Prospective, multicenter, Turkish out‑of‑hospital cardiac arrest study: TROHCA

Abstract

OBJECTIVES: There is no sufficient data to provide a clear picture of out-of-hospital cardiac arrest (OHCA) across Türkiye. This study is the first to present the prognostic outcomes of OHCA cases and the factors associated with these outcomes.

MATERIALS AND METHODS: The study was conducted in a prospective, observational, multicenter design under the leadership of the Emergency Medicine Association of Turkey Resuscitation Study Group. OHCA cases aged 18 years and over who were admitted to 28 centers from Türkiye were included in the study. Survived event, return of spontaneous circulation (ROSC), survival to hospital discharge, and neurological outcome at discharge were investigated as primary outcomes.

RESULTS: One thousand and three patients were included in the final analysis. 61.1% of the patients were male, and the average age was 67.0 ± 15.2. Cardiopulmonary resuscitation (CPR) was performed on 86.5% of the patients in the prehospital period by emergency medical service, and bystander CPR was performed on only 2.9% by nonhealth-care providers. As a result, the survived event rate was found to be 6.9%. The survival rate upon hospital discharge was 4.4%, with 2.7% of patients achieving a good neurological outcome upon discharge. In addition, the overall ROSC and sustained ROSC rates were 45.2% and 33.4%, respectively. In the multiple logistic regression analysis, male gender, initial shockable rhythm, a shorter prehospital duration of CPR, and the lack of CPR requirement in the emergency department were determined to be independent predictors for the survival to hospital discharge.

CONCLUSION: Compared to global data, survival to hospital discharge and good neurological outcome rates appear to be lower in our study. We conclude that this result is related to low bystander CPR rates. Although not the focus of this study, inadequate postresuscitative care and intensive care support should also be discussed in this regard. It is obvious that this issue should be carefully addressed through political moves in the health and social fields.

Introduction

The overall incidence of out-of-hospital cardiac arrests (OHCAs) where cardiopulmonary resuscitation (CPR) was attempted was 56 per 100,000 population annually.[1] Although it is a frequently discussed issue in the literature, it remains an important public health problem. In particular, the American Heart Association (AHA) carries out regular updates of their recommendations.[2] Even if these guidelines are followed, survival data in OHCA cases are far from satisfactory globally and vary widely. These variations may be related to the design of the studies and the lack of standardization in the definitions used. To improve the results, it is necessary to expand these data, determine strategic goals with newly emerging data, and adapt them to life with the support of health-care and social policies. Assessing each step of the survival chain individually, particularly early recognition of cardiac arrest, prompt activation of emergency medical services (EMS), and enhancing bystander CPR rates, can be regarded as strategic objectives aimed at bolstering the survival rates. [3] It is known that bystander CPR rates are not sufficient worldwide and even this rate is far from expectations in Türkiye.

Data on this subject are limited in Türkiye. Generally, there are retrospective, single-center studies, as well as a few prospective studies with low sample size.[4-6] With these limited data, it is not possible to talk about the generalizability of the data such as survival, return of spontaneous circulation (ROSC), and bystander CPR. It is known that monitoring and keeping arrest records influence survival. With this prospective, multicenter study, we aimed to fill this data gap, shed light on future studies, and guide health policies.

Material and Methods

Settings

This prospective, observational, multicenter study was planned to be conducted for 1 year (2023) in 30 health centers in Türkiye within the scope of the Emergency Medicine Association of Turkey Resuscitation Study Group. All study centers were third level emergency department (ED) providing emergency medicine training, and these centers were selected from all 7 geographical regions of Türkiye, and all resuscitation practices are carried out in accordance with the AHA and/or European Resuscitation Council guidelines. Two centers were excluded from the study because data could not be obtained. Ultimately, the study was completed in 28 centers with a total of more than 8 million ED visits annually [Figure 1].

Figure 1. Distribution of the study centers

There is generally no specific protocol used for terminating resuscitation, and the decision depends on the physician’s initiative. EMS system of Türkiye generally operates on the “load and go” principle. In the field, EMS staff rarely make end-of-life decisions, and the majority of patients are transported to the emergency department (ED). It has been accepted that this principle was followed throughout this study. We should also note that it is still not a legal obligation in Türkiye to install automated external defibrillators (AEDs), especially in all densely crowded places such as malls and bus stations.

