bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 270: Non-Invasive Cerebral Perfusion and Autoregulation Monitoring Post-Cardiac Arrest
Authors: Kashlan Reem , Chaudhry Kaleem , Ohlson Eric , Miller Joseph B
Published: July 2021

Objective:
The primary aim of this study was to test the feasibility of non-invasive cerebral perfusion monitoring post-arrest. We secondarily tested the association between measured autoregulation, the presence of cerebral edema, and neurological recovery.

Methods:
This was a prospective, pilot study inclusive of patients successfully resuscitated from cardiac arrest in the Emergency Department (ED). After return of spontaneous circulation, an investigator placed non-invasive, bifrontal monitoring to measure cerebral perfusion. The device uses an acousto-optic sensor to measure continuous cerebral perfusion and measurements are arbitrary units between 0-100, where 0 represents no flow (Ornim, Tel Aviv). Subjects had invasive, continuous arterial monitoring to assess mean arterial pressure (MAP). Multimodal measurements continued for 60 minutes. We calculated a Pearson coefficient between the perfusion measurements and MAP as an assessment of cerebral autoregulation, where a correlation coefficient > 0.3 indicates poor autoregulation, and a coefficient of 1 indicates completely passive cerebral perfusion to changes in MAP. Head computed tomography defined the presence of cerebral edema in the ED.

Results:
We enrolled 14 patients post-arrest with sustained return of circulation. The mean age was 55 ± 14 years, 7 were female, and 10 were African American. Six patients had pulseless electrical activity, 5 asystole, and 2 ventricular fibrillation. Bystander CPR rates were low (4 of 14, 31%). Two patients (14%) survived to hospital discharge. Cerebral perfusion was comparable between patients that survived and those that died (difference 3.1, 95% CI -14 to 8). Cerebral perfusion measurement was higher in patients with cerebral edema (difference 6.1, 95% CI 0.2 - 11.9). Autoregulation was worse in the presence of edema (0.30) compared to no edema (0.14), though this difference did not reach statistical significance (95% CI -0.7 to 0.4).

Conclusions:
In a pilot study, non-invasive post-arrest perfusion measurements plus coupling with MAP for autoregulation was feasible. Perfusion measurements were increased in the presence of cerebral edema but whether such measurements have prognostic value requires further study.
Abstract 274: Verbal Prompts During Pediatric Cardiopulmonary Resuscitation in Emergency Department: A Report From the Videography in Pediatric Emergency Resuscitation (VIPER) Collaborative
Authors: Watanabe Ichiro , Hanna Richard S , Myers Sage R , Kerrey Benjamin , Frey Mary , O’Connell Karen , Sandler Alexis , Donoghue Aaron
Published: July 2021

Introduction:
The quality of chest compressions (CC) is crucial for good outcomes for pediatric cardiac arrest. Verbal prompts from resuscitation leader or CPR coach may help to optimize it. The objective of this study is to describe the frequency of appropriate verbal prompts during pediatric CPR. We hypothesized that verbal prompts for CC would be given less frequently to infants compared to children.

Methods:
A report from the Videography In Pediatric Emergency Resuscitation (VIPER) Collaborative, a prospective observational database from three tertiary PEDs from December 2016 to April 2018. All study sites videorecord and review resuscitations and use a pressure sensor/monitor device during CPR. All events where chest compressions (CC) were performed under videorecorded conditions with the monitor device in use were eligible for inclusion. Events where real-time feedback from monitoring devices for CC was available were excluded (ages > 8). Data on CPR performance was collected by a combination of video review and monitor device; CC rate and depth and ventilation rate were extracted in time periods corresponding to individual CPR providers. Data on verbal prompts (time, who gave prompts, what prompt consisted of) were identified during video review.

Results:
There were 21 cases with total 182 providers included in database during study periods (infants: n=15, children: n=6). Verbal prompts for compression rate and depth were given in 14/21 (67%) of cases. 19/80 (24%) came from the resuscitation leader; 32/80 (40%) and from a CPR coach. 7 (3.9%) providers doing CC watched ZOLL monitor for feedback. Appropriate verbal prompts for CC rate were given to 4.2 % of providers in infants and 8.8 % in children (p=0.024). And 9.2% in infants and 10.5 % in children (p=0.064) were given to providers for CC depth. After adjusting by confounders, there weren’t any significant differences between age groups for both CC rate: OR1.22 (95%CI 0.49-3.05, P=0.670) and depth: OR 2.82 (95%CI 0.73-10.9, P=0.134).

Conclusions:
Verbal prompts frequency for CC rate and depth during pediatric CPR was described. There weren’t any significant differences between infants and children under 8 years old.
Abstract 275: Arterial Hyperoxia Exposure and Survival Among Resuscitated Patients With Out-of-Hospital Cardiac Arrest. Jaam-ohca Registry in Japan
Authors: Kiguchi Takeyuki , Kitamura Tetsuhisa , Kobayashi Daisuke , Nishiyama Chika , Fujimi Satoshi , Kawamura Takashi , Iwami Taku
Published: July 2021

Background:
The effect of hyperoxia for outcomes in resuscitated patients with out-of-hospital cardiac arrest (OHCA) is still controversial.

Objective:
To assess the relationship between the post-ROSC hyperoxia exposure volume (HEV) and survival among resuscitated OHCA patients.

