Abstract
Aim
Although advanced treatments are provided to improve outcomes after out‐of‐hospital ventricular fibrillation, including shock‐resistant ventricular fibrillation, the actual treatments in clinical settings have been insufficiently investigated. The aim of the current study is to describe the actual treatments carried out for out‐of‐hospital ventricular fibrillation patients, including shock‐resistant ventricular fibrillation patients, at critical care medical centers.
Methods
We registered consecutive adult patients suffering bystander‐witnessed out‐of‐hospital cardiac arrest of cardiac origin, for whom resuscitation was attempted by emergency medical service personnel, who had ventricular fibrillation as an initial rhythm, and who were transported to critical care medical centers in Osaka from March 2008 to December 2008. This study merged data on treatments after transportation, collected from 11 critical care medical centers in Osaka with the prehospital Utstein‐style database.
Results
During the study period, there were 260 bystander‐witnessed ventricular fibrillation arrests of cardiac origin. Of them, 252 received defibrillations before hospital arrival, 112 (44.4%) were transported to critical care medical centers, and 35 had shock‐resistant ventricular fibrillation. At the critical care medical centers, 54% (19/35), 40% (14/35), and 46% (16/35) of shock‐resistant ventricular fibrillation patients were treated with extracorporeal life support, percutaneous coronary interventions, and therapeutic hypothermia, respectively, but their treatments differed among institutions. Some patients with prolonged arrest without prehospital return of spontaneous circulation who received advanced treatments had neurologically favorable survival, whereas approximately two‐thirds of shock‐resistant ventricular fibrillation patients with advanced treatments did not.
Conclusion
This pilot descriptive study suggested that actual treatments for prehospital ventricular fibrillation patients differed between critical care medical centers. Further studies are warranted to evaluate the effectiveness of in‐hospital advanced treatments for ventricular fibrillation including shock‐resistant ventricular fibrillation.
Keywords: Advanced life support (ALS), extracorporeal life support, hypothermia, out‐of‐hospital cardiac arrest, ventricular fibrillation
Introduction
Out‐of‐hospital cardiac arrest (OHCA) of cardiac origin is one of the leading causes of death in the industrialized world,1 with approximately 70,000 events occurring every year in Japan.2 However, survival after OHCA is still low.
Recently, we reported that the annual incidence of prehospital shock‐resistant ventricular fibrillation (VF) patients, who had sustained VF at hospital arrival and needed advanced treatments in addition to prehospital care, has remained unchanged and their outcomes were still dismal.3 We also suggested that the transportation of OHCA patients to the critical care medical centers (CCMCs) was associated with better outcomes after OHCA.4 Some reports suggested the effectiveness of extracorporeal life support (ELS) usage before return of spontaneous circulation (ROSC),5, 6 and in‐hospital post‐arrest care such as therapeutic hypothermia (TH)7, 8 and percutaneous coronary intervention (PCI)9 to improve the outcome after OHCA. However, actual advanced treatments carried out for VF at CCMCs, including shock‐resistant VF patients who would especially need to receive advanced treatments, has been insufficiently investigated.
The Utstein Osaka Project, begun in 1998, is a large, ongoing, prospective, population‐based cohort study of OHCA in Osaka Prefecture, Japan, covering a population of 8.8 million.10 In this study, we extracted detailed in‐hospital records on actual treatments at CCMCs, and merged them with the data on resuscitation simultaneously collected based on the Utstein‐style guidelines.11 The aim of this study was to describe the present conditions of treatments for VF at the CCMCs in Osaka, one of Japan's most developed areas of prehospital emergency medical service (EMS) systems.10 In particular, we focused on the conditions of shock‐resistant VF.
Methods
Population and setting
The target area for this study was Osaka Prefecture in Japan, which has an area of 1,897 km2 and a residential population of 8,817,166 inhabitants in 2005.12 Males make up 48.5% of the population, 18.5% of who are aged 65 years or older.
Osaka Prefecture included 541 hospitals (109,503 beds) in 2008.13 Of them, 269 including 13 CCMCs can accept emergency cases of severely ill patients, including OHCA cases, from ambulances.14 As many as 30% of OHCA patients in Osaka Prefecture were transported to CCMCs and then treated.4 In this study, 11 of 13 CCMCs in Osaka participated in our registry.
