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Compression-only cardiopulmonary resuscitation vs standard cardiopulmonary resuscitation: an updated meta-analysis of observational studies
American Journal of Emergency Medicine 32 (2014) 517–523
Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Original Contribution
Compression-only cardiopulmonary resuscitation vs standard cardiopulmonary resuscitation: an updated meta-analysis of observational studies Lan Yao, MD a,b, Peng Wang, PhD b,c, Lili Zhou, MD, PhD b,c, Mingdi Chen, MD b,c, Yuanshan Liu, MD b,c, Xiaozhu Wei, MD b,c, Zitong Huang, MD b,c,⁎ a b c
Department of Emergency Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
a r t i c l e
i n f o
Article history: Received 9 December 2013 Received in revised form 26 January 2014 Accepted 26 January 2014
a b s t r a c t Objectives: To perform an updated meta-analysis of observational studies with unstratified cohort addressing whether compression-only cardiopulmonary resuscitation (CPR), compared with standard CPR, improves outcomes in adult patients with out-of-hospital cardiac arrest and a subgroup meta-analysis for the patients with cardiac etiology arrest. Methods: We searched the relevant literature from MEDLINE and EMBASE databases. The baseline information and outcome data (survival to hospital discharge, favorable neurologic outcome at hospital discharge, and return of spontaneous circulation on hospital arrival) were extracted both in an out-of-hospital cardiac arrest and cardiac origin arrest subgroup. Meta-analyses were performed by using Review Manager 5.0. Results: Eight studies involving 92 033 patients were eligible. Overall meta-analysis showed that standard CPR was associated with statistically improved survival to hospital discharge (risk ratio [RR], 0.95 [95% confidence interval, 0.91-0.99]) and return of spontaneous circulation on hospital arrival (RR, 0.95 [95% confidence interval, 0.92-0.99]) compared with compression-only CPR, but there is no significant difference in favorable neurologic outcome at hospital discharge between 2 CPR methods (RR, 0.97 [95% confidence interval, 0.91-1.04]). In the subgroup of patients with a cardiac cause of arrest, the pooled meta-analysis found compression-only CPR resulted in the similar survival to hospital discharge as standard CPR (RR, 0.99 [95% confidence interval, 0.94-1.05]). Conclusions: This meta-analysis found that compression-only CPR resulted in the similar survival rate as the standard CPR in the cardiac etiology subgroup. It is unclear for the patients with noncardiac cause of arrest and with long periods of untreated arrest. © 2014 Published by Elsevier Inc.
1. Introduction Out-of-hospital cardiac arrest is still a considerable public health issue [1]. The incidence of out-of-hospital cardiac arrest is estimated to be 213.1 per 1 000 000 population [2]. Good-quality and high-incidence of bystander cardiopulmonary resuscitation (CPR) can increase the chance of survival in out-of-hospital cardiac arrest [3,4]. Despite huge efforts to improve the effectiveness of bystander CPR over the past decades, the survival rate of bystander CPR remains low and there are always some controversial comments on the CPR method for bystander CPR [3,5]. Several randomized clinic studies showed that dispatcherassisted compression-only CPR led to better survival rate than standard
⁎ Corresponding author. Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. Tel.: +86 20 81332469; fax: +86 20 81332650. E-mail address: [email protected] (Z. Huang). http://dx.doi.org/10.1016/j.ajem.2014.01.055 0735-6757/© 2014 Published by Elsevier Inc.
CPR, although the difference was not statistically significant [6-8]. A meta-analysis study including only randomized controlled trials also found that compression-only CPR was significantly associated with improved survival rate to discharge compared with standard CPR [9,10]. In contrast, another meta-analysis of observation studies showed that there was no significant difference in survival between the 2 CPR methods [10]. Furthermore, a large-scale prospective study indicated that for patients with arrest due to noncardiac causes, standard CPR may actually have better benefits in survival rate than compression-only CPR [11]. At the same time, a single randomized clinic study and a large-scale observational study both found that compression-only CPR resulted in better outcomes compared with standard CPR in a cardiac origin arrest subgroup [8,12]. Hence, it was indicated that the stratified analysis of out-of-hospital cardiac arrest may be more reasonable and should be performed for the comparison of compression-only CPR and standard CPR. Because cardiac diseases are the most frequent cause of out-ofhospital cardiac arrest, we supposed that compression-only CPR may be more effective in patients with a cardiac cause of arrest. Previous meta-
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L. Yao et al. / American Journal of Emergency Medicine 32 (2014) 517–523
analyses did not conduct the analysis of cardiac origin arrest subgroup. Several new observational studies with stratified analysis have emerged [12,13]. Therefore, we performed an updated meta-analysis of observational studies with unstratified cohort addressing whether compressiononly CPR, compared with standard CPR, improves outcomes in adult patients with out-of-hospital cardiac arrest and a subgroup metaanalysis for the patients with cardiac etiology arrest.
2. Methods The study was performed in accordance with the guidelines from the Meta-analysis Of Observational Studies in Epidemiology group [14].
2.1. Literature search Two authors independently retrieved observational studies that compared compression-only CPR and standard CPR from MEDLINE and EMBASE databases between January 1, 1990, and October 1, 2013. The search terms included “chest compression-only,” “compression alone,” “hands-only,” “bystander CPR,” “standard CPR,” and “out-ofhospital cardiac arrest.” The search strategy is presented in Appendix A. In addition, we also reviewed the reference of retrieved articles for additional pertinent studies. We placed no language restrictions on the searches.