Methods:
The JAAM-OHCA Registry was a multicenter prospective observation using the OHCA database obtained from 73 critical care medical centers in Japan, and the study period were between June 2014 and December 2015. In this study, patients who sustained a cardiac arrest in a prehospital setting, for whom resuscitation was attempted, and who were then transported to participating institutions were included. Patients receiving extracorporeal cardiopulmonary resuscitation and who was dead in emergency room were excluded. Arterial blood gases were sampled on hospital arrival, ROSC, ICU admission, and at least 24-hours post-ROSC. In addition to the 4 sampling times mentioned above, arterial blood gases were sampled, as and when required. Hyperoxia was defined as a PaO2 value of >=300 mm Hg. Hyperoxia exposure time (HET) was defined as the time of a sustained PaO2 value of >=300 mmHg, and hyperoxia excess level (HEL) was defined as the highest PaO2 level from hospital arrival to 24-hours post-ROSC. HEV was calculated by HET*HEV/2. Primary outcome was one-month survival. Multivariable logistic regression adjusting for age, sex, initial shockable rhythm, bystander witness, bystander CPR, time from call to hospital arrival, tracheal intubation, and targeted temperature management was performed to assess the association between HEV and survival.

Results:
A total of 1751 patients were included and 414 (23.6%) had hyperoxia. Among the hyperoxia patients, survival gradually decreased from 50.0% to 44.2% as HEV increased. The adjusted odds ratio of minimum HEV groups or maximum HEV groups for one-month survival compared with non-hyperoxia group was 2.50 (95% confidence interval [CI], 1.33-4.70) and 1.16 (95% CI, 0.62-2.18), respectively.

Conclusions:
Among resuscitated OHCA patients, excessive amounts of HEV was associated with decreased one-month survival.
Abstract 276: Impact of Skin Color on Accuracy of Capillary Refill Time Measurement by Pulse Oximeter
Authors: Nickel Amanda , Jiang Shen , Napolitano Natalie , Saeki Kota , Hirahara Hideaki , Nadkarni Vinay , Nishisaki Akira
Published: July 2021

Capillary refill time(CRT) is a non-invasive method to assess tissue perfusion, routinely performed in pediatric practice. Current methods to measure CRT have limitations in objectivity and reproducibility. The measurement depends on clinician’s assessment. New analytic approach using pulse oximeter waveform has been developed.

Hypothesis:
CRT measured by pulse oximeter device and clinicians(critical care/anesthesiologist attending physicians) were different across skin color and finger thickness.

Method:
Children(1-12 yr) with different skin color tones (Fitzpatrick scale 1-2:fair, 3-4:medium, 5-6:dark) were recruited. Subjects were randomized to a pulse oximeter either on index/middle finger, and had a total 10 CRT measurements (5 with device, 5 with clinician’s visual assessment, alternating). Waveform analysis was performed with quick compression and release on the pulse oximetry device by clinician. The difference between device and clinician measured CRT was calculated. ANOVA for difference in CRT across 3 skin color categories and across 4 finger thickness.

Result:
64 subjects(skin color fair 33, medium 16, dark 15) were recruited (median age 72 m, IQR 42-123m). Out of 640 CRT measurements, 300 pairs had measurable CRTs in both device and clinician. Based on clinician’s measurement, 114 CRTs were >2s and 26 CRTs > 4s. The overall CRT difference was mean 0.97±1.32s. The CRT difference by skin color was fair 0.86±1.35s, medium 0.90±1.31s, dark 1.26±1.22s, p=0.095. Pearson correlation coefficient was all 0.49 (fair 0.31, medium 0.67, and dark 0.41, all p<0.001). There was no significant difference in CRT difference among 4 finger thickness categories(thin to thick); 1.21±1.48s, 0.94±1.48s, 1.12±1.20s, 0.75±1.20s, p=0.108.

Conclusion:
The difference between device and clinician measured CRT did not vary across the different patient skin color or finger thickness. Device measured CRT may be a helpful indicator for peripheral perfusion.
Abstract 277: Prediction of Return of Spontaneous Circulation: Comparison of Cerebral Oximetry and End Tidal CO
2
Authors: Engel Thomas W. , Thomas Craig , Medado Patrick , Reed Brian , O’Neil Brian J
Published: July 2021

Background:
Predicting the outcome of a cardiac arrest (CA) is exceedingly difficult. Previous literature has identified end tidal CO
2
(ETCO
2
)

as a reasonable predictor of both return of spontaneous circulation (ROSC) and futility of resuscitation. Cerebral Oximetry (CerOx) measures the regional O
2
saturation of the frontal lobes of the brain utilizing non-invasive near infrared spectroscopy and has been correlated with cerebral oxygenation.

Objectives:
The objective of this study is to compare measurement of ETCO
2
and CerOx to predict ROSC during both out of hospital cardiac arrests (OHCA) and emergency department cardiac arrests (EDCA).

Methods:
We conducted an IRB approved, prospective study on a convenience sample of patients suffering from OHCA and EDCA. Patients were monitored with ETCO
2
and CerOx simultaneously while CPR was being performed in the ED. All patients were evaluated to predict ROSC by six parameters utilizing area under the curve (AUC) values. Data was analyzed using logistic regression modeling. AUCs were compared using the Delong, Delong, and Clarke-Pearson method.

Results:
Overall, we analyzed 176 patients. The mean age was 62.3 ± 14.4 . 116 (66.7%)were witnessed arrest with 93 (53.8%) having received immediate CPR. The average downtime from EMS call to ED arrival was 39 minutes. The initial rhythm in these patients was 56 (31.8%) asystole, 49 (27.8%) PEA, 45 (25.6%) VF/VT, and non-shockable rhythm in 26 (14.8%) . ROSC was achieved in 46 (26.1%) of patients. The analysis of the individual variable prediction of ROSC, revealed: first value [CerOx AUC = 0.554 p = 0.1143 ; ETCO
2
AUC = 0.533, p = 0.3981], maximum value [CerOx AUC = 0.778 p < 0.0001; ETCO
2
AUC = 0.616 p = 0.0849 ], trend over the last 5 minutes [CerOx AUC = 0.821 p < 0.0001 ; ETCO
2
AUC = 0.744 p = 0.7354 ], delta from first to last value [CerOx AUC = 0.859 p < 0.0001 ; ETCO
2
AUC = 0.734 p = < 0.0001 ], average value of the penultimate minute of resuscitation [CerOx AUC = 0.814 p <0.0001 ; ETCO2 AUC = 0.759 p = 0.0003 ], and average value of the final minute of the resuscitation [CerOx AUC = 0.886 p < 0.0001 ; ETCO2 AUC = 0.770 p = 0.0001}.

