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Meta-analysis of outcomes of the 2005 and 2010 cardiopulmonary resuscitation guidelines for adults with in-hospital cardiac arrest
Meta-Analysis of Outcomes of the 2005 and 2010 CPR Guidelines for Adults with In-Hospital Cardiac Arrest Aiqun Zhu, Jingping Zhang PII: DOI: Reference:
S0735-6757(16)00190-X doi: 10.1016/j.ajem.2016.03.008 YAJEM 55657
To appear in:
American Journal of Emergency Medicine
Received date: Revised date: Accepted date:
14 January 2016 2 March 2016 2 March 2016
Please cite this article as: Zhu Aiqun, Zhang Jingping, Meta-Analysis of Outcomes of the 2005 and 2010 CPR Guidelines for Adults with In-Hospital Cardiac Arrest, American Journal of Emergency Medicine (2016), doi: 10.1016/j.ajem.2016.03.008
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ACCEPTED MANUSCRIPT Title: Meta-Analysis of Outcomes of the 2005 and 2010 CPR Guidelines for Adults with In-Hospital Cardiac Arrest Aiqun Zhu1,2. Jingping Zhang1 1
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Nursing School of Central South University, Tongzipo Road No 172, Changsha, Hunan 410013, China 2 Department of Emergency, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China (Correspondence Author): Nursing School of Central South University, Tongzipo Road No 172, Changsha, Hunan 410013, China Tel:+86 731 82650264 ; Fax:+86 731 82650262; E-mail:[email protected]
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Jingping Zhang
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running title：Meta-analysis of adults CPR Outcomes in hospital
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conflict of interest: The authors declare no financial or other conflicts of interest.
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ACCEPTED MANUSCRIPT Meta-Analysis of Outcomes of the 2005 and 2010 CPR Guidelines for Adults with In-Hospital Cardiac Arrest
Abstract
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Objectives
The post–cardiac arrest survival rate has remained low since the 2010 cardiopulmonary resuscitation (CPR) guidelines were published. The present study aimed to review the 2010 versus 2005 CPR guideline outcomes in adults with in-hospital cardiac arrest.
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Methods
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The Pub Med, EMBASE and Cochrane Library databases were searched for articles published between Jan 2006 and July 2015. We extracted the following from observational studies and intervention studies: first author’s name, publication year, study duration, age of study population, and sample size. The primary outcome variables were return of spontaneous circulation (ROSC) and survival to discharge. The data were divided into 2005 (data collected prior to Dec 2010) and 2010 (data collected in Dec 2010 or later) CPR guidelines groups.
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Results
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Twenty-four original articles (77605 patients) were included. Statistically significant heterogeneity (ROSC: P<0.01, I2=97.9%; survival to discharge: P<0.01, I2=98.3%) was seen, and a random-effects model was used to pool the outcomes. The pooled ROSC rate for the 2010 group (N=5; mean, 48%; 95% confidence interval [CI], 0.38–0.58) was only slightly higher than that of the 2005 group (N=19; mean, 47%; 95% CI, 0.38–0.57). The opposite result was noted in the pooled survival to discharge rates (2010: N=5, mean, 14%; 95% CI, 0.08–0.20 versus 2005: N=19; mean, 15%; 95% CI, 0.10–0.20). there was actually no significant difference in ROSC or survival to discharge outcomes between the two groups.
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Conclusions
The 2010 CPR guidelines emphasized high-quality chest compressions can increase the ROSC rate, but did not show to improve long-term results. Keywords: cardiopulmonary resuscitation, outcome, adult, meta-analysis
1. Introduction The 2010 cardiopulmonary resuscitation (CPR) guidelines published by the American Heart Association especially emphasized the use of high-quality chest compressions during CPR. The most significant adult basic life support (BLS) change in this document is its recommendation of a compressions, airway, breathing (CAB) sequence instead of the airway, breathing, compressions (ABC) sequence of the 2005 guidelines to minimize delays to the initiation of compressions and resuscitation [1]. However, the effect of high-quality CPR on survival has rarely been prospectively assessed in a randomized trial. One study reported that the CPR protocol of the 2010 guidelines was associated with a higher proportion of patients achieving return of spontaneous circulation 2
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(ROSC), but this did not translate to statistically significant improvements in survival to discharge or neurologically intact survival in adults with in-hospital cardiac arrest receiving CPR by an emergency team [2]. However, in children, the CPR intervention research according to the 2010 CPR guidelines was associated with a trend toward improved survival to hospital discharge and favorable neurological outcome but not ROSC [3]. Improved trends in survival to hospital discharge and neurological outcomes occurred in cases of both shockable and non-shockable arrest rhythms from out-of-hospital cardiac arrest between October 2005 and December 2012 [4]. With the increasing rate of dispatcher-assisted bystander CPR, significantly improved survival and neurological outcomes also occurred in cases of metropolitan out-of-hospital cardiac arrest with the bystanders trained according to 2010 CPR guidelines [5]. Survival outcomes after resuscitation were associated with age, electrocardiography rhythm, the timing of cardiac arrest, where CPR was performed, and the duration of CPR [6]. Adults had more frequent ROSC, 24h survival, and survival to discharge than children from in-hospital CPR in emergency department during 2000 to 2010 [7]. It is unknown whether the recent improvements are due to the new 2010 guidelines or to an increased number of trained bystanders or other reasons. Recent meta-analyses of cardiac arrest research have focused on the use of new therapies including mechanical chest compression [8], extracorporeal CPR [9] and defibrillation [10], new medications such as adrenaline [11] and anti-arrhythmics [12] or resuscitation training [13]. However, no group has conducted a systematic review to precisely assess the outcomes of the 2010 CPR guidelines. Usually out-of-hospital CPR is performed by a bystander and subject to availability of first aid equipment, while in-hospital arrests receive CPR by trained health care workers with minimal delay and immediately available equipment. We decided to focus on in-hospital rather than out-of-hospital arrests because the environment is more similar between studies so results would more likely relate to the 2010 vs 2005 guidelines. Therefore, the goal of this study was to summarize and perform a meta-analysis of the 2010 versus 2005 CPR guidelines in a population of adults with in-hospital cardiac arrest.
2. Methods
2.1 Search Strategy A systematic review of the literature was based on the meta-analysis of observational studies in epidemiology statement. Relevant studies were identified from Pub Med, EMBASE, and Cochrane Library searches using the following terms: (outcome of in-hospital cardiopulmonary resuscitation [MeSH Terms]) OR (outcome after in-hospital cardiopulmonary arrest [MeSH Terms]) AND adult. Limits: Only studies of humans within the defined time frame (January 1, 2006 to July 31, 2015) were included. First, the first author selected studies based on the titles and abstracts, and then, two author respectively screened the full texts of the remaining articles more thoroughly. Disagreements were settled by consensus or adjudication of two author. The following eligibility criteria were required for inclusion: (1) observational or intervention study; (2) publication after 2006 with data sources 2006 or newer; (3) in-hospital arrest; (4) adult population (defined as >14 years); (5) survival data available; and (6) publication in English. We excluded studies of: (1) CPR performed or started in the out-of-hospital setting; 3
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(2) CPR performed in the operating room; (3) data combining arrests in both children and adults; (4) CPR performed in a special population, including pregnant women, patients requiring extracorporeal CPR or mechanical resuscitation, or arrest of a patient who is already intubated. 2.2 Data Extraction In addition to study design, patient characteristics, and sample size, we extracted information including actual numbers of survivors and corresponding cohort sizes and event rates. ROSC and survival to discharge were the primary outcome variables, but we also obtained data on survival at 24 hours and favorable neurological outcomes. If survival to discharge data were not available, we considered 30-day survival as survival to discharge. The data were divided into the 2005 and 2010 CPR guidelines groups. The data collected prior to Dec 2010 were entered into the 2005 group; those thereafter were included in the 2010 group. If the detailed data contained outcomes from both before and after 2011, then it was entered into the 2005 or 2010 group, respectively. Study data that lacked specific date were excluded. 2.3 Statistical Analysis All included studies were either observational or clinical trials. We put the extracted clinical data into an Excel database and analyzed it using Stata version 12.0 (Stata Corp, College Station, TX, USA). Estimates were segregated into the 2005 and 2010 CPR guidelines groups. Survival outcomes were ROSC and survival to hospital discharge. Because of the study heterogeneity, a random-effects model was used to combine the studies. To assess study heterogeneity, the Cochrane’s Q test and the I2 index were used. P values < .05 were considered significant in the heterogeneity test. We also explored potential sources of heterogeneity by applying a multivariate meta regression analysis examining: guidelines version, continent, time, sample source, intervention, sample size. Effect sizes were reported as mean differences. Standard errors were calculated using group standard deviation or 95% confidence interval (CI) measures.