2.2. Inclusion and exclusion criteria Two authors independently screened the full texts of eligible articles according to inclusion and exclusion criteria. For inclusion, studies had to meet the following criteria: (1) observational clinic studies, (2) comparison of chest compression-only vs standard CPR, (3) out-of-hospital arrest, and (4) survival rate, return of spontaneous circulation (ROSC), or neurologic outcome data available. We excluded studies if they met the following exclusion criteria: (1) any other intervention (eg, public education plan), (2) duplicate publication and data, (3) only just for arrests of noncardiac origin, and (4) only just for children or old people. 2.3. Data extraction The baseline information was extracted from each study by 3 reviewers independently. We also obtained the following outcome data: survival to hospital discharge, favorable neurologic outcome at hospital discharge, and ROSC on hospital arrival. We considered 30-day survival data as survival rate to hospital discharge if the latter was not available, seeing that the 2 kinds of outcome nearly had the same data in some relevant studies [15]. We also used the rate of consciousness 14 days after CPR instead of survival data to hospital discharge when the information was unavailable [16]. Favorable neurologic outcome was defined as a Glasgow-Pittsburgh cerebral-performance category of 1 or 2 on a 5-category scale [17]. Meanwhile, these outcome data in the subgroup of patients with a cardiac cause of arrest were extracted from
Potentially relevant articles in the initial literature search n = 872
Articles excluded based on title and abstract n = 821
Full-text articles assessed for eligibility n = 51
Observational studies included in the meta-analysis n=8 (n = 3 with survival data of the cardiac etiology subgroup)
Articles excluded according to inclusion and exclusion criteria n = 43 Reasons for exclusion not observational clinic studies n = 19 reviews n = 5 duplicate data n = 2 with any intervention n = 1 just for arrests of non-cardiac origin n = 3 just only for children or old people n = 5
Fig. 1. Flowchart representing the selection process.
L. Yao et al. / American Journal of Emergency Medicine 32 (2014) 517–523
selected articles. The cardiac origin arrest subgroup include the patients whose arrest was presumed to be of cardiac origin, unless it was known to be caused by trauma, hanging, drowning, drug overdose, asphyxia, or any other noncardiac causes [12,18]. 2.4. Statistical analysis Meta-analyses were performed by using Review Manager 5.0 (the Cochrane Information Management System, http://ims.cochrane.org/ revman). Risk ratios (RRs) and 95% confidence intervals were calculated and pooled in both a fixed-effects model and a random-effects model, which was used to control for heterogeneity [19]. The quality of each study was assessed independently by 2 authors with the NewcastleOttawa Scale [20]. Besides the primary meta-analysis with an unstratified cohort in out-of-hospital cardiac arrest, a subgroup meta-analysis for the patients with cardiac etiology arrest was performed. We examined for potential publication bias with funnel plots. The heterogeneity among studies was assessed by the Cochran Q and I2 statistics. Sensitivity analyses were performed by using random-effect methods. 3. Results 3.1. Search results A total of 872 relevant citations were ascertained from the initial literature search. Eight hundred twenty-one articles were excluded based on title and abstract. According to inclusion and exclusion criteria, 2 authors assessed the full text of remained articles and excluded 43 articles. In the final analysis, 8 articles totally were included [12,16-18,21-24] (Fig. 1). 3.2. Study characteristics Baseline information of the 8 observational cohort studies including author's last name, year of publication, country of population studies, numbers of survivors in different groups, and so on (Table 1). All eligible studies included 54 018 patients with compression-only CPR and 38 015 patients with standard CPR. Of the 8 studies, 3 articles provided survival rates in the subgroup of patients with a cardiac cause of arrest. The quality of these studies was high (Table 2).
519
3.3. Data and statistical analysis Most of these observational studies found that there was no significant difference in survival between the compression-only CPR group and the standard CPR group, but overall meta-analysis showed that standard CPR was associated with statistically improved survival data to hospital discharge compared with compression-only CPR (RR, 0.95 [95% confidence interval, 0.91-0.99]; Fig. 2). Standard CPR was also associated with a statistically improved ROSC on hospital arrival (RR, 0.95 [95% confidence interval, 0.92-0.99]; Fig. 3). However, after pooling 4 studies referring to neurologic outcome in a meta-analysis, it showed no difference in favorable neurologic outcome at hospital discharge between the compression-only CPR group and the standard CPR group (RR, 0.97 [95% confidence interval, 0.91-1.04]; Fig. 4). The heterogeneity among these studies was nearly neglected (I 2 = 0). In the subgroup of patients with a cardiac cause of arrest, the pooled meta-analysis found that there was no significant difference in survival rate to hospital discharge (RR, 0.99 [95% confidence interval, 0.94-1.05]) with no evidence of heterogeneity as indicated by an I 2 of 0 (Fig. 5). However, only the study in 2013 referred to neurologic outcome and considered compression-only CPR led to better 30-day favorable neurologic outcome than standard CPR in the subgroup with cardiac etiology [12]. Overall funnel plots were not suggestive for publication bias (Fig. 6). Sensitivity analyses using random-effect methods identified similar results. 4. Discussion In this meta-analysis of 90 706 patients from 7 observational studies with unstratified cohort, we found that standard CPR could lead to better outcome of survival and ROSC than compression-only CPR, but there is no significant difference in favorable neurologic outcome at hospital discharge between the 2 CPR methods. However, some previous metaanalysis studies suggested that compression-only CPR was associated with improved survival rate compared with standard CPR [9,10]. Several reasons could explain this controversy. First, each of the randomized studies in the previous meta-analysis just compares dispatcher-assisted standard CPR with compression-only CPR [6-8]. However, these observational studies included in this meta-analysis focus on
Table 1 Characteristics of the studies included in the meta-analysis Articles
Location, period
Compression Standard ROSC on hospital arrival only CPR CPR Compression- Standard only CPR CPR
Survival to hospital discharge/30 d
Favorable neurologic outcome at hospital discharge/30 d
Compressiononly CPR
Standard CPR
Compression- Standard only CPR CPR
26/263
71/443
6/41
61/437
38/439
58/712
27/439
30/712
591/8209 60/783 (cardiac etiology subgroup) 35/281
14/145
27/281
Van Hoeyweghen et al [16]b Waalewijn et al [21] SOS-Kanto study group [18]a Bohm et al [23]a Iwami et al [22]a
Belgium, NA
263
443
Amsterdam, 19951997 Kanto, 2002-2003
41
437
439
712
Swedish, 1990-2005 1145 Osaka, 1998-2003 544
8209 783
229/1145
1609/8209
Olasveengen et al [24] Ong et al [15]
Oslo, 2003-2006
145
281
42/145
90/281
77/1145 37/544 (cardiac etiology subgroup) 15/145
Singapore, 20012004
154
287
12/154
30/287
4/154
8/287
2/154
6/287
Japan, 2006-2010
51 285
3/120 (cardiac etiology subgroup) 4379/51 286
5/202 (cardiac etiology subgroup) 2407/26 863
2218/51 267
1205/26 845
JCS-ReSS Group [12]a
a b
26 864
13/41
6022/51 286
144/437
3328/26 864
3106/29 572 (cardiac 1671/15 826 (cardiac etiology subgroup) etiology subgroup)
In these studies, we considered 30-day survival data as survival rate to hospital discharge because the latter was not available. In the study, we used the rate of consciousness 14 days after CPR instead of survival data to hospital discharge because the latter was not available.