Conclusion:
Our data shows that both ETCO2 and rSO2 are good predictors of ROSC. We found CerOx superior to ETCO
2
in predicting ROSC.
Abstract 278: A Randomized, Blinded Trial of 100% Oxygen vs. Room Air During Cardiopulmonary Resuscitation in a Large Animal Model of Pediatric Cardiac Arrest
Authors: Marquez Alexandra M , Morgan Ryan W , Karlsson Michael , Ko Tiffany S , Landis William P , Mavroudis Constantine D , Starr Jonathan , Lin Yuxi , Boorady Timothy , Devarajan Mahima , Nadkarni Vinay , Berg Robert A , Licht Daniel J , Sutton Robert M , Kilbaugh Todd J
Published: July 2021

Introduction:
Guidelines recommend CPR with 100% oxygen, but its effect on the pediatric brain is unknown. Hyperoxia during CPR may lead to significant oxidative injury from mitochondrial-derived reactive oxygen species (mtROS).

Hypothesis:
We hypothesized that swine receiving 100% FiO2 during CPR would have similar survival outcomes and mitochondrial oxidative phosphorylation, but would have cerebral hyperoxia and increased mtROS compared to those resuscitated with room air (21%).

Methods:
Four-week-old female piglets (n=25) underwent 7 minutes of asphyxia followed by randomization and blinding to CPR with 100% (n=10) or 21% FiO2 (n=10) during CPR through 10 minutes post-ROSC, at which point FiO2 was set to 21% in all animals. Sham n=5. Brain tissue oxygen tension (PbtO2), cerebral blood flow (CBF), and invasive hemodynamics were continuously monitored. Survivors received 4 hours of post-ROSC care, whereupon cortex and hippocampus were obtained for mitochondrial analysis. ROS were measured simultaneously with mitochondrial respirometry measurements, utilizing high resolution respirometry with concomitant fluorometric analysis. Data are described as median [IQR]. Groups were compared using Fisher’s exact test, Kruskal-Wallis test, Wilcoxon rank-sum, and a generalized estimating equation regression model.

Results:
The two oxygen strategy groups did not differ in 1) systemic, coronary, or pulmonary hemodynamics or 2) cerebral blood flow at baseline, during asphyxia, during CPR, or post-ROSC. Survival was the same in each group (8/10 vs 8/10, p=1.0). PbtO2 was higher with 100% than 21% during CPR (point estimate +54.9±26.7, p=0.04) and during the first ten minutes post-ROSC (point estimate +505±41.4, p<0.001). There were no differences in maximal oxidative phosphorylation in either cerebral cortex or hippocampus between groups. In cortex, mtROS was higher with 100% compared to 21% during maximal oxidative phosphorylation (0.283 [0.275,0.290] vs 0.224 [0.205,0.239] H2O2 pmol/(s*ml), p<0.03).

Conclusions:
Compared to 21% FiO2, provision of 100% FiO2 during CPR confers no difference in survival and is associated with cerebral hyperoxia and increased mtROS generation.
Abstract 281: Is Cerebral Regional Oxygen Saturation (rSO
2
) Useful as a Physiological Monitoring Tool During CPR in Pre-Hospital Settings? An Analysis of 72 Cases in Osaka, Japan
Authors: Sakai Tomohiko , Shiozaki Tadahiko , Ohnishi Mitsuo , Takegawa Ryosuke , Tachino Jotaro , Shimazu Takeshi
Published: July 2021

Introduction:
Simplified monitoring system of regional cerebral oxygen saturation (rSO
2
) is a non-invasive technology for cerebral perfusion, but continuous changes of cerebral rSO
2
values among OHCA patients in pre-hospital settings have been insufficiently investigated.

Methods:
We recently developed a portable rSO
2
monitoring system that is very small (170х100х50mm in size and 600g in weight) and can use in pre-hospital settings. The sensor pad is attached to the patient’s forehead by the emergency-medical-service (EMS) personnel, and it can monitor cerebral rSO
2
immediately and continuously during CPR, from June 2013 through May 2018 in Osaka City, Japan.

Results:
We collected continuous changes in cerebral rSO
2
values for 72 OHCA patients during CPR by EMS personnel. Sixty-six cases were measured rSO
2
before ROSC and 6 cases were measured after ROSC. According to the analyses of continuous changes in rSO
2
values of 66 cases, two patterns of changes in cerebral rSO
2
values were found as follows; Type 1: Increasing rSO
2
type (n=30). Measured rSO
2
increased gradually during CPR or after ROSC. Type 2: Not increasing rSO
2
type (n=36) Measured rSO
2
did not increase during CPR. And we found out two phenomena of changes in cerebral rSO
2
values were found as follows; Phenomenon 1: Dropping rSO
2
type (n=3). Measured rSO
2
dropped after confirmation of ROSC or before arrest, which suggests that the re-arrest or arrest occurred during monitoring. Phenomenon 2: Initially decreasing rSO
2
type (n=6). Measured rSO
2
decreased gradually despite performing CPR by EMS personnel, which suggests that short time has passed after arrest.