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3. Results
In this manner, the search resulted in 3204 articles (Figure 1). 2718 articles were obtained from Pub Med, 469 from EMBASE, and 15 from the Cochrane Library. Of them, 112 articles about systematic review were excluded, 2941 articles which did not meet our eligibility criteria were excluded after reviewing of the title and abstract, leaving 151 studies for review of full papers. Of these, 127 articles were excluded due to lack of ROSC data or survival to hospital discharge data, data including children and adults or including patients with out-of-hospital cardiac arrest, data including pre-2005. Two additional articles were identified in a manual search [14,15]. Finally, a total of 24 studies were included in the meta-analysis. The data from one study [16] was split into both the 2005 and the 2010 group because it contained data from both before 2010 and after 2011. 3.1 Study Characteristics Tables 1 displays the study characteristics and variables used in the meta-analysis. Eight studies were performed in Europe [16-23], seven in Asia [24-30], six in the USA [15,31-35], two in Egypt [14,36] and one in Brazil [37]. The number of patients in each study ranged from 30 to 48841, with a total of 77605 patients in all 24 studies (median, 3104 patients). The 4
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mean patient age ranged from 24.5 years in trauma patients to 73.9 years in general patients. Fifteen articles were from a single hospital, six from multiple hospitals, and four from the National Registry of CPR. Three articles were studies of drug interventions, eight were of CPR teams, and 13 were general research. Of all studies, 20 were of the 2005 CPR guidelines and six were of the 2010 CPR guidelines. 3.2 Return of Spontaneous Circulation A total of 22 articles recorded integrated ROSC data. A random-effects model was applied because of high heterogeneity (P < 0.01, I2 = 97.9%). Figure 2 shows a Forest Plot of the ROSC outcomes of each study, weighting of each study based on sample size, and the meta-analysis results of all studies from 2005 and 2010 CPR guidelines. The ROSC rate after in-hospital CPR was 14–73%, while the overall pooled ROSC rate was 48% (95% CI, 0.41–0.54). The mean ROSC rate for studies of patients treated according to the 2005 CPR guidelines (N = 19, mean = 47%; 95% CI, 0.38–0.57) did not differ significantly from the mean ROSC rate for studies with patients treated according to the 2010 CPR guidelines (N = 5, mean = 48%; 95% CI, 0.38–0.58). Figure 3 displays the ROSC rates by study start year. Examined by simple linear regression, there was no absolute increase in ROSC rate between 2006 and 2012 (β = -0.0039; t=-0.17, P = 0.866). 3.3 Survival to Discharge Twenty-four articles recorded integrated survival to discharge data. The heterogeneity of survival to discharge was P < 0.01, I2 = 98.3%. Figure 4 shows a Forest Plot of the rate of survival to discharge of each study, weighting of each study based on sample size, and the meta-analysis results of all studies. The rate of survival to discharge following in-hospital CPR was 3–40% with an overall pooled rate of 15% (95% CI, 0.12–0.18). The mean survival to discharge rate of studies with patients treated according to the 2005 CPR guidelines (N = 19, mean = 15%; 95% CI, 0.10–0.20) did not differ significantly from the mean survival to discharge rate of studies with patients treated according to the 2010 CPR guidelines (N = 5, mean = 14%; 95% CI, 0.08–0.20). Figure 5 displays the survival to discharge rates by study start year. Examined by simple linear regression, there was no absolute increase in survival to discharge rate between 2006 and 2012 (β = 0.0024; t = -0.21, P = 0.838). 3.4 Survival at 24 hours Only three articles [24,35,36] recorded survival at 24 hours. The three studies found 350 survivals at 24 hours in the total number of 1002 cases, and respectively ranged from 48/380 (13%) [36], 57/131 ( 44%) [24] to 245/491 (50%) [35]. The overall pooled survival at 24 hours rate was 36% (95% CI, 0.08–0.63) with meta-analysis. 3.5 Neurological Outcome Five articles [17,24,19,35,37] recorded neurological outcomes, but their evaluation criteria of the neurological outcome were not exactly the same. A total of 164 survivors achieved a good neurological recovery in these five studies of 1023 cases. The five studies found favorable neurological outcome to be: 16/268 (6%, achieved 1-year survival with a cerebral performance category [CPC] score of 1 or 2) [17], 27/131 (21%, survival at 3 month)[24], 4/52 (8%) [19] and 12/81 (15%) [37] (discharge with a CPC score of 1 or 2), to 105/491 (21%, 30-day CPC score of 1 or 2) [35]. The overall pooled neurological outcome rate of 14% (95% 5
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CI, 0.06–0.22) with meta-analysis. 3.6 Source of heterogeneity Meta regression analyses were used in order to explore source of heterogeneity (Table 2). The multivariate meta regression analyzed rate of ROSC again guidelines version, continent, time, sample source, intervention and showed no statistically significant relationship with the exception of sample size (P=0.030). The rate of survival to discharge showed no statistically significant relationship with these variables.
4. Discussion
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This systematic review reports on the outcomes of more than 77000 episodes of in-hospital adult cardiac arrest treated according to the 2005 and 2010 CPR guidelines from published data in 24 data sets. Most of the studies reported only short-term outcomes such as ROSC and hospital discharge, and fewer studies examined neurological outcomes. The most striking finding is that there was no significant difference in ROSC or survival to discharge between the 2005 and 2010 CPR guidelines. However, the ROSC of the latter was slightly increased compared to the former, which is in line with the goal of the 2010 CPR guidelines; but the hospital discharge findings were contrary. According to the 2010 CPR guidelines, the most important evidence-based recommendations for the performance of BLS are that rescuers should begin CPR with chest compressions rather than rescue breathing, and a strong emphasis on pushing hard to a depth of at least 2 inches (5 cm) at a rate of at least 100 compressions per minute. To provide effective chest compressions, push hard and push fast [1], such high-quality chest compressions can indeed increase the ROSC rate. Research shows that the ROSC rates peaked at a compression rate of ~125/min and then declined, but a higher survival to hospital discharge rate was not seen [38]. Following BLS curriculum revision after publication of the 2010 guidelines, cardiac arrest was associated with a higher proportion of patients achieving ROSC but not survival to discharge [39]. Some research showed that after adjustment for chest compression fraction and depth, compression rates between 100 and 120 per minute were associated with greatest survival to hospital discharge [40]. These data suggest an optimum target of between 100 and 120 compressions per minute. Consistent rates above or below that range appear to reduce survival to discharge [41]. When exceeding a certain range, the faster the compression rate is, the shorter the diastolic time of the heart is, which will lead to a decrease in blood volume of the heart and reduce the effectiveness of compressions. On the other hand, there was an inverse association between depth and compression rate [42], which may imply that the excessive increase of compression speed is difficult to guarantee the depth of compression. For survival to discharge, Stiell’s study revealed that the maximum survival is at a depth of 45.6 mm (15-mm interval with highest survival between 40.3 and 55.3 mm) with no differences between men and women, suggesting that the 2010 American Heart Association cardiopulmonary resuscitation guideline target may be too high [43]. Vadeboncoeur et al. assessed that each 5mm increase in mean chest compressions depth significantly increased the odds of survival and survival with favorable functional outcome: OR 1.29 (95% CI 1.00-1.65) and OR 1.30 (95% CI 1.00-1.70) respectively [44]. Chest compression depth and rate were associated with ROSC and survival outcomes. Our 6
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goal after CPR is to have higher ROSC rates and better neurological function, but this meta-analysis was unable to find any of these statistical improvements after the change to the 2010 guidelines. In another meta document [45], chest compression depth was significantly associated with survival to hospital discharge (mean difference (MD) between survivors and non-survivors 2.59mm, 95% CI: 0.71, 4.47); and with ROSC (MD 0.99mm, 95% CI: 0.04, 1.93). Within the range of approximately 100-120 compressions per minute, compression rate was significantly associated with survival to hospital discharge. Moreover, hospital discharge is related to the patient’s own disease, follow-up treatment, and hypoxia time during CPR process [6]. This review showed that overall pooled rate of hospital discharge from in-hospital CPR do not appear to have made a difference after 2010. But for out-of-hospital cardiac arrest, overall rates of survival improved dramatically with accompanying lower rates of neurological disability, as well as increasing rates of bystander CPR and AED use during the study period [46]. One reason that the 2010 guidelines might make a difference in out-of-hospital but not in-hospital is that bystanders who are not healthcare professionals and who do not have personal protective equipment available are hesitant to provide mouth-to-mouth to strangers, whereas in a healthcare setting responders have gloves, masks, etc., and can treat the airway with bag-valve-masks or intubation while avoiding skin-to-skin contact. Another reason might be that often in-hospital arrests have large code response teams, so someone is able to provide continuous compressions while a second person is able to provide respirations simultaneously. How to get higher ROSC rates and better outcomes are areas which deserve more discussion. This review is based on observational, real-world clinical data from five continents. In heterogeneity analysis, the rate of ROSC is not related to CPR guidelines version, continent, time, sample source, or intervention. In the future, studies on CPR from large databases is a way to reduce heterogeneity, since sample size is one of the sources of heterogeneity.
5. Study limitations
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However, these individual studies had potential limitations. First of all, only reports in English literature were included in our study, which led to the loss of raw data from reports in other languages. There were two studies in other languages were excluded. We also excluded two documents [47,48] because their data come from Get With The Guidelines® (GWTG)‐ Resuscitation (2000 - 2010), which is the same as Chan PS’s study (2007 - 2010) [32]. Only five studies examined the 2010 CPR guidelines. Another limitation is that we do not know when hospitals retrained their staff. Likely there was a fair amount of lag between the announcement of the new guidelines in Dec 2010 and when hospital staff would have started using the new guidelines. Selection bias and confounding seem inevitable because most of the research is from observational studies. Other potential sources of heterogeneity included race, discharge standards and with other specific sources such as hospital size, hospital quality, lag time between arrest and code response, who responded to the code (nurse, physician, resident). Such heterogeneity should be considered in any meta-analysis.