Population

Patients who had a cardiac arrest in an out-of-hospital environment, were 18 years of age or older, and had ROSC before admission or were admitted as cardiac arrest to the ED were included 24/7 in the study. Informed consent was obtained from all patients/ relatives. Patients experiencing traumatic cardiac arrest, those transferred to study centers from other hospitals, defined as deceased prior to admission, whose primary outcome data couldn't be obtained, and whose relatives did not provide consent for their participation in the study, were excluded from the study. According to the sample size calculation, based on the ROSC (24.8%) and survival to hospital discharge (5.6%) rates in the study of Şener et al. and assuming a 5% error, a total of at least 837 cases were planned to be included in the study.[6] Upon reaching this sample, the study was terminated on October 15, 2023, before the planned date.

Ethical approval was received from the Kocaeli University Non-Interventional Clinical Research Ethics Committee (No: KÜ GOKAEK 2022/18.24) at the coordinator center on November 10, 2022, and the study was carried out in accordance with the principles of the World Medical Association Declaration of Helsinki.

Data collection

Data obtained from the patients themselves or their relatives and recorded forms in Hospital Information Management Systems were checked and transferred to the online registry form (Google® Forms) by the local coordinator of the relevant center. Afterward, the relevant data were processed by the authorized researchers and directed for statistical analysis.

Definitions and outcomes

The data collection forms were primarily designed based on the Utstein Resuscitation Registry Templates for out-ofhospital cardiac arrest (OHCA), with additional variables incorporated.[7] Obtaining any rhythm with pulse for at least 5 min during resuscitation was defined as ROSC, and persistence of this condition for at least 20 min was defined as sustained ROSC. Patients who were admitted to the ED with a pulse that persisted 20 min or who completed 20 min with a pulse in the ED were defined as a survived event. Patients who were discharged with sustained ROSC were recorded as survival to hospital discharge. Patients who were still in ROSC at day 30 were also recorded as 30-day survival. Cerebral performance category (CPC) was evaluated at discharge and on the 30^th day, and according to this scale, categories 1 and 2 were recorded as good neurological outcome and 3 and above were recorded as poor neurological outcome. The hospital parameter as cardiac arrest localization refers to patients who had cardiac arrest at the hospital entrance (parking lot, garden, entrance of the outpatient clinics or triage, etc.) before being delivered to the relevant health-care professional. A cardiac arrest which is seen by other people or is monitored by EMS is defined as witnessed arrest. CPR procedure initiated by witnessed people other than the EMS staff is defined as bystander CPR. The rhythm of the patient detected in the first monitoring was recorded as initial cardiac arrest rhythm, and pulseless ventricular tachycardia and ventricular fibrillation rhythms were recorded as shockable rhythm. The concept of airway procedure was used as the most advanced method performed. The concept of unsuccessful airway procedure refers to a patient who cannot be ventilated in any way. Survived event, ROSC, survival to hospital discharge, and neurological outcome at discharge were investigated as primary outcomes.

Statistical analysis

Statistical analyses of the study were performed with IBM SPSS Statistics for Windows, Version 26.0 (Armonk, NY, USA: IBM Corp). In comparing continuous data between two independent groups, the Mann–Whitney U-test or Independent samples t-test was used, depending on distribution. Continuous data are expressed as mean with standard deviation or median with interquartile range in accordance with distribution. The comparison of categorical data between independent groups was performed with Pearson’s Chi-square and Fisher’s exact tests; these data were expressed as sample numbers and percentages. In primary analyses, P < 0.05 level was used for statistical significance. Multiple logistic regression analysis was performed for sustained ROSC and discharge, and variables with P < 0.250 in univariate analysis but thought to be clinically significant were included in the model. For discharge outcome, “prehospital CPR, arrest cause, prehospital airway management, arrest location, use of magnesium sulfate in the emergency department (ED), and experiencing cardiac arrest again in the ED” were unable to be included in the model due to imbalances in sample counts across groups. Similarly, for sustained ROSC, “prehospital CPR, arrest etiology, prehospital airway management, and CPR administered in the ED” couldn't be included due to group imbalances.As a result, odds ratios were expressed with 95% confidence intervals. Cutoff values of pH variable used in logistic regression analysis were determined by ROC analysis.

