Termination-of-resuscitation rule in the emergency department for patients with refractory out-of-hospital cardiac arrest: a nationwide, population-based observational study.

BACKGROUND: In Japan, emergency medical service (EMS) providers are prohibited from field termination-of-resuscitation (TOR) in out-of-hospital cardiac arrest (OHCA) patients. In 2013, we developed a TOR rule for emergency department physicians (Goto's TOR rule) immediately after hospital arrival. However, this rule is subject to flaws, and there is a need for revision owing to its relatively low specificity for predicting mortality compared with other TOR rules in the emergency department. Therefore, this study aimed to develop and validate a modified Goto's TOR rule by considering prehospital EMS cardiopulmonary resuscitation (CPR) duration. METHODS: We analysed the records of 465,657 adult patients with OHCA from the All-Japan Utstein registry from 2016 to 2019 and divided them into two groups: development (n = 231,363) and validation (n = 234,294). The primary outcome measures were specificity, false-positive rate (FPR), and positive predictive value (PPV) of the revised TOR rule in the emergency department for predicting 1-month mortality. RESULTS: Recursive partitioning analysis for the development group in predicting 1-month mortality revealed that a modified Goto's TOR rule could be defined if patients with OHCA met the following four criteria: (1) initial asystole, (2) unwitnessed arrest by any laypersons, (3) EMS-CPR duration > 20 min, and (4) no prehospital return of spontaneous circulation (ROSC). The specificity, FPR, and PPV of the rule for predicting 1-month mortality were 99.2% (95% confidence interval [CI], 99.0-99.4%), 0.8% (0.6-1.0%), and 99.8% (99.8-99.9%), respectively. The proportion of patients who fulfilled the rule and the area under the receiver operating curve (AUC) was 27.5% (95% CI 27.3-27.7%) and 0.904 (0.902-0.905), respectively. In the validation group, the specificity, FPR, PPV, proportion of patients who met the rule, and AUC were 99.1% (95% CI 98.9-99.2%), 0.9% (0.8-1.1%), 99.8% (99.8-99.8%), 27.8% (27.6-28.0%), and 0.889 (0.887-0.891), respectively. CONCLUSION: The modified Goto's TOR rule (which includes the following four criteria: initial asystole, unwitnessed arrest, EMS-CPR duration > 20 min, and no prehospital ROSC) with a > 99% predictor of 1-month mortality is a reliable tool for physicians treating refractory OHCAs immediately after hospital arrival.

Association of dispatcher-assisted cardiopulmonary resuscitation with initial shockable rhythm and survival after out-of-hospital cardiac arrest.

BACKGROUND AND IMPORTANCE: Bystander cardiopulmonary resuscitation (CPR) and initial shockable rhythm are crucial predictors of survival after out-of-hospital cardiac arrest (OHCA). However, the relationship between dispatcher-assisted CPR (DA-CPR) and initial shockable rhythm is not completely elucidated. OBJECTIVE: To examine the association of DA-CPR with initial shockable rhythm and outcomes. DESIGN, SETTING AND PARTICIPANTS: This nationwide population-based observational study conducted in Japan included 59 688 patients with witnessed OHCA of cardiac origin after excluding those without bystander CPR. Patients were divided into DA-CPR (n = 42 709) and CPR without dispatcher assistance (unassisted CPR, n = 16 979) groups. OUTCOME MEASURES AND ANALYSIS: The primary outcome measure was initial shockable rhythm, and secondary outcome measures were 1-month survival and neurologically intact survival. A Cox proportional hazards model adjusted for collapse-to-first-rhythm-analysis time and multivariable logistic regression models were used after propensity score (PS) matching to compare the incidence of initial shockable rhythm and outcomes, respectively. MAIN RESULTS: Among all patients (mean age 76.7 years), the rates of initial shockable rhythm, 1-month survival and neurologically intact survival were 20.8, 10.7 and 7.0%, respectively. The incidence of initial shockable rhythm in the DA-CPR group (20.4%, 3462/16 979) was significantly higher than that in the unassisted CPR group (18.5%, 3133/16 979) after PS matching (P < 0.0001). However, no significant differences were found between the two groups with respect to the incidence of initial shockable rhythm in the Cox proportional hazards model [adjusted hazard ratio of DA-CPR for initial shockable rhythm compared with unassisted CPR, 0.99; 95% confidence interval (CI), 0.97-1.02, P = 0.56]. No significant differences were observed in the survival rates in the two groups after PS matching [10.8% (1833/16 979) vs. 10.3% (1752/16 979), P = 0.16] and neurologically intact survival rates [7.3% (1233/16 979) vs. 6.8% (1161/16 979), P = 0.13]. The multivariable logistic regression model showed no significant differences between the groups with regard to survival (adjusted odds ratio of DA-CPR compared with unassisted CPR: 1.00; 95% CI, 0.89-1.13, P = 0.97) and neurologically intact survival (adjusted odds ratio: 1.12; 95% CI, 0.98-1.29, P = 0.14). CONCLUSION: DA-CPR after OHCA had the same independent association with the likelihood of initial shockable rhythm and 1-month meaningful outcome as unassisted CPR.

