Impact of Updating the Cardiopulmonary Resuscitation Guidelines on Out-of-Hospital Shockable Cardiac Arrest: A Population-Based Cohort Study in Japan.

BACKGROUND: International consensus on cardiopulmonary resuscitation (CPR) and emergency cardiovascular care science and treatment recommendations (CoSTR) have reported updates on CPR maneuvers every 5 years since 2000. However, few national population-based studies have investigated the comprehensive effectiveness of those updates for out-of-hospital cardiac arrest due to shockable rhythms. The primary objective of the present study was to determine whether CPR based on CoSTR 2005 or 2010 was associated with improved outcomes in Japan, as compared with CPR based on Guidelines 2000. METHODS AND RESULTS: From the All-Japan Utstein Registry between 2005 and 2015, we included 73 578 adults who had shockable out-of-hospital cardiac arrest witnessed by bystanders or emergency medical service responders. The study outcomes over an 11-year period were compared between 2005 of the Guidelines 2000 era, from 2006 to 2010 of the CoSTR 2005 era, and from 2011 to 2015 of the CoSTR 2010 era. In the bystander-witnessed group, the adjusted odds ratios for favorable neurological outcomes at 30 days after out-of-hospital cardiac arrest by enrollment year increased year by year (1.19 in 2006, and 3.01 in 2015). Similar results were seen in the emergency medical service responder-witnessed group and several subgroups. CONCLUSIONS: Compared with CPR maneuvers for shockable out-of-hospital cardiac arrest recommended in the Guidelines 2000, CPR maneuver updates in CoSTR 2005 and 2010 were associated with improved neurologically intact survival year by year in Japan. Increased public awareness and greater dissemination of basic life support may be responsible for the observed improvement in outcomes. REGISTRATION: URL: https://www.umin.ac.jp/ctr/; Unique identifier: 000009918.

Prediction of the neurological outcome using regional cerebral oxygen saturation in patients with extracorporeal cardiopulmonary resuscitation after out-of-hospital cardiac arrest: a multicenter retrospective cohort study.

AIM: To investigate the association between regional cerebral oxygen saturation (rSO2) and neurological outcomes in extracorporeal cardiopulmonary resuscitation (ECPR) patients after out-of-hospital cardiac arrest (OHCA). METHODS: We used data from the Japan-Prediction of Neurological Outcomes in Patients Post-Cardiac Arrest Registry. This registry included consecutive comatose patients after OHCA who were transferred to 15 hospitals in Japan from 2011 to 2013. Our primary end-point was a good neurological outcome (cerebral performance categories 1 or 2) at 90 days after OHCA. RESULTS: Among the enrolled patients, 121 (6.3%) received ECPR. Eleven (9.1%) had a good neurological outcome. Receiver operating characteristic curve analysis revealed the optimal cut-off value as >16%. Good neurological outcomes were observed in 19.6% (9/46) and 2.7% (2/74) of patients with rSO2 >16% and rSO2 ≤16%, respectively. CONCLUSION: The neurological outcome of ECPR patients differed according to their rSO2 values. When considering ECPR, the rSO2 value could be important in addition to other criteria. Further studies that focus on ECPR patients and serial rSO2 values are needed.

Duration of Prehospital Resuscitation Efforts After Out-of-Hospital Cardiac Arrest.