Conclusion:
We measured continuous changes in cerebral rSO
2
values among 72 patients with OHCA pre-hospital settings and found the 2 patterns and 2-specific phenomena regarding continuous changes in rSO
2
values. Furthermore, it is needed to collect many cases to establish resuscitation strategies for OHCA by using cerebral rSO
2
monitoring.
Abstract 282: Relation Between the Post-Cardiac Arrest Cerebral Regional Saturation of Oxygen and Outcomes
Authors: Chang Chih-Heng , Su Pei-I , Tsai Min-Shan , Chen Wei-Ting , Chang Wei-Tien , Chen Wen-Jone , Huang Chien-Hua
Published: July 2021

Background:
Outcome prognostication is still challenging in post-cardiac arrest patients although many methods have been introduced. Cerebral regional saturation of oxygen (crSO2) is one method that might relate to tissue viability, but its correlation with outcome of post-cardiac arrest patient remains unclear. We assessed the hypothesis that there might be significant correlation between the crSO2 level and the pre-cardiac arrest state and the prognosis of post-cardiac arrest patients.

Methods:
Adult post-cardiac arrest patients who received targeted temperature management (TTM) as our ICU protocol and who were under monitoring of frontal crSO2 by cerebral near-infrared spectroscopy (NIRS) were included. TTM was divided into phase 1 induction, phase 2 maintenance, and phase 3 rewarming. We recorded the value of frontal crSO2 every hour, and further data calculation (minimal, maximal, average, difference between phases) were done. Demographic and resuscitation variables, including pre-arrest CPC status were recorded. The primary outcome was the relation between crSO2 and mortality outcomes. The Mann-Whitney test was applied for analysis.

Results:
There were 28 post-cardiac arrest adult patients included since Nov. 2015 to Nov. 2017. In-hospital mortality rate were 53.6 % (15/28). For all patients, we found no significance between any crSO2 data of each phase and in-hospital mortality or neurological outcome when discharge. The median level of both side maximal average crSO2 at phase 3 in mortality group were 59 and was 62 in survival group, p= 0.354. Interestingly, the median level of both side maximal average crSO2 at phase 3 were 66 in the patients of pre-arrest CPC 1 and was 56 in pre-arrest CPC 2 (P=0.0328). In pre-arrest CPC 2 group, the both side maximal average crSO2 in phase 3 was significant lower in the in-hospital mortality group (median level 50 vs. 58, p=0.029).

Conclusion:
The crSO2 levels among different TTM phases were not significant correlated with mortality or neurological outcome. However, the pre-arrest CPC status may correlate with the crSO2. In patients with pre-arrest CPC 2, crSO2 had significant correlation with mortality. The crSO2 recorded by NIRS might be correlated to outcome in selected post-cardiac arrest patients.
Abstract 283: Estimating the Impact of Bystander Interventions on Disability-Adjusted Life Years Following Adult Out-of-Hospital Cardiac Arrest in the United States
Authors: Coute Ryan A , Nathanson Brian , Panchal Ashish , Kurz Michael , Haas Nathan , McNally Bryan , Neumar Robert , Mader Timothy
Published: July 2021

Background:
Disability-adjusted life years (DALY) are a common public health metric used to consistently estimate and compare disease burden. The impact of bystander interventions on DALY following out-of-hospital cardiac arrest (OHCA) is unknown. Our objective was to estimate the effect of bystander CPR (B-CPR) and bystander AED (B-AED) application on DALY following OHCA in the United States (U.S.).

Methods:
DALY were calculated as the sum of years of life lost (YLL) and years lived with disability (YLD) using all adult non-traumatic EMS-treated OHCA from the national CARES database for 2016. A multivariable linear regression model was constructed for effect estimation with DALY values as the outcome and standard Utstein variables as independent variables. Marginal effect estimates for B-CPR and B-AED were derived in models that used all independent variables as main effects. A sensitivity analysis included interaction terms. The analysis for B-CPR was limited to bystander witnessed events. The B-AED analysis was limited to public OHCA events. The marginal effects on DALY were used to derive national estimates of life years saved.

Results:
A total of 19,324 OHCA cases met study inclusion criteria. The provision of B-CPR was associated with an absolute mean decrease of -0.36 DALY; 95% CI (-0.44, -0.27) per OHCA, when compared to cases without B-CPR (p<0.001). When extrapolated to a national level, the cumulative effect of B-CPR resulted in an estimated 25,317 healthy life years saved; 95% CI (19,342, 31,292). Bystander AED application was associated with a mean reduction of -0.32 DALY; 95% CI (-0.41, -0.23) per OHCA (p<0.001). The cumulative effect of B-AED application was an estimated 22,755 healthy life years saved 95% CI (16292, 29218). From a regression model that incorporated interaction effects, B-CPR with defibrillation was associated with an estimated 74,758; 95% CI (58511, 91004) healthy life years saved.

Conclusion:
Bystander interventions are associated with a decrease in DALY following adult OHCA. These results highlight the importance of national bystander CPR and AED education and surveillance.
Abstract 284: Association of Neurological Outcome and Survival With Interventions by Bystander and Emergency Medical Service for Unwitnessed Out-of-Hospital Cardiac Arrest Patient; Results From the JCS-ReSS Study
Authors: Okamoto Chisato , Tahara Yoshio , Hirayama Atsushi , Yasuda Satoshi , Noguchi Teruo , Nishimura Kunihiro , Yonemoto Naohiro , Shimokawa Hiroaki , Nonogi Hiroshi , Nagao Ken
Published: July 2021

Introduction:
Although studies have shown that bystander cardiopulmonary resuscitation (CPR) in witnessed out-of-hospital cardiac arrest (OHCA) is associated with better neurological prognosis, whether bystander and Emergency Medical Service (EMS) interventions are associated with prognosis in unwitnessed OHCA patients is not fully elucidated. We aimed to investigate the prognostic importance of bystander and EMS interventions among unwitnessed OHCA patients in Japan.