Dispatcher-assisted conventional cardiopulmonary resuscitation and outcomes for paediatric out-of-hospital cardiac arrests.

AIM: As asphyxial cardiac arrest is more common than cardiac arrest from a primary cardiac event in paediatric cardiac arrest, effective ventilation is important during paediatric cardiopulmonary resuscitation (CPR). We aimed to determine optimal dispatcher-assisted CPR instructions for bystanders after paediatric out-of-hospital cardiac arrest (OHCA). METHODS: We analysed the records of 8172 children who received bystander dispatcher-assisted CPR. Data were obtained from an All-Japan Utstein-style registry from 2005 to 2017. Patients were divided into conventional CPR and compression-only CPR groups. The primary study endpoint was 1-month neurologically intact survival, defined as a Cerebral Performance Category score of 1 or 2 (CPC 1-2). RESULTS: The 1-month CPC 1-2 rate was significantly higher in the dispatcher-assisted conventional CPR group than in the dispatcher-assisted compression-only CPR group (before propensity score matching, 5.7% [175/3077] vs. 3.1% [160/5095], p < 0.0001, adjusted odds ratio 2.48, 95% confidence interval 1.19-3.22; after propensity score matching, 6.0% [156/2618] vs. 2.6% [69/2618], p < 0.0001, adjusted odds ratio 2.42, 95% confidence interval 1.76-3.32). In most subgroup analyses after matching, dispatcher-assisted conventional CPR had a higher CPC 1-2 rate than dispatcher-assisted compression-only CPR; however, CPC 1-2 rates were similar between the two groups for patients with an initial shockable rhythm, those with total prehospital CPR time ≥ 20 min, those receiving public access defibrillation, advanced airway management, or adrenaline administration. CONCLUSION: Within the limitations of this retrospective observational study, dispatcher-assisted conventional CPR was preferable to dispatcher-assisted compression-only CPR as optimal CPR instructions for coaching callers to perform bystander CPR.

Dispatcher instructions for bystander cardiopulmonary resuscitation and neurologically intact survival after bystander-witnessed out-of-hospital cardiac arrests: a nationwide, population-based observational study.

BACKGROUND: The International Liaison Committee on Resuscitation recommends that dispatchers provide instructions to perform compression-only cardiopulmonary resuscitation (CPR) to callers responding to adults with out-of-hospital cardiac arrest (OHCA). This study aimed to determine the optimal dispatcher-assisted CPR (DA-CPR) instructions for OHCA. METHODS: We analysed the records of 24,947 adult patients (aged ≥ 18 years) who received bystander DA-CPR after bystander-witnessed OHCA. Data were obtained from a prospectively recorded Japanese nationwide Utstein-style database for a 2-year period (2016-2017). Patients were divided into compression-only DA-CPR (n = 22,778) and conventional DA-CPR (with a compression-to-ventilation ratio of 30:2, n = 2169) groups. The primary outcome measure was 1-month neurological intact survival, defined as a cerebral performance category score of 1-2 (CPC 1-2). RESULTS: The 1-month CPC 1-2 rate was significantly higher in the conventional DA-CPR group than in the compression-only DA-CPR group (before propensity score (PS) matching, 7.5% [162/2169] versus 5.8% [1309/22778], p < 0.01; after PS matching, 7.5% (162/2169) versus 5.7% (123/2169), p < 0.05). Compared with compression-only DA-CPR, conventional DA-CPR was associated with increased odds of 1-month CPC 1-2 (before PS matching, adjusted odds ratio 1.39, 95% confidence interval [CI] 1.14-1.70, p < 0.01; after PS matching, adjusted odds ratio 1.34, 95% CI 1.00-1.79, p < 0.05). CONCLUSION: Within the limitations of this retrospective observational study, conventional DA-CPR with a compression-to-ventilation ratio of 30:2 was preferable to compression-only DA-CPR as an optimal DA-CPR instruction for coaching callers to perform bystander CPR for adult patients with bystander-witnessed OHCAs.

Association of subsequent treated shockable rhythm with outcomes after paediatric out-of-hospital cardiac arrests: A nationwide, population-based observational study.