Results

A total of 1060 patients were recorded in the data system from 28 centers in Türkiye. After ruling out missing data and samples that did not meet the criteria (such as trauma patients, inhospital arrests, and referrals from other hospitals), 1002 patients were included in the final analysis [Figure 2]. It was determined that 61.1% of the patients were male, the mean age was 67.0 ± 15.2 years, the etiology was acute coronary syndrome in 46.3%, and the localization of cardiac arrest was “home” in 61.3%. Witnessed arrest was detected in 83.9% of patients, transport with EMS in 97.4%, and shockable first arrest rhythm in 10.8%. CPR was performed on 86.5% of the patients in the prehospital period by EMS personnel, and bystander CPR was performed on only 2.9% by nonhealth-care providers (higher in male gender; 3.8 vs. 1.5). While the prehospital bag-valve-mask rate was 31.7%, successful endotracheal intubation (ETI) was found to be 47.6%. Peripheral intravenous access was presented in 88.4% of the patients, and 11.2% were delivered to the ED without any venous access [Table 1].

Figure 2. Flow diagram

Table 1. Demographic characteristics and prehospital descriptive variables

Table 1. Contd...

Primary outcomes

As a result, while the prehospital ROSC rate was 13.6%, the survived event rate was found to be 6.9% [Table 1]. While the mortality rate in the ED was 72.3%, 4.4% were discharged alive from the hospital and 2.7% were discharged with good neurological outcome. In addition, the ROSC rate for the entire process was determined as 45.2% and the sustained ROSC rate was 33.4%.

Secondary outcomes

In the EDs, mechanical chest compression device was used in 41.5% of patients, EtCO2 monitoring in 30.1%, and ultrasound-guided CPR performed in 52.1% of patients [Table 2]. Primary comparative analyses between the two groups for the outcomes of survived event, overall sustained ROSC, survival to hospital discharge, and discharge with good neurological outcome are provided as supplemental files [Supplementary Tables 1 8]. It has been determined that the survival to hospital discharge rate is higher in male gender and patients with shockable rhythm and is lower, especially in the group of home localization and with mechanical chest compression devices [Supplementary Table 5]. In addition, it has been determined that both survived event, survival and good neurological outcome rates were higher in cases where bystander CPR was performed [Supplementary Tables 1, 5, and 7].

Table 2. Descriptive variables of emergency department period

Table 2. Contd...

According to regional distribution, the highest bystander CPR rates were found in the Marmara and Aegean regions and the highest survival rates in the Mediterranean and Black Sea regions. The good neurological outcome rate is higher in the Mediterranean region [Supplementary Table 9].

Multiple logistic regression analysis

As a result of multiple regression analyses, male gender (odds ratio [OR]: 2.691; 95% confidence interval [CI]: 1.186–6.103), prehospital initial shockable rhythm (OR: 6.480; 95% CI: 3.055–13.744), a shorter prehospital duration of CPR (OR: 0.919; 95% CI: 0.880– 0.961), and the lack of CPR requirement in the ED (OR: 12.038; 95% CI: 5.000–28.984) were found to be positive independent predictors for the survival to hospital discharge [Table 3]. For sustained ROSC, presence of chronic pulmonary disease (OR: 1.677; 95% CI: 1.088– 2.585), witnessed arrest (OR: 2.910; 95% CI: 1.588–5.336), arrest localization being hospital (OR: 3.703; 95% CI: 1.310–10.467; reference: home), shorter prehospital CPR duration (OR: 0.954; 95% CI: 0.933–0.975), not using mechanical chest compression device in ED (OR: 2.598; 95% CI: 1.774–3.803), the venous route used in the ED being other than peripheral intravenous route (OR: 2.105; 95% CI: 1.051–4.219), and higher pH levels (for “6.9 ≤ pH < 7.0” OR: 2.106; 95% CI: 1.257–3.528 and for “pH ≥ 7.0” OR: 3.005; 95% CI: 1.941–4.652) were determined as independent predictors [Table 4].