*
* * * * * *
* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * Van Hoeyweghen et al [16] Waalewijn et al [21] SOS-Kanto Study Group [18] Bohm et al [23] Iwami et al [22] Olasveengen et al [24] Ong et al [15] JCS-ReSS Group [12]
Each one symbol asterisk indicated that the article met the corresponding requirement and scored 1 point.
1A 3A 2 1B
Studies
Table 2 Quality assessment (Newcastle-Ottawa Scale) of the studies included in the meta-analysis
3B
* * * * * * * *
1A
Compatibility
1A
4 Selection
1B
Outcome
1B
2A
3A
3B
8 9 9 9 9 9 8 9
L. Yao et al. / American Journal of Emergency Medicine 32 (2014) 517–523 Total scores
520
investigating the outcome between the compression-only CPR group and the standard CPR group, not restricted in dispatcher-assisted bystander CPR. The incidence of bystander-initiated CPR as a more common method affects the outcome of pooled analysis. In the Japanese study, it found that dispatcher-assisted CPR was associated with better short-term outcome than bystander-initiated CPR, and compressiononly CPR had the same benefits compared with standard CPR [12]. Also, this study suggested that, like some previous meta-analysis studies, dispatcher-assisted compression-only CPR should be recommend in outof-hospital cardiac arrest in adults. Furthermore, it showed that dispatcher-assisted CPR contributed to the benefits of compressiononly CPR [12]. However, other studies that just only included dispatcherunassisted bystanders found that no significant difference was seen in short-term outcome between the compression-only CPR group and the standard CPR group [15,22]. It is likely that CPR with dispatcher assist or not is an important factor, which would affect the outcome of comparison between compression-only CPR and standard CPR. However, there are few studies that considered this influencing factor and conducted the related stratified analysis. Second, both the previous and the present meta-analysis studies investigate the overall outcome of outof-hospital cardiac arrest. However, for the patients with noncardiac cause of arrest, rescue breathing is an important element of successful resuscitation stated by the American Heart Association guidelines [2]. Furthermore, the nationwide observational study by Kitamura et al [11] indicated that standard CPR (chest compressions plus rescue breathing) had a significant benefit in survival rates and neurologic outcome for out-of-hospital cardiac arrest of noncardiac etiology. The proportion of patients with noncardiac etiology arrest may have an evidently impact on overall survival rates of out-of-hospital cardiac arrest. The results stratified by cause of arrest may be more convincing. Third, the time interval between collapse and first bystander CPR is very important for survival rates of out-of-hospital cardiac arrest. For the patients with the prolonged duration of arrest, rescue breathing may improve outcomes of out-of-hospital cardiac arrest [25]. The study by the SOS-KANTO study group identified that compression-only CPR resulted in a higher rate of favourable neurologic outcome than standard CPR for the patients with resuscitation starting within 4 minutes of collapse, but not for the patients with resuscitation delayed for 4 minutes from collapse [18]. However, most randomized and observational articles did not perform the comparison of the time-dependent effectiveness between the compression-only CPR and the standard CPR [18,21]. This unstratified analysis also affects the results of meta-analysis. The cardiac etiology subgroup analysis of this study showed that compression-only CPR resulted in the similar survival to hospital discharge as standard CPR. An estimate of the difference in 30-day favorable neurologic outcome between compression-only CPR and standard CPR could not be done with certainty because only one observational study conducted it and suggested that compression-only CPR led to better 30-day favorable neurologic outcome than standard CPR in the subgroup with cardiac etiology arrest. These results indirectly enforce the importance of chest compression in resuscitation of the patients with cardiac etiology arrest. The American Heart Association guidelines also stated that it was important for successful resuscitation to minimize the interruption of chest compression [2]. Furthermore, one randomized study demonstrated compression-only CPR resulted in a higher proportion of patients surviving to hospital discharge for patients with a cardiac cause of arrest compared with the standard CPR, not for overall patient with out-of-hospital cardiac arrest [8]. Besides that, there are more patients with compression-only CPR (54 018) than standard CPR (38 015) in the meta-analysis including 8 observational studies. It may indicate that the compression-only CPR is more likely to be accepted by bystanders [12,26]. Maybe it can improve the incidence of bystander CPR and lead to more benefits for patients with out-of-hospital cardiac arrest. This study has some limitations. One is that this study did not adjust the final data for characteristics of the resuscitation episode just like age, location, race, and so on. Some studies included in the meta-analysis
L. Yao et al. / American Journal of Emergency Medicine 32 (2014) 517–523 compression-only CPR Study or Subgroup
standard CPR
Risk Ratio
Total
Events
26
264
71
443
1.5%
0.61 [0.40, 0.94]
1993
6
41
61
437
0.3%
1.05 [0.48, 2.28]
2001
SOS-Kanto group 2007
38
439
58
712
1.3%
1.06 [0.72, 1.57]
2007
Bohm 2007
77
1145
591
8209
4.2%
0.93 [0.74, 1.17]
2007
olasveengen 2008
15
145
35
281
0.7%
0.83 [0.47, 1.47]
2008
4
154
8
287
0.2%
0.93 [0.29, 3.05]
2008
4379
51286
2407
26863
91.8%
0.95 [0.91, 1.00]
2013
37232
100.0%
0.95 [0.91, 0.99]
Waalewijn 2001
Ong 2008 JCS-ReSS Group 2013 Total (95% CI)
Total Weight
Risk Ratio
Events
Van Hoeyweghen 1993
53474
Total events
4545
521
M-H, Fixed, 95% CI Year
M-H, Fixed, 95% CI
3231
Heterogeneity: Chi² = 4.70, df = 6 (P = 0.58); I² = 0%
0.5
Test for overall effect: Z = 2.31 (P = 0.02)
0.7
1
compreesion-only CPR
1.5
2
standard CPR
Fig. 2. Forest plot of RR for survival to hospital discharge in out-of-hospital cardiac arrest.
