The global survival rate among adult out-of-hospital cardiac arrest patients who received cardiopulmonary resuscitation: a systematic review and meta-analysis

Background To quantitatively summarize the available epidemiological evidence on the survival rate of out-of-hospital cardiac arrest (OHCA) patients who received cardiopulmonary resuscitation (CPR). Methods We systematically searched the PubMed, Embase, and Web of Science databases, and the references of retrieved articles were manually reviewed to identify studies reporting the outcome of OHCA patients who received CPR. The overall incidence and outcome of OHCA were assessed using a random-effects meta-analysis. Results A total of 141 eligible studies were included in this meta-analysis. The pooled incidence of return of spontaneous circulation (ROSC) was 29.7% (95% CI 27.6–31.7%), the rate of survival to hospital admission was 22.0% (95% CI 20.7–23.4%), the rate of survival to hospital discharge was 8.8% (95% CI 8.2–9.4%), the pooled 1-month survival rate was 10.7% (95% CI 9.1–13.3%), and the 1-year survival rate was 7.7% (95% CI 5.8–9.5%). Subgroup analysis showed that survival to hospital discharge was more likely among OHCA patients whose cardiac arrest was witnessed by a bystander or emergency medical services (EMS) (10.5%; 95% CI 9.2–11.7%), who received bystander CPR (11.3%, 95% CI 9.3–13.2%), and who were living in Europe and North America (Europe 11.7%; 95% CI 10.5–13.0%; North America: 7.7%; 95% CI 6.9–8.6%). The survival to discharge (8.6% in 1976–1999 vs. 9.9% in 2010–2019), 1-month survival (8.0% in 2000–2009 vs. 13.3% in 2010–2019), and 1-year survival (8.0% in 2000–2009 vs. 13.3% in 2010–2019) rates of OHCA patients who underwent CPR significantly increased throughout the study period. The Egger’s test did not indicate evidence of publication bias for the outcomes of OHCA patients who underwent CPR. Conclusions The global survival rate of OHCA patients who received CPR has increased in the past 40 years. A higher survival rate post-OHCA is more likely among patients who receive bystander CPR and who live in Western countries. Electronic supplementary material The online version of this article (10.1186/s13054-020-2773-2) contains supplementary material, which is available to authorized users.

results were inconsistent across studies. The purpose of this systematic review and meta-analysis was to estimate the overall incidence of the return of spontaneous circulation (ROSC), the survival to admission rate, the survival to discharge rate, the 1-month survival rate, and the 1-year survival rate of patients after OHCA who received CPR worldwide.

Methods
This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [14] and the Metaanalysis of Observational Studies in Epidemiology (MOOSE) checklist [15].

Search strategy
Studies that reported survival rates among OHCA patients who underwent CPR were identified from the PubMed, Embase, and Web of Science databases from their inception to February 2019. The search terms were "out-of-hospital cardiac arrest" or "out-of-hospital ventricular fibrillation/ventricular tachycardia/ asystole/pulseless electrical activity" or "cardiopulmonary resuscitation" or "CPR" or "mouth to mouth" or "resuscitation" or "resuscitation orders" or "survival" or "survival rate" or "mortality" or "sudden cardiac death". Only articles published in English were considered. Additionally, we manually reviewed the references listed in the retrieved articles to identify additional pertinent publications.

Inclusion criteria and exclusion criteria
Studies were included if they met the following eligibility criteria: (1) the study design was based on the Utsteinstyle reporting guidelines; (2) the study population was composed of adults, which included any study in which less than 20% of study population were pediatric patients (age < 18 years); (3) the outcome variables were at least one of the following: ROSC, survival to admission rate, survival to hospital discharge rate, 1-month survival rate, and 1-year survival rate; (4) cardiac arrest happened outside the hospital; and (5) the study design was prospective, retrospective, or interventional. Reviews, letters, editorials, guidelines, and case reports were excluded. When multiple publications were produced using the same study population, the most recent and informative paper was included.

Data extraction
Two independent reviewers (YG and NJ) performed the data extraction. The following data were extracted from the studies: the first author's name, region of population, year of publication, sex, number of cardiac arrests and survivors, cardiac arrest witness type, provision of CPR, and origin of cardiac arrest. The rate of survival to hospital discharge was considered the primary outcome; ROSC, the rate of survival to hospital admission, 1-month survival rate and 1-year survival rate were also analyzed as outcome variables. Any disagreements between the investigators were discussed, and an agreement was reached through consensus.

Statistical analysis
A random-effects model was used to estimate the survival rates among OHCA patients who received CPR [16]. Studies that reported the survival outcomes of OHCA patients who received CPR (ROSC, survival to admission rate, survival to discharge rate, 1-month survival rate, and 1-year survival rate) were treated as independent reports.
Statistical heterogeneity across studies was assessed with the I 2 statistic, where values of 25%, 50%, and 75% represented the cut-off points for low, moderate, and high levels of heterogeneity, respectively [17]. Publication bias was evaluated with funnel plots and Egger's test [18]. Subgroup analyses stratified by sex, study location, study period, origin of OHCA, CPR type, and cardiac arrest witness type were conducted to investigate potential sources of heterogeneity across subgroups and examine the robustness of the primary results. We performed sensitivity analyses by omitting one study at a time to assess the influence of any single study on the pooled survival rate estimates. All statistical analyses were conducted with STATA V.12.0 (StataCorp, College Station, TX). All tests were two-tailed with a significance level of 0.05.

