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Original article| Volume 75, ISSUE 3, P315-322, March 2020

Effectiveness of dispatcher instructions-dependent or independent bystander cardiopulmonary resuscitation on neurological survival among patients with out-of-hospital cardiac arrest

Open ArchivePublished:September 18, 2019DOI:https://doi.org/10.1016/j.jjcc.2019.08.007

      Highlights

      • This study evaluated dispatcher instructions (DI) for cardiac arrests.
      • We analyzed data from the large population-based registry in Osaka City, Japan.
      • DI-dependent cardiopulmonary resuscitation (CPR) did not raise favorable outcome.
      • Independent CPR had higher favorable neurological survival than no CPR.
      • This suggested the importance of bystander CPR quality and effective DI programs.

      Abstract

      Background

      We evaluated the association between survival and bystandercardiopulmonary resuscitation (CPR) with or without dispatcher instructions (DI) considering the time from emergency call receipt by the dispatch center to emergency medical services (EMS) personnel’s contact with the patient (i.e. time to EMS arrival).

      Methods

      This prospective study conducted in Osaka City, Japan, from 2009 to 2015 included patients with medical cause-related out-of-hospital cardiac arrest who were ≥18 years old. The primary outcome was one-month favorable neurological survival. Using multiple logistic regression models, the adjusted odds ratios (AOR) of independent and DI-dependent CPR for the primary outcome were compared with no CPR. Adjustments were made for patients’ age, sex, activities of daily living before the cardiac arrest, year of cardiac arrest, location, presence or absence of witnesses, etiology of cardiac arrest, and the time from EMS contact with the patient to patient’s arrival at the hospital. The effective estimated “time to EMS arrival” was also calculated.

      Results

      For analyses 10,925 individuals were eligible. Independent CPR had a significantly higher one-month favorable neurological survival than no CPR whereas there was no significant difference between DI-dependent CPR and no CPR (AOR, 1.90 [1.47–2.46] and 1.16 [0.91–1.47], respectively). The estimated “time to EMS arrival” for a one-month favorable neurological survival after independent CPR was ≤13 min.

      Conclusions

      Bystander CPR that did not need DI was associated with significantly higher one-month favorable neurological survival than no CPR, with an effective estimated “time to EMS arrival” of ≤13 min.

      Keywords

      Introduction

      Out-of-hospital cardiac arrest (OHCA) is a major public health issue in the developed world [
      • Nolan J.P.
      • Hazinski M.F.
      • Aickin R.
      • Bhanji F.
      • Billi J.E.
      • Callaway C.W.
      • et al.
      Part 1: executive summary 2015 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations.
      ,
      • Monsieurs K.G.
      • Nolan J.P.
      • Bossaert L.L.
      • Greif R.
      • Maconochie I.K.
      • Nikolaou N.I.
      • et al.
      European resuscitation council guidelines for resuscitation 2015: section 1. Executive summary.
      ,
      • Neumar R.W.
      • Shuster M.
      • Callaway C.W.
      • Gent L.M.
      • Atkins D.L.
      • Bhanji F.
      • et al.
      Part 1: executive summary 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care.
      ,
      • Chung S.P.
      • Sakamoto T.
      • Lim S.H.
      • Ma M.H.
      • Wang T.L.
      • Lavapie F.
      • et al.
      The 2015 Resuscitation Council of Asia (RCA) guidelines on adult basic life support for lay rescuers.
      ]. More than 70,000 cases occur every year in Japan [
      • Japan Resuscitation Council
      Resuscitation guidelines 2015.
      ]. The burden of OHCA is also substantial, with estimated yearly incidences of 110 per 100,000 people in the USA [
      • Benjamin E.J.
      • Blaha M.J.
      • Chiuve S.E.
      • Cushman M.
      • Das S.R.
      • Deo R.
      • et al.
      Heart disease and stroke statistics-2017 update: a report from the American Heart Association.
      ] and of 84 per 100,000 people in Europe [
      • Gräsner J.T.
      • Lefering R.
      • Koster R.W.
      • Masterson S.
      • Böttiger B.W.
      • Herlitz J.
      • et al.
      EuReCa ONE-27 Nations, ONE Europe, ONE Registry: a prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe.
      ]. However, survival after OHCA remains low regardless of the region [
      • Benjamin E.J.
      • Blaha M.J.
      • Chiuve S.E.
      • Cushman M.
      • Das S.R.
      • Deo R.
      • et al.
      Heart disease and stroke statistics-2017 update: a report from the American Heart Association.
      ,
      • Gräsner J.T.
      • Lefering R.
      • Koster R.W.
      • Masterson S.
      • Böttiger B.W.
      • Herlitz J.
      • et al.
      EuReCa ONE-27 Nations, ONE Europe, ONE Registry: a prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe.
      ,

      Reports from Fire and Disaster Management Agency of Japan 2018 (in Japanese). https://www.fdma.go.jp/publication/rescue/post7.html (accessed July 24, 2019).