compression-only CPR
Waalewijn 2001
standard CPR
Total
Events
Study or Subgroup
Events
Risk Ratio
Total
Weight
M-H, Fixed, 95% CI
Risk Ratio
Year
13
41
144
437
0.5%
0.96 [0.60, 1.54]
2001
229
1145
1609
8209
8.1%
1.02 [0.90, 1.15]
2007
olasveengen 2008
42
145
90
281
1.3%
0.90 [0.67, 1.23]
2008
Ong 2008
12
154
30
287
0.4%
0.75 [0.39, 1.41]
2008
6022
51286
3328
26864
89.7%
0.95 [0.91, 0.99]
2013
36078
100.0%
0.95 [0.92, 0.99]
Bohm 2007
JCS-ReSS Group 2013 Total (95% CI)
52771
6318
Total events
M-H, Fixed, 95% CI
5201
Heterogeneity: Chi² = 1.92, df = 4 (P = 0.75); I² = 0%
0.5
Test for overall effect: Z = 2.56 (P = 0.01)
0.7
1
compreesion-only CPR
1.5
2
standard CPR
Fig. 3. Forest plot of RR for ROSC on hospital arrival in out-of-hospital cardiac arrest.
compression-only CPR Study or Subgroup
Risk Ratio
Events
Total
27
439
30
712
1.4%
1.46 [0.88, 2.42]
2007
2
154
6
287
0.3%
0.62 [0.13, 3.04]
2008
Ong 2008 olasveengen 2008
Weight
M-H, Fixed, 95% CI
Year
14
145
27
281
1.1%
1.00 [0.54, 1.86]
2008
2218
51267
1205
26845
97.2%
0.96 [0.90, 1.03]
2013
28125
100.0%
0.97 [0.91, 1.04]
Total (95% CI)
52005
Total events
Risk Ratio
Total
SOS-Kanto group 2007
JCS-ReSS Group 2013
standard CPR
Events
2261
M-H, Fixed, 95% CI
1268
Heterogeneity: Chi² = 2.85, df = 3 (P = 0.41); I² = 0%
0.2
Test for overall effect: Z = 0.87 (P = 0.38)
0.5
1
compreesion-only CPR
2
5
standard CPR
Fig. 4. Forest plot of RR for favorable neurologic outcome at hospital discharge in out-of-hospital cardiac arrest.
compression-only CPR Study or Subgroup
Events
Iwami 2007 JCS-ReSS Group 2013
Events
Risk Ratio
Total
Risk Ratio
Weight
M-H, Fixed, 95% CI
37
544
60
783
2.2%
0.89 [0.60, 1.32]
3106
29572
1671
15826
97.6%
0.99 [0.94, 1.05]
202
0.2%
1.01 [0.25, 4.15]
100.0%
0.99 [0.94, 1.05]
Ong 2008
3
Total (95% CI) Total events
standard CPR Total
120
5
30236 3146
Heterogeneity: Chi² = 0.31, df = 2 (P = 0.85); I² = 0%
Test for overall effect: Z = 0.27 (P = 0.79)
16811
M-H, Fixed, 95% CI
1736 0.5
0.7
compreesion-only CPR
Fig. 5. Forest plot of RR for survival to hospital discharge in cardiac origin arrest subgroup.
1
1.5
2
standard CPR
522
L. Yao et al. / American Journal of Emergency Medicine 32 (2014) 517–523
Fig. 6. Funnel plot of the meta-analysis. A, Survival to hospital discharge in out-of-hospital cardiac arrest. B, ROSC on hospital arrival in out-of-hospital cardiac arrest. C, Favorable neurologic outcome at hospital discharge in out-of-hospital cardiac arrest. D, Survival to hospital discharge in cardiac origin arrest subgroup.
have done this adjustment and avoid the bias [12,15]. However, for our study, it is difficult to get enough information to control these factors and bias from all of the included studies. Another limitation is that the ratios of compression to ventilation are different among the included studies because of the updating CPR guideline, which increasingly supports and stresses the importance of chest compression. It may bring some invisible benefit to compression-only CPR. In conclusion, this study found that compression-only CPR resulted in the similar survival rate as standard CPR in the cardiac etiology subgroup. Considering its possibly higher acceptance rate and easier performance, compression-only CPR should be recommended to bystander for patients with a cardiac cause of out-of-hospital arrest. It also should be considered that compression-only CPR with dispatcher assist may lead to better outcomes for those patients. However, it is unclear for the patients with noncardiac cause of arrest and with long periods of untreated arrest. Appendix A. Search strategy used for the literature search in MEDLINE and EMBASE Each search used a combination of free text and subject headings. #1 bystander CPR OR bystander cardiopulmonary resuscitation #2 bystander AND cardiopulmonary resuscitation #3 lay rescuer AND cardiopulmonary resuscitation #4 bystander AND resuscitation
#5 lay rescuer AND resuscitation #6 #1 OR #2 OR #3 OR #4 OR #5 #7 chest compression-only OR chest compression only #8 compression alone OR compression only #9 hands-only #10 #7 OR #8 OR #9 #11 standard CPR OR standard cardiopulmonary resuscitation #12 conventional CPR OR conventional cardiopulmonary resuscitation #13 #11 OR #12 #14 out-of-hospital cardiac arrest OR out of hospital cardiac arrest #15 cardiac arrest AND out-of-hospital, #16 arrest AND out-of-hospital, #17 cardiac arrest AND out of hospital, #18 arrest AND out of hospital, #19 #14 OR #15 OR #16 OR #17 OR #18 #20 #6 OR #10 OR #13 #21 #19 AND #20 #22 #21 limit to human
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Contents lists available at ScienceDirect
American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem
Original Contribution
Compression-only cardiopulmonary resuscitation vs standard cardiopulmonary resuscitation: an updated meta-analysis of observational studies Lan Yao, MD a,b, Peng Wang, PhD b,c, Lili Zhou, MD, PhD b,c, Mingdi Chen, MD b,c, Yuanshan Liu, MD b,c, Xiaozhu Wei, MD b,c, Zitong Huang, MD b,c,⁎ a b c
Department of Emergency Medicine, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
a r t i c l e
i n f o
Article history: Received 9 December 2013 Received in revised form 26 January 2014 Accepted 26 January 2014
