4 (95% CI, 0.08-1.80) for a less than 1-minute response interval to 3 (95% Յ5 min CI, 1.06-8.79) for a 7-minute interval, (n = 64) (n = 55) and 6.1 (95% CI, 1.34-27.80) for a Discharged from hospital 9 (23) 12 (29) 0.70 (0.26-1.91) .61 9-minute interval. ROSC 21 (52) 23 (56) 0.87 (0.36-2.08) .82 1-Year survival 8 (20) 12 (29) 0.60 (0.22-1.69) .44 COMMENT Ͼ 5 min In this study, there were no overall dif- (n = 40) (n = 41) ferences in survival for patients with Discharged from hospital 14 (22) 2 (4) 7.42 (1.61-34.3) .006 out-of-hospital ventricular fibrillation ROSC 37 (58) 21 (38) 2.22 (1.06-4.63) .04 who received standard care vs CPR first 1-Year survival 13 (20) 2 (4) 6.76 (1.42-31.4) .01 prior to defibrillation. However, for pa- Abbreviations: CI, confidence interval; CPR, cardiopulmonary resuscitation; OR, odds ratio; ROSC, return of spontaneous circulation. tients with longer ambulance re- *Patients received ventricular fibrillation posthospitalization and 3 minutes of CPR before defibrillation vs standard treat- Ͼ ment with immediate defibrillation. sponse times ( 5 minutes), the hos- †ORs and 95% CIs were calculated by logistic regression. pital discharge and 1-year survival rates ‡Calculated from the Fisher exact test. were higher for patients who had re-

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 Յ5 min Ͼ5 min

CPR First Standard CPR First Standard CPR First Standard (n = 104) (n = 96) (n = 40) (n = 41) (n = 64) (n = 55)

At 1 At 1 At 1 At 1 At 1 At 1 Outcome Discharge Year Discharge Year Discharge Year* Discharge Year Discharge Year Discharge Year Overall performance category 1 1189932778622 2 974342435500 3 101000101000 4 200020000000 5 (Dead) 81 82 82 82 31 32 29 29 50 50 53 53 Unknown* 070204020300 Cerebral performance category 1 14677435510322 2 694431443800 3 101100111000 4 200020000000 5 (Dead) 81 83 82 83 31 33 29 30 50 50 53 53 Unknown* 062103210300 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 questionnaire. The other patients with unknown scores lived longer than 1 year, but died before the questionnaire was sent out in May 2002. ceived 3 minutes of CPR prior to defi- of defibrillation first was questioned as Figure 2. Estimated Probability of Survival brillation and then 3-minute intervals these investigators found their sur- to Hospital Discharge Plotted Against of CPR (instead of 1 minute) between vival rate compared favorably with re- Response Time defibrillation attempts. This finding is ports from systems using the defibril- 8 0.5 in agreement with Cobb et al who lation first strategy. CPR First Standard Care found 27% survival to hospital dis- Some experimental studies of ven- 0.4 charge with 90 seconds predefibrilla- tricular fibrillation demonstrate that CPR tion CPR vs 17% in a historic control increases the defibrillation success 0.3 group without predefibrillation CPR for rate.7,17,18 In dogs with 7.5 minutes of ini- 0.2 response times of 4 minutes or longer. tially untreated ventricular fibrillation,