AIM: Among patients with paediatric out-of-hospital cardiac arrests (OHCAs), most have an initial non-shockable rhythm with poor outcomes. There is a subset who developed shockable rhythms. This study aimed to investigate the association between subsequent shock delivery and outcomes after paediatric OHCAs. METHODS: We analysed records of 19,095 children (aged <18 years) with OHCA and initial non-shockable rhythm. Data were obtained from a Japanese nationwide database for 13 years (2005-2017). The primary outcome measure was 1-month neurologically intact survival, defined as cerebral performance category 1-2. RESULTS: Among patients with pulseless electrical activity (PEA, n = 3,326), there was no significant difference between those with subsequent treated shockable rhythm (10.0% [11/109]) and those with sustained non-shockable rhythm (6.0% [192/3,217], p = 0.10) with respect to the neurologically intact survival rate. Among asystole patients (n = 15,769), the neurologically intact survival rate was significantly higher in the subsequent treated shockable rhythm group (4.4% [10/227]) than in the sustained non-shockable rhythm group (0.7% [106/15,542], p < 0.0001). Subsequent treated shockable rhythm with a shock delivery time (time from emergency medical services [EMS]-initiated cardiopulmonary resuscitation [CPR] to shock delivery) ≤9 min was associated with increased odds of neurologically intact survival compared with sustained non-shockable rhythm (PEA, adjusted odds ratio, 2.45 [95% confidence interval, 1.16-5.16], p = 0.018; asystole, 9.77 [4.2-22.5], p < 0.0001). CONCLUSION: After paediatric OHCAs, subsequent treated shockable rhythm was associated with increased odds of 1-month neurologically intact survival regardless of whether the initial rhythm was PEA or asystole, only when the shock was delivered ≤9 min of EMS-initiated CPR.

Time boundaries of the three-phase time-sensitive model for ventricular fibrillation cardiac arrest.

AIM: Ventricular fibrillation (VF) cardiac arrest may consist of three time-sensitive phases: electrical, circulatory, and metabolic. However, the time boundaries of these phases are unclear. We aimed to determine the time boundaries of the three-phase model for VF cardiac arrest. METHODS: We reviewed 20,741 out-of-hospital cardiac arrest cases with initial VF and presumed cardiac origin from the All-Japan Utstein-style registry between 2013 and 2017. The study endpoint was 1-month neurologically intact survival. The collapse-to-shock interval was defined as the time from collapse to the first shock delivery by emergency medical service personnel. The patients were divided into the bystander cardiopulmonary resuscitation (CPR, n = 11,606) and non-bystander CPR (n = 9135) groups. RESULTS: In the bystander CPR group, the collapse-to-shock times that were associated with increased adjusted 1-month neurologically intact survival, compared with those in the non-bystander CPR group, ranged from 7 min (42.9% [244/4999] vs. 26.0% [119/458], adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.44-2.63; P < 0.0001) to 17 min (17.1% [70/410] vs. 7.3% [21/288], aOR, 2.82; 95% CI, 1.62-4.91; P = 0.0002). However, the neurologically intact survival rate of the bystander CPR group was statistically insignificant compared with that of the non-bystander CPR group when the collapse-to-shock time was outside this range. CONCLUSIONS: The time boundaries of the three-phase time-sensitive model for VF cardiac arrest may be defined as follows: electrical phase, from collapse to <7 min; circulatory phase, from 7 to 17 min; and metabolic phase, from >17 min onward.

Temporal trends in neurologically intact survival after paediatric bystander-witnessed out-of-hospital cardiac arrest: A nationwide population-based observational study.

AIM: Trends in neurologically intact survival after paediatric out-of-hospital cardiac arrest (OHCA) remain unclear. In the present study, we aimed to determine trends in 1-month neurologically intact survival after paediatric OHCA over time. METHODS: We reviewed the data of 5461 children (aged < 18 years) who experienced bystander-witnessed OHCA and were included in the nationwide Japanese registry from 2005 to 2017. Patients were divided into three groups according to study period: 2005-2010, 2011-2015, and 2016-2017. We analysed the trends in 1-month neurologically intact survival rates over time. RESULTS: The risk-adjusted odds of 1-month neurologically intact survival (odds ratio, 1.86; 95% confidence interval, 1.41-2.44) were significantly improved by 2016-2017 compared with baseline. Similar improvements in 1-month neurologically intact survival rates were observed with both standard bystander cardiopulmonary resuscitation (CPR) with rescue breaths and chest compression-only bystander CPR (P for trend < 0.05 and < 0.001, respectively). In the subgroup analyses by aetiology, the 1-month neurologically intact survival rate in patients with OHCA of non-traumatic origin significantly increased from 11.8%-15.1% to 19.7% (P for trend < 0.001) but not in those with OHCA of traumatic origin (from 4.9% to 3.4% to 4.1%; P for trend = 0.29). CONCLUSION: The 1-month neurologically intact survival rate significantly increased from 2005 to 2017 in Japanese children with bystander-witnessed OHCA, regardless of bystander CPR type; This increase was noted in patients with OHCA of non-traumatic origin but not in those with OHCA of traumatic origin.

Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases.

AIMS: The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines as well as evaluating the usefulness of functional studies for determining them. METHODS AND RESULTS: We performed WES of 23 probands diagnosed with early-onset (<65 years) CCSD and analysed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. We focused on rare variants (minor allele frequency < 0.1%) that were absent from population databases. Five probands had protein truncating variants in EMD and LMNA which were classified as 'pathogenic' by 2015 ACMG standards and guidelines. To evaluate the functional changes brought about by these variants, we generated a knock-out zebrafish with CRISPR-mediated insertions or deletions of the EMD or LMNA homologs in zebrafish. The mean heart rate and conduction velocities in the CRISPR/Cas9-injected embryos and F2 generation embryos with homozygous deletions were significantly decreased. Twenty-one variants of uncertain significance were identified in 11 probands. Cellular electrophysiological study and in vivo zebrafish cardiac assay showed that two variants in KCNH2 and SCN5A, four variants in SCN10A, and one variant in MYH6 damaged each gene, which resulted in the change of the clinical significance of them from 'Uncertain significance' to 'Likely pathogenic' in six probands. CONCLUSION: Of 23 CCSD probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%). Functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants in patients with CCSD. SCN10A may be one of the major genes responsible for CCSD.

Sex-specific differences in survival after out-of-hospital cardiac arrest: a nationwide, population-based observational study.

BACKGROUND: It remains unclear whether men have more favorable survival outcomes after out-of-hospital cardiac arrest (OHCA) than women. METHODS: We reviewed a total of 386,535 patients aged ≥ 18 years with OHCA who were included in the Japanese registry from 2013 to 2016. The study endpoints were the rates of 1-month survival and neurologically intact survival (Cerebral Performance Category Scale score = 1 or 2). Based on age, the reviewed patients were categorized into the following eight groups: < 30, 30-39, 40-49, 50-59, 60-69, 70-79, 80-89, and ≥ 90 years. The survival outcomes in men and women were compared using hierarchical propensity score matching. RESULTS: The crude survival rate was significantly higher in men than in women in five groups: 30-39, 40-49, 50-59, 60-69, and 70-79 years (all P < 0.001). Similarly, the crude neurologically intact survival rate was significantly higher in men than in women in seven groups: < 30, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-89 years (all P < 0.005). However, multivariate logistic regression analysis of each group revealed no significant sex-specific differences in 1-month survival outcomes (all P > 0.02). Moreover, after hierarchical propensity score matching, the survival outcomes did not significantly differ between both sexes (all P > 0.05). CONCLUSIONS: No significant sex-specific differences were found in the rates of 1-month survival and neurologically intact survival after OHCA.

Impact of prehospital physician-led cardiopulmonary resuscitation on neurologically intact survival after out-of-hospital cardiac arrest: A nationwide population-based observational study.

AIM: The impact of prehospital physician care for out-of-hospital cardiac arrest (OHCA) on long-term neurological outcome is unclear. We aimed to determine the association between emergency medical services (EMS) physician-led cardiopulmonary resuscitation (CPR) versus paramedic-led CPR and neurologically intact survival after OHCA. METHODS: We assessed 613,251 patients using All-Japan Utstein Registry data from 2011 to 2015 retrospectively. The main outcome measure was 1-month neurologically intact survival after OHCA, defined as Cerebral Performance Category 1 or 2 (CPC 1-2). RESULTS: Before propensity score matching, the 1-month CPC 1-2 rate was significantly higher in EMS physician-led CPR than in paramedic-led CPR [5.7% (1114/19,551) vs. 2.5% (14,859/593,700), P < 0.001; adjusted odds ratio (aOR), 1.50; 95% confidence interval (CI), 1.40-1.61]. After propensity score matching, EMS physician-led CPR showed more favourable neurological outcomes than paramedic-led CPR [6.0% (996/16,612) vs. 4.6% (766/16,612), P < 0.001; aOR, 1.44; 95% CI, 1.29-1.60]. In most subgroup analyses after matching, physician-led CPR had higher 1-month CPC 1-2 rates than paramedic-led CPR did; however, 1-month CPC 1-2 rates were similar between the two CPR configurations for patients aged <18 years (5.6% vs. 8.2%, P = 0.10; aOR, 0.82; 95% CI, 0.46-1.47) and those who received bystander defibrillation (26.3% vs. 21.5%; P = 0.10; aOR, 1.07; 95% CI, 0.74-1.53). CONCLUSION: Within the limitations of this retrospective observational research, EMS physician-led CPR for OHCA was associated with improved 1-month neurologically intact survival compared with paramedic-led CPR. However, neurologically intact survival was similar for patients aged <18 years and those receiving bystander defibrillation.