Study patients
From March 8, 2008 to December 31, 2008 we registered consecutive patients aged ≥18 years suffering OHCA of presumed cardiac origin, who were witnessed by bystanders and for whom attempted resuscitation was attempted by EMS, who had VF as an initial rhythm, and were then transported to CCMCs. The Ethics Committee of Osaka University Hospital (Osaka, Japan) approved this study as the principal institution, and after the approval each hospital individually approved our study protocol as necessary. The requirement of giving individual informed consent for the review of patient outcomes was waived by the Personal Information Protection Law and the national research ethics guidelines of Japan.
Emergency Medical Service organization and equipment in metropolitan Osaka
The 119 emergency telephone number is accessible anywhere in Japan. On receipt of a 119 call, an emergency dispatch center sends the nearest available ambulance to the site. These dispatch centers are operated by each fire station managed by the municipal government; 34 fire stations with a dispatch center were located across this catchment area in 2008. Each ambulance includes a three‐person unit providing life support 24 h a day. Most highly trained EMS personnel are called emergency life‐saving technicians. They are allowed to insert an i.v. line and an adjunct airway and to use a semi‐automated external defibrillator for OHCA patients. Emergency life‐saving technicians were permitted to provide shocks without consulting a physician from 2003. Specially trained emergency life‐saving technicians were allowed to carry out tracheal intubation and to administer epinephrine for OHCA patients. All EMS providers carried out cardiopulmonary resuscitation (CPR) according to the 2005 Japanese CPR guidelines during this study period.15 Details of the EMS systems in Osaka were described previously.10
Data collection and quality control
Data were collected prospectively with the use of a data form based on the Utstein‐style international guideline of reporting OHCA, including age, gender, origin of cardiac arrest, location of cardiac arrest, initial cardiac rhythm, bystander‐initiated CPR, activities of daily living before arrests, and prehospital time‐course of resuscitation, as well as ROSC, 1‐month survival, and neurological status 1 month after the event.11 Initial rhythm was recorded and diagnosed by EMS personnel with semi‐automated defibrillators on the scene. A data form was filled out by EMS personnel in cooperation with the physicians in charge of the patient, transferred to the Information Center for Emergency Medical Services of Osaka, and then checked by the investigators. If the data sheet was incomplete, the relevant EMS personnel were interviewed and the data sheet completed.
All survivors were followed for up to 1 month after the events by the EMS personnel in charge. Neurological outcomes 1 month after the events were determined by the physician responsible for the care of the patient, using the Cerebral Performance Category (CPC) scale: category 1, good cerebral performance; category 2, moderate cerebral disability; category 3, severe cerebral disability; category 4, coma or vegetative state; category 5, death.11 The primary outcome measure was neurologically favorable 1‐month survival. Neurologically favorable outcomes were defined as CPC categories 1 or 2.11
In‐hospital data were also prospectively collected using an original report form by the physician in charge of the patient at each CCMC. The report form required the following data on the actual treatments and their resuscitation time‐courses; anti‐arrhythmic drug therapies (amiodarone, nifekalant, and lidocaine), tracheal intubation, ELS, cardioangiography and PCI, and TH within 1 week after the transportation of OHCA patients to the CCMCs. These data were merged with the data based on the Utstein‐style guidelines by the principal investigators.
Definition of shock‐resistant VF
Ventricular fibrillation or pulseless ventricular tachycardia (VT) as an initial rhythm that persisted upon hospital arrival following at least one preceding EMS' electrical shock was defined as shock‐resistant VF.3
Statistical analysis
Patient and EMS characteristics were compared between the groups using anova for numerical variables and the χ2‐test for categorical variables. All the tests were two‐tailed, and P‐values of <0.05 were considered statistically significant. All statistical analyses were carried out using the spss statistical package version 16.0J (SPSS, Inc., Chicago, IL, USA).