BACKGROUND: During out-of-hospital cardiac arrest, it is unclear how long prehospital resuscitation efforts should be continued to maximize lives saved. METHODS AND RESULTS: Between 2005 and 2012, we enrolled 282 183 adult patients with bystander-witnessed out-of-hospital cardiac arrest from the All-Japan Utstein Registry. Prehospital resuscitation duration was calculated as the time interval from call receipt to return of spontaneous circulation in cases achieving prehospital return of spontaneous circulation or from call receipt to hospital arrival in cases not achieving prehospital return of spontaneous circulation. In each of 4 groups stratified by initial cardiac arrest rhythm (shockable versus nonshockable) and bystander resuscitation (presence versus absence), we calculated minimum prehospital resuscitation duration, defined as the length of resuscitation efforts in minutes required to achieve ≥99% sensitivity for the primary end point, favorable 30-day neurological outcome after out-of-hospital cardiac arrest. Prehospital resuscitation duration to achieve prehospital return of spontaneous circulation ranged from 1 to 60 minutes. Longer prehospital resuscitation duration reduced the likelihood of favorable neurological outcome (adjusted odds ratio, 0.84; 95% confidence interval, 0.838-0.844). Although the frequency of favorable neurological outcome was significantly different among the 4 groups, ranging from 20.0% (shockable/bystander resuscitation group) to 0.9% (nonshockable/bystander resuscitation group; P<0.001), minimum prehospital resuscitation duration did not differ widely among the 4 groups (40 minutes in the shockable/bystander resuscitation group and the shockable/no bystander resuscitation group, 44 minutes in the nonshockable/bystander resuscitation group, and 45 minutes in the nonshockable/no bystander resuscitation group). CONCLUSIONS: On the basis of time intervals from the shockable arrest groups, prehospital resuscitation efforts should be continued for at least 40 minutes in all adults with bystander-witnessed out-of-hospital cardiac arrest. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/. Unique identifier: 000009918.

Regional cerebral oxygen saturation monitoring for predicting interventional outcomes in patients following out-of-hospital cardiac arrest of presumed cardiac cause: A prospective, observational, multicentre study.

AIM: This study investigated the value of regional cerebral oxygen saturation (rSO2) monitoring upon arrival at the hospital for predicting post-cardiac arrest intervention outcomes. METHODS: We enrolled 1195 patients with out-of-hospital cardiac arrest of presumed cardiac cause from the Japan-Prediction of Neurological Outcomes in Patients Post-cardiac Arrest Registry. The primary endpoint was a good neurologic outcome (cerebral performance categories 1 or 2 [CPC1/2]) 90 days post-event. RESULTS: A total of 68 patients (6%) had good neurologic outcomes. We found a mean rSO2 of 21%±13%. A receiver operating characteristic curve analysis indicated an optimal rSO2 cut-off of ≥40% for good neurologic outcomes (area under the curve 0.92, sensitivity 0.81, specificity 0.96). Good neurologic outcomes were observed in 53% (55/103) and 1% (13/1092) of patients with high (≥40%) and low (<40%) rSO2, respectively. Even without return of spontaneous circulation (ROSC) upon arrival at the hospital, 30% (9/30) of patients with high rSO2 had good neurologic outcomes. Furthermore, 16 patients demonstrating ROSC upon arrival at the hospital and low rSO2 had poor neurologic outcomes. Multivariate analyses indicated that high rSO2 was independently associated with good neurologic outcomes (odds ratio=14.07, P<0.001). Patients with high rSO2 showed favourable neurologic prognoses if they had undergone therapeutic hypothermia or coronary angiography (CPC1/2, 69% [54/78]). However, 24% (25/103) of those with high rSO2 did not undergo these procedures and exhibited unfavourable neurologic prognoses (CPC1/2, 4% [1/25]). CONCLUSION: rSO2 is a good indicator of 90-day neurologic outcomes for post-cardiac arrest intervention patients.

Characteristics of regional cerebral oxygen saturation levels in patients with out-of-hospital cardiac arrest with or without return of spontaneous circulation: A prospective observational multicentre study.