Study selection
The process of study selection, identification, and inclusion using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram is presented in Fig. 1. Initially, 5502 articles were retrieved from the PubMed, Embase, and Web of Science databases. In addition, we identified 13 articles by manually searching the reference lists of the retrieved articles. After removing 915 duplicate articles, we further excluded 4371 articles based on the titles and abstracts, including 336 nonhuman studies and 280 reviews, editorials, letters, guidelines or case reports. A total of 229 articles were selected for further full texts assessment. After retrieving the full-text for evaluation in detail, 88 articles were excluded because their study populations were pediatric patients, their primary outcome focused on the neurological survival rate or they were multiple publications produced using the same study population. Finally, a total of 141 studies were included in the present meta-analysis. The references of the studies included in the meta-analysis are listed in the Additional file 1.

Characteristics and quality of the studies included
The characteristics of the 141 included studies are shown in Supplementary Table 1. These studies were conducted on 4 continents. Fifty-six studies were conducted in Europe, 48 in North America, 29 in Asia, 6 in Oceania, and two in both Europe and North America. A total of 31 studies reported the survivors and study population stratified by sex. The year of publication ranged from 1976 to 2019. In total, 4,610,669 OHCA patients who underwent CPR were involved in this study.
We included 62 studies that reported the incidence of ROSC, 88 studies that explored the rate of survival to admission, 103 studies that assessed the rate of survival to discharge, 33 studies that investigated the 1-month survival rate, and 22 studies that reported the 1-year survival rate. Nineteen studies included pediatric patients, but less than 20% of study population was younger than 18 years.

ROSC
In this study, 62 studies with 74 reports reported the outcome of ROSC in OHCA patients who underwent CPR. From the random-effects meta-analysis, we found that the pooled incidence of ROSC among OHCA patients was 29.7% (95% CI, 27.6-31.7%) with significant heterogeneity across studies (I 2 = 99.9%, P < 0.001). Subgroup analyses showed significant differences in the incidence of prehospital ROSC by study location, the provider of CPR, and study period (Table 1). With regard to study location, Oceania had the highest incidence of ROSC (38.6%; 95% CI 22.9-54.2%), followed by Europe (36.7%; 95% CI 32.4-40.9%). Asia had the lowest incidence of ROSC (22.1%; 95% CI 18.1-26.0%). Regarding the provider of CPR, the incidence of ROSC was the highest among OHCA patients who had received CPR from emergency medical services (EMS) (36.3%; 95% CI 23.8-48.9%).

Survival to admission
A total of 88 studies with 122 reports estimated the incidence of survival to admission of OHCA patients who underwent CPR. From the random-effects meta-analysis, an incidence of 22.0% (95% CI 20.7-23.4%) for survival to admission was estimated globally among OHCA patients who received CPR.

Survival to discharge
One hundred and three studies with 168 reports investigated the rate of survival to discharge of OHCA patients who underwent CPR. From the random-effects metaanalysis, an incidence of 8.8% (95% CI 8.2-9.4%) for survival to discharge was estimated globally among OHCA patients, and there was high heterogeneity across studies (P < 0.001; I 2 = 97.6%) ( Table 1). The rate of survival to discharge of OHCA patients who received CPR increased from 8.6% (95% CI 7.7-9.5%) in 1976-1999 to 9.9% (95% CI 8.4-11.4%) in 2010-2019.

One-month survival rate
In total, 33 studies with 54 reports investigated the 1 month survival rate of OHCA patients who underwent CPR. From the random-effects meta-analysis, an incidence of 10.7% (95% CI 9.1-12.3%) for 1-month survival was estimated globally among OHCA patients who had received CPR, and there was high heterogeneity among the studies (P < 0.001; I 2 = 99.9%).

One-year survival rate
Twenty-seven reports from 22 studies investigated the 1 year survival rate of OHCA patients who underwent CPR. From the random-effects meta-analysis, an incidence of 7.7% (95% CI 5.8-9.5%) for 1-year survival was estimated globally among OHCA patients who received CPR, and there was high heterogeneity among the studies (P < 0.001; I 2 = 97.5%).

Publication bias
The funnel plot was symmetrical for the meta-analysis of the incidence of ROSC, survival to hospital admission, survival to hospital discharge, 1-month survival, and 1year survival in OHCA patients who received CPR (see Figs. 2, 3, 4, 5, and 6). The Egger's test revealed no evidence of publication bias among the studies that reported the incidence of ROSC, survival to admission, survival to hospital discharge, and 1-year survival rate (Egger's P = 0.362 for ROSC; Egger's P = 0.128 for survival to admission; Egger's P = 0.112 for survival to hospital discharge; Egger's P = 0.168 for 1-year survival). However, for the 1-month survival among OHCA patients who underwent CPR, we found that Egger's test revealed evidence of publication bias across studies (Egger's P < 0.05).