a b s t r a c t Objectives: To perform an updated meta-analysis of observational studies with unstratified cohort addressing whether compression-only cardiopulmonary resuscitation (CPR), compared with standard CPR, improves outcomes in adult patients with out-of-hospital cardiac arrest and a subgroup meta-analysis for the patients with cardiac etiology arrest. Methods: We searched the relevant literature from MEDLINE and EMBASE databases. The baseline information and outcome data (survival to hospital discharge, favorable neurologic outcome at hospital discharge, and return of spontaneous circulation on hospital arrival) were extracted both in an out-of-hospital cardiac arrest and cardiac origin arrest subgroup. Meta-analyses were performed by using Review Manager 5.0. Results: Eight studies involving 92 033 patients were eligible. Overall meta-analysis showed that standard CPR was associated with statistically improved survival to hospital discharge (risk ratio [RR], 0.95 [95% confidence interval, 0.91-0.99]) and return of spontaneous circulation on hospital arrival (RR, 0.95 [95% confidence interval, 0.92-0.99]) compared with compression-only CPR, but there is no significant difference in favorable neurologic outcome at hospital discharge between 2 CPR methods (RR, 0.97 [95% confidence interval, 0.91-1.04]). In the subgroup of patients with a cardiac cause of arrest, the pooled meta-analysis found compression-only CPR resulted in the similar survival to hospital discharge as standard CPR (RR, 0.99 [95% confidence interval, 0.94-1.05]). Conclusions: This meta-analysis found that compression-only CPR resulted in the similar survival rate as the standard CPR in the cardiac etiology subgroup. It is unclear for the patients with noncardiac cause of arrest and with long periods of untreated arrest. © 2014 Published by Elsevier Inc.
1. Introduction Out-of-hospital cardiac arrest is still a considerable public health issue [1]. The incidence of out-of-hospital cardiac arrest is estimated to be 213.1 per 1 000 000 population [2]. Good-quality and high-incidence of bystander cardiopulmonary resuscitation (CPR) can increase the chance of survival in out-of-hospital cardiac arrest [3,4]. Despite huge efforts to improve the effectiveness of bystander CPR over the past decades, the survival rate of bystander CPR remains low and there are always some controversial comments on the CPR method for bystander CPR [3,5]. Several randomized clinic studies showed that dispatcherassisted compression-only CPR led to better survival rate than standard
⁎ Corresponding author. Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. Tel.: +86 20 81332469; fax: +86 20 81332650. E-mail address: [email protected] (Z. Huang). http://dx.doi.org/10.1016/j.ajem.2014.01.055 0735-6757/© 2014 Published by Elsevier Inc.
CPR, although the difference was not statistically significant [6-8]. A meta-analysis study including only randomized controlled trials also found that compression-only CPR was significantly associated with improved survival rate to discharge compared with standard CPR [9,10]. In contrast, another meta-analysis of observation studies showed that there was no significant difference in survival between the 2 CPR methods [10]. Furthermore, a large-scale prospective study indicated that for patients with arrest due to noncardiac causes, standard CPR may actually have better benefits in survival rate than compression-only CPR [11]. At the same time, a single randomized clinic study and a large-scale observational study both found that compression-only CPR resulted in better outcomes compared with standard CPR in a cardiac origin arrest subgroup [8,12]. Hence, it was indicated that the stratified analysis of out-of-hospital cardiac arrest may be more reasonable and should be performed for the comparison of compression-only CPR and standard CPR. Because cardiac diseases are the most frequent cause of out-ofhospital cardiac arrest, we supposed that compression-only CPR may be more effective in patients with a cardiac cause of arrest. Previous meta-
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L. Yao et al. / American Journal of Emergency Medicine 32 (2014) 517–523
analyses did not conduct the analysis of cardiac origin arrest subgroup. Several new observational studies with stratified analysis have emerged [12,13]. Therefore, we performed an updated meta-analysis of observational studies with unstratified cohort addressing whether compressiononly CPR, compared with standard CPR, improves outcomes in adult patients with out-of-hospital cardiac arrest and a subgroup metaanalysis for the patients with cardiac etiology arrest.
2. Methods The study was performed in accordance with the guidelines from the Meta-analysis Of Observational Studies in Epidemiology group [14].
2.1. Literature search Two authors independently retrieved observational studies that compared compression-only CPR and standard CPR from MEDLINE and EMBASE databases between January 1, 1990, and October 1, 2013. The search terms included “chest compression-only,” “compression alone,” “hands-only,” “bystander CPR,” “standard CPR,” and “out-ofhospital cardiac arrest.” The search strategy is presented in Appendix A. In addition, we also reviewed the reference of retrieved articles for additional pertinent studies. We placed no language restrictions on the searches.