Methods and Results:
This study was a nation-wide population-based observational study of OHCA in Japan from 2011 to 2015 based on data from the All-Japan Utstein Registry. The outcome measures were neurological outcome and survival at 30-day. The neurologically favorable outcome was defined as Glasgow-Pittsburgh cerebral performance category score 1 or 2. First, to investigate the effectiveness of bystander interventions, we included 105,655 unwitnessed cardiogenic OHCA patients (aged 18-80 years). Of these, 1,614 (1.5%) showed neurologically favorable outcome and 3,273 (3.1%) survived at 30-day. Multivariate logistic regression analysis adjusting for age, sex, geographical region, year and EMS response time showed that bystander CPR was associated with neurologically favorable outcome (adjusted odds ratio [aOR] 1.49, 95% CI 1.35-1.65, P<0.001). Additionally, to investigate the effectiveness of EMS interventions for patients with non-shockable rhythm, we examined 43,342 patients who were performed public CPR and had the initial rhythm of pulseless electrical activity (PEA) or asystole. Of these, 101 (0.2%) showed neurologically favorable outcome and 453 (1.0%) were survival at 30-day. Advanced airway management by EMS was negatively associated with neurologically favorable outcome (aOR 0.55, 95% CI 0.37-0.81, P=0.003) and administration of epinephrine by EMS was associated with survival (aOR 2.35, 95% CI 1.89-2.92, P<0.001).

Conclusions:
Among unwitnessed OHCA patients, bystander CPR was associated with neurologically favorable prognosis. For unwitnessed OHCA patients with non-shockable rhythm, epinephrine administration was associated with survival, but advanced airway management was negatively associated with neurological outcome.
Abstract 288: High Mobility Group Box 1 (HMGB1) is Involved in the Physiopathology of Post-Cardiac Arrest Syndrome
Authors: Boissady Emilie , El Hedjaj Cynthia , Kohlhauer Matthias , Ghaleh Bijan , Tissier Renaud
Published: July 2021

Introduction:
After cardiac arrest, a sepsis-like syndrome is observed and contributes to poor prognosis.

Hypothesis:
This syndrome could be provoked by the massive release of Damage Associated Molecular Patterns (DAMP). Our aim was to investigate the role of the High mobility group box 1 (HMGB1), a well-characterized nuclear DAMP, in an experimental model of cardiac arrest.

Methods:
Rabbits were anesthetized and submitted to 10 min of ventricular fibrillation. After resuscitation, they either received an administration of the inhibitor of HMGB1 release glycyrrhizin (4 mg/kg i.v.. (GL group, n=6), or saline (5 ml, i.v.; CT group, n=6). Two additional groups received glycyrrhizin (n=4) or saline (n=4) alone without cardiac arrest (Sham groups). Blood samples were withdrawn to evaluate the kinetics of HMGB1 release. After awakening, survival and neurological dysfunction were evaluated during 3 days. Animals were then euthanized and brain histologic damages were assessed (fluorojade-C staining).

Results:
In the Sham groups, glycyrrhizin did not modify hemodynamic nor clinical parameter as compared to saline. In the CT group, HMGB1 blood levels increased since 30 min after cardiac arrest and remained elevated until the end of the follow-up. This increase in HMGB1 concentrations was significantly attenuated in GL vs CR (18±1 vs 29±5 and ng/ml at 30 min after cardiac arrest, respectively). Neurological dysfunction score or survival were not significantly improved in GL vs CT (e.g., survival = 50 vs 33 % at day 3 in GT vs CT group). However, fluorojade C staining showed a dramatic attenuation of degenerating neurons in GL vs CT groups in all brain regions (e.g., 7±3 vs 32±10 neurons/field in cortex, respectively).

Conclusion:
HMGB1 played a key role in early inflammation and promoted neuronal death after cardiac arrest. Its inhibition alone does not provide sufficient benefits to improve the clinical outcome. It emphasizes the importance of other contributors, beyond inflammation and neurons cell death. Adjunction of HMGB1 inhibitors to other therapies could still be of interest.
Abstract 289: Relationship Between Myocardial Glycogen Concentrations and Amplitude Spectrum Area During Ventricular Fibrillation in a Rat Model of Cardiac Arrest and Resuscitation
Authors: Hu Qiaohua , Fang Xiangshao , Yang Zhengfei , Tang Wanchun
Published: July 2021

Introduction:
Myocardial high-energy phosphate (ATP) levels has been demonstrated correlating with amplitude spectrum area (AMSA) during ventricular fibrillation (VF) in previous experimental studies. In the present study, we investigated the relationship between AMSA and myocardial glycogen content (MGC),which can be used to reflect the status of myocardial energy metabolism indirectly during VF.

Hypothesis:
AMSA has a significantly correlation with MGC during VF in a rat model of cardiac arrest and resuscitation.

Methods:
Twenty male Sprague-Dawley rats weighing 350 to 450 g were utilized and randomized into two groups: VF and cardiopulmonary resuscitation (CPR) (VF/CPR group) or untreated VF (VF group). 5 mins of CPR was performed after 10 mins of untreated VF in VF/CPR animals. Amplitude spectrum area (AMSA) at VF 5, 10 and 15 mins were calculated from ECG signals. The rats’ hearts were quickly removed at the predetermined time of 15 min for determines the glycogen contents by the anthrone reagent method using a glycogen assay kit.

Results:
AMSA values significantly decreased during untreated VF in both VF and VF/CPR animals. However, much greater AMSA during CPR was achieved by the VF/CPR group in comparison with the VF group. There was a marked and negative relationship between AMSA at VF 15 min and MGC. (Figure).