Field termination-of-resuscitation rule for refractory out-of-hospital cardiac arrests in Japan.

BACKGROUND: Guidelines for cardiopulmonary resuscitation (CPR) recommend using the universal termination-of-resuscitation (TOR) rule to identify out-of-hospital cardiac arrest (OHCA) patients eligible for field termination of resuscitation, thus avoiding medically futile transportation to the hospital. However, in Japan, emergency medical services (EMS) personnel are forbidden from terminating CPR in the field and transport almost all patients with OHCA to hospitals. We aimed to develop and validate a novel TOR rule to identify patients eligible for field termination of CPR. METHODS: We analyzed 540,478 patients with OHCA from 2011 to 2015 using a Japanese registry. Main outcome measures were specificity and positive predictive value (PPV) of the newly developed TOR rule in predicting 1-month mortality after OHCA. RESULTS: Recursive partitioning analysis in the development group (n=434,208) showed that EMS personnel could consider TOR if patients with OHCA met all of the following five criteria: (1) initial asystole, (2) arrest unwitnessed by a bystander, (3) age ≥81 years, (4) no bystander-administered CPR or automated external defibrillator use before EMS arrival, and (5) no return of spontaneous circulation after EMS-initiated CPR for 14min. For patients meeting these criteria, specificity and PPV for predicting 1-month mortality were 99.2% [95% confidence interval (CI), 99.0-99.3%] and 99.7% (95% CI, 99.6-99.7%), respectively, for the development group and were 99.5% (95% CI, 99.3-99.7%) and 99.8% (95% CI, 99.7-99.9%), respectively, for the validation group. Implementation of this novel rule would reduce patient transports to hospitals by 10.6% in the development group and 10.4% in the validation group. CONCLUSIONS: Having both high specificity and PPV of >99% for predicting 1-month mortality, our developed TOR rule may be applied in the field for Japanese patients with OHCA who meet all five criteria. Prospective validation studies and establishment of prehospital EMS protocol are required before implementing this rule.

Effects of prehospital epinephrine administration on neurologically intact survival in bystander-witnessed out-of-hospital cardiac arrest patients with non-shockable rhythm depend on prehospital cardiopulmonary resuscitation duration required to hospital arrival.

The effects of prehospital epinephrine administration on post-arrest neurological outcome in out-of-hospital cardiac arrest (OHCA) patients with non-shockable rhythm remain unclear. To examine the time-dependent effectiveness of prehospital epinephrine administration, we analyzed 118,396 bystander-witnessed OHCA patients with non-shockable rhythm from the prospectively recorded all-Japan OHCA registry between 2011 and 2014. Patients who achieved prehospital return of spontaneous circulation without prehospital epinephrine administration were excluded. Patients with prehospital epinephrine administration were stratified according to the time from the initiation of cardiopulmonary resuscitation (CPR) by emergency medical service (EMS) providers to the first epinephrine administration (≤ 10, 11-19, and ≥ 20 min). Patients without prehospital epinephrine administration were stratified according to the time from CPR initiation by EMS providers to hospital arrival (≤ 10, 11-19, and ≥ 20 min). The primary outcome was 1-month neurologically intact survival (cerebral performance category 1 or 2; CPC 1-2). Multivariate logistic regression analysis demonstrated that there was no significant difference in the chance of 1-month CPC 1-2 between patients who arrived at hospital in ≤ 10 min without prehospital epinephrine administration and patients with time to epinephrine administration ≤ 19 min. However, compared to patients who arrived at hospital in ≤ 10 min without prehospital epinephrine administration, patients with time to epinephrine administration ≥ 20 min and patients who arrived at hospital in 11-19, and ≥ 20 min without prehospital epinephrine administration were significantly associated with decreased chance of 1-month CPC 1-2 (p < 0.05, < 0.05, and < 0.001, respectively). In conclusion, when prehospital CPR duration from CPR initiation by EMS providers to hospital arrival estimated to be ≥ 11 min, prehospital epinephrine administered ≤ 19 min from CPR initiation by EMS providers could improve neurologically intact survival in bystander-witnessed OHCA patients with non-shockable rhythm.