Results
Figure 1 shows an overview of study patients based on the Utstein template. A total of 5,289 adult OHCA patients were documented during the study period. Among them, 4,917 were resuscitated, and 1,080 were witnessed by bystanders. Among the witnessed cases, 260 (24.1%) had VF including pulseless VT, 355 (32.9%) pulseless electrical activity (PEA), and 443 (41.0%) asystole as prehospital initial rhythm. Data on the initial rhythm was not applicable for 22 (2.0%) cases. Among 260 initial VF arrests, 252 (96.9%) were delivered at least one shock by EMS personnel before hospital arrival. Of them, 112 (44.4%) were transported to CCMCs, and were eligible for our analyses. Among the 112 CCMC treated cases, 43 (38.4%) had prehospital ROSC, 35 (31.3%) persisting VF, 17 (15.2%) PEA, and 17 (15.2%) asystole at hospital arrival.
Figure 1.
Overview of emergency medical service (EMS)‐treated cardiac arrests in Osaka Prefecture with an abridged Utstein template (March 8, 2008–December 31, 2008). Values in parentheses are mean percentages. CCMC, critical care medical center; PEA, pulseless electrical activity; ROSC, return of spontaneous circulation; VF, ventricular fibrillation; VT, ventricular tachycardia.
Demographic and resuscitation characteristics among prehospital VF patients according to their cardiac rhythm at CCMC arrival are noted in Table 1. Patient characteristics were similar between the groups. The proportion of bystander‐initiated CPR was lower in the PEA group than the other groups (P = 0.040). The mean time intervals from collapse to call and hospital arrival showed no significant differences between the groups. The mean time intervals from collapse to EMS arrival at the scene (P = 0.013) and first shock (P = 0.004) were shorter in the ROSC group than in the other groups.
Table 1.
Characteristics of ventricular fibrillation (VF) patients at emergency medical service (EMS) arrival according to cardiac rhythm on critical care medical center arrival
| ROSC (n = 43) | VF/VT (n = 35) | PEA (n = 17) | Asystole (n = 17) | P‐value | |
|---|---|---|---|---|---|
| Age, year, mean (SD) | 62.7 (14.0) | 60.2 (13.4) | 60.3 (17.1) | 63.1 (14.5) | 0.826 |
| Gender, male, n (%) | 35 (81.4) | 30 (85.7) | 11 (64.7) | 15 (88.2) | 0.255 |
| Location of arrests, home, n (%) | 17 (39.5) | 19 (54.3) | 7 (41.2) | 11 (64.7) | 0.261 |
| Good daily living activities before arrests, n (%) | 36 (83.7) | 31 (88.6) | 15 (88.2) | 13 (76.5) | 0.683 |
| Bystander‐initiated CPR, n (%) | 21 (48.8) | 13 (37.1) | 2 (11.8) | 9 (52.9) | 0.040 |
| Epinephrine administration by EMS, n (%) | 16 (37.2) | 11 (31.4) | 6 (35.3) | 5 (29.4) | 0.925 |
| Intubation by EMS, n (%) | 14 (32.6) | 13 (37.1) | 5 (29.4) | 4 (23.5) | 0.791 |
| Collapse to call, min, mean (SD) | 1.3 (2.4) | 1.3 (2.0) | 3.7 (7.9) | 2.4 (2.7) | 0.121 |
| Collapse to EMS arrival at scene, min, mean (SD) | 7.5 (2.6) | 8.0 (2.7) | 11.1 (7.9) | 9.6 (4.0) | 0.013 |
| Collapse to first shock by EMS, min, mean (SD) | 9.0 (2.5) | 10.1 (2.9) | 13.5 (8.7) | 11.1 (3.9) | 0.004 |
| Collapse to hospital arrival, min, mean (SD) | 29.6 (6.2) | 31.2 (10.5) | 36.1 (14.6) | 31.8 (12.0) | 0.178 |
CPR, cardiopulmonary resuscitation; PEA, pulseless electrical activity; ROSC, return of spontaneous circulation; SD, standard deviation; VT, ventricular tachycardia.
Table 2 shows the outcomes among prehospital VF patients according to the cardiac rhythm at CCMC arrival. With regard to 112 patients transported to CCMCs, the proportion of neurologically favorable 1‐month survival among those with ROSC before hospital arrival, persisting VF, PEA, and asystole was 65.1% (28/43), 28.6% (10/35), 11.8% (2/17), and 11.8% (2/17), respectively.
Table 2.