      ]. Bystander cardiopulmonary resuscitation (CPR) performed before the arrival of emergency medical services (EMS) increases the likelihood of survival after OHCA [
      • Nakahara S.
      • Tomio J.
      • Ichikawa M.
      • Nakamura F.
      • Nishida M.
      • Takahashi H.
      • et al.
      Association of bystander interventions with neurologically intact survival among patients with bystander-witnessed out-of-hospital cardiac arrest in Japan.
      ,
      • Iwami T.
      • Kitamura T.
      • Kiyohara K.
      • Kawamura T.
      Dissemination of chest compression-only cardiopulmonary resuscitation and survival after out-of-hospital cardiac arrest.
      ]. To increase the administration of bystander CPR on the scene, many countries and regions, including Japan, have aggressively introduced dispatcher instructions (DI) [
      • Lerner E.B.
      • Rea T.D.
      • Bobrow B.J.
      • Acker 3rd, J.E.
      • Berg R.A.
      • Brooks S.C.
      • et al.
      Emergency medical service dispatch cardiopulmonary resuscitation prearrival instructions to improve survival from out-of-hospital cardiac arrest: a scientific statement from the American Heart Association.
      ]. That the availability of over-the-telephone CPR instructions increased the frequency of bystander CPR was demonstrated [
      • Rea T.D.
      • Eisenberg M.S.
      • Culley L.L.
      • Becker L.
      Dispatcher-assisted cardiopulmonary resuscitation and survival in cardiac arrest.
      ,
      • Japanese Circulation Society Resuscitation Science Study Group
      Chest-compression-only bystander cardiopulmonary resuscitation in the 30:2 compression-to-ventilation ratio era. Nationwide observational study.
      ,
      • Shimamoto T.
      • Iwami T.
      • Kitamura T.
      • Nishiyama C.
      • Sakai T.
      • Nishiuchi T.
      • et al.
      Dispatcher instruction of chest compression-only CPR increases actual provision of bystander CPR.
      ].
      A previous report showed that the 30-day survival after OHCA was significant when bystander CPR was performed within 12 min after a sudden collapse [
      • Rajan S.
      • Wissenberg M.
      • Folke F.
      • Hansen S.M.
      • Gerds T.A.
      • Kragholm K.
      • et al.
      Association of bystander cardiopulmonary resuscitation and survival according to ambulance response times after out-of-hospital cardiac arrest.
      ]. In addition, a report from Japan indicated that laypersons who initiated CPR without DI were in many cases well-trained rescuers [
      • Takei Y.
      • Nishi T.
      • Matsubara H.
      • Hashimoto M.
      • Inaba H.
      Factors associated with quality of bystander CPR: the presence of multiple rescuers and bystander-initiated CPR without instruction.
      ]. Thus, the effective performance time of bystander CPR would be influenced by its quality, which is related to the bystanders’ need for DI.
      In Osaka City, Japan, we have developed a prospective population-based OHCA registry. During the 7-year period of 2009–2015, approximately 11,000 cases of OHCA with a medical etiology occurred before EMS arrival. The aim of this study was to evaluate the association of bystander CPR with or without DI and neurologically favorable one-month survival with a cerebral performance category (CPC) score 1 or 2 compared with no CPR. In addition, when analyzing the data, we considered the time from emergency call receipt by the dispatch center to EMS personnel’s contact with the OHCA patient because bystander CPR could play an important role in patients’ survival during this period.

      Materials and methods

      Study design and setting

      Details of our registry have been described [
      • Matsuyama T.
      • Kitamura T.
      • Kiyohara K.
      • Hayashida S.
      • Kawamura T.
      • Iwami T.
      • et al.
      Characteristics and outcomes of emergency patients with self-inflicted injuries: a report from ambulance records in Osaka City, Japan.
      ,
      • Kiyohara K.
      • Nishiyama C.
      • Hayashida S.
      • Matsuyama T.
      • Hatakeyama T.
      • Shimamoto T.
      • et al.
      Characteristics and outcomes of bath-related out-of-hospital cardiac arrest in Japan.
      ,
      • Kobayashi D.
      • Kitamura T.
      • Kiyohara K.
      • Nishiyama C.
      • Hayashida S.
      • Fujii T.
      • et al.
      High-rise buildings and neurologically favorable outcome after out-of-hospital cardiac arrest.
      ]. Osaka City, the third largest city in Japan, has a population of approximately 2.7 million (2019) in an area of 223 km2 [

      Reports from Osaka City of Japan. (in Japanese) http://www.city.osaka.lg.jp/toshikeikaku/page/0000014987.html (accessed July 24, 2019).