Relationship Between Emergency Medical Services Response Time and Bystander Intervention in Patients With Out-of-Hospital Cardiac Arrest.

BACKGROUND: The response time of emergency medical services (EMS) is an important determinant of survival after out-of-hospital cardiac arrest. We sought to identify upper limits of EMS response times and bystander interventions associated with neurologically intact survival. METHODS AND RESULTS: We analyzed the records of 553 426 patients with out-of-hospital cardiac arrest in a Japanese registry between 2010 and 2014. The primary study end point was 1-month neurologically intact survival (Cerebral Performance Category scale 1 or 2). Increased EMS response time was associated with significantly decreased adjusted odds of 1-month neurologically intact survival (adjusted odds ratio [aOR] for each 1-minute increase, 0.89; 95% confidence interval [CI], 0.89-0.90), although this relationship was modified by bystander interventions. The bystander interventions and the ranges of EMS response times that were associated with increased adjusted 1-month neurologically intact survival were as follows: bystander defibrillation, from ≤2 minutes (aOR, 3.10 [95% CI, 1.25-7.31]) to 13 minutes (aOR, 5.55 [95% CI, 2.66-11.2]); bystander conventional cardiopulmonary resuscitation, from 3 minutes (aOR 1.48 [95% CI, 1.02-2.12]) to 11 minutes (aOR 2.41 [95% CI, 1.61-3.56]); and bystander chest-compression-only cardiopulmonary resuscitation, from ≤2 minutes (aOR 1.57 [95% CI, 1.01-2.25]) to 11 minutes (aOR 1.92 [95% CI, 1.45-2.56]). However, the increase in neurologically intact survival of those receiving bystander interventions became statistically insignificant compared with no bystander interventions when the EMS response time was outside these ranges. CONCLUSIONS: The upper limits of the EMS response times associated with improved 1-month neurologically intact survival were 13 minutes when bystanders provided defibrillation (typically with cardiopulmonary resuscitation) and 11 minutes when bystanders provided cardiopulmonary resuscitation without defibrillation.

Duration of cardiopulmonary resuscitation in patients without prehospital return of spontaneous circulation after out-of-hospital cardiac arrest: Results from a severity stratification analysis.

BACKGROUND: The relationship between duration of cardiopulmonary resuscitation (CPR) and post-arrest outcomes based on severity stratification in out-of-hospital cardiac arrest (OHCA) patients without prehospital return of spontaneous circulation (ROSC) remains unclear. METHODS: We analysed 420,959 adult patients without prehospital ROSC in the All-Japan OHCA registry for 4 years. Prehospital CPR duration was defined as the time from CPR initiation by emergency medical service (EMS) providers to hospital arrival. The primary outcome was 1-month neurologically intact survival (cerebral performance category 1 or 2, CPC 1-2). RESULTS: The rate of overall 1-month CPC 1-2 was 0.45% (1899/420,959). Using recursive partitioning analysis to predict 1-month CPC 1-2, we stratified patients into 4 groups with 3 predictors: patients aged <75 years with initial shockable rhythm (1-month CPC 1-2 rate, 6.15%), those aged ≥75 years with initial shockable rhythm (1.32%), those with EMS-witnessed arrest and initial non-shockable rhythm (1.62%), and those with EMS-unwitnessed arrest and initial non-shockable rhythm (0.15%). Prehospital CPR duration was negatively associated with 1-month CPC 1-2 (adjusted odds ratio 0.94 per 1-min increment; 95% confidence interval 0.94-0.95). Prehospital CPR durations beyond which the dynamic probability of 1-month CPC 1-2 decreased to <1% were 26 min, 10 min, 7 min, and at all times in above-mentioned stratification, respectively. CONCLUSIONS: In OHCA patients without prehospital ROSC, those aged <75 years with initial shockable rhythm had acceptable 1-month CPC 1-2 rate. However, CPR efforts lasting 26 min or over before hospital arrival could be futile.

Conventional versus chest-compression-only cardiopulmonary resuscitation by bystanders for children with out-of-hospital cardiac arrest.