Outcomes of prehospital ventricular fibrillation (VF) patients at emergency medical service arrival according to cardiac rhythm on critical care medical center CCMC and non‐registered hospital arrival
| ROSC | VF/VT | PEA | Asystole | P‐value | |
|---|---|---|---|---|---|
| 112 patients transported to CCMCs | (n = 43) | (n = 35) | (n = 17) | (n = 17) | |
| Admission, n (%) | 43 (100.0) | 22 (62.9) | 12 (70.6) | 5 (29.4) | <0.001 |
| Survival at 1 month, n (%) | 37 (86.0) | 15 (42.9) | 6 (35.3) | 3 (17.6) | <0.001 |
| Neurologically favorable 1‐month survival, n (%) | 28 (65.1) | 10 (28.6) | 2 (11.8) | 2 (11.8) | <0.001 |
| 140 patients transported to non‐registered hospitals | (n = 34) | (n = 35) | (n = 35) | (n = 36) | |
| Admission, n (%) | 34 (100.0) | 17 (48.6) | 20 (57.1) | 13 (36.1) | <0.001 |
| Survival at 1 month, n (%) | 30 (88.2) | 9 (25.7) | 10 (28.6) | 2 (5.6) | <0.001 |
| Neurologically favorable 1‐month survival, n (%) | 24 (70.6) | 6 (17.1) | 2 (5.7) | 1 (2.8) | <0.001 |
PEA, pulseless electrical activity; ROSC, return of spontaneous circulation; VT, ventricular tachycardia.
Table 3 shows the present conditions of advanced treatments for prehospital VF patients according to their cardiac rhythm at CCMC arrival. Among VF cases at CCMC arrival, amiodarone and nifekalant were used for 40.0% (14/35) and 45.7% (16/35) cases, respectively. Tracheal intubation was carried out for all cases, and TH was carried out for 60.5% (26/43) among the ROSC group, 45.7% (16/35) VF, 23.5% (4/17) PEA, and 17.6% (3/17) asystole group. Figure 2 shows the time‐series of advanced treatments against shock‐resistant VF cases according to CCMCs. A total of 35 shock‐resistant VF patients were transferred to eight CCMCs from the scene. At the CCMCs, 54.3% (19/35), 40.0% (14/35), and 45.7% (16/35) of shock‐resistant VF patients were treated with ELS, PCI, and TH, respectively. The introduction and timing of anti‐arrhythmic drug administration, ELS, PCI, and TH, and termination of resuscitation (TOR) for these patients differed exceedingly between CCMCs. At one CCMC (Hospital H), no shock‐resistant VF patients received any advanced treatments excluding amiodarone. Two cases in Hospitals A and C with prolonged resuscitation of ≥60 min after collapse who received advanced treatments including TH, ELS, and PCI had neurologically favorable survival, whereas approximately two‐thirds (17/27) of shock‐resistant VF patients who received advanced treatments did not.
Table 3.
Conditions of treatment for 112 ventricular fibrillation (VF) patients at emergency medical service arrival according to cardiac rhythm on critical care medical center arrival
| ROSC (n = 43) | VF/VT (n = 35) | PEA (n = 17) | Asystole (n = 17) | P‐value | |
|---|---|---|---|---|---|
| Anti‐arrhythmic drug, n (%) | |||||
| Amiodarone | 5 (11.9) | 14 (40.0) | 1 (5.9) | 0 (0.0) | <0.001 |
| Nifekalant | 3 (7.1) | 16 (45.7) | 2 (11.8) | 6 (35.3) | <0.001 |
| Lidocaine | 5 (11.9) | 12 (34.3) | 3 (17.6) | 6 (35.3) | 0.070 |
| Tracheal intubation, n (%) | 0.634 | ||||
| Inserted at scene | 10 (23.3) | 10 (28.6) | 5 (29.4) | 3 (17.6) | |
| Inserted at hospital | 30 (69.8) | 25 (71.4) | 12 (70.6) | 13 (76.5) | |
| Not inserted | 3 (7.0) | 0 (0.0) | 0 (0.0) | 1 (5.9) | |
| Extracorporeal life support, n (%) | 4 (9.3) | 19 (54.3) | 1 (5.9) | 3 (17.6) | <0.001 |
| Cardioangiography, n (%) | 33 (76.7) | 21 (60.0) | 6 (35.3) | 3 (17.6) | <0.001 |
| Percutaneous coronary intervention, n (%) | 13 (31.7) | 14 (40.0) | 3 (17.6) | 1 (5.9) | 0.002 |
| Therapeutic hypothermia, n (%) | 26 (60.5) | 16 (45.7) | 4 (23.5) | 3 (17.6) | 0.006 |
PEA, pulseless electrical activity; ROSC, return of spontaneous circulation; VT, ventricular tachycardia.