Table 3. Multiple regression analysis for survival to hospital discharge

Table 4. Multiple regression analysis for overall sustained return of the spontaneous circulation

Discussion

This descriptive prospective multicenter study investigated the epidemiology and outcomes of OHCA patients in prehospital and emergency settings across Türkiye and aims to provide a comprehensive overview of this critical patient population. Of the OHCA patients, 453 (45.2%) achieved any ROSC, 334 (33.4%) achieved sustained ROSC, and 278 (27.7%) had survived event, which were the outcomes that primarily pertain to prehospital and emergency medicine department settings. Upon reviewing our findings, it can be concluded that our results closely align with data reported in European and Australian studies. The EuRoCa TWO study, published in 2020, documented that any ROSC was achieved in 32.7% of 25,171 patients who experienced cardiac arrest and received CPR initiated by EMS or bystanders.[1] Similar findings have also been reported (23.8-37.8% for prehospital ROSC) in Australian and New Zealand data published by Beck et al. [8]

In a meta-analysis that examines 141 studies and nearly 4.6 million OHCA patients, the rate of sustained ROSC was reported as 29.7%. The authors conducted subgroup analyses by region and observed the highest sustained ROSC rate in Oceania countries (38.6%), followed by Europe (36.7%), and then Asian countries (22.1%).[9] While our sustained ROSC rates may not match those observed in Oceania and Europe, it can be inferred that our results are closely approximated. In the meta-analysis by Yan et al., the global incidence of survived event rates among OHCA patients was reported as 22%. Oceanic countries exhibited the highest rate of survived events at 33.5%, while Asian countries showed the lowest at 15.6%.[9] Comparatively, British and Australian data suggest a survived event rate of 22% and 28%, respectively, while European data indicate a higher survived event rate of 35%.[1,8,10] Upon the examination of prehospital and emergency setting data, Türkiye’s outcomes appear to closely align with studies conducted in developed countries.

Upon closer examination of the primary outcome measures, markedly different results stand out compared to those observed in the aforementioned studies. Of the OHCA patients in our study, 44 (4.4%) were discharged from the hospital. We can argue that our results were notably inferior compared to the findings reported in the literature conducted in the developed countries. Yan et al. reported a global hospital discharge rate of 8.8% in OHCA patients, which is approximately double the rate observed in our findings. In this meta analysis, subgroup analyses by region revealed the highest survival to discharge rate in Oceania countries (16.2%) and the lowest in Asian countries (4.5%).[9] The rates of survival to discharge in Australia and New Zealand were reported to be 12.1%, while European countries reported rates of 8% and England 7.2%.[1,8,10] Consequently, our findings closely parallel the outcomes observed in Asian countries regarding survival to hospital discharge.

An intriguing detail worth noting from the EuRoCa TWO study, was a specific subgroup outcome. Among patients brought to the hospital while CPR was ongoing, the survival to hospital discharge rate was notably lower at 4%. All patients who received CPR exhibited an 8% survival to hospital discharge rate, whereas those brought directly to the hospital showed a 26% survival rate, and individuals achieving ROSC in the prehospital setting demonstrated a notably higher rate of 35%.[1] One potential explanation for the low survival-to-hospital discharge rate observed in our data could be the predominance of patients within this subgroup.

2021 data by Kotini-Shah et al. indicate that the rate of favorable neurological outcome of OHCA patients in the United States is 8.7%.[11] However, similar to the findings regarding survival to hospital discharge, our study revealed a relatively low rate of favorable neurological outcomes, with only 27 patients (2.7%) demonstrating positive results. We can observe similar rates in Asian countries in this aspect. In the study conducted by Okubo et al. in 2014, which analyzed OHCA data from a sizable cohort, the rate of favorable neurological outcomes was reported to be only 2%.[12]

It is interesting to note that while our outcomes that are related to the prehospital and emergency care are notably similar to the literature, our rates of discharge and favorable neurological survival are considerably low. This observation prompts consideration of potential factors influencing these relatively long term outcomes.

The factors contributing to lower survival rates in Türkiye compared to global data warrant further investigation. While factors such as ED crowding in Türkiye may play a role, the lack of intensive care unit capacity in certain regions, coupling with the need for transfer of the critical patients, may have contributed to the observed poor outcomes. A comprehensive examination of all potential causes is necessary. It is imperative to escalate quality improvement initiatives nationwide to address this issue effectively. While the effectiveness of CPR is pivotal for inpatient discharge and favorable neurological outcomes, its success hinges on the coordination of multiple disciplines and is subject to various confounding factors. In this study, while ROSC rates in EMS and EDs align with global data, the underlying factors contributing to lower rates of live discharges and favorable neurological outcomes warrant investigation. These results suggest the possibility that patients in Türkiye may lack adequate support from intensive care and other multidisciplinary aspects in subsequent stages of treatment. Future studies should conduct detailed analyses to address this issue, and we believe the data presented here can significantly contribute to enhancing CPR success nationwide.