Conclusion:
MGC was significantly and negatively correlated with AMSA during VF in this rat model of cardiac arrest and resuscitation. In clinical practice, we can use AMSA to reflect the state of myocardial energy metabolism indirectly. Figure The changes of AMSA and relationship between AMSA and glycogen content:(A) The change of AMSA between VF/CRP group and VF group;(B) The relationship between AMSA and glycogen content. AMSA, amplitude spectrum area; V, time of ventricular fibrillation;
#
p
<0.05 vs. V4.
Abstract 29: A Neighborhood Local Volunteer Response Network Improves Response Time for Cardiac Arrest
Authors: Kern Karl B , Newton Carter , Wunder Charles " , Colberg Thomas P , Slepian Marvin J
Published: July 2021

Background:
Minutes are crucial in the treatment of out-of-hospital cardiac arrest (CA). Immediate chest compressions and early defibrillation are keys to good outcomes. Local neighborhood volunteer (vol) response programs may decrease delays to early CPR and AED use. We hypothesized that a coordinated effort of alerting trained neighborhood vols simultaneously with 911 activation of professional EMS providers would provide earlier CPR and defibrillation in such communities.

Methods:
We developed a program of simultaneously alerting CPR and AED trained neighborhood vols and the local EMS system for cardiac arrest events in a retirement community in Southern Arizona, encompassing approximately 17,300 homes and 21,500 residents. EMS services are provided by 5 stations within the community boundaries. Within a single housing development neighborhood, 9 vols and the closest EMS station were involved in 3 days of mock CA notifications (total of 12 different alerts at various times during daytime hours were sent). This provided a total of 120 response opportunities, 12 for EMS and 108 for vols. The distance to the mock event and the time from alert to arrival were recorded and compared.

Results:
In the selected 55+ neighborhood, the two groups differed significantly in both distance to the mock cardiac arrest event and in response times. The volunteers average 0.33±0.19 miles from the mock CA incidences while the closest EMS station was 3.3 miles from the tested neighborhood (p<0.0001). Response times (time from call to arrival) were also different. The earliest Vol arrived at 1min 30sec±48sec*, 2 Vols & AED at 1min 38 sec±53sec*, all arriving Vols at 3min 23 sec*, and EMS at 7min 20 sec±1min 13sec (*p<0.0001 vs EMS).

Conclusion:
When the neighborhood volunteers in this testing period were geographically closer to the mock CA event, they arrived significantly sooner to the scene than did the EMS service. The mean time of arrival for at least 2 vols with an AED was 5 min 42 sec faster than the professional rescuers. The implications for such a time saving could be as much as a 240% increase (25% to 85%) in survival for those with shockable rhythms.
Abstract 290: Fibroblast Growth Factor 21 After Out-of-Hospital Cardiac Arrest
Authors: Pekkarinen Pirkka T , Skrifvars Markus B , Jakkula Pekka , Lievonen Ville , Albrecht Laura , Loisa Pekka , Tiainen Marjaana , Pettilä Ville , Reinikainen Matti , Hästbacka Johanna
Published: July 2021

Introduction:
Fibroblast growth factor (FGF) 21 is a novel marker of mitochondrial and cellular stress. Due to the pivotal role of mitochondria in oxidative metabolism and oxidative stress we tested the hypothesis that FGF 21 would reflect the severity of hypoxia-reperfusion injury after cardiac arrest.

Methods:
We measured serum concentration of FGF 21 upon ICU admission and 24, 48 and 72 hours after out-of hospital cardiac arrest (OHCA) in 112 patients. All patients had ventricular fibrillation/tachycardia (VF/VT) as initial rhythm and received targeted temperature management (TTM) of 33 or 36 °C for 24 hours. We defined 6-month Cerebral Performance Category (CPC) 1-2 as good and 3-5 as poor neurologic outcome. We used samples from 40 age- and gender-matched non-critically ill emergency room patients as controls. Group differences were assessed with the Mann Whitney U test and temporal differences with Friedman’s ANOVA and Wilcoxon signed ranks test.

Results:
The median (inter-quartile range, IQR) FGF 21 concentration at ICU admission was 790 (370-1600) pg/ml and the peak value was 1200 (460-2500) pg/ml at 48 hours. Compared to the ICU admission values, the concentrations in control samples [250 (94-910) pg/ml] were significantly lower (P < 0.001). The ICU admission FGF 21 levels were higher in patients with poor neurologic outcome (P = 0.04) and they correlated weakly with the time from collapse to return of spontaneous circulation (Spearman’s rho 0.23). Serum FGF 21 levels changed over time (P < 0.001). Figure 1 presents serum FGF 21 median levels with IQR (box) and 10-90 percentiles (whiskers).

Conclusion:
Patients after OHCA have elevated FGF 21 levels after successful resuscitation. Higher ICU admission FGF 21 levels associate with poor 6-month neurologic outcome.
Abstract 291: Galectin-3 as a Risk Predictor of Short-Term Mortality in the Resuscitated Cohorts of Out-of-Hospital Cardiac Arrest
Authors: Al Jebaje Zaid , Sharma Umesh C , Mosleh Wassim , Chaudhari Milind
Published: July 2021

Introduction:
Out of Hospital Cardiac Arrest (OHCA) is a common and catastrophic manifestation of multiple cardiac and non-cardiac illnesses. Recent studies showed increase in survival rate, reaching to about one third of those who suffer a bystander witnessed OHCA with a shockable rhythm; yet biomarkers to predict outcomes in this group is still missing.

Hypothesis:
We tested the hypothesis that serum galectin-3, alone or together with galectin-3 binding protein (G3BP),brain natriuretic peptide (BNP) and troponin, can predict the risk of early (30-day) mortality in ResCOHS.

Methods:
ResCOHS prospective multicenter pilot study enrolled 117 patients with aborted out-of-hospital cardiac arrest, and 10 healthy volunteers. Transthoracic Echocardiogram was performed for cardiac morphology and function. Serum levels of galectin-3, G3BP, BNP and peak troponin were analyzed. Patients were prospectively followed up for 30-days to determine all-cause in-hospital mortality.