6. Conclusions In conclusion, the 2010 CPR guidelines emphasize that high-quality chest compressions can increase the ROSC rate when initiated early without delaying for airway interventions, 7
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however this change to the 2010 guidelines has not improved ROSC rates or survival-to-discharge for in-hospital cardiac arrest when compared to 2005 CPR guidelines. It is worth considering that appropriate compression rate and depth appears to have stronger evidence for improvement in outcomes of cardiopulmonary resuscitation.
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Competing interest
The authors declare that they have no conflict of interest. The study was not supported by any fund.
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References
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1. Hazinski MF, Nolan JP, Billi JE, Böttiger BW, Bossaert L, de Caen AR, et al. Part 1: Executive summary: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation. 2010; 122(16 Suppl 2):S250-75 2. Couper K, Kimani PK, Abella BS, Chilwan M, Cooke MW, Davies RP, et al. The System-Wide Effect of Real-Time Audiovisual Feedback and Postevent Debriefing for In-Hospital Cardiac Arrest: The Cardiopulmonary Resuscitation Quality Improvement Initiative. Crit Care Med. 2015;43(11):2321-31 3. Wolfe H, Zebuhr C, Topjian AA, Nishisaki A, Niles DE, Meaney PA, etal. Interdisciplinary ICU cardiac arrest debriefing improves survival outcomes. Crit Care Med. 2014;42(7):1688-95 4. Chan PS, McNally B, Tang F, Kellermann A; CARES Surveillance Group. Recent Trends in Survival from Out-of-Hospital Cardiac Arrest in the United States. Circulation. 2014; 130(21): 1876–82 5. Song KJ, Shin SD, Park CB, Kim JY, Kim do K, Kim CH, et al. Dispatcher-assisted bystander cardiopulmonary resuscitation in a metropolitan city: a before–after population-based study. Resuscitation. 2014 ;85(1):34-41 6. Siriphuwanun V, Punjasawadwong Y, Lapisatepun W, Charuluxananan S, Uerpairojkit K. Prognostic factors for death and survival with or without complications in cardiac arrest patients receiving CPR within 24 hours of anesthesia for emergency surgery[J]. Risk Management & Healthcare Policy, 2014, 7(7):199-210 7.Donoghue AJ, Abella BS, Merchant R, Praestgaard A, Topjian A, Berg R, et al. Cardiopulmonary resuscitation for in-hospital events in the emergency department: A comparison of adult and pediatric outcomes and care processes. Resuscitation. 2015;92:94-100 8. Gates S, Quinn T, Deakin CD, Blair L, Couper K, Perkins GD. Mechanical chest compression for out of hospital cardiac arrest: Systematic review and meta-analysis. Resuscitation. 2015;94:91-7 9. Morimura N, Sakamoto T, Nagao K, Asai Y, Yokota H, Tahara Y, et al. Extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A review of the Japanese literature. Resuscitation. 2011;82(1):10-4 10. Wang CH, Huang CH, Chang WT, Tsai MS, Liu SS, Wu CY, et al. Biphasic versus monophasic defibrillation in out-of-hospital cardiac arrest: a systematic review and 8
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CE
PT
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SC
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meta-analysis. Am J Emerg Med. 2013;31(10):1472-78 11. Lin S, Callaway CW, Shah PS, Wagner JD, Beyene J, Ziegler CP, et al. Adrenaline for out-of-hospital cardiac arrest resuscitation: a systematic review and meta-analysis of randomized controlled trials. Resuscitation. 2014;85(6):732-40 12. Huang Y, He Q, Yang M, Zhan L. Antiarrhythmia drugs for cardiac arrest: a systemic review and meta-analysis. Crit Care. 2013;17(4):R173 13. Mundell WC, Kennedy CC, Szostek JH, Cook DA. Simulation technology for resuscitation training: a systematic review and meta-analysis. Resuscitation. 2013;84(9):1174-83 14. Hesham S. Taha , Sameh W.G. Bakhoum, Hussein H. Kasem, Mera A.S. Fahim. Quality of cardiopulmonary resuscitation of in-hospital cardiac arrest and its relation to clinical outcome: An Egyptian University Hospital Experience. The Egyptian Heart Journal. 2015; 67:137–43. 15. S.M. Lutchmedial, A.B. Levitov, P. Katyal, J. John, R.K. Herbertson, S. Malaisamy. In-hospital Cardiopulmonary Arrest: The Role Of BMI, Central Venous Catheter And Other Predictors Of Outcome. Am J Respir Crit Care Med. 2010;181:A4544 16. Müller MP, Richter T, Papkalla N, Poenicke C, Herkner C, Osmers A, et al. Effects of a mandatory basic life support training programme on the no-flow fraction during in-hospital cardiac resuscitation: an observational study. Resuscitation. 2014;85(7):874-8. 17. Mentzelopoulos SD, Malachias S, Chamos C, Konstantopoulos D, Ntaidou T, Papastylianou A, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA. 2013;310(3):270-9. 18. Akhtar N, Field RA, Greenwood L, Davies RP, Woolley S, Cooke MW, et al. Quality of in-hospital cardiac arrest calls: a prospective observational study. BMJ Qual Saf. 2012; 21(3):184-90. 19. Tarmey NT, Park CL, Bartels OJ, Konig TC, Mahoney PF, Mellor AJ. Outcomes following military traumatic cardiorespiratory arrest: A prospective observational study. Resuscitation. 2011;82(9):1194-7. 20. Olasveengen TM, Vik E, Kuzovlev A, Sunde K. Effect of implementation of new resuscitation guidelines on quality of cardiopulmonary resuscitation and survival. Resuscitation. 2009;80(4):407-11. 21. Mentzelopoulos SD, Zakynthinos SG, Tzoufi M, Katsios N, Papastylianou A, Gkisioti S et al. Vasopressin, epinephrine, and corticosteroids for in-hospital cardiac arrest. Arch Intern Med. 2009;169(1):15-24. 22. Nolan JP, Soar J, Smith GB, Gwinnutt C, Parrott F, Power S, et al. Incidence and outcome of in-hospital cardiac arrest in the United Kingdom National Cardiac Arrest Audit. Resuscitation. 2014;85(8):987-92. 23. M Ahmed, A Kochhar and O Rose. One-year assessment of in-hospital cardiac arrest. Critical Care. 2014;18(Suppl 1):P493 24. Lee HK, Lee H, No JM, Jeon YT, Hwang JW, Lim YJ, et al. Factors influencing outcome in patients with cardiac arrest in the ICU. Acta Anaesthesiol Scand. 2013;57(6):784-92. 25. Chon GR, Lee J, Shin Y, Huh JW, Lim CM, Koh Y, et al. Clinical outcomes of witnessed and monitored cases of in-hospital cardiac arrest in the general ward of auniversity hospital in 9
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CE
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Korea. Respir Care. 2013;58(11):1937-44. 26. Chan JC, Wong TW, Graham CA. Factors associated with survival after in-hospital cardiac arrest in Hong Kong. Am J Emerg Med. 2013;31(5):883-5. 27. Chakravarthy M, Mitra S, Nonis L. Outcomes of in-hospital, out of intensive care and operation theatre cardiac arrests in a tertiary referral hospital. Indian Heart J. 2012;64(1):7-11. 28. Sodhi K, Singla MK, Shrivastava A. Impact of advanced cardiac life support training program on the outcome of cardiopulmonary resuscitation in atertiary care hospital. Indian J Crit Care Med. 2011;15(4):209-12. 29. Einav S, Bromiker R, Weiniger CF, Matot I. Mathematical modeling for prediction of survival from resuscitation based on computerized continuous capnography: proof of concept. Acad Emerg Med. 2011;18(5):468-75. 30. Ong ME, Tiah L, Leong BS, Tan EC, Ong VY, Tan EA, et al. A randomised, double-blind, multi-centre trial comparing vasopressin and adrenaline in patients with cardiac arrest presenting to or in the Emergency Department. Resuscitation. 2012;83(8):953-60. 31. Khasawneh FA, Kamel MT, Abu-Zaid MI. Predictors of cardiopulmonary arrest outcome in a comprehensive cancer center intensive care unit. Scand J Trauma Resusc Emerg Med. 2013, Mar 20;21:18 32. Chan PS, Berg RA, Spertus JA, Schwamm LH, Bhatt DL, Fonarow GC, et al. Risk-standardizing survival for in-hospital cardiac arrest to facilitate hospital comparisons. J Am Coll Cardiol. 