      ]. The Osaka Municipal Fire Department has registered details of EMS activities in the city and linked them to data on resuscitation practices and patient outcomes that were simultaneously collected according to the international Utstein-style guidelines on OHCA reports. Details of the EMS system in Japan, including that in Osaka City, were also described previously [
      • Matsuyama T.
      • Kitamura T.
      • Kiyohara K.
      • Hayashida S.
      • Kawamura T.
      • Iwami T.
      • et al.
      Characteristics and outcomes of emergency patients with self-inflicted injuries: a report from ambulance records in Osaka City, Japan.
      ,
      • Kiyohara K.
      • Nishiyama C.
      • Hayashida S.
      • Matsuyama T.
      • Hatakeyama T.
      • Shimamoto T.
      • et al.
      Characteristics and outcomes of bath-related out-of-hospital cardiac arrest in Japan.
      ,
      • Kobayashi D.
      • Kitamura T.
      • Kiyohara K.
      • Nishiyama C.
      • Hayashida S.
      • Fujii T.
      • et al.
      High-rise buildings and neurologically favorable outcome after out-of-hospital cardiac arrest.
      ]. Briefly, there are three EMS technicians with at least one being an emergency life-saving technician who had undergone advanced training for providing pre-hospital emergency care in each ambulance vehicle. All were allowed to insert an intravenous line and an adjunct airway. The specially trained emergency life-saving technicians were permitted to insert tracheal tubes and administer intravenous adrenaline. Japanese law prohibits EMS personnel from terminating resuscitation in the field. Accordingly, most OHCA patients receive CPR administered by EMS technicians and are transported to the hospital [
      • Goto Y.
      • Funada A.
      • Maeda T.
      • Okada H.
      • Goto Y.
      Field termination-of-resuscitation rule for refractory out-of-hospital cardiac arrests in Japan.
      ]. Dispatcher CPR instructions on conventional CPR with rescue breathing that is provided over the telephone was introduced in Japan in July 1999 [
      • Iwami T.
      • Nichol G.
      • Hiraide A.
      • Hayashi Y.
      • Nishiuchi T.
      • Kajino K.
      • et al.
      Continuous improvements in "chain of survival" increased survival after out-of-hospital cardiac arrests: a large-scale population-based study.
      ]. Instructions on chest compression-only CPR also can be given over the telephone if it is difficult for bystanders to administer rescue breathing [
      • Iwami T.
      • Kitamura T.
      • Kiyohara K.
      • Kawamura T.
      Dissemination of chest compression-only cardiopulmonary resuscitation and survival after out-of-hospital cardiac arrest.
      ]. If a bystander started CPR by himself or herself before the emergency call or the situation on the scene was unsuitable for CPR practice, such as in a traffic accident, telephone assistance was not provided in Osaka City.

      Study population

      Analyzed for the current study were OHCA patients who were ≥18 years of age, whose collapse was of medical etiology, and who received CPR from EMS personnel between January 2009 and December 2015. Cases of cardiac arrest after EMS arrival and those in whom the collapse occurred in a health care facility were excluded from the analysis.
      Cardiac arrest was defined as the cessation of cardiac mechanical activity confirmed through the absence of signs of circulation. The signs of circulation were confirmed by EMS personnel checking movements, breathing, and whether carotid artery was pulsating and by the findings of electrocardiogram. The OHCA was presumed to be of medical origin unless it was caused by trauma, drowning, drug overdose, electrocution, or asphyxia [
      • Perkins G.D.
      • Jacobs I.G.
      • Nadkarni V.M.
      • Berg R.A.
      • Bhanji F.
      • Biarent D.
      • et al.
      Cardiac arrest and cardiopulmonary resuscitation outcome reports: update of the Utstein resuscitation registry templates for out-of-hospital cardiac arrest: a statement for healthcare professionals from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian and New Zealand Council on Resuscitation, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa, Resuscitation Council of Asia); and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation.
      ]. These diagnoses were clinically made by the physicians in charge of the patients in collaboration with the EMS personnel.

      Data collection and quality control

      Data were uniformly collected via international Utstein-style reporting forms that included questions about the following: patient age, sex, and activities of daily living before the cardiac arrest, collapse date and location, presence or absence of witnesses, etiology of cardiac arrest, first-documented cardiac rhythm, time course of resuscitation, DI, bystander CPR, and one-month neurological status after the event [
      • Cummins R.O.
      • Chamberlain D.A.
      • Abramson N.S.
      • Allen M.
      • Baskett P.J.
      • Becker L.
      • et al.
      Recommended guidelines for uniform reporting of data from out-of-hospital cardiac arrest: the Utstein Style. A statement for health professionals from a task force of the American Heart Association, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, and the Australian Resuscitation Council.
      ,
      • Jacobs I.
      • Nadkarni V.
      • Bahr J.
      • Berg R.A.
      • Billi J.E.
      • Bossaert L.
      • et al.
      Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries. A statement for healthcare professionals from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa).
      ]. EMS-related time data, such as emergency call receipt, arrival at the scene, contact with the patient, and arrival at the hospital were recorded at the emergency dispatch center [
      • Matsuyama T.
      • Kitamura T.
      • Kiyohara K.
      • Hayashida S.
      • Kawamura T.
      • Iwami T.
      • et al.
      Characteristics and outcomes of emergency patients with self-inflicted injuries: a report from ambulance records in Osaka City, Japan.
      ,
      • Kiyohara K.
      • Nishiyama C.
      • Hayashida S.
      • Matsuyama T.
      • Hatakeyama T.
      • Shimamoto T.
      • et al.
      Characteristics and outcomes of bath-related out-of-hospital cardiac arrest in Japan.
      ,
      • Kobayashi D.
      • Kitamura T.
      • Kiyohara K.
      • Nishiyama C.
      • Hayashida S.
      • Fujii T.
      • et al.
      High-rise buildings and neurologically favorable outcome after out-of-hospital cardiac arrest.
      ].
      The data form was completed by EMS personnel in cooperation with the attending physicians. These data were then transferred to the EMS Information Center of the Osaka Municipal Fire Department and checked by researchers. If any data sheets were incomplete, the relevant EMS personnel were contacted and asked to complete the sheets [
      • Matsuyama T.
      • Kitamura T.
      • Kiyohara K.
      • Hayashida S.
      • Kawamura T.
      • Iwami T.
      • et al.
      Characteristics and outcomes of emergency patients with self-inflicted injuries: a report from ambulance records in Osaka City, Japan.
      ,
      • Kiyohara K.
      • Nishiyama C.
      • Hayashida S.
      • Matsuyama T.
      • Hatakeyama T.
      • Shimamoto T.
      • et al.
      Characteristics and outcomes of bath-related out-of-hospital cardiac arrest in Japan.
      ,
      • Kobayashi D.
      • Kitamura T.
      • Kiyohara K.
      • Nishiyama C.
      • Hayashida S.
      • Fujii T.
      • et al.
      High-rise buildings and neurologically favorable outcome after out-of-hospital cardiac arrest.
      ]. All OHCA survivors were followed up for a maximum of one month after the event by the EMS personnel in charge. Neurological outcome was determined by the attending physicians using the cerebral performance category scale (CPC) [
      • Cummins R.O.
      • Chamberlain D.A.
      • Abramson N.S.
      • Allen M.
      • Baskett P.J.
      • Becker L.
      • et al.
      Recommended guidelines for uniform reporting of data from out-of-hospital cardiac arrest: the Utstein Style. A statement for health professionals from a task force of the American Heart Association, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, and the Australian Resuscitation Council.
      ,
      • Jacobs I.
      • Nadkarni V.
      • Bahr J.
      • Berg R.A.
      • Billi J.E.
      • Bossaert L.
      • et al.
      Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries. A statement for healthcare professionals from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa).
      ].

