Introduction
Despite significant advances in the delivery of care, the survival rate of out-of-hospital cardiac arrest (OHCA) is poor [1]. According to study by Nadolny et al. [2] return of spontaneous circulation refers to 35.1% OHCA patients and only 28.7% patients are admitted to the hospital. Current recommendations of the American Heart Association (AHA) [3], as well as the European Resuscitation Council (ERC) [4], place great emphasis on high-quality cardiopulmonary resuscitation (CPR). This includes high-quality chest compressions [5] and minimizing interruptions during chest compressions [6].
Cardiopulmonary resuscitation can be a heavy burden for bystanders. In the past, bystanders often did not undertake CPR due to the resistance associated with the need to perform mouth-to-mouth ventilation [7, 8]. For this reason, the ERC and AHA guidelines have introduced two possible CPR techniques for bystanders. The first is the standard method of performing cycles based on 30 compressions with a pause for two ventilations (30:2). The second is based on continuous chest compression without the need for pauses for rescue breaths — which is intended to encourage people to undertake more frequent resuscitation efforts [9].
The systematic review and meta-analysis are aimed to evaluate the effect of standard CPR (sCPR) (30:2) and continuous chest compressions without rescue breaths (CCC) on resuscitation outcomes in patients with OHCA.
Methods
This systematic review and meta-analysis were conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions [10] and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [11].
Search strategy
Screening of papers and the data extraction were undertaken by two independent authors (K.B. and M.P.), using predefined selection criteria and a data extraction sheet. Disagreements were resolved by a third investigator (L.S.). PubMed, Web of Science, Scopus, EMBASE and Cochrane Collaboration database, English language articles published from the databases inception to 21st July 2021 were searched. The search was performed using the following terms: “cardiopulmonary arrest” OR “heart arrest” OR “cardiac arrest” OR “heart attack” OR “sudden cardiac death” OR “out-oh-hospital cardiac arrest” OR “OHCA” OR “asystole” OR “PEA” OR “pulseless electrical activity” OR “VF” OR “ventricular fibrillation” OR “VT” OR “ventricular tachycardia” AND “resuscitation” OR “CPR” OR “chest compression” OR “30:2” OR “conventional resuscitation” OR “continuous compression”. Additionally, we reviewed the bibliographies of the identified trials and evaluated review articles for relevant references.
Study selection
Included studies were required to document the following parameters: (1) Participants; OHCA in adult patients, (2) Intervention; conventional cardiopulmonary resuscitation, (3) Comparison; chest compression without ventilation (CC-CPR), (4) Outcomes; detailed information for mortality, (5) Study design; randomized controlled trials and observational studies.
Studies were excluded if they met the following criteria: (A) studies including pediatric patient; (B) were classed as Letter to Editor, Correspondence, or as an Editorial; (C) animal or simulation trials; (D) conference abstract; (E) guidelines. Studies were also excluded if the full paper was not available in English.
Outcomes
Primary end points were in-hospital or 30-day mortality and survival to hospital discharge with good neurological outcome defined as the cerebral performance category (CPC) score 1 or 2 [12]. Secondary end points were return of spontaneous circulation (ROSC) and survival to hospital admission.
Data extraction and quality assessment
Two reviewers (K.B. and J.C.) independently extracted and entered the following data into a predefined extraction table: study characteristics, mortality, and neurologic outcome. If multiple publications of the same dataset were obvious or confirmed by the authors, the one with the most extractable and complete information was chosen. Any discrepancies were resolved through discussion with a third reviewer (L.S.).
The risk of bias (RoB) of the included studies was independently assessed by 3 reviewers (K.B., A.G. and J.S.) according to the revised tool for risk of bias in randomized trials (RoB 2 tool) [13] and Risk of Bias in Non-randomized Studies — of Interventions (ROBINS-I) [14]. All disagreements were resolved by referral to a third author (L.S.) if necessary. ROBINS examines seven domains of bias: (1) confounding; (2) selection of participants; (3) classification of interventions; (4) deviations from intended interventions; (5) missing data; (6) measurement of outcomes; and (7) selection of the reported result. The overall ROBINS-I judgment at domain and study level was attributed according to the criteria specified in the ROBVIS tool [15].
Statistical analysis
All statistical analysis were performed using the STATA software (Version 13.0 StataCorp) and the Review Manager software (RevMan version 5.4; The Cochrane Collaboration 2014). Random-effects meta-analyses of continuous data with mean deviations (MDs) and their 95% confidence intervals (95% CIs) [16] were performed. For dichotomous data, odds ratios (ORs) as the effect measure with 95% CI were used. When the continuous outcome was reported in a study as median, range, and interquartile range, means and standard deviations were estimated using the formula described by Hozo et al. [17]. For meta-analysis the random effects model was used (assuming a distribution of effects across studies) to weigh estimates of studies in proportion to their significance [10].
Heterogeneity was assessed by the Cochran’s Q test and I2 statistics, with low, moderate, and high levels of heterogeneity designated as 25%, 50%, and 75%, respectively [18]. All variables were analyzed using the DerSimonian–Laird random effects model. Where there were fewer than 10 included studies, publication bias was unable to be formally assessed [10]. A p-value of less than 0.05 (2-tailed) was considered statistically significant.