In the EuRoCa TWO study, approximately 58.8% of OHCA patients who received CPR had bystander CPR, leading to significantly higher rates of ROSC and discharge compared to those in whom EMS initiated CPR.[1] Similarly, data from Australia and New Zealand, as reported by Beck et al. in 2018, indicated that bystander CPR was administered in 67% of OHCA cases.[8] Despite relatively lower rates in British data, standing at 39.5%, these rates still surpass those observed in our study.[10] The notable discrepancy in bystander CPR rates in our data may be attributed to cultural disparities and variations in CPR awareness levels.[13] Barriers to access to AEDs and the lack of awareness of AED use remain important handicaps in Türkiye. In addition, the absence of Good Samaritan Law rules in Turkey may partially explain the hesitations about performing CPR in cardiac arrest cases.

We identified several independent predictors of survival to hospital discharge in the logistic regression analysis, including male gender, recorded initial shockable rhythm, a shorter prehospital duration of CPR, and the lack of CPR requirement in the ED.

The male gender predominance, which varies between 56% and 65% in the literature, is also evident in this study.[1,11,12] In the study of Kotini-Shah et al., it was observed that better results were obtained in the male gender in terms of survival to hospital discharge and neurological outcome, but in multivariate analysis, the adjusted odds ratios were seen to be in favor of the female gender.[11] On the contrary, we observed better outcomes in male patients; we can attribute these results to the higher rates of bystander CPR in male gender.

The presence of an initial shockable rhythm as an independent predictor of survival to hospital discharge has been observed in various studies in different settings.[14-17] Additionally, in Li et al.’s data from Singapore, which shares similar characteristics and settings with our study and demonstrates a survival rate of 3.4%, shockable initial rhythm and shorter prehospital CPR duration were also identified as independent predictors.[14] It is evident that increasing the rate of bystander-initiated CPR can lead to improved outcome rates, highlighting the necessity for a nationwide educational campaign.

The presence of chronic pulmonary disease, witnessed arrest, cardiac arrest occurring at hospital perimeters, brief prehospital CPR duration, absence of mechanical CPR device uses in the ED, utilization of a venous access other than the peripheral intravenous route, and higher pH levels in the first blood gas obtained during CPR were identified as independent predictors of sustained ROSC.

A recent study by Balan et al. reported that witnessed cardiac arrest, initial shockable rhythm, and cardiac arrest occurring outside of home were found to be the independent predictors of hospital discharge in 3952 OHCA patients who achieved sustained ROSC.[16] Although our study populations and outcomes may differ, it is noteworthy that we obtained similar results.

The debate regarding whether mechanical or manual chest compressions yield different outcomes in cardiac arrest patients remains a hot topic of current research. Only a single 2015 randomized controlled study reported significant harm of mechanical compression device in OHCA patients in terms of survival with favorable neurological outcome.[18] A 2018 Cochrane review categorized existing studies as of medium-to-low quality and concluded that both methods were not superior to each other except in certain circumstances. It is important to note that this review included evaluations of both inhospital and OHCA patients, with trauma patients excluded.[19] Therefore, our findings may not align precisely with those of the aforementioned review.

We found that the sustained ROSC rate was significantly higher in patients who received prehospital respiratory support, particularly among those who underwent successful ETI before arrival at the hospital. However, the observational design of our study limits our ability to make definitive conclusions based solely on these findings. For instance, the recent AIRWAY-2 study investigated the impact of prehospital ETI and supraglottic airway (SGA) placement on 30 day survival in OHCA patients, finding no significant difference between the two methods.[20]

In our study, we observed a significantly higher rate of sustained ROSC among patients who received epinephrine prior to hospital arrival. This finding aligns with the PARAMEDIC2 study, a large-scale investigation conducted in 2018, which demonstrated higher rates of ROSC, survival to hospital admission, and 30-day survival in OHCA patients treated with prehospital epinephrine administration.[21] Consequently, the use of epinephrine in OHCA patients has gained stronger support, as reflected in the 2023 update of the AHA advanced cardiac life support guidelines.[22]

Limitations

First, it should be noted that significant missing data exist, and consecutive sampling could not be properly implemented. Disruption of the operational functioning of study centers due to the earthquake on February 6, 2023, was a major contributing factor to these missing data. Additionally, two of the study centers had to be excluded from the study due to data unavailability. However, it has not been assessed whether this situation negatively impacts the regional representation of the country. The inclusion of tertiary hospitals in the study may introduce bias when extrapolating the results to the general public and rural ED.