Figure 2.
Treatments for patients with shock‐resistant ventricular fibrillation (VF) (n = 35) in eight Osaka Prefecture critical care medical centers (March 8, 2008–December 31, 2008). Each line with arrowhead indicates one shock‐resistant VF patient. The number in parentheses after each hospital identifier (HP‐A–H) represents the number of all out‐of‐hospital cardiac arrest patients transported to each hospital in 2008. The horizontal axis shows the time‐course from collapse based on hospital arrival time. On the right side of the figure, TH, CAG, and PCI, indicate the actual treatments of therapeutic hypothermia, cardioangiography, and percutaneous coronary intervention, respectively, carried out for each shock‐resistant VF patient. A, amiodarone; CA, cardioangiography start time; E, timing of extracorporeal life support (ELS) pump‐on time; L, lidocaine; N, nifekalant; PR, prehospital ROSC.
Discussion
This registry of VF at CCMCs in Osaka suggested that approximately 30% of out‐of‐hospital VF patients had persistent VF at hospital arrival, and advanced treatments such as use of anti‐arrhythmic drugs, ELS, PCI, and TH, and TOR for shock‐resistant VF patients differed among the CCMCs even in the same area. Some hospitals provided treatments far beyond that recommended by the CPR guidelines, whereas some provided less treatment than recommended. Advanced treatments such as ELS, PCI, and TH have been recommended for persistent VF patients,16, 17 but, to our knowledge, few studies have investigated in detail the actual condition of treatments for shock‐resistant VF patients covering a certain population.
Although the CPR guidelines recommend that comatose cardiac arrest survivors should receive TH after VF,1, 18, 19 the present study showed that the implementation of TH was quite different by institutions even in the developed area of the EMS system. In addition, it was difficult to compare the present conditions on TH because the definition of TH itself and protocol differed in each CCMC. Indeed, the implementation of TH after cardiac arrest has remained very low in the USA,20 and these findings suggest that it takes a long time to disseminate practice guidelines in real medical settings, as previously reported.21, 22
In this study group, approximately 50% of shock‐resistant VF patients were treated with ELS. Although some published reports showed the effectiveness of ELS, such evidence is scarce,5, 6 and there is no recommendation for the use of ELS at present.1, 18, 19 In addition, ELS would need many medical personnel and resources for emergency settings, and it might be difficult to conduct ELS at all hours of the day and night even in CCMCs. The effectiveness and cost‐effectiveness of ELS for OHCA patients remains a matter of debate, and this evidence should be reported from Japan where ELS is relatively common.
In Japan, both amiodarone and nifekalant have generally been available at CCMCs. Two prospective randomized studies showed that use of amiodarone improved survival until hospital admission, and amiodarone became a first‐line anti‐arrhythmic agent for refractory VF/pulseless VT.23, 24 In Japan, nifekalant, another class III anti‐arrhythmic agent for refractory VT and VF, has been available since 1999, and some studies have indicated its effectiveness in emergency settings.25, 26 Further studies into what kind of anti‐arrhythmic agent would be effective for shock‐resistant VF should be undertaken.
In this study, 44% of out‐of‐hospital VF patients were transported to CCMCs. Previously, we reported that approximately 30% of OHCA patients transported to the CCMCs in Osaka, and the proportion of witnessed cases and VF tended to be greater in the CCMC group.4 Because VF cases should be considered to have the best chance of survival, the greater proportion of those who were transported to the CCMCs than in a previous report involving non‐VF or non‐witnessed cases might suggest that the ambulance crews were likely to choose the CCMCs for such cases with the best chance of survival. Consistent with previous reports showing the effectiveness of cardiac arrest centers,27 our previous report showed that survival after OHCA was better in those who were transported to CCMCs rather than non‐CCMC hospitals if they did not achieve field ROSC, however, there was no information on what kind of treatments were provided. Because our medical resources are limited, we should consider the effective transportation strategy to the CCMCs or advance treatments that would lead to improved survival after VF in the area, by establishing a registry including hospital care.