2.2. Inclusion and exclusion criteria Two authors independently screened the full texts of eligible articles according to inclusion and exclusion criteria. For inclusion, studies had to meet the following criteria: (1) observational clinic studies, (2) comparison of chest compression-only vs standard CPR, (3) out-of-hospital arrest, and (4) survival rate, return of spontaneous circulation (ROSC), or neurologic outcome data available. We excluded studies if they met the following exclusion criteria: (1) any other intervention (eg, public education plan), (2) duplicate publication and data, (3) only just for arrests of noncardiac origin, and (4) only just for children or old people. 2.3. Data extraction The baseline information was extracted from each study by 3 reviewers independently. We also obtained the following outcome data: survival to hospital discharge, favorable neurologic outcome at hospital discharge, and ROSC on hospital arrival. We considered 30-day survival data as survival rate to hospital discharge if the latter was not available, seeing that the 2 kinds of outcome nearly had the same data in some relevant studies [15]. We also used the rate of consciousness 14 days after CPR instead of survival data to hospital discharge when the information was unavailable [16]. Favorable neurologic outcome was defined as a Glasgow-Pittsburgh cerebral-performance category of 1 or 2 on a 5-category scale [17]. Meanwhile, these outcome data in the subgroup of patients with a cardiac cause of arrest were extracted from
Potentially relevant articles in the initial literature search n = 872
Articles excluded based on title and abstract n = 821
Full-text articles assessed for eligibility n = 51
Observational studies included in the meta-analysis n=8 (n = 3 with survival data of the cardiac etiology subgroup)
Articles excluded according to inclusion and exclusion criteria n = 43 Reasons for exclusion not observational clinic studies n = 19 reviews n = 5 duplicate data n = 2 with any intervention n = 1 just for arrests of non-cardiac origin n = 3 just only for children or old people n = 5
Fig. 1. Flowchart representing the selection process.
L. Yao et al. / American Journal of Emergency Medicine 32 (2014) 517–523
selected articles. The cardiac origin arrest subgroup include the patients whose arrest was presumed to be of cardiac origin, unless it was known to be caused by trauma, hanging, drowning, drug overdose, asphyxia, or any other noncardiac causes [12,18]. 2.4. Statistical analysis Meta-analyses were performed by using Review Manager 5.0 (the Cochrane Information Management System, http://ims.cochrane.org/ revman). Risk ratios (RRs) and 95% confidence intervals were calculated and pooled in both a fixed-effects model and a random-effects model, which was used to control for heterogeneity [19]. The quality of each study was assessed independently by 2 authors with the NewcastleOttawa Scale [20]. Besides the primary meta-analysis with an unstratified cohort in out-of-hospital cardiac arrest, a subgroup meta-analysis for the patients with cardiac etiology arrest was performed. We examined for potential publication bias with funnel plots. The heterogeneity among studies was assessed by the Cochran Q and I2 statistics. Sensitivity analyses were performed by using random-effect methods. 3. Results 3.1. Search results A total of 872 relevant citations were ascertained from the initial literature search. Eight hundred twenty-one articles were excluded based on title and abstract. According to inclusion and exclusion criteria, 2 authors assessed the full text of remained articles and excluded 43 articles. In the final analysis, 8 articles totally were included [12,16-18,21-24] (Fig. 1). 3.2. Study characteristics Baseline information of the 8 observational cohort studies including author's last name, year of publication, country of population studies, numbers of survivors in different groups, and so on (Table 1). All eligible studies included 54 018 patients with compression-only CPR and 38 015 patients with standard CPR. Of the 8 studies, 3 articles provided survival rates in the subgroup of patients with a cardiac cause of arrest. The quality of these studies was high (Table 2).
519
3.3. Data and statistical analysis Most of these observational studies found that there was no significant difference in survival between the compression-only CPR group and the standard CPR group, but overall meta-analysis showed that standard CPR was associated with statistically improved survival data to hospital discharge compared with compression-only CPR (RR, 0.95 [95% confidence interval, 0.91-0.99]; Fig. 2). Standard CPR was also associated with a statistically improved ROSC on hospital arrival (RR, 0.95 [95% confidence interval, 0.92-0.99]; Fig. 3). However, after pooling 4 studies referring to neurologic outcome in a meta-analysis, it showed no difference in favorable neurologic outcome at hospital discharge between the compression-only CPR group and the standard CPR group (RR, 0.97 [95% confidence interval, 0.91-1.04]; Fig. 4). The heterogeneity among these studies was nearly neglected (I 2 = 0). In the subgroup of patients with a cardiac cause of arrest, the pooled meta-analysis found that there was no significant difference in survival rate to hospital discharge (RR, 0.99 [95% confidence interval, 0.94-1.05]) with no evidence of heterogeneity as indicated by an I 2 of 0 (Fig. 5). However, only the study in 2013 referred to neurologic outcome and considered compression-only CPR led to better 30-day favorable neurologic outcome than standard CPR in the subgroup with cardiac etiology [12]. Overall funnel plots were not suggestive for publication bias (Fig. 6). Sensitivity analyses using random-effect methods identified similar results. 4. Discussion In this meta-analysis of 90 706 patients from 7 observational studies with unstratified cohort, we found that standard CPR could lead to better outcome of survival and ROSC than compression-only CPR, but there is no significant difference in favorable neurologic outcome at hospital discharge between the 2 CPR methods. However, some previous metaanalysis studies suggested that compression-only CPR was associated with improved survival rate compared with standard CPR [9,10]. Several reasons could explain this controversy. First, each of the randomized studies in the previous meta-analysis just compares dispatcher-assisted standard CPR with compression-only CPR [6-8]. However, these observational studies included in this meta-analysis focus on
Table 1 Characteristics of the studies included in the meta-analysis Articles
Location, period
Compression Standard ROSC on hospital arrival only CPR CPR Compression- Standard only CPR CPR
Survival to hospital discharge/30 d
Favorable neurologic outcome at hospital discharge/30 d
Compressiononly CPR
Standard CPR
Compression- Standard only CPR CPR
26/263
71/443
6/41
61/437
38/439
58/712
27/439
30/712
591/8209 60/783 (cardiac etiology subgroup) 35/281
14/145
27/281
Van Hoeyweghen et al [16]b Waalewijn et al [21] SOS-Kanto study group [18]a Bohm et al [23]a Iwami et al [22]a
Belgium, NA
263
443
Amsterdam, 19951997 Kanto, 2002-2003
41
437
439
712
Swedish, 1990-2005 1145 Osaka, 1998-2003 544
8209 783
229/1145
1609/8209
Olasveengen et al [24] Ong et al [15]
Oslo, 2003-2006
145
281
42/145
90/281
77/1145 37/544 (cardiac etiology subgroup) 15/145
Singapore, 20012004
154
287
12/154
30/287
4/154
8/287
2/154
6/287
Japan, 2006-2010
51 285
3/120 (cardiac etiology subgroup) 4379/51 286
5/202 (cardiac etiology subgroup) 2407/26 863
2218/51 267
1205/26 845
JCS-ReSS Group [12]a
a b
26 864
13/41
6022/51 286
144/437
3328/26 864
3106/29 572 (cardiac 1671/15 826 (cardiac etiology subgroup) etiology subgroup)
In these studies, we considered 30-day survival data as survival rate to hospital discharge because the latter was not available. In the study, we used the rate of consciousness 14 days after CPR instead of survival data to hospital discharge because the latter was not available.