AIM: It is unclear whether chest-compression-only cardiopulmonary resuscitation (CC-CPR) is therapeutically equivalent to conventional CPR for children with out-of-hospital cardiac arrest (OHCA). We aimed to determine the association of CC-CPR and conventional CPR with outcomes in discrete child patient populations with OHCA. METHODS: We analysed 6810 children (aged <18years) using Japanese registry from 2007 to 2014. Main outcomes measure was 30-day neurologically intact survival after OHCA, defined as Glasgow-Pittsburgh cerebral performance categories 1 or 2. RESULTS: In propensity score-matched children aged 1-17 years (n=2682), overall neurologically intact survival rate was significantly higher after conventional CPR than after CC-CPR (9.4% vs. 6.0%, P=0.001). However, there was no significant difference between the two CPR modalities in patients with cardiac aetiology (14.2% vs. 11.8%, P=0.32), initial shockable rhythm (35.3% vs. 31.7%, P=0.59), or age ≥8 years (12.4% vs. 9.8%, P=0.13). For matched infants (n=1994), no significant differences were observed in overall neurological intact survival between conventional CPR and CC-CPR (2.2% vs. 1.3%, P=0.17). In infant subgroup analyses, neurologically intact survival was similar between the CPR modalities for cardiac aetiology (0.3% vs. 1.0%; P=0.37) and for witnessed arrest (6.2% vs. 6.0%; P=0.98). CONCLUSIONS: In the majority of the paediatric subgroups, conventional CPR was associated with improved outcomes compared to CC-CPR. CC-CPR was associated with 30-day neurologically intact survival similar to conventional CPR for children with OHCA aged ≥8 years, for children aged 1-17 years with cardiac aetiology or initial shockable rhythm, and for infants with cardiac aetiology or witnessed arrest.

Age-Specific Differences in the Duration of Prehospital Cardiopulmonary Resuscitation Administered by Emergency Medical Service Providers Necessary to Achieve Favorable Neurological Outcome After Out-of-Hospital Cardiac Arrest.

BACKGROUND: The appropriate duration of prehospital cardiopulmonary resuscitation (CPR)administered by emergency medical service (EMS) providers for patients with out-of-hospital cardiac arrest (OHCA) necessary to achieve 1-month survival with favorable neurological outcome (Cerebral Performance Category 1 or 2, CPC 1-2) is unclear and could differ by age.Methods and Results:We analyzed the records of 35,709 adult OHCA patients with return of spontaneous circulation (ROSC) before hospital arrival in a prospectively recorded Japanese registry between 2011 and 2014. The CPR duration was defined as the time from CPR initiation by EMS providers to prehospital ROSC. The rate of 1-month CPC 1-2 was 21.4% (7,650/35,709). The CPR duration was independently and inversely associated with 1-month CPC 1-2 (adjusted odds ratio, 0.93 per 1-min increment; 95% confidence interval, 0.93-0.94). The CPR duration increased with age (P<0.001). However, the CPR duration beyond which the proportion of OHCA patients with 1-month CPC 1-2 decreased to <1% declined with age: 28 min for patients aged 18-64 years, 25 min for 65-74 years, 23 min for 75-84 years, 20 min for 85-94 years, and 18 min for ≥95 years. CONCLUSIONS: In patients who achieved prehospital ROSC after OHCA, the duration of CPR administered by EMS providers necessary to achieve 1-month CPC 1-2 varied by age.

Prehospital predictors of neurological outcomes in out-of-hospital cardiac arrest patients aged 95 years and older: A nationwide population-based observational study.

BACKGROUND: Population aging has rapidly progressed in Japan. However, few data exist regarding the characteristics of extremely elderly patients with out-of-hospital cardiac arrest (OHCA). We aimed to determine the prehospital predictors of one-month survival with favorable neurological outcomes (Cerebral Performance Category scale, category 1 or 2; CPC 1-2) in this population. METHODS: We investigated 23,520 OHCA patients aged ≥95 years from a prospectively recorded, nationwide, Utstein-style Japanese database between 2008 and 2012. The primary study endpoint was one-month CPC 1-2 after OHCA. RESULTS: The one-month CPC 1-2 rate was 0.27% (63/23,520). Only two variables were significantly associated with one-month CPC 1-2 in a multivariate logistic regression model: prehospital return of spontaneous circulation (ROSC) [adjusted odds ratio (aOR), 94.4; 95% confidential interval (CI), 50.1-191.7] and emergency medical service (EMS)-witnessed arrest (aOR, 5.1; 95% CI, 2.6-10.2). When stratified by these two predictors, the one-month CPC 1-2 rates were 20.2% (18/89) for patients who had both prehospital ROSC and EMS-witnessed arrest, 4.2% (33/783) for those who had prehospital ROSC without EMS-witnessed arrest, 0.28% (3/1065) for those who had EMS-witnessed arrest without prehospital ROSC, and 0.04% (9/21,583) for those who had neither predictor, respectively. CONCLUSIONS: The crucial prehospital predictors for one-month CPC 1-2 in elderly OHCA patients aged ≥95 years in Japan were prehospital ROSC and EMS-witnessed arrest and the former was the predominant predictor.