Results
Search results and study characteristics
A PRISMA flowchart, including the reasons for excluding studies, is shown in Figure 1. A total of 1319 records were identified, of which duplicate records and further 783 records were excluded based on the title and abstract evaluation. After review of the remaining 39 articles in full, 15 articles [19–33] ultimately met the inclusive criteria and were included in the meta-analysis.
Table 1 details the characteristics of the selected trials. Included trials were published between 2000 and 2021, totaling 220,945 OHCA patients (80,051 in standard CPR group and 140,894 in the CCC group). Overall, 3 studies were randomized controlled trials [19–21] with the remaining being non-randomized [22–33].
|
Study |
Country |
Study design |
Standard cardiopulmonary |
Continuous chest compression |
||||
|
No. |
Age |
Sex, male |
No. |
Age |
Sex, male |
|||
|
Hallstrom et al. 2000 |
USA |
Randomized controlled trials |
279 |
68.5 |
181 (64.9%) |
241 |
67.9 |
145 (60.2%) |
|
Rea et al. 2010 |
Multi-country |
Randomized controlled trials |
960 |
63.9 ± 16.3 |
613 (63.9%) |
981 |
63.4 ± 16.5 |
659 (67.2%) |
|
Svensson et al. 2010 |
Sweden |
Randomized controlled trials |
656 |
NS |
444 (67.7%) |
620 |
NS |
412 (66.5%) |
|
Bobrow et al. 2010 |
USA |
Prospective observational |
666 |
63.8 ± 15.2 |
458 (68.8%) |
849 |
63.1 ± 15.1 |
578 (68.1%) |
|
Bohm et al. 2007 |
Sweden |
Retrospective cohort study |
8,209 |
63 ± 18 |
6,157 (75.0%) |
1,145 |
66 ± 16 |
882 (77.0%) |
|
Iwami et al. 2007 |
Japan |
Prospective, population-based, |
783 |
69.1 ± 16.1 |
483 (61.8%) |
544 |
68.2 ± 15.3 |
359 (66.2%) |
|
Javaudin et al. 2020 |
French |
Multicenter retrospective study |
1,544 |
64.1 ± 16.7 |
1,057 (68.5%) |
6,997 |
64.1 ± 16.7 |
1,057 (68.5%) |
|
Kitamura et al. 2018 |
Japan |
Retrospective cohort study |
41,013 |
74.1 ± 18.2 |
22,155 (54.0%) |
102,487 |
75.3 ± 15.9 |
60,901 (59.4%) |
|
Olasveengen 2008 |
Norway |
Retrospective, observational study |
281 |
63 ± 18 |
209 (74.4%) |
145 |
62 ± 18 |
97 66.9%) |
|
Ong et al. 2008 |
Singapore |
Prospective, multi-phase, |
287 |
56.0 ± 20.1 |
218 (76.0%) |
154 |
58.6 ± 15.8 |
115 (74.7%) |
|
Riva et al. 2019 |
Sweden |
Multicenter retrospective study |
11,920 |
69.5 ± 3.3 |
8,511 (71.4%) |
6,339 |
71.8 ± 3.2 |
4,412 (69.6%) |
|
Schmicker et al. 2021 |
USA |
Retrospective cohort study |
10,942 |
65.5 ± 4 |
6,904 (63.1%) |
15,868 |
66 ± 4 |
10,075 (63.5%) |
|
SOS-KANTO 2017 |
Japan |
Prospective, multi-center, |
712 |
68.3 ± 7.2 |
462 (64.9%) |
439 |
67.8 ± 7.2 |
316 (72.0%) |
|
Waalewijn et al. 2001 |
Netherlands |
Prospective study |
437 |
NS |
NS |
41 |
NS |
NS |
|
Wnent et al. 2021 |
Multi-center |
Prospective, multi-center study |
1,362 |
65.1 ± 19.0 |
912 (67.1%) |
4,044 |
66.7 ± 16.6 |
2,777 (68.7%) |
Risk of bias in included studies
RoB 2 and ROBINS-I tools were used to evaluate methodological quality and risk of bias respectively for the randomized and non-randomized studies. Summary of the risk of bias of included trials is presented in Supplementary data (Suppl. Figs. S1, S2).
Meta-analysis outcomes
A polled analysis of the 13 studies indicated survival to hospital discharge with sCPR was 10.2% compared to the 9.3% in CCC group (OR = 1.04; 95% CI: 0.93–1.16; p = 0.46; Table 2). Sub-analysis comparing survival to hospital discharge between sCPR and CCC was not significantly different in randomized (6.2% vs. 6.1%, respectively; OR = 0.94; 95% CI: 0.78–1.12; p=0.48) or non-randomized trials (10.9% vs. 9.8%; OR = 1.08; 95% CI: 0.95–1.24; p = 0.24).