The hospital admission rate of 46% the defibrillation success was higher af- of Survival Probability 0.1 and discharge rate of 15% in the stan- ter predefibrillation CPR and high-dose dard group in our study are similar to epinephrine than after immediate defi- 0 previously reported results for pa- brillation.7 The same laboratory later re- 0 2 4 6 8 10 12 14 Response Time, min tients with ventricular fibrillation of ported better results with immediate de- 39% to 47% and 16% to 18% even in fibrillation than CPR first in swine with Average fraction of surviving patients for each 2-minute retrospective studies from this same 5 minutes of initially untreated ventricu- interval. Lines indicate logistic regression models with 13,14 19 time as independent variable fitted separately for each EMS system. When considering lar fibrillation. In a study of dogs, im- of the 2 groups. these rates along with the fact that car- mediate defibrillation was effective for diac arrest results continuously re- episodes of fibrillation if it was limited ceive specific focus in this EMS sys- to approximately 3 minutes.17 Similar to the results of Cobb et al,8 tem, we believe a Hawthorne effect There may be a cut-off time also in we did not find a higher survival rate with (important in prospective clinical re- patients below which defibrillation first CPR prior to defibrillation for patients search15) is unlikely to specifically affect is best. Immediate defibrillation is with short response times, but nor was the results in our study. highly effective in monitored patients survival worse. We cannot exclude that Robinson et al16 reported ROSC in treated within the first minute or this could be due to a type II error, and 16% of unwitnessed out-of-hospital car- two.1,20,21 Such patients have excellent a much larger study with a finer divi- diac arrests with a 4% overall survival outcomes as shown by many years of sion of the response times may give bet- rate to hospital discharge. All patients experience in coronary care units and ter survival with immediate defibrilla- were given CPR for at least 2 minutes in other situations in which defibrillation for short response times. The best prior to first shock, and the principle tors are immediately available.22 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 CPR PRIOR TO DEFIBRILLATION fibrillation first is therefore not pres- lar fibrillation, lack of oxygen supply, groups. The concern that a strategy that ently known. From our calculations and an ultimate depletion of meta- results in a higher rate of ROSC after based on this limited material, we hy- bolic substrates and high-energy phos- longer periods of cardiac arrest would pothesized this to be around a 4- to phate stores.3 Cardiopulmonary resus- generate more survivors with severe neu- 5-minute response time. citation might provide a critical amount rological damage did not occur. There There did not appear to be a differ- of cardiac perfusion and improve the was no difference in neurological out- ence in outcome in the CPR first group metabolic state of the myocytes in pa- come in the patients who survived in the between patients with response times ei- tients with ventricular fibrillation, with 2 groups, and the results compare fa- ther up to or longer than 5 minutes. The a potentially more favorable response vorably with previous research.8,26 In the probability of being discharged alive to defibrillation. study by Cobb et al,8 there was a ten- tended to decrease with time when es- In our study, defibrillation prior to dency toward improved neurological timated in a logistic regression model CPR by the ambulance personnel had an outcome (PϽ.11) in the group who re- (Figure 2), but the fall-off rate with time effect on outcomes, even though more ceived defibrillation prior to CPR. before defibrillation was much more ap- than half the patients had received CPR Use of the Glasgow-Pittsburgh out- parent in the standard group, which is performed by a bystander, which also comes (CPC and OPC) is recom- consistent with previously suggested was associated with survival. Previous mended in the international Utstein rates.2 However, even though the studies have indicated that the effects of guidelines for reporting results after car- 5-minute cut point was prespecified in CPR performed by a bystander depends diac arrest.11 Most outcome studies only this study, the findings are based on non- on the quality.25 In a study from Oslo,13 report CPC and OPC at the time of hos- randomized subgroups, and therefore re- only 47% of the CPR performed by a by- pital discharge, and the accuracy of this quire confimation in future clinical trials. stander was rated as good. for predicting the function and quality There is no contrast between our Cobb et al8 used 1.5 minutes of CPR, of life later after discharge has been chal- study and studies concluding that time Robinson et al16 used 2 minutes, and we lenged by Hsu et al,27 who reported that to defibrillation is the most important used 3 minutes of CPR before defibril- a CPC score of 1 at hospital discharge had factor for survival.1,23,24 In those stud- lation. The optimal duration of delay- a sensitivity of 78% and a specificity of ies, defibrillation was attempted as soon ing defibrillation to perform CPR may 43% for predicting that quality of life at as possible, while deliberately delaying be difficult to define, and most likely a later date was the same as or better than defibrillation to provide CPR was not depends on the condition of the myo- prior to cardiac arrest. They also found evaluated. Also, the response time in the cardium, which is dependent on the du- poor correlation between the CPC and present study and thus the time before ration of the cardiac arrest and the qual- a functional status questionnaire, and defibrillation was an important factor for ity of CPR performed by a bystander. stated that part of problem might be survival, but the analysis indicates that Ideally, whether CPR should be started caused by the CPC and OPC being scored there was an interaction between time and defibrillation postponed should be by physicians and not patients, and that and whether the ambulance personnel determined by the frequency spec- physicians appear to be inaccurate judges performed defibrillation prior to CPR. trum of the electrocardiogram, which of patient function.27 In the present study, The delay before defibrillation is still im- can predict the probability of ROSC af- we are reporting 1-year follow-up and the portant. The outcome from ventricular ter defibrillation.5 basis of the scores is the patient or rela- fibrillation is better with response times In this study, we also increased the tive’s own evaluation of function, mood, of 3 minutes than of 7 or 10 minutes. duration of CPR between defibrillation and memory compared with abilities For response times longer than 5 min- series from 1 to 3 minutes. The prob- prior to cardiac arrest. In May 2002 when utes, the outcomes appear to improve if ability of ROSC after defibrillation as the follow-up questionnaire was sent out, defibrillation is delayed to perform CPR judged from spectral analysis of the elec- 29 patients were still alive. Twenty- first. Other evidence from both clinical trocardiogram appears to deteriorate rap- seven patients or their relatives answered and animal studies suggests that elec- idly in the absence of CPR.6 In patients the follow-up questionnaire. With a troshock of prolonged ventricular fibril- with a median probability of ROSC of response rate of 93%, we believe it is lation commonly is unsuccessful,17 with 50%, there was a decrease to a median unlikely that this can have created much an increased probability of converting of 8% after 20 seconds without CPR.6 A of a bias in the results. ventricular fibrillation to a more resus- series of 3 defibrillation attempts usu- In most cardiac arrest studies, the time citation-refractory rhythm, such as asys- ally takes approximately 45 seconds, and intervals from patient collapse are only tole or pulseless electrical activity.17 it was hypothesized that 3 minutes of estimates, but probably are fairly rea- The basis for the worsened electri- CPR might be more appropriate than the sonable estimates in our study because cal and mechanical cardiac function traditional 1 minute if the myocardium 93% were witnessed. This high percent- with prolonged ventricular fibrilla- can be improved with CPR. age of cardiac arrests that were wit- tion6 seems related to the relatively high In this study, the neurological out- nessed probably explains why this was metabolic requirements for ventricu- come was good in survivors in both not an independent predictor of sur-