2013;62(7):601-9. 33. Bhalala US, Bonafide CP, Coletti CM, Rathmanner PE, Nadkarni VM, Berg RA, et al. Antecedent bradycardia and in-hospital cardiopulmonary arrest mortality in telemetry-monitored patients outside the ICU. Resuscitation. 2012;83(9):1106-10. 34. Edelson DP, Litzinger B, Arora V, Walsh D, Kim S, Lauderdale DS, et al. Improving in-hospital cardiac arrest process and outcomes with performance debriefing. Arch Intern Med. 2008;168(10):1063-69. 35. Yokoyama H, Yonemoto N, Yonezawa K, Fuse J, Shimizu N, Hayashi T, et al. Report from the Japanese registry of CPR for in-hospital cardiac arrest (J-RCPR). Circ J. 2011;75(4):815-22. 36. Amer MS, Abdel Rahman TT, Aly WW, Ahmad NG. Cardiopulmonary resuscitation: outcome and its predictors among hospitalized elderly patients in Egypt. Geriatr Gerontol Int. 2014;14(2):309-14. 37. Toledo FO, Gonzalez MM, Sebbag I, Lelis RG, Aranha GF, Timerman S, et al. Outcomes of patients with trauma and intraoperative cardiac arrest. Resuscitation. 2013;84(5):635-38. 38. Idris AH, Guffey D, Aufderheide TP, Brown S, Morrison LJ, Nichols P, et al. Relationship between chest compression rates and outcomes from cardiac arrest. Circulation. 2012;125(24):3004-12. 39. Müller MP, Richter T, Papkalla N, Poenicke C, Herkner C, Osmers A, et al. Effects of a mandatory basic life support training programme on the no-flow fraction during in-hospital cardiac resuscitation: an observational study. Resuscitation. 2014;85(7):874-8. 40. Idris AH, Guffey D, Pepe PE , Brown SP, Brooks SC, Callaway CW, et al . Chest compression rates and survival following out-of-hospital cardiac arrest. Crit Care Med. 2015;43(4):840-8 41. Meaney PA, Bobrow BJ, Mancini ME, Christenson J, de Caen AR, Bhanji F, et al. 10
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Cardiopulmonary resuscitation quality: [corrected] improving cardiac resuscitation outcomes both inside and outside the hospital: a consensus statement from the American Heart Association. Circulation. 2013;128(4):417-35 42. Stiell IG, Brown SP, Christenson J, Cheskes S, Nichol G, Powell J, et al. What is the Role of Chest Compression Depth during Out-of-Hospital Cardiac Arrest Resuscitation? Crit Care Med. 2012;40(4):1192-8 43. Stiell IG, Brown SP, Nichol G, Cheskes S, Vaillancourt C, Callaway CW, et al. What is the optimal chest compression depth during out-of-hospital cardiac arrest resuscitation of adult patients? Circulation. 2014;130(22):1962-70 44. Vadeboncoeur T, Stolz U, Panchal A, Silver A, Venuti M, Tobin J, et al. Chest compression depth and survival in out-of-hospital cardiac arrest. Resuscitation. 2014;85(2):182-8. 45. Talikowska M, Tohira H, Finn J. Cardiopulmonary resuscitation quality and patient survival outcome in cardiac arrest: A systematic review and meta-analysis. Resuscitation. 2015 Nov;96:66-77. 46. Chan PS, McNally B, Tang F, Kellermann A, CARES Surveillance Group. Recent trends in survival from out-of-hospital cardiac arrest in the United States. Circulation. 2014;130(21):1876-82. 47. Bradley SM, Huszti E, Warren SA, Merchant RM, Sayre MR, Nichol G. Duration of hospital participation in Get With the Guidelines-Resuscitation and survival of in-hospital cardiac arrest. Resuscitation. 2012;83(11):1349-57 48. Girotra S, Cram P, Spertus JA, Nallamothu BK, Li Y, Jones PG, et al. Hospital variation in survival trends for in-hospital cardiac arrest. J Am Heart Assoc. 2014;3(3):e000871.
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ACCEPTED MANUSCRIPT Table 1
The Characteristics of The Studies Included in This Meta-analysis.
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Survival Age
to
Reference
Countr
Sample
Inclusion
Interven
N(%Mal
ran
Mean
ROSC
discharge
(first author)
y
source
period
tion
e)
ge
age
(%)
(%)
67-68
28(48)
11(19)
Study in 2005 CPR guidelines
2014
[16]
Germa
single
CPR
ny
hospital
2008-2010
team
multipl
58(72.4)
lt
e
os SD,
hospital
2008.9-201
interven
268(68.
≧1
s
0.10
tion
3)
8
63
104(62.
adu
49.7±1
5)
lt
5.3
131(64.
≧1
61.0±1
2013
Greece
ICU of Khasawneh [31]
FA, 2013
USA
single
2008.1-200
hospital
9.6
ICU of
Korea
Chon G.R, 2013
[25]
Korea
2009.1-201
ED
2013
single
[24]
NI
200(75 )
25(9)
36(35)
6(6)
hospital
0.6
NI
9)
8
6.5
96(73)
single
2008.3-201
CPR
238(59.
≧1
61.3±1
151(63
0.2
7)
8
5.2
)
431(61.
24-
7)
97
PT
Lee HK,
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Mentzelopoul [17]
drug
adu
SC
Müller MP,
hospital
team
s
8.12
NI
single
2007.1-200
hospital
9.12
46(19)
two
2013
hospital
[26]
China
Toledo FO, 2013[37] [32]
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Brazil
Chan PS, 2013
CE
Chan JC,
USA
2008.1-200
73.6
)
23(5)
55±22
46(57)
13(16)
≧1 NI
81(61.7)
8
48841(5 GWTG
139(32
2007-2010
NI
8.3)
>18
65.6±1
10290(2
6.1
1)
multipl e
Akhtar N, 2012
[18]
Englan
hospital
2009.12-20
CPR
d
s
10.4
team
adu 191(/)
lt
/
73(38)
64.6-6
225(31
4.9
)
39(20)
multipl e Ong ME, 2012
[30]
drug
Singap
hospital
2006.3-200
interven
727(69.
ore
s
9.1
tion
4)
>16
19(3)
two Bhalala US, 2012
[33]
2008-
s
2010
single
2007.3-200
India
hospital
9.3
NI
78(60.3)
lt
/
50(64)
24(31)
UK
single
2009.12-20
hospital’
52(100)
18-
24.5
14(27)
4(8)
USA
Chakravarthy M, 2012
[27]
Tarmey NT,
≧1
hospital
NI
98(63.3)
8
73
39(40)
adu
12
ACCEPTED MANUSCRIPT 2011[19]
hospital
10.6
s trauma
36
India
Yokoyama H, 2011
[35]
Japan
Einav S, 2011
single
2009.1-201
CPR
627(55.
hospital
0.6
team
8)
>14
57
)
J-RCP
2008.1-200
491(63.
≧1
71.0±1
318(65
R
9.12
3)
8
)
136(28)
74
17(57)
6(20)
36(14)
29(11)
NI
single
[29]
Israel
Lutchmedial
CPR
hospital
2008-2010
single
2008.7-200
team
S, 2010[15]
USA
hospital
9.4
NI
Olasveengen
Norwa
single
2006.1-200
CPR
y
hospital
7.12
team
TM, 2009
[20]
drug
2009
)
63(13)
66(66)
11(11)
73(59)
9(7)
8
65-69
single
2006.2-200
CPR
123(48.
≧1
60.7±1
USA
hospital
7.3
team
0)
8
6
23554(5
≧1
UK
NCAA
3.3
5.0)
6
73.9
45)
single
2011.1-201
380(36.
≧6
67.98±
124(33
8)
0
7.9
)
32(8)
67-72
44(72)
21(34)
2011.4-201
Egypt
hospital
Germa
single
Ahmed M, UK
2.6
NI
NI
CPR
OD
NI
hospital
2011-2012
NCEP
2011.1-201
CE
2014
64±18
0)
ny
[23]
lt
tion
PT
2014
[16]
6)
147(30
7.3
Michael P. Müller,
adu
hospital
ED
2014
482(66.
≧1
Amer M.S, [36]
lt
100(59.
Nolan J.P, 2014[ [22]
adu
interven
Edelson DP, 2008
92
264(70.
2006.6-200
Greece
[34]
30(50.0)
0)
4.9
79(13)
single
os SD, [21]
16-
MA NU
Mentzelopoul
149(24
RI P
2011
[28]
SC
Sodhi K,
T
team
2.9
team
10607( 4153(18)
adu 61(63.9)
lt adu
69(/)
lt
/
126(63.
≧1
56.4±1
5)
8
4.8
7(10)
multipl
AC
e
Taha H.S, 2015
[14]
Egypti
hospital
2012.3-201
an
s
2.12
NI
60(48)
9(7)
NCEPOD: National Confidential Enquiry into Patient Outcome and Death GWTG: Get With The Guidelines (GWTG)-Resuscitation NCAA: United Kingdom (UK) National Cardiac Arrest Audit database J-RCPR: registry of in-hospital CPA and resuscitation in Japan ROSC: return of spontaneous circulation NI: no intervention N: number of patients in the study
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-0.21-0.54 -0.10-0.10 -.016-0.17 -0.11-0.07 -0.07-0.28 -0.54-0.03
0.361 0.939 0.097 0.597 0.214 0.030
-0.25-0.17 -0.08-0.03 -0.05-0.05 -0.05-0.05 -0.16-0.03 -0.13-0.12
0.691 0.298 0.869 0.973 0.187 0.935
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16.57 -00.36 7.96 -2.28 10.46 -28.74 -4.00 -2.75 -0.40 00.08 -6.32 -0.51
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Return of spontaneous circulation Guide Version(2005 CPR VS 2010 CPR) Continent a Sample source b Time to start collecting data Intervention c Sample size (≥500 vs. <500) Survival to hospital discharge Guide Version(2005 CPR VS 2010 CPR) Continent Sample source Time to start collecting data Intervention Sample size (≥500 vs. <500)
95%CI
T
Meta regression coefficient (%)
Continent: Europe, Asia, USA, others
b
Sample source: ICU of hospital, single hospital, multiple hospitals, the National Registry of CPR.