AIM: Our study aimed at filling the fundamental knowledge gap on the characteristics of regional brain oxygen saturation (rSO2) levels in out-of-hospital cardiac arrest (OHCA) patients with or without return of spontaneous circulation (ROSC) upon arrival at the hospital for estimating the quality of cardiopulmonary resuscitation and neurological prognostication in these patients. METHODS: We enrolled 1921 OHCA patients from the Japan - Prediction of Neurological Outcomes in Patients Post-cardiac Arrest Registry and measured their rSO2 immediately upon arrival at the hospital by near-infrared spectroscopy using two independent forehead probes (right and left). We also assessed the percentage of patients with a good neurological outcome (defined as cerebral performance categories 1 or 2) 90 days post cardiac arrest. RESULTS: After 90 days, 79 (4%) patients had good neurological outcomes and a median lower rSO2 level of 15% (15-20%). Compared to patients without ROSC upon arrival at the hospital, those with ROSC had significantly higher rSO2 levels (56% [39-65%] vs. 15% [15-17%], respectively; P<0.01), and significantly correlated right- and left-sided regional brain oxygen saturation levels (R=0.94 vs. 0.66, respectively). In both groups, the percentage of patients with a good 90-day neurological outcome increased significantly in proportion to their rSO2 levels upon arrival at the hospital (P<0.01). CONCLUSION: Our data indicate that measuring rSO2 levels might be effective for both monitoring the quality of resuscitation and neurological prognostication in patients with OHCA.

Estimated cerebral oxyhemoglobin as a useful indicator of neuroprotection in patients with post-cardiac arrest syndrome: a prospective, multicenter observational study.

INTRODUCTION: Little is known about oxyhemoglobin (oxy-Hb) levels in the cerebral tissue during the development of anoxic and ischemic brain injury. We hypothesized that the estimated cerebral oxy-Hb level, a product of Hb and regional cerebral oxygen saturation (rSO2), determined at hospital arrival may reflect the level of neuroprotection in patients with post-cardiac arrest syndrome (PCAS). METHODS: The Japan Prediction of neurological Outcomes in patients with Post cardiac arrest (J-POP) registry is a prospective, multicenter, cohort study to test whether rSO2 predicts neurological outcomes after out-of-hospital cardiac arrest (OHCA). This study assessed a subgroup of consecutive patients who fulfilled the J-POP registry criteria and successfully achieved return of spontaneous circulation (ROSC) from OHCA. The primary outcome measure was the neurological status at 90 days. RESULTS: We analyzed data from 495 consecutive comatose survivors who were successfully resuscitated from OHCA, including 119 comatose patients with prehospital return of spontaneous circulation (ROSC; 24.0%) and 376 cardiac arrests at hospital arrival. In total, 75 patients (15.1%) presented with good neurological outcomes. Univariate analysis revealed that the cerebral oxy-Hb levels were significantly higher in patients with good outcomes. Multivariate logistic regression using the backward elimination method confirmed that the oxy-Hb level was a significant predictor of good neurological outcomes (adjusted odds ratio: 1.27, 95% confidence interval (CI): 1.11 to 1.46). Analysis of the area under the receiver operating characteristic curve (AUC) revealed that an oxy-Hb cut-off of 5.5 provided optimal sensitivity and specificity for predicting good neurological outcomes (AUC: 0.87, 95% CI: 0.83 to 0.91; sensitivity: 77.3%; specificity: 85.6%). The oxy-Hb level appeared to be an excellent prognostic indicator with significant advantages over rSO2 and base excess according to AUC analysis. The significant trend for good neurological outcomes was consistent, even in the subgroup of patients who achieved return of spontaneous circulation upon hospital arrival (1st quartile: 0%; 2nd quartile: 16.7%; 3rd quartile: 29.4%; 4th quartile: 53.3%, P <0.05). CONCLUSIONS: The cerebral oxy-Hb level may predict neurological outcomes and is a simple and excellent indicator of neuroprotection in patients with PCAS. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000005065. Registered 1 April 2011.

Noninvasive regional cerebral oxygen saturation for neurological prognostication of patients with out-of-hospital cardiac arrest: a prospective multicenter observational study.