      Statistical analysis

      The primary outcome in the study was one-month survival with a favorable neurological outcome, which was designated according to a CPC of 1 or 2. CPC 1 denotes good cerebral performance; CPC 2, moderate cerebral disability; CPC 3, severe cerebral disability; CPC 4, coma or vegetative state; and CPC 5, death [
      • Perkins G.D.
      • Jacobs I.G.
      • Nadkarni V.M.
      • Berg R.A.
      • Bhanji F.
      • Biarent D.
      • et al.
      Cardiac arrest and cardiopulmonary resuscitation outcome reports: update of the Utstein resuscitation registry templates for out-of-hospital cardiac arrest: a statement for healthcare professionals from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian and New Zealand Council on Resuscitation, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa, Resuscitation Council of Asia); and the American Heart Association Emergency Cardiovascular Care Committee and the Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation.
      ,
      • Cummins R.O.
      • Chamberlain D.A.
      • Abramson N.S.
      • Allen M.
      • Baskett P.J.
      • Becker L.
      • et al.
      Recommended guidelines for uniform reporting of data from out-of-hospital cardiac arrest: the Utstein Style. A statement for health professionals from a task force of the American Heart Association, the European Resuscitation Council, the Heart and Stroke Foundation of Canada, and the Australian Resuscitation Council.
      ,
      • Jacobs I.
      • Nadkarni V.
      • Bahr J.
      • Berg R.A.
      • Billi J.E.
      • Bossaert L.
      • et al.
      Cardiac arrest and cardiopulmonary resuscitation outcome reports: update and simplification of the Utstein templates for resuscitation registries. A statement for healthcare professionals from a task force of the International Liaison Committee on Resuscitation (American Heart Association, European Resuscitation Council, Australian Resuscitation Council, New Zealand Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Southern Africa).
      ].
      Bystander CPR was designated as either DI-dependent CPR or independent CPR. Time to EMS arrival was defined as the time from the emergency call receipt by the dispatch center to the EMS personnel’s contact with the OHCA patient. Bystanders’ responses in this study are no CPR, DI-dependent CPR, and independent CPR.
      Baseline characteristics were compared among groups using the chi-square test for categorical variables and Student’s t-test for numerical variables. Univariate analysis was performed to calculate unadjusted odds ratios and their 95% confidence intervals (CIs) of the associations between bystanders’ responses and one-month survival with favorable neurological outcomes. Multivariate logistic regression was further performed to detect the associations between bystanders’ responses and one-month favorable neurological survival. Then adjusted odds ratios (AOR) and their 95% CIs were calculated. In the multiple logistic regression models, the following variables were fitted as numerical: patients’ age and the time from EMS contact with the patient to arrival at the hospital. The following variables were fitted as categorical: patients’ sex, activities of daily living before the cardiac arrest, collapse year and location, presence or absence of witnesses, and etiology of cardiac arrest. However, the first cardiac rhythm recorded by EMS personnel and the automatic external defibrillator’s shock by bystanders were not adjusted because these were intermediate variables between bystander CPR and one-month favorable neurological survival (Online Fig. 1) [
      • Rajan S.
      • Wissenberg M.
      • Folke F.
      • Hansen S.M.
      • Gerds T.A.
      • Kragholm K.
      • et al.
      Association of bystander cardiopulmonary resuscitation and survival according to ambulance response times after out-of-hospital cardiac arrest.
      ]. As an additional analysis, one-month favorable neurological survival was evaluated according to bystanders’ responses and time to EMS arrival using a multivariate logistic regression model. We calculated standardized one-month favorable neurological survival according to time to EMS arrival and bystanders’ responses using multiple logistic regression models. First, we performed multiple logistic regression to analyze the association between one-month favorable neurological survival and bystanders’ responses including independent CPR and no CPR. In addition, we performed multiple logistic regression to analyze the association between one-month favorable neurological survival and bystanders’ responses including DI-dependent CPR and no CPR. Second, we plugged the mean values for numerical variables and the most common categories of categorical variables into the models. We calculated standardized one-month favorable neurological survival for all possible values for the time to EMS arrival from 1 to 20 min. Finally, we estimated 95% CIs on standardized one-month favorable neurological survival according to the method used in a previous study [
      • Sofroniou N.
      • Hutcheson G.D.
      Confidence intervals for the predictions of logistic regression in the presence and absence of a variance-covariance matrix.
      ]. In addition, we calculated point estimations and 95% CIs regarding each group’s differences in the standardized one-month favorable neurological survival [
      • Sofroniou N.
      • Hutcheson G.D.
      Confidence intervals for the predictions of logistic regression in the presence and absence of a variance-covariance matrix.
      ].
      All the tests were two-tailed, and p-values <0.05 were considered statistically significant. Statistical analyses were performed using SPSS version 22.0 J (IBM Corp, Armonk, NY, USA).