The present study also suggested that the decision for TOR might differ with the institution even among CCMCs in the same area. In Japan, EMS personnel are not legally permitted to terminate resuscitation for OHCA patients in the prehospital setting. Therefore, EMS personnel in Japan are required to transport almost all OHCA patients to a hospital regardless of the success or failure of their resuscitation efforts.28 Studies on the TOR rule in the prehospital settings have been carried out,29, 30 but there are no definitive criteria for in‐hospital TOR. One study suggested that the increased duration of in‐hospital resuscitation efforts was associated with the improved outcome after in‐hospital cardiac arrests.31 In the present study, some cases with very prolonged resuscitation yielded neurologically favorable survival. Therefore, further studies are required to assess the appropriate resuscitation duration or TOR rule for OHCA patients after hospital arrival.
By collecting further data on OHCA patients, we could formulate criteria for transportation to hospitals in line with each patient's condition. Indeed, we have launched a large multicenter cohort to verify the effectiveness of in‐hospital advanced treatments such as the use of drugs, ELS, PCI, and TH for OHCA patients in order to determine their prognostic factors.32 We believe that this new prospective cohort would contribute to the improvement of outcomes after OHCA, including shock‐resistant VF. Further evidence to evaluate the effect of advanced treatments should be accumulated in order to build a uniform protocol that can be used in all hospitals including CCMCs.
Study limitations
As with any study, there are several limitations that deserve mention. First, we did not obtain data on all prehospital shock‐resistant VF patients in Osaka, and could not assess actual treatments in emergency hospitals excluding CCMCs. A second limitation was the lack of data on the hospital performance, such as the number of staff and the emergency PCI availability. Third, we did not collect data on continuous electrocardiographic changes. These would be important to assess the timing and effect of drug administration. Finally, there might be regional variations in the transportation and treatment of OHCA patients between CCMCs in Japan.33
Conclusions
This pilot descriptive study suggested that the actual treatments for VF patients differed among CCMCs. Further studies are warranted to evaluate the effectiveness of in‐hospital advanced treatments for VF, including shock‐resistant VF patients.
Conflict of Interest
None.
Acknowledgments
We are deeply grateful to all members of the Utstein Osaka Project for their contribution as a steering committee to the organization, coordination, and oversight of this study. The following institutions are members of the Multi‐Institutional Joint Research Group for Shock‐Resistant VF: Osaka University Hospital Trauma and Acute Critical Care Center; Department of Emergency Medicine, Osaka Medical College Hospital; Osaka Mishima Emergency Critical Care Center; Senri Critical Care Medical Center, Osaka Saiseikai Senri Hospital; Emergency and Critical Care Medical Center, Osaka City General Hospital; Osaka Prefectural Nakakawachi Medical Center of Acute Medicine; Traumatology and Critical Care Medical Center, National Hospital Organization Osaka National Hospital; Emergency and Critical Care Medical Center, Osaka Police Hospital; Critical Care and Trauma Center, Osaka General Medical Center; Department of Emergency and Critical Care Medicine, Kinki University School of Medicine; Osaka Prefectural Senshu Critical Care Medical Center; Osaka Prefectural Council of Emergency Care Facilities. We are also deeply grateful to all of the EMS personnel and concerned physicians in Osaka Prefecture and to the Osaka Medical Association for their indispensable cooperation and support. This study was supported by a scientific research grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan (24592733).
References
- 1. American Heart Association . 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2010; 122: S639–946. [DOI] [PubMed] [Google Scholar]
- 2. Ministry of Internal Affairs and Communications of Japan . 2012 Effect of First Aid for Cardiopulmonary Arrest [homepage on the internet]. Ambulance Service Planning Office of Fire and Disaster Management Agency of Japan, 2012; [cited 23 Aug 2013]. (In Japanese.) Available from: http://www.fdma.go.jp/neuter/topics/kyukyukyujo_genkyo/h24/01_kyukyu.pdf.