AIM: To investigate the association between regional brain oxygen saturation (rSO2) at hospital arrival and neurological outcomes at 90 days in patients with out-of-hospital cardiac arrest (OHCA). METHODS: The Japan-Prediction of neurological Outcomes in patients post cardiac arrest (J-POP) registry is a prospective, multicenter, cohort study to test whether rSO2 predicts neurological outcomes after OHCA. We measured rSO2 in OHCA patients immediately after hospital arrival using a near-infrared spectrometer placed on the forehead with non-blinded fashion. The primary endpoint was "neurological outcomes" at 90 days after OHCA. RESULTS: EMS providers are not permitted to terminate CPR in the field in Japan, and so most patients with OHCA who are treated by EMS personnel are transported to emergency hospitals. Among 1017 OHCA patients, 672 patients including 52 comatose patients with pulses detectable (8%) and 620 cardiac arrest patients (92%) at hospital arrival were enrolled prospectively and consecutively. Twenty-nine patients with good neurological outcome had a significantly higher value of rSO2 at hospital arrival than 643 patients with poor neurological outcome (mean [±SD] 55.6±20.8% vs. 19.7±11.0%, p<0.001). Receiver operating curve analysis indicated an optimal rSO2 cutoff point of >42% for predicting good neurological outcome, with sensitivity 0.79 (95% confidence interval [CI], 0.60-0.92), specificity 0.95 (95% CI, 0.93-0.96), positive predictive value, 0.41 (95% CI, 0.28-0.55), negative predictive value, 0.99 (95% CI, 0.98-1.00), and area under the curve 0.90 (95% CI, 0.88-0.92). CONCLUSION: The rSO2 at hospital arrival can predict good neurological outcome at 90 days after OHCA.

Beneficial effects of intracoronary nicorandil on microvascular dysfunction after primary percutaneous coronary intervention: demonstration of its superiority to nitroglycerin in a cross-over study.

PURPOSE: In patients undergoing primary percutaneous coronary intervention (PCI) for the treatment of ST-segment elevation myocardial infarction (STEMI), coronary microvascular dysfunction is associated with poor prognosis. Coronary microvascular resistance is predominantly regulated by ATP-sensitive potassium (KATP) channels. The aim of this study was to clarify whether nicorandil, a hybrid KATP channel opener and nitric oxide donor, may be a good candidate for improving microvascular dysfunction even when administered after primary PCI. METHODS: We compared the beneficial effects of nicorandil and nitroglycerin on microvascular function in 60 consecutive patients with STEMI. After primary PCI, all patients received single intracoronary administrations of nitroglycerin (250 µg) and nicorandil (2 mg) in a randomized order; 30 received nicorandil first, while the other 30 received nitroglycerin first. Microvascular dysfunction was evaluated with the index of microcirculatory resistance (IMR), defined as the distal coronary pressure multiplied by the hyperemic mean transit time. RESULTS: As a first administration, nicorandil decreased IMR significantly more than did nitroglycerin (median [interquartile ranges]: 10.8[5.2-20.7] U vs. 2.1[1.0-6.0] U, p=0.0002).As a second administration, nicorandil further decreased IMR, while nitroglycerin did not (median [interquartile ranges]: 6.0[1.3-12.7] U vs. -1.4[-2.6 to 1.3] U, p<0.0001). The IMR after the second administration was significantly associated with myocardial blush grade, angiographic TIMI frame count after the procedure, and peak creatine kinase level. CONCLUSION: Intracoronary nicorandil reduced microvascular dysfunction after primary PCI more effectively than did nitroglycerin in patients with STEMI, probably via its KATP channel-opening effect.

Regional cerebral oxygen saturation on hospital arrival is a potential novel predictor of neurological outcomes at hospital discharge in patients with out-of-hospital cardiac arrest.