      Ethical considerations

      As all personal identifiers were removed from the database by the EMS Information Center, the requirement for individual informed consent was waived by the act on the Protection of Personal Information and the Ethical Guidelines for Medical and Health Research Involving Human Subjects of Japan [

      Ethical guidelines for medical and health research involving human subjects of Japan http://www.mhlw.go.jp/file/06-Seisakujouhou-10600000-Daijinkanboukouseikagakuka/0000080278.pdf (accessed July 24, 2019).

      ]. The research protocol was approved by the Ethics Committee of Kyoto University Graduate School of Medicine (R0416).

      Results

      Patient flow and baseline characteristics

      Fig. 1 is an overview of study patients based on the Utstein reports that are linked to the EMS records of Osaka City. A total of 18,458 patients who had OHCA during the study period were documented; of those, 16,828 OHCAs occurred before EMS arrival. After the exclusion of 2592 patients whose cardiac arrests occurred in a health care facility, 297 patients who did not have EMS resuscitation attempts, 189 patients <18 years old or of unknown age, and 2825 patients with non-medical causes for the OHCA, 10,925 individuals were eligible for analyses. Among these patients, 6754 (61.8%) did not receive bystander CPR, 3103 (28.4%) received DI-dependent bystander CPR, and 1068 (9.8%) received independent bystander CPR.
      Fig. 1
      Fig. 1Overview of OHCA cases with an abridged Utstein template from January 2009 through December 2015.
      OHCA, out-of-hospital cardiac arrest; EMS, emergency medical services; CPR, cardiopulmonary resuscitation; DI-dependent CPR, cardiopulmonary resuscitation that depended on dispatcher instructions; Independent CPR, cardiopulmonary resuscitation that did not depend on dispatcher instructions; CPC, cerebral performance category score.
      Baseline patient characteristics are shown in Table 1. The patients in all groups tended to be >65 years of age and were more likely to be male. Patients who received independent bystander CPR were less likely to have had cardiac arrest at home and more likely to have cardiac arrest at a public place compared to those who received DI-dependent bystander CPR or no CPR. Additionally, patients who received independent bystander CPR were more likely to have a cardiac arrest witnessed by bystanders and have a shockable initial cardiac rhythm administered by EMS personnel arriving at the scene.
      Table 1Characteristics of out-of-hospital cardiac arrest patients who received no CPR, DI-dependent CPR, and independent CPR.
      No CPR (n = 6754)DI-dependent CPR (n = 3103)Independent CPR (n = 1068)p-value
      Age, year, mean (SD)72.3 (14.3)73.8 (14.5)69.0 (15.3)< 0.001
      Men, n (%)4281 (63.4)1789 (57.7)732 (68.5)< 0.001
      Location, n (%)< 0.001
       home5,306 (78.6)2690 (86.7)519 (48.6)
       Public space1,122 (16.6)329 (10.6)442 (41.4)
       Others326 (4.8)84 (2.7)107 (10.0)
      Activities of daily living before the cardiac arrest, n (%)< 0.001
       Good (no disability)4552 (67.4)2065 (66.5)742 (69.5)
       Moderate disability1,029 (15.2)561 (18.1)135 (12.6)
       Severe disability573 (8.5)366 (11.8)97 (9.1)
       Vegetative state5 (0.1)3 (0.1)0 (0.0)
       Unknown595 (8.8)108 (3.5)94 (8.8)
      Witnessed by bystanders, n (%)2706 (40.1)1031 (33.2)571 (53.5)< 0.001
      Chest compression only CPR, n (%)0 (0.0)2477 (79.8)812 (76.0)< 0.001
      Etiology of cardiac arrest, n (%)6135 (90.8)2873 (92.6)973 (91.1)< 0.001
      The time from EMS contact with the patient to patient's arrival at the hospital, min, mean (SD)22.4 (9.0)22.3 (8.1)21.2 (7.8)< 0.001
      AED shock by bystanders, n (%)3 (0.04)28 (0.9)98 (9.2)< 0.001
      Shockable first cardiac rhythm recorded by EMS personnel, n (%)689 (10.2)298 (9.6)205 (19.2)< 0.001
      CPR, cardiopulmonary resuscitation; DI-dependent CPR, cardiopulmonary resuscitation that depended on dispatcher instructions; Independent CPR, cardiopulmonary resuscitation that did not depend on dispatcher instructions; SD, standard deviation; EMS, emergency medical services; min, minutes; AED, automatic external defibrillator.