Results:
Among the ResCOHS, patients who died within 30-days had higher BNP and galectin-3 levels, with no differences in the G3BP, peak troponin, CK and CK-MB levels. Receiver operating characteristic analysis for mortality prediction showed that, for 30-day prognosis, galectin-3 had the greatest area under the curve (AUC) at 0.764 (p = 0.001), whereas G3BP, BNP and troponin had an AUC of 0.518 (p = 0.735), 0.759 (p = 0.001)and 0.540 (p=0.460) respectively. In a multivariate logistic regression analysis, an elevated level of galectin-3 was the strongest independent predictor of 30-day mortality (odds ratio 1.04, p = 0.002). The Kaplan-Meier analyses showed that the combination of an elevated galectin-3 with NT-proBNP was a better predictor of mortality than either of the 2 markers alone.

Conclusions:
In the ResCOHS, higher serum galectin-3 levels are associated with increased chances of death within 30-days of the first episode of cardiac arrest. These findings have implications to target specific therapies to those at the greatest risk of mortality after OHCA.
Abstract 292: TRPA1 Promoting Myofibroblast Differentiation Mediate Pressure Overload-Induced Cardiac Fibrosis
Authors: Li Shuang , Han Dong , Yang Dachun
Published: July 2021

Background:
Hypertensive ventricular remodeling is a common cause of heart failure. Activation and accumulation of cardiac fibroblasts is the key contributors to this progression. Our previous studies indicate that transient receptor potential ankyrin 1 (TRPA1), a Ca
2+
channel necessary and sufficient, play a prominent role in ventricular remodeling. However, the molecular mechanisms regulating remain poorly understood.

Methods:
We used TRPA1 agonists cinnamaldehyde (CA) pretreatment and TRPA1 knockout mice to understand the role of TRPA1 in ventricular remodeling of hypertensive heart. We also examine the mechanisms through gene transfection and in vitro experiments.

Results:
TRPA1 overexpression fully activated myofibroblast transformation, while fibroblasts lacking TRPA1 were refractory to transforming growth factor β (TGF-β) -induced transdifferentiation. TRPA1 knockout mice showed hypertensive ventricular remodeling reversal following pressure overload. We found that the TGF-β induced TRPA1 expression through calcineurin-NFAT-Dyrk1A signaling pathway via the TRPA1 promoter. Once induced, TRPA1 activates the Ca
2+
-responsive protein phosphatase calcineurin, which itself induced myofibroblast transdifferentiation. Moreover, inhibition of calcineurin prevented TRPA1-dependent transdifferentiation.

Conclusion:
Our study provides the first evidence that TRPA1 regulation in cardiac fibroblasts transformation in response to hypertensive stimulation. The results suggesting a comprehensive pathway for myofibroblast formation in conjunction with TGF-β, Calcineurin, NFAT and Dyrk1A. Furthermore, these data indicate that negative modulation of cardiac fibroblast TRPA1 may represent a therapeutic strategy against hypertensive cardiac remodeling.
Abstract 296: Early Mitochondrial Gene Regulation in Pediatric Cardiac Arrest
Authors: Hefti Marco M , Senthil Kumaran , Karlsson Michael , Ehinger Johannes , Mavroudis Constantine D , Nadkarni Vina M , Berg Robert A , Sutton Robert M , Morgan Ryan W , Kilbaugh Todd J
Published: July 2021

Introduction:
Cerebral mitochondrial dysfunction is thought to play a role in the post-cardiac arrest syndrome, propagating secondary morbidity and mortality after return of spontaneous circulation (ROSC).

Hypothesis:
Based on our previous studies showing a persistent decrease in oxidative phosphorylation (particularly Complex I) and increased mitochondrial fission in a swine model of in-hospital cardiac arrest, we hypothesized that nuclear and mitochondrial genes related to respiratory function would be downregulated and genes promoting mitochondrial fission would be upregulated four hours post-ROSC.

Methods:
One-month old piglets were subjected to sham anesthesia (n=5) or asphyxial cardiac arrest (n=6; 7 minutes of asphyxia followed by induction of ventricular fibrillation) and treated with 10-20 minutes of AHA guideline-based CPR followed by four hours of standardized post-arrest management and humane euthanasia. RNA was extracted from flash-frozen sections of cerebral cortex using a QIAsymphony robot and sequenced on an Illumina HiSeq. Reads were aligned to the reference (SusScrofa11.1 and NC_012095) using STAR and quantified using subreads. Normalization and differential expression analysis were performed using DESeq2 with RNA quality, intra-arrest and post-ROSC physiologic variables as covariates. All p values were adjusted for multiple comparisons (Benjamini-Hochberg) with a significance cutoff of 0.05.

Results:
Compared to sham, cardiac arrest animals demonstrated reduced expression of multiple components of the respiratory chain, including NDUFA5 (2.4-fold, p<0.001) and NDUFC1 (2.0-fold, p=0.02), key components of Complex I. Components of Complex III (UQCRB, UQCRH) and Complex IV (COX1, COX7C, COX7A2, COX7B) were also downregulated. Dynamin-2 (DNM2), which increases mitochondrial fission, was upregulated (2.3-fold, p=0.005). There was also differential expression of inner membrane solute channel expression (SLC44A1, SLC25A48 and SLC25A16).

Conclusions:
Multiple components of the mitochondrial respiratory chain are downregulated 4 hours post-ROSC in the brain, including key components of Complex I with concurrent upregulation of the mitochondrial fission protein dynamin-2.
Abstract 297: Mitochondrial Cyclophilin D as a Target for Cardiac Arrest Resuscitation: Insight From Knockout Mice
Authors: Cour Martin , Jahandiez Vincent , Pillot Bruno , Ovize Michel , Argaud Laurent
Published: July 2021

Introduction:
Solid evidence support that cyclophilin D (CypD), which promotes the lethal opening of the mitochondrial permeability transition pore (mPTP), is involved in the pathogenesis of ischemia-reperfusion injury, including after cardiac arrest (CA). However, a recent trial (CYRUS study) showed that cyclosporine A, the reference mPTP inhibitor (via its binding to CypD), failed to limit the severity of the post-CA syndrome, raising the question of whether CypD is a viable target for protection in CA. Therefore, we aimed to reassess the role of CypD in CA resuscitation using CypD knockout mice.