AIM: To investigate the association between regional brain oxygen saturation (rSO(2)) on hospital arrival and neurological outcomes at hospital discharge in patients with out-of-hospital cardiac arrest (OHCA). METHODS: A prospective cohort study was conducted, registering 179 patients with OHCA who were referred to Senri Critical Care Medical Centre between April 2009 and June 2010. Of these patients, 92 met the inclusion criteria. The primary end point was "neurological outcomes" at hospital discharge according to the "Utstein style" guidelines. RESULTS: The overall rate of good neurological outcome at hospital discharge was 14% (n=13). Sixty-one patients with rSO(2) ≤25% showed poor neurological outcome in the receiver operating curve analysis (optimal cut-off point, 25%; sensitivity, 0.772; specificity, 1.000; positive predictive value, 1.000; area under the curve (AUC), 0.919; p<0.0001). The AUC for rSO(2) was greater than that for base excess (p=0.0461) or lactate (p=0.0128) measured on hospital arrival. Since rSO(2) >40% was previously collated with good neurological outcome after cardiovascular surgery, we categorised our patients into three groups in a post hoc analysis: patients with rSO(2) ≤25% (n=61); patients with rSO(2) 26-40% (n=9) and patients with rSO(2) >40% (n=22). Patients with good neurological outcome were as follows: 0 (0%)/61 with rSO(2) ≤25%; two (22.2%)/9 with rSO(2) 26-40% and 11 (50.0%)/22 with rSO(2) >40% (p<0.0001). CONCLUSION: rSO(2) on hospital arrival may help predict neurological outcomes at hospital discharge in patients with OHCA.

Distal protection during primary coronary intervention can preserve the index of microcirculatory resistance in patients with acute anterior ST-segment elevation myocardial infarction.

BACKGROUND: The objective of this study was to investigate whether a distal protection (DP) device can preserve the index of microcirculatory resistance (IMR) after primary percutaneous coronary intervention (PCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: The study group of 36 consecutive patients with anterior STEMI were randomized into 2 groups of primary PCI with or without DP: stenting without DP (non-DP group, n = 17) and with DP (DP group, n = 19). The DP in all cases was Filtrap (Nipro, Japan). Following final coronary angiography after successful PCI, IMR was measured using PressureWire™ Certus (St Jude Medical, USA) at maximal hyperemia. The averaged IMR of the 36 patients with STEMI after primary PCI was 31.6U. The IMR in the DP group was significantly lower than that in the non-DP group (26.6 ± 25.8U vs. 37.2 ± 23.2U, P = 0.03242). CONCLUSIONS: DP as an adjunctive therapy of PCI for acute anterior STEMI may have beneficial effects on myocardial microcirculation because of preservation of IMR.

High index of microcirculatory resistance level after successful primary percutaneous coronary intervention can be improved by intracoronary administration of nicorandil.

BACKGROUND: Although microvascular dysfunction following percutaneous coronary intervention (PCI) can be evaluated with the index of microcirculatory resistance (IMR), no method of treatment has been established. We hypothesized that intracoronary administration of nicorandil can improve IMR after successful primary PCI in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: In 40 patients with first STEMI after successful primary PCI, IMR was measured using PressureWire(TM) Certus (St. Jude Medical, MN, USA). In 20 of the patients (Group N), IMR was measured at baseline and after intracoronary nicorandil (2 mg/10 ml). In the other 20 patients (Control), IMR was measured at baseline, after intracoronary saline (10 ml) and after intracoronary nicorandil (2 mg/10 ml). In Group N, IMR significantly decreased after intracoronary nicorandil (median IMR, 27.7-18.7 U, P<0.0001). In the Control group, IMR did not change after saline administration (median IMR, 24.3-23.8 U, P=0.8193), but was significantly decreased after intracoronary nicorandil (median IMR, 23.8-14.9 U, P<0.0001). Next, all 40 patients were divided into subgroups by tertile of baseline IMR. In those with intermediate to high IMR (baseline IMR > or =21), intracoronary nicorandil significantly decreased IMR, although it did not change IMR in those with low IMR (baseline IMR <21). CONCLUSIONS: High IMR levels in patients with STEMI after successful primary PCI can be improved by intracoronary administration of nicorandil.