c
Intervention: no intervention, drug interventions, CPR teams or trauma team
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S0735-6757(16)00190-X doi: 10.1016/j.ajem.2016.03.008 YAJEM 55657
To appear in:
American Journal of Emergency Medicine
Received date: Revised date: Accepted date:
14 January 2016 2 March 2016 2 March 2016
Please cite this article as: Zhu Aiqun, Zhang Jingping, Meta-Analysis of Outcomes of the 2005 and 2010 CPR Guidelines for Adults with In-Hospital Cardiac Arrest, American Journal of Emergency Medicine (2016), doi: 10.1016/j.ajem.2016.03.008
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Title: Meta-Analysis of Outcomes of the 2005 and 2010 CPR Guidelines for Adults with In-Hospital Cardiac Arrest Aiqun Zhu1,2. Jingping Zhang1 1
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Nursing School of Central South University, Tongzipo Road No 172, Changsha, Hunan 410013, China 2 Department of Emergency, The Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, China (Correspondence Author): Nursing School of Central South University, Tongzipo Road No 172, Changsha, Hunan 410013, China Tel:+86 731 82650264 ; Fax:+86 731 82650262; E-mail:[email protected]
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running title：Meta-analysis of adults CPR Outcomes in hospital
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conflict of interest: The authors declare no financial or other conflicts of interest.
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Abstract
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Objectives
The post–cardiac arrest survival rate has remained low since the 2010 cardiopulmonary resuscitation (CPR) guidelines were published. The present study aimed to review the 2010 versus 2005 CPR guideline outcomes in adults with in-hospital cardiac arrest.
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Methods
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The Pub Med, EMBASE and Cochrane Library databases were searched for articles published between Jan 2006 and July 2015. We extracted the following from observational studies and intervention studies: first author’s name, publication year, study duration, age of study population, and sample size. The primary outcome variables were return of spontaneous circulation (ROSC) and survival to discharge. The data were divided into 2005 (data collected prior to Dec 2010) and 2010 (data collected in Dec 2010 or later) CPR guidelines groups.
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Results
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Twenty-four original articles (77605 patients) were included. Statistically significant heterogeneity (ROSC: P<0.01, I2=97.9%; survival to discharge: P<0.01, I2=98.3%) was seen, and a random-effects model was used to pool the outcomes. The pooled ROSC rate for the 2010 group (N=5; mean, 48%; 95% confidence interval [CI], 0.38–0.58) was only slightly higher than that of the 2005 group (N=19; mean, 47%; 95% CI, 0.38–0.57). The opposite result was noted in the pooled survival to discharge rates (2010: N=5, mean, 14%; 95% CI, 0.08–0.20 versus 2005: N=19; mean, 15%; 95% CI, 0.10–0.20). there was actually no significant difference in ROSC or survival to discharge outcomes between the two groups.
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Conclusions
The 2010 CPR guidelines emphasized high-quality chest compressions can increase the ROSC rate, but did not show to improve long-term results. Keywords: cardiopulmonary resuscitation, outcome, adult, meta-analysis
1. Introduction The 2010 cardiopulmonary resuscitation (CPR) guidelines published by the American Heart Association especially emphasized the use of high-quality chest compressions during CPR. The most significant adult basic life support (BLS) change in this document is its recommendation of a compressions, airway, breathing (CAB) sequence instead of the airway, breathing, compressions (ABC) sequence of the 2005 guidelines to minimize delays to the initiation of compressions and resuscitation [1]. However, the effect of high-quality CPR on survival has rarely been prospectively assessed in a randomized trial. One study reported that the CPR protocol of the 2010 guidelines was associated with a higher proportion of patients achieving return of spontaneous circulation 2
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(ROSC), but this did not translate to statistically significant improvements in survival to discharge or neurologically intact survival in adults with in-hospital cardiac arrest receiving CPR by an emergency team [2]. However, in children, the CPR intervention research according to the 2010 CPR guidelines was associated with a trend toward improved survival to hospital discharge and favorable neurological outcome but not ROSC [3]. Improved trends in survival to hospital discharge and neurological outcomes occurred in cases of both shockable and non-shockable arrest rhythms from out-of-hospital cardiac arrest between October 2005 and December 2012 [4]. With the increasing rate of dispatcher-assisted bystander CPR, significantly improved survival and neurological outcomes also occurred in cases of metropolitan out-of-hospital cardiac arrest with the bystanders trained according to 2010 CPR guidelines [5]. Survival outcomes after resuscitation were associated with age, electrocardiography rhythm, the timing of cardiac arrest, where CPR was performed, and the duration of CPR [6]. Adults had more frequent ROSC, 24h survival, and survival to discharge than children from in-hospital CPR in emergency department during 2000 to 2010 [7]. It is unknown whether the recent improvements are due to the new 2010 guidelines or to an increased number of trained bystanders or other reasons. Recent meta-analyses of cardiac arrest research have focused on the use of new therapies including mechanical chest compression [8], extracorporeal CPR [9] and defibrillation [10], new medications such as adrenaline [11] and anti-arrhythmics [12] or resuscitation training [13]. However, no group has conducted a systematic review to precisely assess the outcomes of the 2010 CPR guidelines. Usually out-of-hospital CPR is performed by a bystander and subject to availability of first aid equipment, while in-hospital arrests receive CPR by trained health care workers with minimal delay and immediately available equipment. We decided to focus on in-hospital rather than out-of-hospital arrests because the environment is more similar between studies so results would more likely relate to the 2010 vs 2005 guidelines. Therefore, the goal of this study was to summarize and perform a meta-analysis of the 2010 versus 2005 CPR guidelines in a population of adults with in-hospital cardiac arrest.
2. Methods
2.1 Search Strategy A systematic review of the literature was based on the meta-analysis of observational studies in epidemiology statement. Relevant studies were identified from Pub Med, EMBASE, and Cochrane Library searches using the following terms: (outcome of in-hospital cardiopulmonary resuscitation [MeSH Terms]) OR (outcome after in-hospital cardiopulmonary arrest [MeSH Terms]) AND adult. Limits: Only studies of humans within the defined time frame (January 1, 2006 to July 31, 2015) were included. First, the first author selected studies based on the titles and abstracts, and then, two author respectively screened the full texts of the remaining articles more thoroughly. Disagreements were settled by consensus or adjudication of two author. The following eligibility criteria were required for inclusion: (1) observational or intervention study; (2) publication after 2006 with data sources 2006 or newer; (3) in-hospital arrest; (4) adult population (defined as >14 years); (5) survival data available; and (6) publication in English. We excluded studies of: (1) CPR performed or started in the out-of-hospital setting; 3
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(2) CPR performed in the operating room; (3) data combining arrests in both children and adults; (4) CPR performed in a special population, including pregnant women, patients requiring extracorporeal CPR or mechanical resuscitation, or arrest of a patient who is already intubated. 2.2 Data Extraction In addition to study design, patient characteristics, and sample size, we extracted information including actual numbers of survivors and corresponding cohort sizes and event rates. ROSC and survival to discharge were the primary outcome variables, but we also obtained data on survival at 24 hours and favorable neurological outcomes. If survival to discharge data were not available, we considered 30-day survival as survival to discharge. The data were divided into the 2005 and 2010 CPR guidelines groups. The data collected prior to Dec 2010 were entered into the 2005 group; those thereafter were included in the 2010 group. If the detailed data contained outcomes from both before and after 2011, then it was entered into the 2005 or 2010 group, respectively. Study data that lacked specific date were excluded. 2.3 Statistical Analysis All included studies were either observational or clinical trials. We put the extracted clinical data into an Excel database and analyzed it using Stata version 12.0 (Stata Corp, College Station, TX, USA). Estimates were segregated into the 2005 and 2010 CPR guidelines groups. Survival outcomes were ROSC and survival to hospital discharge. Because of the study heterogeneity, a random-effects model was used to combine the studies. To assess study heterogeneity, the Cochrane’s Q test and the I2 index were used. P values < .05 were considered significant in the heterogeneity test. We also explored potential sources of heterogeneity by applying a multivariate meta regression analysis examining: guidelines version, continent, time, sample source, intervention, sample size. Effect sizes were reported as mean differences. Standard errors were calculated using group standard deviation or 95% confidence interval (CI) measures.