*
* * * * * *
* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * Van Hoeyweghen et al [16] Waalewijn et al [21] SOS-Kanto Study Group [18] Bohm et al [23] Iwami et al [22] Olasveengen et al [24] Ong et al [15] JCS-ReSS Group [12]
Each one symbol asterisk indicated that the article met the corresponding requirement and scored 1 point.
1A 3A 2 1B
Studies
Table 2 Quality assessment (Newcastle-Ottawa Scale) of the studies included in the meta-analysis
3B
* * * * * * * *
1A
Compatibility
1A
4 Selection
1B
Outcome
1B
2A
3A
3B
8 9 9 9 9 9 8 9
L. Yao et al. / American Journal of Emergency Medicine 32 (2014) 517–523 Total scores
520
investigating the outcome between the compression-only CPR group and the standard CPR group, not restricted in dispatcher-assisted bystander CPR. The incidence of bystander-initiated CPR as a more common method affects the outcome of pooled analysis. In the Japanese study, it found that dispatcher-assisted CPR was associated with better short-term outcome than bystander-initiated CPR, and compressiononly CPR had the same benefits compared with standard CPR [12]. Also, this study suggested that, like some previous meta-analysis studies, dispatcher-assisted compression-only CPR should be recommend in outof-hospital cardiac arrest in adults. Furthermore, it showed that dispatcher-assisted CPR contributed to the benefits of compressiononly CPR [12]. However, other studies that just only included dispatcherunassisted bystanders found that no significant difference was seen in short-term outcome between the compression-only CPR group and the standard CPR group [15,22]. It is likely that CPR with dispatcher assist or not is an important factor, which would affect the outcome of comparison between compression-only CPR and standard CPR. However, there are few studies that considered this influencing factor and conducted the related stratified analysis. Second, both the previous and the present meta-analysis studies investigate the overall outcome of outof-hospital cardiac arrest. However, for the patients with noncardiac cause of arrest, rescue breathing is an important element of successful resuscitation stated by the American Heart Association guidelines [2]. Furthermore, the nationwide observational study by Kitamura et al [11] indicated that standard CPR (chest compressions plus rescue breathing) had a significant benefit in survival rates and neurologic outcome for out-of-hospital cardiac arrest of noncardiac etiology. The proportion of patients with noncardiac etiology arrest may have an evidently impact on overall survival rates of out-of-hospital cardiac arrest. The results stratified by cause of arrest may be more convincing. Third, the time interval between collapse and first bystander CPR is very important for survival rates of out-of-hospital cardiac arrest. For the patients with the prolonged duration of arrest, rescue breathing may improve outcomes of out-of-hospital cardiac arrest [25]. The study by the SOS-KANTO study group identified that compression-only CPR resulted in a higher rate of favourable neurologic outcome than standard CPR for the patients with resuscitation starting within 4 minutes of collapse, but not for the patients with resuscitation delayed for 4 minutes from collapse [18]. However, most randomized and observational articles did not perform the comparison of the time-dependent effectiveness between the compression-only CPR and the standard CPR [18,21]. This unstratified analysis also affects the results of meta-analysis. The cardiac etiology subgroup analysis of this study showed that compression-only CPR resulted in the similar survival to hospital discharge as standard CPR. An estimate of the difference in 30-day favorable neurologic outcome between compression-only CPR and standard CPR could not be done with certainty because only one observational study conducted it and suggested that compression-only CPR led to better 30-day favorable neurologic outcome than standard CPR in the subgroup with cardiac etiology arrest. These results indirectly enforce the importance of chest compression in resuscitation of the patients with cardiac etiology arrest. The American Heart Association guidelines also stated that it was important for successful resuscitation to minimize the interruption of chest compression [2]. Furthermore, one randomized study demonstrated compression-only CPR resulted in a higher proportion of patients surviving to hospital discharge for patients with a cardiac cause of arrest compared with the standard CPR, not for overall patient with out-of-hospital cardiac arrest [8]. Besides that, there are more patients with compression-only CPR (54 018) than standard CPR (38 015) in the meta-analysis including 8 observational studies. It may indicate that the compression-only CPR is more likely to be accepted by bystanders [12,26]. Maybe it can improve the incidence of bystander CPR and lead to more benefits for patients with out-of-hospital cardiac arrest. This study has some limitations. One is that this study did not adjust the final data for characteristics of the resuscitation episode just like age, location, race, and so on. Some studies included in the meta-analysis
L. Yao et al. / American Journal of Emergency Medicine 32 (2014) 517–523 compression-only CPR Study or Subgroup
standard CPR
Risk Ratio
Total
Events
26
264
71
443
1.5%
0.61 [0.40, 0.94]
1993
6
41
61
437
0.3%
1.05 [0.48, 2.28]
2001
SOS-Kanto group 2007
38
439
58
712
1.3%
1.06 [0.72, 1.57]
2007
Bohm 2007
77
1145
591
8209
4.2%
0.93 [0.74, 1.17]
2007
olasveengen 2008
15
145
35
281
0.7%
0.83 [0.47, 1.47]
2008
4
154
8
287
0.2%
0.93 [0.29, 3.05]
2008
4379
51286
2407
26863
91.8%
0.95 [0.91, 1.00]
2013
37232
100.0%
0.95 [0.91, 0.99]
Waalewijn 2001
Ong 2008 JCS-ReSS Group 2013 Total (95% CI)
Total Weight
Risk Ratio
Events
Van Hoeyweghen 1993
53474
Total events
4545
521
M-H, Fixed, 95% CI Year
M-H, Fixed, 95% CI
3231
Heterogeneity: Chi² = 4.70, df = 6 (P = 0.58); I² = 0%
0.5
Test for overall effect: Z = 2.31 (P = 0.02)
0.7
1
compreesion-only CPR
1.5
2
standard CPR
Fig. 2. Forest plot of RR for survival to hospital discharge in out-of-hospital cardiac arrest.