Subclinical hypothyroidism is an independent predictor of adverse cardiovascular outcomes in patients with acute decompensated heart failure.

AIMS: Altered thyroid hormone metabolism characterized by a low triiodothyronine (T3), so-called low-T3 syndrome, is a common finding in patients with severe systemic diseases. Additionally, subclinical thyroid dysfunction, defined as abnormal thyroid stimulating hormone (TSH) and normal thyroxine (T4), causes left ventricular dysfunction. Our objective was to identify the prevalence and prognostic impact of low-T3 syndrome and subclinical thyroid dysfunction in patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: We examined 274 ADHF patients who were not receiving thyroid medication or amiodarone on admission (70 ± 15 years, 156 male), who underwent thyroid function tests. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L; subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L; and subclinical hyperthyroidism as TSH < 0.45 mIU/L, with normal free T4 level for the last two. Additionally, low-T3 syndrome was defined as free T3 < 4.0 pmol/L among euthyroidism subjects. On admission, 188 patients (69%) showed euthyroidism, 58 (21%) subclinical hypothyroidism, 5 (2%) subclinical hyperthyroidism, and 95 (35%) low-T3 syndrome. Cox proportional hazards models revealed that higher TSH, but not free T3 and free T4, was independently associated with composite cardiovascular events, including cardiac death and re-hospitalization for heart failure. Indeed, subclinical hypothyroidism was an independent predictor (hazard ratio: 2.31; 95% confidence interval: 1.44 to 3.67; P < 0.001), whereas low-T3 syndrome and subclinical hyperthyroidism were not. CONCLUSIONS: Subclinical hypothyroidism on admission was an independent predictor of adverse cardiovascular outcomes in ADHF patients, suggesting a possible interaction between thyroid dysfunction and the pathophysiology of ADHF.

Duration of Prehospital Cardiopulmonary Resuscitation and Favorable Neurological Outcomes for Pediatric Out-of-Hospital Cardiac Arrests: A Nationwide, Population-Based Cohort Study.

BACKGROUND: The appropriate duration of cardiopulmonary resuscitation (CPR) for pediatric out-of-hospital cardiac arrests (OHCAs) remains unclear and may differ based on initial rhythm. We aimed to determine the relationship between the duration of prehospital CPR by emergency medical services (EMS) personnel and post-OHCA outcomes. METHODS: We analyzed the records of 12 877 pediatric patients who experienced OHCAs (<18 years of age). Data were recorded in a nationwide Japanese database between 2005 and 2012. Study end points were 30-day survival and 30-day survival with favorable neurological outcomes (Cerebral Performance Category [CPC] scale 1-2). Prehospital EMS-initiated CPR duration was defined as the time from CPR initiation by EMS personnel to prehospital return of spontaneous circulation (ROSC) or to hospital arrival when prehospital ROSC was not achieved during prehospital CPR efforts. RESULTS: The rates of 30-day survival and 30-day CPC 1 to 2 were 9.1% (n=1167) and 2.5% (n=325), respectively. Prehospital EMS-initiated CPR duration was significantly and inversely associated with 30-day outcomes (adjusted odds ratio for 1-minute increments: 0.94, 95% confidence interval: 0.93-0.95 for survival; adjusted odds ratio: 0.90, 95% confidence interval: 0.88-0.92 for CPC 1-2). The duration of prehospital EMS-initiated CPR, beyond which the chance for favorable outcomes diminished to <1%, was 42 minutes for each key outcome, 30-day survival, and 30-day survival with CPC 1 to 2. When categorized by initial rhythm, the prehospital EMS-initiated CPR durations beyond which the chance for 30-day survival with CPC 1 to 2 diminished to <1% were 39 minutes for shockable rhythms, 42 minutes for pulseless electric activity, and 46 minutes for asystole, respectively. In patients with bystander-initiated CPR, the prehospital CPR duration, beyond which the chance for favorable outcome diminished to <1%, was 46 minutes from call receipt. CONCLUSIONS: Prehospital EMS-initiated CPR duration for pediatric OHCAs was independently and inversely associated with 30-day favorable outcomes. The duration of prehospital EMS-initiated CPR, beyond which the chance for 30-day favorable outcomes diminished to <1%, was 42 minutes. However, the CPR duration to achieve this proportion of outcomes differed based on initial rhythm. Further research is required to elucidate appropriate CPR duration for pediatric OHCAs, including in-hospital CPR time. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02432196.