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3. Results
In this manner, the search resulted in 3204 articles (Figure 1). 2718 articles were obtained from Pub Med, 469 from EMBASE, and 15 from the Cochrane Library. Of them, 112 articles about systematic review were excluded, 2941 articles which did not meet our eligibility criteria were excluded after reviewing of the title and abstract, leaving 151 studies for review of full papers. Of these, 127 articles were excluded due to lack of ROSC data or survival to hospital discharge data, data including children and adults or including patients with out-of-hospital cardiac arrest, data including pre-2005. Two additional articles were identified in a manual search [14,15]. Finally, a total of 24 studies were included in the meta-analysis. The data from one study [16] was split into both the 2005 and the 2010 group because it contained data from both before 2010 and after 2011. 3.1 Study Characteristics Tables 1 displays the study characteristics and variables used in the meta-analysis. Eight studies were performed in Europe [16-23], seven in Asia [24-30], six in the USA [15,31-35], two in Egypt [14,36] and one in Brazil [37]. The number of patients in each study ranged from 30 to 48841, with a total of 77605 patients in all 24 studies (median, 3104 patients). The 4
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mean patient age ranged from 24.5 years in trauma patients to 73.9 years in general patients. Fifteen articles were from a single hospital, six from multiple hospitals, and four from the National Registry of CPR. Three articles were studies of drug interventions, eight were of CPR teams, and 13 were general research. Of all studies, 20 were of the 2005 CPR guidelines and six were of the 2010 CPR guidelines. 3.2 Return of Spontaneous Circulation A total of 22 articles recorded integrated ROSC data. A random-effects model was applied because of high heterogeneity (P < 0.01, I2 = 97.9%). Figure 2 shows a Forest Plot of the ROSC outcomes of each study, weighting of each study based on sample size, and the meta-analysis results of all studies from 2005 and 2010 CPR guidelines. The ROSC rate after in-hospital CPR was 14–73%, while the overall pooled ROSC rate was 48% (95% CI, 0.41–0.54). The mean ROSC rate for studies of patients treated according to the 2005 CPR guidelines (N = 19, mean = 47%; 95% CI, 0.38–0.57) did not differ significantly from the mean ROSC rate for studies with patients treated according to the 2010 CPR guidelines (N = 5, mean = 48%; 95% CI, 0.38–0.58). Figure 3 displays the ROSC rates by study start year. Examined by simple linear regression, there was no absolute increase in ROSC rate between 2006 and 2012 (β = -0.0039; t=-0.17, P = 0.866). 3.3 Survival to Discharge Twenty-four articles recorded integrated survival to discharge data. The heterogeneity of survival to discharge was P < 0.01, I2 = 98.3%. Figure 4 shows a Forest Plot of the rate of survival to discharge of each study, weighting of each study based on sample size, and the meta-analysis results of all studies. The rate of survival to discharge following in-hospital CPR was 3–40% with an overall pooled rate of 15% (95% CI, 0.12–0.18). The mean survival to discharge rate of studies with patients treated according to the 2005 CPR guidelines (N = 19, mean = 15%; 95% CI, 0.10–0.20) did not differ significantly from the mean survival to discharge rate of studies with patients treated according to the 2010 CPR guidelines (N = 5, mean = 14%; 95% CI, 0.08–0.20). Figure 5 displays the survival to discharge rates by study start year. Examined by simple linear regression, there was no absolute increase in survival to discharge rate between 2006 and 2012 (β = 0.0024; t = -0.21, P = 0.838). 3.4 Survival at 24 hours Only three articles [24,35,36] recorded survival at 24 hours. The three studies found 350 survivals at 24 hours in the total number of 1002 cases, and respectively ranged from 48/380 (13%) [36], 57/131 ( 44%) [24] to 245/491 (50%) [35]. The overall pooled survival at 24 hours rate was 36% (95% CI, 0.08–0.63) with meta-analysis. 3.5 Neurological Outcome Five articles [17,24,19,35,37] recorded neurological outcomes, but their evaluation criteria of the neurological outcome were not exactly the same. A total of 164 survivors achieved a good neurological recovery in these five studies of 1023 cases. The five studies found favorable neurological outcome to be: 16/268 (6%, achieved 1-year survival with a cerebral performance category [CPC] score of 1 or 2) [17], 27/131 (21%, survival at 3 month)[24], 4/52 (8%) [19] and 12/81 (15%) [37] (discharge with a CPC score of 1 or 2), to 105/491 (21%, 30-day CPC score of 1 or 2) [35]. The overall pooled neurological outcome rate of 14% (95% 5
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CI, 0.06–0.22) with meta-analysis. 3.6 Source of heterogeneity Meta regression analyses were used in order to explore source of heterogeneity (Table 2). The multivariate meta regression analyzed rate of ROSC again guidelines version, continent, time, sample source, intervention and showed no statistically significant relationship with the exception of sample size (P=0.030). The rate of survival to discharge showed no statistically significant relationship with these variables.
4. Discussion
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This systematic review reports on the outcomes of more than 77000 episodes of in-hospital adult cardiac arrest treated according to the 2005 and 2010 CPR guidelines from published data in 24 data sets. Most of the studies reported only short-term outcomes such as ROSC and hospital discharge, and fewer studies examined neurological outcomes. The most striking finding is that there was no significant difference in ROSC or survival to discharge between the 2005 and 2010 CPR guidelines. However, the ROSC of the latter was slightly increased compared to the former, which is in line with the goal of the 2010 CPR guidelines; but the hospital discharge findings were contrary. According to the 2010 CPR guidelines, the most important evidence-based recommendations for the performance of BLS are that rescuers should begin CPR with chest compressions rather than rescue breathing, and a strong emphasis on pushing hard to a depth of at least 2 inches (5 cm) at a rate of at least 100 compressions per minute. To provide effective chest compressions, push hard and push fast [1], such high-quality chest compressions can indeed increase the ROSC rate. Research shows that the ROSC rates peaked at a compression rate of ~125/min and then declined, but a higher survival to hospital discharge rate was not seen [38]. Following BLS curriculum revision after publication of the 2010 guidelines, cardiac arrest was associated with a higher proportion of patients achieving ROSC but not survival to discharge [39]. Some research showed that after adjustment for chest compression fraction and depth, compression rates between 100 and 120 per minute were associated with greatest survival to hospital discharge [40]. These data suggest an optimum target of between 100 and 120 compressions per minute. Consistent rates above or below that range appear to reduce survival to discharge [41]. When exceeding a certain range, the faster the compression rate is, the shorter the diastolic time of the heart is, which will lead to a decrease in blood volume of the heart and reduce the effectiveness of compressions. On the other hand, there was an inverse association between depth and compression rate [42], which may imply that the excessive increase of compression speed is difficult to guarantee the depth of compression. For survival to discharge, Stiell’s study revealed that the maximum survival is at a depth of 45.6 mm (15-mm interval with highest survival between 40.3 and 55.3 mm) with no differences between men and women, suggesting that the 2010 American Heart Association cardiopulmonary resuscitation guideline target may be too high [43]. Vadeboncoeur et al. assessed that each 5mm increase in mean chest compressions depth significantly increased the odds of survival and survival with favorable functional outcome: OR 1.29 (95% CI 1.00-1.65) and OR 1.30 (95% CI 1.00-1.70) respectively [44]. Chest compression depth and rate were associated with ROSC and survival outcomes. Our 6
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goal after CPR is to have higher ROSC rates and better neurological function, but this meta-analysis was unable to find any of these statistical improvements after the change to the 2010 guidelines. In another meta document [45], chest compression depth was significantly associated with survival to hospital discharge (mean difference (MD) between survivors and non-survivors 2.59mm, 95% CI: 0.71, 4.47); and with ROSC (MD 0.99mm, 95% CI: 0.04, 1.93). Within the range of approximately 100-120 compressions per minute, compression rate was significantly associated with survival to hospital discharge. Moreover, hospital discharge is related to the patient’s own disease, follow-up treatment, and hypoxia time during CPR process [6]. This review showed that overall pooled rate of hospital discharge from in-hospital CPR do not appear to have made a difference after 2010. But for out-of-hospital cardiac arrest, overall rates of survival improved dramatically with accompanying lower rates of neurological disability, as well as increasing rates of bystander CPR and AED use during the study period [46]. One reason that the 2010 guidelines might make a difference in out-of-hospital but not in-hospital is that bystanders who are not healthcare professionals and who do not have personal protective equipment available are hesitant to provide mouth-to-mouth to strangers, whereas in a healthcare setting responders have gloves, masks, etc., and can treat the airway with bag-valve-masks or intubation while avoiding skin-to-skin contact. Another reason might be that often in-hospital arrests have large code response teams, so someone is able to provide continuous compressions while a second person is able to provide respirations simultaneously. How to get higher ROSC rates and better outcomes are areas which deserve more discussion. This review is based on observational, real-world clinical data from five continents. In heterogeneity analysis, the rate of ROSC is not related to CPR guidelines version, continent, time, sample source, or intervention. In the future, studies on CPR from large databases is a way to reduce heterogeneity, since sample size is one of the sources of heterogeneity.
5. Study limitations
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However, these individual studies had potential limitations. First of all, only reports in English literature were included in our study, which led to the loss of raw data from reports in other languages. There were two studies in other languages were excluded. We also excluded two documents [47,48] because their data come from Get With The Guidelines® (GWTG)‐ Resuscitation (2000 - 2010), which is the same as Chan PS’s study (2007 - 2010) [32]. Only five studies examined the 2010 CPR guidelines. Another limitation is that we do not know when hospitals retrained their staff. Likely there was a fair amount of lag between the announcement of the new guidelines in Dec 2010 and when hospital staff would have started using the new guidelines. Selection bias and confounding seem inevitable because most of the research is from observational studies. Other potential sources of heterogeneity included race, discharge standards and with other specific sources such as hospital size, hospital quality, lag time between arrest and code response, who responded to the code (nurse, physician, resident). Such heterogeneity should be considered in any meta-analysis.