      Temporal trends in bystander response

      Temporal trends of DI-dependent and independent bystander CPR are shown in Fig. 2. The proportion of DI-dependent bystander CPR increased from 24.8% in 2009 to 36.1% in 2015 (p for trend, 0.01), whereas that of no CPR decreased from 64.0% in 2009 to 54.8% in 2015 (p for trend, 0.02). Independent bystander CPR remained nearly stable throughout the study period (11.1% in 2009 to 9.2% in 2015; p for trend, 0.10).
      Fig. 2
      Fig. 2Temporal trend in the proportions of no CPR, DI-dependent CPR, and independent CPR.
      CPR, cardiopulmonary resuscitation; DI-dependent CPR, cardiopulmonary resuscitation that depended on dispatcher instructions; Independent CPR, cardiopulmonary resuscitation that did not depend on dispatcher instructions.

      Neurological outcomes according to bystander responses

      After the adjustment, patients who received independent bystander CPR had a significantly higher one-month favorable neurological survival than those who did not receive CPR (10.42% vs 3.72%; AOR, 1.90; 95% CI, 1.47–2.46). However, there was no significant difference in one-month favorable neurological survival between those who received DI-dependent bystander CPR and those who did not receive CPR (3.71% vs 3.72%; AOR, 1.16; 95% CI, 0.91–1.47; Table 2).
      Table 2One-month survival with favorable neurological outcomes among no CPR, DI-dependent CPR, and independent CPR.
      No CPR (n = 6754)DI-dependent CPR (n = 3103)Independent CPR (n = 1068)
      One-month survival with favorable neurological outcomes, n (%)251 (3.72)115 (3.71)111 (10.42)
      Unadjusted OR (95% CI)Reference1.00 (0.80–1.25)3.01 (2.39–3.81)
      Adjusted OR (95% CI)Reference1.16 (0.91–1.47)1.90 (1.47–2.46)
      Adjusted ORs (95% CIs) are adjusted to patients’ age, sex, activities of daily living before the cardiac arrest, year of cardaic arrest, location, presence or absence of witnesses, etiology of cardiac arrest, and the time from emergency medical services' contact with the patient to patient's arrival at the hospital.
      CPR, cardiopulmonary resuscitation; DI-dependent CPR, cardiopulmonary resuscitation that depended on dispatcher instructions; Independent CPR, cardiopulmonary resuscitation that did not depend on dispatcher instructions; OR, odds ratio; CI, confidence interval.
      Favorable neurological outcomes were defined as a cerebral performance category score of 1 or 2.

      Time dependence of the effectiveness of bystander CPR according to need for DI

      Fig. 3A and B shows the association between the time to EMS arrival at the scene and neurologically favorable one-month survival according to the need for DI (independent bystander CPR or DI-dependent vs. no CPR). The point estimations and 95% CIs of the standardized one-month favorable neurological survival are shown in these figures. One-month favorable neurological survival decreased with increases in time to EMS arrival irrespective of the type of bystander response.
      Fig. 3
      Fig. 3(A,B) Standardized one-month favorable neurological survival according to time to EMS arrival and bystanders’ responses. The favorable neurological outcomes based on the multiple logistic regression analysis were standardized to the bystanders’ responses, including no CPR and any CPR (Independent CPR or DI-dependent CPR) according to time to EMS arrival. The model is adjusted for patients’ age, sex, activities of daily living before the cardiac arrest, year of cardiac arrest, location, presence or absence of witnesses, etiology of cardiac arrest, and the time from EMS contact with the patient to patient’s arrival at the hospital.
      EMS, emergency medical services; CPR, cardiopulmonary resuscitation; Independent CPR, cardiopulmonary resuscitation that did not depend on dispatcher instructions; DI-dependent CPR, cardiopulmonary resuscitation that depended on dispatcher instructions; time to EMS arrival, time from the emergency call receipt by the dispatch center to the emergency medical services personnel’s contact with patient.
      The one-month favorable neurological survival of patients receiving independent bystander CPR was significantly greater than that of those who did not receive bystander CPR when the time to EMS arrival was ≤13 min (2.84; point estimation, 0.03–5.64; 95% CI of the difference between groups at CPR duration = 13 min). On the other hand, there was no statistically significant difference between the DI-dependent bystander CPR and no bystander CPR. Online Fig. 2 clearly indicates the cut-off value at 13 min for one-month favorable neurological results between no CPR and independent CPR. Online Fig. 3 shows 95% CIs of the differences in the logits of probabilities of one-month favorable neurological survival between no CPR and DI-dependent CPR according to the time to EMS arrival. Online Fig. 2 suggests that the one-month favorable neurological survival of patients receiving independent bystander CPR was significantly greater than that of those who did not receive bystander CPR when the time to EMS arrival was ≤13 min since the 95% CIs did not include zero when the time to EMS arrival was from 1 to 13 min. In addition, Online Fig. 3 shows 95% CIs of the differences in the logits of probabilities of one-month favorable neurological survival between no CPR and DI-dependent CPR according to time to EMS arrival. This suggests that there was no statistically significant difference between no CPR and DI-dependent CPR because each 95% CI included zero.