|
Parameter |
No. of |
Events/participants |
Events |
Heterogeneity between trials |
P-value for |
|||
|
Standard cardiopulmonary resuscitation (sCPR) (30:2) |
Continuous chest |
OR |
95%CI |
P-value |
I2 statistic |
|||
|
SHD |
13 |
8,005/78,659 (10.2%) |
13,066/139,786 (9.3%) |
1.04 |
0.93–1.16 |
< 0.001 |
76% |
0.46 |
|
RCT |
3 |
753/12,176 (6.2%) |
1,036/17,086 (6.1%) |
0.94 |
0.78–1.12 |
0.20 |
37% |
0.48 |
|
Non-RCT |
10 |
7,252/66,483 (10.9%) |
12,030/122,700 (9.8%) |
1.08 |
0.95–1.24 |
< 0.001 |
78% |
0.24 |
|
SHD with good |
7 |
2,945/45,286 (6.5%) |
6,476/111,615 (5.8%) |
1.00 |
0.84–1.20 |
0.06 |
51% |
0.98 |
|
ROSC |
5 |
6,962/43,726 (15.9%) |
15,940/107,374 (14.8%) |
1.13 |
0.91–1.39 |
< 0.001 |
86% |
0.26 |
|
Survival to hospital |
5 |
1,154/3,911 (29.5%) |
3,229/11,381 (28.4%) |
1.20 |
0.89–1.63 |
< 0.001 |
85% |
0.24 |
Survival to hospital discharge with good neurological outcome (CPC 1 or 2) was reported in 7 studies and was 6.5% for sCPR compared to 5.8% for CCC (OR = 1.00; 95% CI: 0.84–1.20; p = 0.98). Five studies reported ROSC. Polled analysis showed that ROSC in sCPR and CCC groups was 15.9% and 14.8%, respectively (OR = 1.13; 95% CI: 0.91–1.39; p = 0.26).
Survival to hospital admission after ROSC was observed in 29.5% of participants in the sCPR group compared to 28.4% in CCC group (OR = 1.20; 95% CI: 0.89–1.63; p = 0.24).
Discussion
In this systematic review and meta-analysis, standard CPR with chest compression only for adult OHCA resuscitation was compared. No significant differences were found between both arms for all outcomes. It was felt that data supporting this important finding is sufficient to recommend changes in standard practice. While the number of individuals enrolled in the totality of randomized controlled trials [19–21] included in the present analysis is relatively limited (n = 3,737), not a single randomized trial demonstrated a significant clinical outcome benefit with the application of rescue breathing. When considered in conjunction with the large number of patients included in the observational trials (n = 213,123), the summation of the data equates to 216,680 patients and is sufficient to support the removal of rescue breathing from standard guidelines of bystander CPR in OHCA.
There are multiple reasons that compression only CPR should be the preferred option for bystander CPR. These include the fact that shared secretions that occur from mouth-to-mouth resuscitation serves as an impediment for adoption in unrelated bystanders, and because it is easier to instruct an unexperienced provider by telephone in the performance of chest compression only CPR when guidance is obtained remotely [34, 35]. Furthermore, in the time of a global pandemic, the performance of rescue breathing must be considered an avoidable high-risk activity for the transmission of pathogens from the patient to the rescue breathing provider [36–39].
It should be noted that the findings of the randomized controlled trials most likely represent the “best case scenario”. This is because the performance of these trials occurred in environments with extremely well-developed Emergency Medical Service (EMS) systems; most likely some of the most sophisticated on the globe. The fact that their outcomes show no benefit with the addition of rescue breathing to standard CPR practice suggests that there would be even less outcome improvement in systems with longer times to advanced cardiac life support and transport to hospital. Further, the majority of patients enrolled in the randomized controlled trials occurred in urban environments, in areas of relative wealth. It would not be expected that the addition of rescue breathing would be improved in a rural or poor environment.
Finally, while the numeric majority of the present data is obtained from observational trials performed in industrialized nations with relatively high performing EMS infrastructure, it was found that the summation of their reported outcomes were similar to the randomized controlled trials. In the largest (n = 143,500) observational trial [26], multivariate analysis and propensity matching reported significant outcome improvements with chest compression only CPR. Considering the next 3 largest observational studies [23, 29, 30], n = 68,530, found mixed results, with both Riva et al. [29], n = 30,445, and Schmicker et al. [30], n = 26,810, reporting improvements by the addition of rescue breathing, and Bohm et al. [23], n = 11,275, no difference in outcomes was found.
This meta-analysis should be interpreted with consideration of certain limitations. First, only 3 of the included studies are randomized controlled trials. The others are non-randomized studies that are assumed to carry a higher risk of unmeasured bias than randomized controlled trials. Another limitation is the fact that the included studies limited outcomes to discharge from hospital or 30 days after cardiac arrest. Only one study by Iwami et al. [24] reported an annual survival rate of 5.5% for standard CPR and 5.0% for CC-CPR, respectively.
Conclusions
In conclusion, the systematic review and meta-analysis concluded that there were no significant differences in the resuscitation outcomes between the use of standard CPR and chest compression only. The choice of standard CPR and chest compression without mouth-to-mouth ventilation remains the bystander’s preference, however guideline changes may be considered.
Acknowledgments
The study was supported by the ERC Research Net and by the Polish Society of Disaster Medicine.