6. Conclusions In conclusion, the 2010 CPR guidelines emphasize that high-quality chest compressions can increase the ROSC rate when initiated early without delaying for airway interventions, 7
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however this change to the 2010 guidelines has not improved ROSC rates or survival-to-discharge for in-hospital cardiac arrest when compared to 2005 CPR guidelines. It is worth considering that appropriate compression rate and depth appears to have stronger evidence for improvement in outcomes of cardiopulmonary resuscitation.
RI P
Competing interest
The authors declare that they have no conflict of interest. The study was not supported by any fund.
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References
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1. Hazinski MF, Nolan JP, Billi JE, Böttiger BW, Bossaert L, de Caen AR, et al. Part 1: Executive summary: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation. 2010; 122(16 Suppl 2):S250-75 2. Couper K, Kimani PK, Abella BS, Chilwan M, Cooke MW, Davies RP, et al. The System-Wide Effect of Real-Time Audiovisual Feedback and Postevent Debriefing for In-Hospital Cardiac Arrest: The Cardiopulmonary Resuscitation Quality Improvement Initiative. Crit Care Med. 2015;43(11):2321-31 3. Wolfe H, Zebuhr C, Topjian AA, Nishisaki A, Niles DE, Meaney PA, etal. Interdisciplinary ICU cardiac arrest debriefing improves survival outcomes. Crit Care Med. 2014;42(7):1688-95 4. Chan PS, McNally B, Tang F, Kellermann A; CARES Surveillance Group. Recent Trends in Survival from Out-of-Hospital Cardiac Arrest in the United States. Circulation. 2014; 130(21): 1876–82 5. Song KJ, Shin SD, Park CB, Kim JY, Kim do K, Kim CH, et al. Dispatcher-assisted bystander cardiopulmonary resuscitation in a metropolitan city: a before–after population-based study. Resuscitation. 2014 ;85(1):34-41 6. Siriphuwanun V, Punjasawadwong Y, Lapisatepun W, Charuluxananan S, Uerpairojkit K. Prognostic factors for death and survival with or without complications in cardiac arrest patients receiving CPR within 24 hours of anesthesia for emergency surgery[J]. Risk Management & Healthcare Policy, 2014, 7(7):199-210 7.Donoghue AJ, Abella BS, Merchant R, Praestgaard A, Topjian A, Berg R, et al. Cardiopulmonary resuscitation for in-hospital events in the emergency department: A comparison of adult and pediatric outcomes and care processes. Resuscitation. 2015;92:94-100 8. Gates S, Quinn T, Deakin CD, Blair L, Couper K, Perkins GD. Mechanical chest compression for out of hospital cardiac arrest: Systematic review and meta-analysis. Resuscitation. 2015;94:91-7 9. Morimura N, Sakamoto T, Nagao K, Asai Y, Yokota H, Tahara Y, et al. Extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: A review of the Japanese literature. Resuscitation. 2011;82(1):10-4 10. Wang CH, Huang CH, Chang WT, Tsai MS, Liu SS, Wu CY, et al. Biphasic versus monophasic defibrillation in out-of-hospital cardiac arrest: a systematic review and 8
ACCEPTED MANUSCRIPT
AC
CE
PT
ED
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T
meta-analysis. Am J Emerg Med. 2013;31(10):1472-78 11. Lin S, Callaway CW, Shah PS, Wagner JD, Beyene J, Ziegler CP, et al. Adrenaline for out-of-hospital cardiac arrest resuscitation: a systematic review and meta-analysis of randomized controlled trials. Resuscitation. 2014;85(6):732-40 12. Huang Y, He Q, Yang M, Zhan L. Antiarrhythmia drugs for cardiac arrest: a systemic review and meta-analysis. Crit Care. 2013;17(4):R173 13. Mundell WC, Kennedy CC, Szostek JH, Cook DA. Simulation technology for resuscitation training: a systematic review and meta-analysis. Resuscitation. 2013;84(9):1174-83 14. Hesham S. Taha , Sameh W.G. Bakhoum, Hussein H. Kasem, Mera A.S. Fahim. Quality of cardiopulmonary resuscitation of in-hospital cardiac arrest and its relation to clinical outcome: An Egyptian University Hospital Experience. The Egyptian Heart Journal. 2015; 67:137–43. 15. S.M. Lutchmedial, A.B. Levitov, P. Katyal, J. John, R.K. Herbertson, S. Malaisamy. In-hospital Cardiopulmonary Arrest: The Role Of BMI, Central Venous Catheter And Other Predictors Of Outcome. Am J Respir Crit Care Med. 2010;181:A4544 16. Müller MP, Richter T, Papkalla N, Poenicke C, Herkner C, Osmers A, et al. Effects of a mandatory basic life support training programme on the no-flow fraction during in-hospital cardiac resuscitation: an observational study. Resuscitation. 2014;85(7):874-8. 17. Mentzelopoulos SD, Malachias S, Chamos C, Konstantopoulos D, Ntaidou T, Papastylianou A, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA. 2013;310(3):270-9. 18. Akhtar N, Field RA, Greenwood L, Davies RP, Woolley S, Cooke MW, et al. Quality of in-hospital cardiac arrest calls: a prospective observational study. BMJ Qual Saf. 2012; 21(3):184-90. 19. Tarmey NT, Park CL, Bartels OJ, Konig TC, Mahoney PF, Mellor AJ. Outcomes following military traumatic cardiorespiratory arrest: A prospective observational study. Resuscitation. 2011;82(9):1194-7. 20. Olasveengen TM, Vik E, Kuzovlev A, Sunde K. Effect of implementation of new resuscitation guidelines on quality of cardiopulmonary resuscitation and survival. Resuscitation. 2009;80(4):407-11. 21. Mentzelopoulos SD, Zakynthinos SG, Tzoufi M, Katsios N, Papastylianou A, Gkisioti S et al. Vasopressin, epinephrine, and corticosteroids for in-hospital cardiac arrest. Arch Intern Med. 2009;169(1):15-24. 22. Nolan JP, Soar J, Smith GB, Gwinnutt C, Parrott F, Power S, et al. Incidence and outcome of in-hospital cardiac arrest in the United Kingdom National Cardiac Arrest Audit. Resuscitation. 2014;85(8):987-92. 23. M Ahmed, A Kochhar and O Rose. One-year assessment of in-hospital cardiac arrest. Critical Care. 2014;18(Suppl 1):P493 24. Lee HK, Lee H, No JM, Jeon YT, Hwang JW, Lim YJ, et al. Factors influencing outcome in patients with cardiac arrest in the ICU. Acta Anaesthesiol Scand. 2013;57(6):784-92. 25. Chon GR, Lee J, Shin Y, Huh JW, Lim CM, Koh Y, et al. Clinical outcomes of witnessed and monitored cases of in-hospital cardiac arrest in the general ward of auniversity hospital in 9
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PT
ED
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Korea. Respir Care. 2013;58(11):1937-44. 26. Chan JC, Wong TW, Graham CA. Factors associated with survival after in-hospital cardiac arrest in Hong Kong. Am J Emerg Med. 2013;31(5):883-5. 27. Chakravarthy M, Mitra S, Nonis L. Outcomes of in-hospital, out of intensive care and operation theatre cardiac arrests in a tertiary referral hospital. Indian Heart J. 2012;64(1):7-11. 28. Sodhi K, Singla MK, Shrivastava A. Impact of advanced cardiac life support training program on the outcome of cardiopulmonary resuscitation in atertiary care hospital. Indian J Crit Care Med. 2011;15(4):209-12. 29. Einav S, Bromiker R, Weiniger CF, Matot I. Mathematical modeling for prediction of survival from resuscitation based on computerized continuous capnography: proof of concept. Acad Emerg Med. 2011;18(5):468-75. 30. Ong ME, Tiah L, Leong BS, Tan EC, Ong VY, Tan EA, et al. A randomised, double-blind, multi-centre trial comparing vasopressin and adrenaline in patients with cardiac arrest presenting to or in the Emergency Department. Resuscitation. 2012;83(8):953-60. 31. Khasawneh FA, Kamel MT, Abu-Zaid MI. Predictors of cardiopulmonary arrest outcome in a comprehensive cancer center intensive care unit. Scand J Trauma Resusc Emerg Med. 2013, Mar 20;21:18 32. Chan PS, Berg RA, Spertus JA, Schwamm LH, Bhatt DL, Fonarow GC, et al. Risk-standardizing survival for in-hospital cardiac arrest to facilitate hospital comparisons. J Am Coll Cardiol. 2013;62(7):601-9. 