      Discussion

      Using a large-scale population-based OHCA registry in Osaka City, we demonstrated that CPR performed by bystanders who did not need DI was associated with a significantly higher one-month favorable neurological survival proportion than no CPR, whereas the survival proportion after DI-dependent bystander CPR was not greater than with no CPR. In addition, this study suggested that the expected time for favorable neurological survival of bystander CPR without DI was ≤13 min. This is the first study evaluating the association between effectiveness of bystander CPR and “time to EMS arrival” by the DI-dependence. According to previous studies, the expected time for patients’ survival with bystander CPR was dependent on CPR quality [
      • Huseyin T.S.
      • Matthews A.J.
      • Wills P.
      • O’Neill V.M.
      Improving the effectiveness of continuous closed chest compressions: an exploratory study.
      ,
      • Ashton A.
      • McCluskey A.
      • Gwinnutt C.L.
      • Keenan A.M.
      Effect of rescuer fatigue on performance of continuous external chest compressions over 3 min.
      ,
      • Sugerman N.T.
      • Edelson D.P.
      • Leary M.
      • Weidman E.K.
      • Herzberg D.L.
      • Vanden Hoek T.L.
      • et al.
      Rescuer fatigue during actual in-hospital cardiopulmonary resuscitation with audiovisual feedback: a prospective multicenter study.
      ]. Prior to the study we had regarded the time to EMS arrival as the time period during which bystander CPR would play a vital role in patients’ survival. The current findings indicated the importance of bystander CPR quality and the necessity of systematic CPR training and sophisticated DI programs to further improve the outcomes after OHCA.
      Our results showed that only bystander CPR that did not require DI yielded a better outcome than no bystander CPR. In our area, the dispatch center does not help rescuers once they have started CPR. As noted previously, bystanders who performed CPR without DI may have effective CPR training [
      • Takei Y.
      • Nishi T.
      • Matsubara H.
      • Hashimoto M.
      • Inaba H.
      Factors associated with quality of bystander CPR: the presence of multiple rescuers and bystander-initiated CPR without instruction.
      ] so that they would be able to perform higher quality CPR than untrained or poorly trained rescuers.
      Surprisingly, our study did not indicate any improvements in neurological survival when the bystanders required DI. The insufficient quality of the instructions provided by the dispatcher, the delay in commencing bystander CPR while awaiting dispatcher assistance, and differences in previous CPR training of bystanders across the 3 groups might be possible explanations. The dispatcher in this study setting generally gives instructions as much as possible when the rescuer has any difficulties to provide CPR. Thus, bystanders who required DI could be composed of less experienced bystanders than the bystanders who performed CPR without DI. Therefore, the results of this study do not necessarily imply that DI is not efficacious. Although the current program of dispatcher CPR instructions increased the proportion of bystander CPR, the quality of bystander CPR requiring DI might be inadequate to improve favorable neurological survival. These results are consistent with past studies showing the effectiveness of dispatcher-assisted CPR to increase bystander CPR [
      • Japanese Circulation Society Resuscitation Science Study Group
      Chest-compression-only bystander cardiopulmonary resuscitation in the 30:2 compression-to-ventilation ratio era. Nationwide observational study.
      ,
      • Shimamoto T.
      • Iwami T.
      • Kitamura T.
      • Nishiyama C.
      • Sakai T.
      • Nishiuchi T.
      • et al.
      Dispatcher instruction of chest compression-only CPR increases actual provision of bystander CPR.
      ,
      • Rajan S.
      • Wissenberg M.
      • Folke F.
      • Hansen S.M.
      • Gerds T.A.
      • Kragholm K.
      • et al.
      Association of bystander cardiopulmonary resuscitation and survival according to ambulance response times after out-of-hospital cardiac arrest.
      ] but failure to improve favorable neurological survival [
      • Akahane M.
      • Ogawa T.
      • Tanabe S.
      • Koike S.
      • Horiguchi H.
      • Yasunaga H.
      • et al.
      Impact of telephone dispatcher assistance on the outcomes of pediatric out-of-hospital cardiac arrest.
      ]. From these results, we believe that CPR training for bystanders is critical to favorable neurological survival not only improvements in DI programs. Thus, both further improvements in DI and educational training for lay people are needed to improve survival after cardiac arrest [
      • Johnsen E.
      • Bolle S.R.
      To see or not to see—better dispatcher-assisted CPR with video-calls? A qualitative study based on simulated trials.
      ,
      • Melbye S.
      • Hotvedt M.
      • Bolle S.R.
      Mobile videoconferencing for enhanced emergency medical communication—a shot in the dark or a walk in the park?—a simulation study.
      ]. For example, a bystander’s delay in performing CPR in an actual setting might be a potential problem on the scene [
      • Berger S.
      Gasping, survival, and the science of resuscitation.
      ]. That gasping or other forms of abnormal breathing commonly occur soon after an OHCA has been suggested [
      • Bobrow B.J.
      • Zuercher M.
      • Ewy G.A.
      • Clark L.
      • Chikani V.
      • Donahue D.
      • et al.
      Gasping during cardiac arrest in humans is frequent and associated with improved survival.
      ]. These abnormal patterns can cause bystander delay in recognizing cardiac arrest [
      • Fukushima H.
      • Imanishi M.
      • Iwami T.
      • Kitaoka H.
      • Asai H.
      • Seki T.
      • et al.
      Implementation of a dispatch-instruction protocol for cardiopulmonary resuscitation according to various abnormal breathing patterns: a population-based study.