compression-only CPR
Waalewijn 2001
standard CPR
Total
Events
Study or Subgroup
Events
Risk Ratio
Total
Weight
M-H, Fixed, 95% CI
Risk Ratio
Year
13
41
144
437
0.5%
0.96 [0.60, 1.54]
2001
229
1145
1609
8209
8.1%
1.02 [0.90, 1.15]
2007
olasveengen 2008
42
145
90
281
1.3%
0.90 [0.67, 1.23]
2008
Ong 2008
12
154
30
287
0.4%
0.75 [0.39, 1.41]
2008
6022
51286
3328
26864
89.7%
0.95 [0.91, 0.99]
2013
36078
100.0%
0.95 [0.92, 0.99]
Bohm 2007
JCS-ReSS Group 2013 Total (95% CI)
52771
6318
Total events
M-H, Fixed, 95% CI
5201
Heterogeneity: Chi² = 1.92, df = 4 (P = 0.75); I² = 0%
0.5
Test for overall effect: Z = 2.56 (P = 0.01)
0.7
1
compreesion-only CPR
1.5
2
standard CPR
Fig. 3. Forest plot of RR for ROSC on hospital arrival in out-of-hospital cardiac arrest.
compression-only CPR Study or Subgroup
Risk Ratio
Events
Total
27
439
30
712
1.4%
1.46 [0.88, 2.42]
2007
2
154
6
287
0.3%
0.62 [0.13, 3.04]
2008
Ong 2008 olasveengen 2008
Weight
M-H, Fixed, 95% CI
Year
14
145
27
281
1.1%
1.00 [0.54, 1.86]
2008
2218
51267
1205
26845
97.2%
0.96 [0.90, 1.03]
2013
28125
100.0%
0.97 [0.91, 1.04]
Total (95% CI)
52005
Total events
Risk Ratio
Total
SOS-Kanto group 2007
JCS-ReSS Group 2013
standard CPR
Events
2261
M-H, Fixed, 95% CI
1268
Heterogeneity: Chi² = 2.85, df = 3 (P = 0.41); I² = 0%
0.2
Test for overall effect: Z = 0.87 (P = 0.38)
0.5
1
compreesion-only CPR
2
5
standard CPR
Fig. 4. Forest plot of RR for favorable neurologic outcome at hospital discharge in out-of-hospital cardiac arrest.
compression-only CPR Study or Subgroup
Events
Iwami 2007 JCS-ReSS Group 2013
Events
Risk Ratio
Total
Risk Ratio
Weight
M-H, Fixed, 95% CI
37
544
60
783
2.2%
0.89 [0.60, 1.32]
3106
29572
1671
15826
97.6%
0.99 [0.94, 1.05]
202
0.2%
1.01 [0.25, 4.15]
100.0%
0.99 [0.94, 1.05]
Ong 2008
3
Total (95% CI) Total events
standard CPR Total
120
5
30236 3146
Heterogeneity: Chi² = 0.31, df = 2 (P = 0.85); I² = 0%
Test for overall effect: Z = 0.27 (P = 0.79)
16811
M-H, Fixed, 95% CI
1736 0.5
0.7
compreesion-only CPR
Fig. 5. Forest plot of RR for survival to hospital discharge in cardiac origin arrest subgroup.
1
1.5
2
standard CPR
522
L. Yao et al. / American Journal of Emergency Medicine 32 (2014) 517–523
Fig. 6. Funnel plot of the meta-analysis. A, Survival to hospital discharge in out-of-hospital cardiac arrest. B, ROSC on hospital arrival in out-of-hospital cardiac arrest. C, Favorable neurologic outcome at hospital discharge in out-of-hospital cardiac arrest. D, Survival to hospital discharge in cardiac origin arrest subgroup.
have done this adjustment and avoid the bias [12,15]. However, for our study, it is difficult to get enough information to control these factors and bias from all of the included studies. Another limitation is that the ratios of compression to ventilation are different among the included studies because of the updating CPR guideline, which increasingly supports and stresses the importance of chest compression. It may bring some invisible benefit to compression-only CPR. In conclusion, this study found that compression-only CPR resulted in the similar survival rate as standard CPR in the cardiac etiology subgroup. Considering its possibly higher acceptance rate and easier performance, compression-only CPR should be recommended to bystander for patients with a cardiac cause of out-of-hospital arrest. It also should be considered that compression-only CPR with dispatcher assist may lead to better outcomes for those patients. However, it is unclear for the patients with noncardiac cause of arrest and with long periods of untreated arrest. Appendix A. Search strategy used for the literature search in MEDLINE and EMBASE Each search used a combination of free text and subject headings. #1 bystander CPR OR bystander cardiopulmonary resuscitation #2 bystander AND cardiopulmonary resuscitation #3 lay rescuer AND cardiopulmonary resuscitation #4 bystander AND resuscitation
#5 lay rescuer AND resuscitation #6 #1 OR #2 OR #3 OR #4 OR #5 #7 chest compression-only OR chest compression only #8 compression alone OR compression only #9 hands-only #10 #7 OR #8 OR #9 #11 standard CPR OR standard cardiopulmonary resuscitation #12 conventional CPR OR conventional cardiopulmonary resuscitation #13 #11 OR #12 #14 out-of-hospital cardiac arrest OR out of hospital cardiac arrest #15 cardiac arrest AND out-of-hospital, #16 arrest AND out-of-hospital, #17 cardiac arrest AND out of hospital, #18 arrest AND out of hospital, #19 #14 OR #15 OR #16 OR #17 OR #18 #20 #6 OR #10 OR #13 #21 #19 AND #20 #22 #21 limit to human
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