Hypothesis:
We hypothesized that CypD is a target of interest for CA treatment.

Methods:
Wild type (WT) or CypD knockout (CypD
-/-
) mice underwent 5 minutes of asphyxia-induced CA followed by cardiopulmonary resuscitation. Additional mice were treated with therapeutic hypothermia (32-34°C) as the gold standard intervention to confer protection after CA. In a first set of experiments, animals were euthanized after 2 hours of reperfusion for biochemical and mitochondrial assays. In a second set of experiments, animals were observed for up to 7 days for survival and neurological status.

Results:
All animals underwent similar durations of asphyxia before CA. Rate of ROSC was significantly higher in CypD
-/-
group (with a shorter cardiac massage duration) compared to WT group (p<0.05). CA-induced myocardial dysfunction and increase in plasma levels of troponin were both attenuated by CypD deletion (p<0.05 versus WT) without additional benefits of hypothermia. CypD
-/-
mice exhibited significantly less brain damage than WT. CypD deletion prevented both CA-induced mPTP opening and respiration impairment in isolated brain mitochondria (p<0.05 versus WT). Short-term survival (24 hours) was significantly higher in CypD
-/-
than WT mice (p<0.05). Only therapeutic hypothermia significantly improved both short-term and neurological intact survival at day 7 after CA compared to WT (p<0.05).

Conclusions:
Our results suggest that CypD remains a potential major target to improve resuscitability and early but not long-term outcomes. Supplementary interventions, such as therapeutic hypothermia, are needed to enhance long-term recovery.
Abstract 299: Out-of-Hospital Cardiac Arrest: A 25 Years Registry
Authors: Cassuto Margot , Severin Armelle , Ursat Cecile , Ozguler Anna , Baer Michel , Loeb Thomas
Published: July 2021

Introduction:
For many years, organizations like American Heart Association (AHA) published guidelines for the management of Out-of-Hospital Cardiac Arrest (OHCA). Our Emergency Medical Service (EMS), in a catchment of 500,000 inhabitants, has registered all OHCA since 1993. The aim of this study was to describe evolution of the on scene return of spontaneous circulation (ROSC) after OHCA from cardio-vascular cause (CV) over the past years.

Methods:
Data were collected from an EMS registry since 1993. The study included adult patients with OHCA from CV. Collected data were evolution (death or ROSC), gender, age group (older than 15) and periods (1993-1999, 2000-2004, 2005-2009, 2010-2014, 2015-2017). The primary outcome was rate of on scene ROSC. Comparisons were performed with Chi-2 test and logistic regression.

Results:
The registry included 8761 adults with OHCA, 7165 (82.2%) of which had a CV. Mean age was 71.6 years old (SD 16.9), 58.7% were male. ROSC rate was 15.2%. ROSC increased from 10.3% before 2000 to 19.8% after 2015, addressing significantly all age groups except the oldest (figure 1). ROSC rate was 17% for men and 12% for women. Logistic regression results (adjusted and not) showed a greater chance of ROSC for younger patients (OR ranging from 2.1 for age group 60-74 until 4.3 for 16-29 age group, compared with ≥ 75 age group), if OHCA occurred recently (OR ranging from 1.5 for 2010-214 period to 2.6 for < 2000 period compared with ≥ 2015) and for males (OR=1.3).

Conclusion:
This study shows increase of ROSC after OHCA, mainly for younger age groups, during this last 25 years. This may be due to evolution of public awareness and medical practice according to guidelines. In addition, women did not benefit from this evolution as much as men did. In the future, as the "Go Red for Women" campaign, efforts to improve survival of OHCA should focus on women.
Abstract 30: Increasing the Uptake of Cardiopulmonary Resuscitation Training Within Australian Cardiac Rehabilitation Programs
Authors: Cartledge Susie , Bray Janet E , Stub Dion , Finn Judith , Neubeck Lis
Published: July 2021

Introduction:
Outpatient cardiac rehabilitation programs provide an ideal environment to deliver targeted cardiopulmonary resuscitation (CPR) training to cardiac patients and their family members. However, the prevalence of CPR training in Australian programs is low (24%). This study sought to identify the best strategy to implement CPR training into cardiac rehabilitation programs.

Hypothesis:
We hypothesise that coordinators who receive a higher level of education (information pack including two self-instructional CPR video training kits and a face-to-face education session) compared to those who only receive an information pack, will be more likely to incorporate CPR training into their cardiac rehabilitation programs.

Methods:
A two-arm randomised controlled implementation study is currently being conducted across Australia. One cardiac rehabilitation coordinator per cardiac rehabilitation program, where the program is not currently providing regular CPR training to patients and families, is eligible to participate. Coordinators will be randomised 1:1 to either receive an information pack or information pack plus face-to-face education session.

Results:
To date 23 coordinators (59% metropolitan programs, 41% rural programs) have been randomised. Few programs (19%) have previously offered CPR training and only 25% currently include information about CPR. Common barriers to incorporating CPR training into programs are time (71%), resources (67%) and a lack of awareness to include CPR training (24%). Motivations for including CPR training are driven by coordinators assessment that patients and families are interested in CPR training (81%). Implementation data will be presented including information on the level of implementation in addition to a sample of brief qualitative telephone interviews to further discuss enablers and barriers.

Conclusions:
Cardiac rehabilitation represents a logical location to provide targeted CPR training to high-risk cardiac groups at scale across Australia. This study will aid in better understanding how cardiac rehabilitation coordinators can be supported to enable more programs to incorporate CPR training.