      ]. To provide CPR immediately, an improved DI protocol that recognizes cardiac arrests is required.
      In this study, the expected time for favorable neurological survival of bystander CPR was ≤13 min. Although this result is consistent with the study from Denmark showing a statistically significant association between an EMS response time within 12 min and one-month survival, one-month survival was lower in our study (one-month survival; 7.9% vs. 14.5%) [
      • Rajan S.
      • Wissenberg M.
      • Folke F.
      • Hansen S.M.
      • Gerds T.A.
      • Kragholm K.
      • et al.
      Association of bystander cardiopulmonary resuscitation and survival according to ambulance response times after out-of-hospital cardiac arrest.
      ]. Citizen CPR training may be one explanation for these results. Denmark has a national CPR training program, one of the most aggressive in the world [
      • Viereck S.
      • Palsgaard Møller T.
      • Kjær Ersbøll A.
      • Folke F.
      • Lippert F.
      Effect of bystander CPR initiation prior to the emergency call on ROSC and 30 day survival—an evaluation of 548 emergency calls.
      ]. For instance, basic life support and training on the use of an automatic external defibrillator are mandatory in elementary schools in Denmark.
      To expand the expected time for favorable neurological survival of bystander CPR and improve survival from OHCAs, more aggressive basic life support programs are needed to improve bystander CPR quality. Revision of the DI protocol is also required as documented in the current international resuscitation statement [
      • Rea T.D.
      • Eisenberg M.S.
      • Culley L.L.
      • Becker L.
      Dispatcher-assisted cardiopulmonary resuscitation and survival in cardiac arrest.
      ]. New technologies like the introduction of video materials contribute to improving the quality of bystander CPR [
      • Johnsen E.
      • Bolle S.R.
      To see or not to see—better dispatcher-assisted CPR with video-calls? A qualitative study based on simulated trials.
      ,
      • Melbye S.
      • Hotvedt M.
      • Bolle S.R.
      Mobile videoconferencing for enhanced emergency medical communication—a shot in the dark or a walk in the park?—a simulation study.
      ]. Using social media to summon registered lay rescuers to the scene might be beneficial to ensure continuous high-quality CPR by bystanders before handing over “effective” resuscitation to EMS personnel [
      • Finn J.C.
      • Bhanji F.
      • Lockey A.
      • Monsieurs K.
      • Frengley R.
      • Iwami T.
      • et al.
      Part 8: education, implementation, and teams: 2015 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations.
      ,
      • Sakai T.
      • Kitamura T.
      • Nishiyama C.
      • Murakami Y.
      • Ando M.
      • Kawamura T.
      • et al.
      Cardiopulmonary resuscitation support application on a smartphone—randomized controlled trial.
      ,
      • Ringh M.
      • Rosenqvist M.
      • Hollenberg J.
      • Jonsson M.
      • Fredman D.
      • Nordberg P.
      • et al.
      Mobile-phone dispatch of laypersons for CPR in out-of-hospital cardiac arrest.
      ].
      This study has several limitations. First, as in previous observational studies, unmeasured possible confounding factors may have influenced the association between bystander CPR and patient outcomes. Second, details of DI were not described and DI was not standardized and there were no data on the quality of DI. Third, we were unable to assess several important factors, including quality of CPR performed by bystanders and EMS personnel; bystanders’ characteristics including age, sex, weight, and experience with basic life support; bystanders’ occupation (medical professional or not); and time from patient collapse to initiation of bystander CPR. In addition, the outcomes after aggressive in-hospital treatments such as percutaneous coronary intervention and targeted temperature management may be improved [
      • Takahashi M.
      • Kondo Y.
      • Senoo K.
      • Fujimoto Y.
      • Kobayashi Y.
      Incidence and prognosis of cardiopulmonary arrest due to acute myocardial infarction in 85 consecutive patients.
      ], but we were not able to obtain the data on in-hospital treatments. Bystanders who performed CPR without DI tended to witness the patients’ collapse compared with bystanders who required DI. Despite that “presence or absence of witnesses” was adjusted as one of the major confounding factors, we could not measure the exact period of time during which no CPR was performed among resuscitation. These major unmeasured factors may have critically biased our study findings. Further studies including a randomized controlled trial are required to control for these factors. Finally, our findings may not be thoroughly generalizable to other districts because this study was conducted in a single large city and the proportions of major confounding factors among three groups were not equal although we adjusted for these factors.

      Conclusions

      Analysis of the large database of the OHCA registry in Osaka City, Japan, revealed that bystander CPR that did not depend on DI was associated with a significantly better one-month favorable neurological survival after medically associated OHCA, whereas CPR performed under DI yielded no significant difference in outcome compared with no CPR. The expected time for favorable neurological survival of bystander CPR without DI was ≤13 min.

      Funding

      This research received no grant from any funding agencies in the public, commercial, or not-for-profit sectors.

      Disclosures

      The authors have no conflicting financial or personal relationships to declare.

      Acknowledgments

      We greatly appreciate the EMS personnel and physicians in Osaka City for their indispensable cooperation and support including quality control regarding resuscitation practices and data collection. We would like to thank NAI (https://www.nai.co.jp) for English language editing.

      Appendix C. Supplementary data

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