33. Bhalala US, Bonafide CP, Coletti CM, Rathmanner PE, Nadkarni VM, Berg RA, et al. Antecedent bradycardia and in-hospital cardiopulmonary arrest mortality in telemetry-monitored patients outside the ICU. Resuscitation. 2012;83(9):1106-10. 34. Edelson DP, Litzinger B, Arora V, Walsh D, Kim S, Lauderdale DS, et al. Improving in-hospital cardiac arrest process and outcomes with performance debriefing. Arch Intern Med. 2008;168(10):1063-69. 35. Yokoyama H, Yonemoto N, Yonezawa K, Fuse J, Shimizu N, Hayashi T, et al. Report from the Japanese registry of CPR for in-hospital cardiac arrest (J-RCPR). Circ J. 2011;75(4):815-22. 36. Amer MS, Abdel Rahman TT, Aly WW, Ahmad NG. Cardiopulmonary resuscitation: outcome and its predictors among hospitalized elderly patients in Egypt. Geriatr Gerontol Int. 2014;14(2):309-14. 37. Toledo FO, Gonzalez MM, Sebbag I, Lelis RG, Aranha GF, Timerman S, et al. Outcomes of patients with trauma and intraoperative cardiac arrest. Resuscitation. 2013;84(5):635-38. 38. Idris AH, Guffey D, Aufderheide TP, Brown S, Morrison LJ, Nichols P, et al. Relationship between chest compression rates and outcomes from cardiac arrest. Circulation. 2012;125(24):3004-12. 39. Müller MP, Richter T, Papkalla N, Poenicke C, Herkner C, Osmers A, et al. Effects of a mandatory basic life support training programme on the no-flow fraction during in-hospital cardiac resuscitation: an observational study. Resuscitation. 2014;85(7):874-8. 40. Idris AH, Guffey D, Pepe PE , Brown SP, Brooks SC, Callaway CW, et al . Chest compression rates and survival following out-of-hospital cardiac arrest. Crit Care Med. 2015;43(4):840-8 41. Meaney PA, Bobrow BJ, Mancini ME, Christenson J, de Caen AR, Bhanji F, et al. 10
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Cardiopulmonary resuscitation quality: [corrected] improving cardiac resuscitation outcomes both inside and outside the hospital: a consensus statement from the American Heart Association. Circulation. 2013;128(4):417-35 42. Stiell IG, Brown SP, Christenson J, Cheskes S, Nichol G, Powell J, et al. What is the Role of Chest Compression Depth during Out-of-Hospital Cardiac Arrest Resuscitation? Crit Care Med. 2012;40(4):1192-8 43. Stiell IG, Brown SP, Nichol G, Cheskes S, Vaillancourt C, Callaway CW, et al. What is the optimal chest compression depth during out-of-hospital cardiac arrest resuscitation of adult patients? Circulation. 2014;130(22):1962-70 44. Vadeboncoeur T, Stolz U, Panchal A, Silver A, Venuti M, Tobin J, et al. Chest compression depth and survival in out-of-hospital cardiac arrest. Resuscitation. 2014;85(2):182-8. 45. Talikowska M, Tohira H, Finn J. Cardiopulmonary resuscitation quality and patient survival outcome in cardiac arrest: A systematic review and meta-analysis. Resuscitation. 2015 Nov;96:66-77. 46. Chan PS, McNally B, Tang F, Kellermann A, CARES Surveillance Group. Recent trends in survival from out-of-hospital cardiac arrest in the United States. Circulation. 2014;130(21):1876-82. 47. Bradley SM, Huszti E, Warren SA, Merchant RM, Sayre MR, Nichol G. Duration of hospital participation in Get With the Guidelines-Resuscitation and survival of in-hospital cardiac arrest. Resuscitation. 2012;83(11):1349-57 48. Girotra S, Cram P, Spertus JA, Nallamothu BK, Li Y, Jones PG, et al. Hospital variation in survival trends for in-hospital cardiac arrest. J Am Heart Assoc. 2014;3(3):e000871.
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ACCEPTED MANUSCRIPT Table 1
The Characteristics of The Studies Included in This Meta-analysis.
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Survival Age
to
Reference
Countr
Sample
Inclusion
Interven
N(%Mal
ran
Mean
ROSC
discharge
(first author)
y
source
period
tion
e)
ge
age
(%)
(%)
67-68
28(48)
11(19)
Study in 2005 CPR guidelines
2014
[16]
Germa
single
CPR
ny
hospital
2008-2010
team
multipl
58(72.4)
lt
e
os SD,
hospital
2008.9-201
interven
268(68.
≧1
s
0.10
tion
3)
8
63
104(62.
adu
49.7±1
5)
lt
5.3
131(64.
≧1
61.0±1
2013
Greece
ICU of Khasawneh [31]
FA, 2013
USA
single
2008.1-200
hospital
9.6
ICU of
Korea
Chon G.R, 2013
[25]
Korea
2009.1-201
ED
2013
single
[24]
NI
200(75 )
25(9)
36(35)
6(6)
hospital
0.6
NI
9)
8
6.5
96(73)
single
2008.3-201
CPR
238(59.
≧1
61.3±1
151(63
0.2
7)
8
5.2
)
431(61.
24-
7)
97
PT
Lee HK,
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Mentzelopoul [17]
drug
adu
SC
Müller MP,
hospital
team
s
8.12
NI
single
2007.1-200
hospital
9.12
46(19)
two
2013
hospital
[26]
China
Toledo FO, 2013[37] [32]
AC
Brazil
Chan PS, 2013
CE
Chan JC,
USA
2008.1-200
73.6
)
23(5)
55±22
46(57)
13(16)
≧1 NI
81(61.7)
8
48841(5 GWTG
139(32
2007-2010
NI
8.3)
>18
65.6±1
10290(2
6.1
1)
multipl e
Akhtar N, 2012
[18]
Englan
hospital
2009.12-20
CPR
d
s
10.4
team
adu 191(/)
lt
/
73(38)
64.6-6
225(31
4.9
)
39(20)
multipl e Ong ME, 2012
[30]
drug
Singap
hospital
2006.3-200
interven
727(69.
ore
s
9.1
tion
4)
>16
19(3)
two Bhalala US, 2012
[33]
2008-
s
2010
single
2007.3-200
India
hospital
9.3
NI
78(60.3)
lt
/
50(64)
24(31)
UK
single
2009.12-20
hospital’
52(100)
18-
24.5
14(27)
4(8)
USA
Chakravarthy M, 2012
[27]
Tarmey NT,
≧1
hospital
NI
98(63.3)
8
73
39(40)
adu
12
ACCEPTED MANUSCRIPT 2011[19]
hospital
10.6
s trauma
36
India
Yokoyama H, 2011
[35]
Japan
Einav S, 2011
single
2009.1-201
CPR
627(55.
hospital
0.6
team
8)
>14
57
)
J-RCP
2008.1-200
491(63.
≧1
71.0±1
318(65
R
9.12
3)
8
)
136(28)
74
17(57)
6(20)
36(14)
29(11)
NI
single
[29]
Israel
Lutchmedial
CPR
hospital
2008-2010
single
2008.7-200
team
S, 2010[15]
USA
hospital
9.4
NI
Olasveengen
Norwa
single
2006.1-200
CPR
y
hospital
7.12
team
TM, 2009
[20]
drug
2009
)
63(13)
66(66)
11(11)
73(59)
9(7)
8
65-69
single
2006.2-200
CPR
123(48.
≧1
60.7±1
USA
hospital
7.3
team
0)
8
6
23554(5
≧1
UK
NCAA
3.3
5.0)
6
73.9
45)
single
2011.1-201
380(36.
≧6
67.98±
124(33
8)
0
7.9
)
32(8)
67-72
44(72)
21(34)
2011.4-201
Egypt
hospital
Germa
single
Ahmed M, UK
2.6
NI
NI
CPR
OD
NI
hospital
2011-2012
NCEP
2011.1-201
CE
2014
64±18
0)
ny
[23]
lt
tion
PT
2014
[16]
6)
147(30
7.3
Michael P. Müller,
adu
hospital
ED
2014
482(66.
≧1
Amer M.S, [36]
lt
100(59.
Nolan J.P, 2014[ [22]
adu
interven
Edelson DP, 2008
92
264(70.
2006.6-200
Greece
[34]
30(50.0)
0)
4.9
79(13)
single
os SD, [21]
16-
MA NU
Mentzelopoul
149(24
RI P
2011
[28]
SC
Sodhi K,
T
team
2.9
team
10607( 4153(18)
adu 61(63.9)
lt adu
69(/)
lt
/
126(63.
≧1
56.4±1
5)
8
4.8
7(10)
multipl
AC
e
Taha H.S, 2015
[14]
Egypti
hospital
2012.3-201
an
s
2.12
NI
60(48)
9(7)
NCEPOD: National Confidential Enquiry into Patient Outcome and Death GWTG: Get With The Guidelines (GWTG)-Resuscitation NCAA: United Kingdom (UK) National Cardiac Arrest Audit database J-RCPR: registry of in-hospital CPA and resuscitation in Japan ROSC: return of spontaneous circulation NI: no intervention N: number of patients in the study
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-0.21-0.54 -0.10-0.10 -.016-0.17 -0.11-0.07 -0.07-0.28 -0.54-0.03
0.361 0.939 0.097 0.597 0.214 0.030
-0.25-0.17 -0.08-0.03 -0.05-0.05 -0.05-0.05 -0.16-0.03 -0.13-0.12
0.691 0.298 0.869 0.973 0.187 0.935
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16.57 -00.36 7.96 -2.28 10.46 -28.74 -4.00 -2.75 -0.40 00.08 -6.32 -0.51
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Return of spontaneous circulation Guide Version(2005 CPR VS 2010 CPR) Continent a Sample source b Time to start collecting data Intervention c Sample size (≥500 vs. <500) Survival to hospital discharge Guide Version(2005 CPR VS 2010 CPR) Continent Sample source Time to start collecting data Intervention Sample size (≥500 vs. <500)
95%CI
T
Meta regression coefficient (%)
Continent: Europe, Asia, USA, others
b
Sample source: ICU of hospital, single hospital, multiple hospitals, the National Registry of CPR.
c
Intervention: no intervention, drug interventions, CPR teams or trauma team
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