1394 JAMA, March 19, 2003—Vol 289, No. 11 (Reprinted) ©2003 American Medical Association. All rights reserved. CPR PRIOR TO DEFIBRILLATION vival in this study. The high propor- spite global, systematic implementa- termine the optimal duration of CPR first tion of men in our study (87%) is some- tion of current resuscitation guidelines, in patients with ventricular fibrillation. 8 what higher than previously reported in and based on the study by Cobb et al Author Affiliations: Norwegian Competence Center the same EMS service (76%)28or that re- and our data, signal the need for reevalu- for Emergency Medicine, Institute for Experimental ported in a large Swedish study with ation of the recommendations. Weis- Medical Research (Dr Wik), Division of Surgery (Drs T. Steen and P. A. Steen, and Messrs Hansen and 29 32 10966 patients (72%). We have no spe- feldt and Becker have recently pro- Fylling), Ulleval University Hospital, Oslo, Norway; Nor- cific explanation—it could be due to posed a 3-phase time-sensitive model for wegian Defense Research Establishment Division of Protection and Material, Kjeller, Norway (Dr Vaa- chance. treatment of ventricular fibrillation. An genes); and Department of Technology and Natural While defibrillation is the essential in- approximately 4-minute electric phase Science, Stavanger University College, Stavanger, Nor- way (Dr Auestad). tervention in ventricular fibrillation, de- with immediate defibrillation, followed Author Contributions: Study concept and design: Wik, fibrillation alone does not ensure re- by a circulatory phase from approxi- Hansen, Fylling, P. A. Steen. Acquisition of data: Wik, T. Steen, Vaagenes. turn of an organized cardiac rhythm, mately 4 to 10 minutes with CPR prior Analysis and interpretation of data: Wik, Vaagenes, restoration of circulation, or long-term to defibrillation, and a third metabolic Auestad, P. A. Steen. survival, particularly when the start of phase when circulating metabolic fac- Drafting of the manuscript: Wik, Hansen, Fylling, Auestad. treatment has been delayed. Providing tors, can cause additional injury be- Critical revision of the manuscript for important in- CPR prior to delivery of a precordial yond the factors of the local ischemia. tellectual content: Wik, T. Steen, Vaagenes, Auestad, P. A. Steen. shock for ventricular fibrillation is not In summary, our findings support pre- Statistical expertise: Wik, Vaagenes, Auestad, P. A. novel. For a number of years it was con- vious experimental and clinical work Steen. Obtained funding: Wik, P. A. Steen. sidered useful to apply CPR to “coarsen suggesting that CPR prior to defibrilla- Administrative, technical, or material support: Wik, ventricular fibrillation.” However, that tion may be of benefit when there has Hansen, Fylling. policy was abandoned in favor of defi- 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- brillation can be delivered to patients from the Norwegian Air Ambulance and Laerdal Foun- tients with ventricular fibrillation.30,31 with out-of-hospital ventricular fibrilla- dation for Acute Medicine. Acknowledgment: We thank the paramedics, Mona Lack of improvement in survival rate and tion. Further trials are needed to evalu- Monsen, and the physicians of Oslo EMS for their work outcome after sudden cardiac arrest de- ate this resuscitation strategy and to de- over the years.

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