Patients who received CPR outside and were not brought to the study centers were not included in the study; excluding these data also increases the bias factor. Most previous registry studies included only patients transported by EMS.[1,8-10,12] Although the rate of patients transported by non-EMS people is very low (2.6%), the inclusion of this patient group should be taken into consideration when discussing results with previous literature. Since reliable data could not be obtained about the time for prehospital transport, it was not included in the analysis. In most of the patients, the possible etiology of cardiac arrest was estimated by the physician based on the available history. Lack of knowledge about exact no flow time (for lay person) may have a negative influence on results.

Another point, the hospital arrest localization group causes confusion for the results. In this group, cardiac arrest occurs at the triage or the hospital entrance. Therefore, it is understood that interventions such as prehospital chest compressions and respiratory support are not applied in a significant part of this group, and it is understood that the prognosis is better, probably due to rapid access to health-care providers.

Given the study’s nonrandomized controlled trial design, it is important to acknowledge that certain subgroup analysis findings may be influenced by confounding factors. For instance, while the lower success rate of CPR with mechanical devices might appear accurate, it is plausible that this outcome could be influenced by factors such as the preference for mechanical CPR devices in patients with a lower life expectancy and longer CPR duration.

Conclusion

This study is the first multicenter, prospective study conducted in Türkiye revealing OHCA data. As a result, prognostic data obtained in the prehospital and ED periods are similar to those in developed countries; however, survival and good neurological outcome rates appear to be worse. Concepts such as ED crowding and intensive care quality can be discussed here. However, success in hospital discharge and neurological survival is an issue that requires multidisciplinary coordination. Although it is not the focus of this study, the correct approach would be to discuss these poor outcomes by focusing on the postcardiac arrest care step in the chain of survival.

Consistent with the literature, shockable initial rhythm and witnessed arrest were found to be associated with good outcomes. On the other hand, the bystander CPR rate, which is very low compared to developed countries, should be particularly scrutinized and efforts should be made to improve it by developing health policies and social policies.

Suppl. 1. Factors associated with survived event

Suppl. 2. Factors associated with survived event ‑ continues variables

Suppl. 3. Factors associated with sustained return of the spontaneous circulation (overall)

Suppl. 3. Contd...

Suppl. 4 . Factors associated with sustained return of the spontaneous circulation (overall) ‑ continues variables

Suppl. 5. Factors associated with survival to hospital discharge

Suppl. 5. Contd...

Suppl. 6. Factors associated with survival to hospital discharge ‑ continues variables

Suppl. 7. Factors associated with good neurological outcome at discharge

Suppl. 7. Contd...

Suppl. 8. Factors associated with good neurological outcome at discharge ‑ continuous variables

Suppl. 9. Distribution of outcomes in terms of regions

How to cite this article: Şener A, Pekdemir M, İslam MM, Aksay E, Karahan S, Aksel G, et al. Prospective, multicenter, Turkish out-of-hospital cardiac arrest study: TROHCA. Turk J Emerg Med 2024;24:133-44.

This multicenter study was carried out in 28 health centers in Türkiye within the scope of the Emergency Medicine Association of Türkiye (EMAT) Resuscitation Study Group, and approval was obtained from the Kocaeli University Non-Interventional Clinical Research Ethics Committee (KÜ GOKAEK‑2022/18.24; November 10, 2022).

All authors conducted the study concept and design and acquisition of the data. AŞ and SK conducted the statistical analysis and interpretation of the data. AŞ and MMİ conducted the drafting of the manuscript. All authors conducted critical revision of the manuscript for important intellectual content.

None declared.

None.

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The researchers would like to thank the Emergency Medicine Association of Türkiye Resuscitation Study Group Members for their valuable contribution to the study.