- 3. Sakai T, Iwami T, Tasaki O et al Incidence and outcomes of out‐of‐hospital cardiac arrest with shock‐resistant ventricular fibrillation: data from a large population‐based cohort. Resuscitation 2010; 81: 956–961. [DOI] [PubMed] [Google Scholar]
- 4. Kajino K, Iwami T, Daya M et al Impact of transport to critical care medical centers on outcomes after out‐of‐hospital cardiac arrest. Resuscitation 2010; 81: 549–554. [DOI] [PubMed] [Google Scholar]
- 5. Morimura N, Sakamoto T, Nagao K et al Extracorporeal cardiopulmonary resuscitation for out‐of‐hospital cardiac arrest: a review of the Japanese literature. Resuscitation 2011; 82: 10–14. [DOI] [PubMed] [Google Scholar]
- 6. Chen YS, Lin JW, Yu HY et al Cardiopulmonary resuscitation with assisted extracorporeal life‐support versus conventional cardiopulmonary resuscitation in adults with in‐hospital cardiac arrest: an observational study and propensity analysis. Lancet 2008; 372: 554–561. [DOI] [PubMed] [Google Scholar]
- 7. The Hypothermia after Cardiac Arrest Study Group . Mild therapeutic hypothermia to improve the neurological outcomes after cardiac arrest. N. Engl. J. Med. 2002; 346: 549–556. [DOI] [PubMed] [Google Scholar]
- 8. Bernard SA, Gray TW, Buist MD et al Treatment of comatose survivors of out‐of‐hospital cardiac arrest with induced hypothermia. N. Engl. J. Med. 2002; 346: 557–563. [DOI] [PubMed] [Google Scholar]
- 9. Kagawa E, Dote K, Kato M et al Should we emergently revascularize occluded coronaries for cardiac arrest?: rapid‐response extracorporeal membrane oxygenation and intra‐arrest percutaneous coronary intervention. Circulation 2012; 126: 1605–1613. [DOI] [PubMed] [Google Scholar]
- 10. Iwami T, Nichol G, Hiraide A et al Continuous improvements in “chain of survival” increased survival after out‐of‐hospital cardiac arrests: a large‐scale population‐based study. Circulation 2009; 119: 728–734. [DOI] [PubMed] [Google Scholar]
- 11. Jacobs I, Nadkarni V, Bahr J 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 Councils of Southern Africa). Circulation 2004; 110: 3385–3397. [DOI] [PubMed] [Google Scholar]
- 12. Osaka Prefectural Government . 2005 Population in Osaka Prefecture [homepage on the internet]. Statistics Bureau, Ministry of Internal Affair and Communications of Japan, 2006; [cited 23 Aug 2013]. (In Japanese.) Available from: http://www.stat.go.jp/data/kokusei/2005/kihon1/00/pdf/27.pdf.
- 13. Osaka Prefectural Government . 2008 Report on Medical Institutions in Osaka Prefecture [homepage on the internet]. 2009; [cited 23 Aug 2013]. (In Japanese.) Available from: http://www.pref.osaka.jp/kenisomu/syuyoufukusidate/hoken.html.
- 14. Osaka Prefectural Government . 2008 Report on the Type of Hospitals in Osaka Prefecture [homepage on the internet]. Osaka Prefectural Government, 2009; [cited 23 Aug 2013]. (In Japanese.) Available from: http://www.pref.osaka.jp/iryo/keikaku/keikakuhenkou.html
- 15. Japan Resuscitation Council . 2005 Japanese Guidelines for Emergency Care and Cardiopulmonary Resuscitation, 3rd edn. Tokyo, Japan: Health Shuppansha, 2007.
- 16. Sung K, Lee YT, Park PW et al Improved survival after cardiac arrest using emergent autopriming percutaneous cardiopulmonary support. Ann. Thorac. Surg. 2006; 82: 651–656. [DOI] [PubMed] [Google Scholar]
- 17. Tanno K, Itoh Y, Takeyama Y, Nara S, Mori K, Asai Y. Utstein style study of cardiopulmonary bypass after cardiac arrest. Am. J. Emerg. Med. 2008; 26: 649–654. [DOI] [PubMed] [Google Scholar]
- 18. Japan Resuscitation Council . 2010 Japanese guidelines for emergency care and cardiopulmonary resuscitation, 1st edn. Tokyo: Health Shuppansha, 2011.