Discussion
This is the first comprehensive systematic review and metaanalysis bringing together 40 years of research to estimate the incidence of ROSC, rate of survival to admission, rate of survival to discharge, 1-month survival rate, and 1-year survival rate among OHCA patients who received CPR worldwide. We found that the pooled incidence of ROSC, and survival to admission, survival to discharge, 1-month survival, and 1-year survival rates were 29.7%, 22.0%, 8.8%, 10.7%, and 7.7%, respectively. In addition, much lower rates of the incidence of ROSC, survival to admission, and survival to discharge were observed across Asian countries and much higher survival to discharge, 1-month survival, and 1-year survival rates were found among OHCA patients who had received bystander CPR. Finally, survival to Two previous studies published in 2010 [19] and 2013 [20] investigated the survival rate of OHCA patients who received CPR. The results of this current metaanalysis generally concur and further complement the findings of a previous review in several important aspects. Van de Glind et al. [20] reported that the pooled survival to discharge among patients > 70 years of age was 4.1% (95% CI 3.0-5.6%), which was lower than that in the present study (8.8%: 95% CI 8.2-9.4%). One possible reason was that there were differences in the study population and sample size. The review by Van de Glind and colleagues included only 23 studies among older patients aged > 70 years. However, our study population included all age groups. Several studies showed that increasing age was significantly associated with worse survival [21][22][23]. Additionally, their review did not fully investigate other subgroups or perform sensitivity analyses. Sasson et al. [19] found that the pooled survival to hospital discharge rate was 7.6% (95% CI 6.7-8.4%). However, 62 studies were not included in their analysis because their search time was limited to 2008, which may have led to overestimation of the survival rate. In  addition, our review performed more detailed subgroup analyses (stratified by sex, study location, study period, type of OHCA, type of CPR, and type of cardiac arrest witness) to test the robustness of the results and explore the potential heterogeneity. Our subgroup analyses led to two valuable findings. First, much lower rates of ROSC, survival to admission, and survival to discharge were observed in Asian countries than in European counties. These observed differences may in part reflect the differences in first registered arrhythmia as VT/VF, witnessed collapse, bystander CPR, and early defibrillation in various countries [4,24]. These factors were significantly associated with the survival rates of OHCA patients [25][26][27]. Another explanation is that compared with North America and Europe, and the popularization of bystander CPR has been relatively delayed in Asia; thus, the quality of bystander CPR might be lower in Asia. In addition, a previous study showed that the thresholds of EMS protocols for initiating resuscitation are lower in Asian countries, [1] which was likely to contribute to the differences in the survival rates.
We also found much higher rates of survival to discharge, 1 month survival, and 1 year survival among OHCA patients who received bystander CPR, which was  consistent with the findings of previous studies [26,[28][29][30]. This suggests that efforts, such as targeted CPR training to increase the bystander CPR rate, will have a substantial effect on improving the survival rates after OHCA [6,31]. Thus, facilitating bystander CPR training is an important and effective measure that governments worldwide can implement to improve the outcome of OHCA patients.

Strengths and limitations
The present study has several strengths. First, this is the first study to date investigating the survival of OHCA patients worldwide. Second, based on the subgroup analysis, we showed that the survival to discharge rate was much lower in developing countries than in developed counties, and the ROSC and survival to discharge rates were decreasing. Finally, as the incidence of OHCA is increasing in modern society, the results of our study can not only serve as baseline data for the global assessment of OHCA prevention interventions (evidence-based region-specific guideline updates of CPR for OHCA) but also provide a reference for international comparisons. Potential limitations in this study need to be acknowledged. A high degree of heterogeneity was observed in this meta-analysis. The heterogeneity across studies may result from differences in the EMS system, research method, samples, provider and quality of CPR (e.g., bystander CPR, EMS CPR), and Utstein definition. However, the sensitivity analyses and consistent results from various subgroup analyses suggested that the estimates were relatively robust, and the heterogeneity can be overestimated when studies with large sample sizes are pooled. Second, only those studies published in English were included in this meta-analysis and studies in other languages were omitted. Third, the literature searches were carried out in three databases, which may be considered a source of bias.

Suggestions for further research
More effort should be put into future research. First, more studies should be included to explore the predictors of survival of OHCA and investigate the associations between survival after OHCA and the predictors (age, sex, location of cardiac arrest, response time, CPR by bystander or EMS-physician-guided CPR, AED utilization). This would help elucidate the reasons for improved survival and the underlying mechanisms. Second, investigating the quality of life and cognitive and functional changes in survivors after OHCA will be valuable. Finally, more studies validating the cost-effectiveness of bystander CPR training or AED utilization are warranted.

Conclusion
In conclusion, this meta-analysis suggests that the rates of survival to discharge, 1 month survival, and 1 year survival are increasing among OHCA patients who receive CPR globally. Relatively lower survival to discharge rates were observed in Asian countries. Higher rates of survival to discharge, 1-month survival, and 1-year survival were found among OHCA patients who had their cardiac arrest witnessed by EMS or a bystander and who received bystander CPR.