- 19. European Resuscitation Council . European Resuscitation Council Guidelines for Resuscitation 2010. Resuscitation 2010; 81: 1219–1451. [DOI] [PubMed] [Google Scholar]
- 20. Mikkelsen ME, Christie JD, Abella BS et al Use of therapeutic hypothermia after in‐hospital cardiac arrest. Crit. Care Med. 2013; 41: 1385–1395. [DOI] [PubMed] [Google Scholar]
- 21. Binks AC, Murphy RE, Prout RE et al Therapeutic hypothermia after cardiac arrest—implementation in UK intensive care units. Anaesthesia 2010; 65: 260–265. [DOI] [PubMed] [Google Scholar]
- 22. Berdowski J, Schmohl A, Tijssen JG, Koster RW. Time needed for a regional emergency medical system to implement resuscitation Guidelines 2005—the Netherlands experience. Resuscitation 2009; 80: 1336–1341. [DOI] [PubMed] [Google Scholar]
- 23. Dorian P, Cass D, Schwartz B, Cooper R, Gelaznikas R, Barr A. Amiodarone as compared with lidocaine for shock‐resistant ventricular fibrillation. N. Engl. J. Med. 2002; 346: 884–890. [DOI] [PubMed] [Google Scholar]
- 24. Kudenchuk PJ, Cobb LA, Copass MK et al Amiodarone for resuscitation after out‐of‐hospital cardiac arrest due to ventricular fibrillation. N. Engl. J. Med. 1999; 341: 871–878. [DOI] [PubMed] [Google Scholar]
- 25. Tahara Y, Kimura K, Kosuge M et al Comparison of nifekalant and lidocaine for the treatment of shock‐refractory ventricular fibrillation. Circ. J. 2006; 70: 442–446. [DOI] [PubMed] [Google Scholar]
- 26. Yoshioka K, Amino M, Usui K et al Nifekalant hydrochloride administration during cardiopulmonary resuscitation improves the transmural dispersion of myocardial repolarization: experimental study in a canine model of cardiopulmonary arrest. Circ. J. 2006; 70: 1200–1207. [DOI] [PubMed] [Google Scholar]
- 27. Donnino MW, Rittenberger JC, Gaieski D et al The development and implementation of cardiac arrest centers. Resuscitation 2011; 82: 974–978. [DOI] [PubMed] [Google Scholar]
- 28. Kajino K, Kitamura T, Iwami T et al Current termination of resuscitation (TOR) guidelines predict neurologically favorable outcome in Japan. Resuscitation 2013; 84: 54–59. [DOI] [PubMed] [Google Scholar]
- 29. Morrison LJ, Visentin LM, Kiss A et al Validation of a rule for termination of resuscitation in out‐of‐hospital cardiac arrest. N. Engl. J. Med. 2006; 355: 478–487. [DOI] [PubMed] [Google Scholar]
- 30. Sasson C, Hegg AJ, Macy M, Park A, Kellermann A, McNally B. Prehospital termination of resuscitation in cases of refractory out‐of‐hospital cardiac arrest. JAMA 2008; 300: 1432–1438. [DOI] [PubMed] [Google Scholar]
- 31. Goldberger ZD, Chan PS, Berg RA et al Duration of resuscitation efforts and survival after in‐hospital cardiac arrest: an observational study. Lancet 2012; 380: 1473–1481. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32. The CRITICAL Study Group . UMIN‐CTR (UMIN000007528) [homepage on the internet]. Comprehensive Registry of Intensive Cares for OHCA Survival (CRITICAL) Study, 2012; [cited 23 Aug 2013]. (In Japanese.) Available from: https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000008833&language=J.
- 33. Tagami T, Hirata K, Takeshige T et al Implementation of the fifth link of the chain of survival concept for out‐of‐hospital cardiac arrest. Circulation 2012; 126: 589–597. [DOI] [PubMed] [Google Scholar]