Abstract 11243: Novel Peptide for Cardiopulmonary Resuscitation

Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Jing Li ◽  
Xiangdong Zhu ◽  
Matt Oberdier ◽  
Chunpei Lee ◽  
Misha Granado ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Therapeutic Hypothermia ◽  
Protective Effects ◽  
Ph Domain ◽  
Biologic Treatment ◽  
Hospital Arrival ◽  
Shockable Rhythm ◽  
Arterial Blood ◽  
Atp Generation ◽  
Neurologically Intact

Introduction: While effective for out-of-hospital cardiac arrest, therapeutic hypothermia can be difficult to timely implement clinically. No drugs exist for improving neurologically intact survival. We have developed a novel peptide (TAT-PHLPP) that inhibits PH domain and Leucine rich repeat Protein Phosphatases (PHLPP), leading to Akt activation and mimicking of the protective effects of therapeutic hypothermia without the need of physical cooling. Hypothesis: We hypothesize that when administered intravenously during CPR, TAT-PHLPP improves neurologically intact survival. Methods: We conducted parallel studies in mouse and swine models. In C57BL6 mice (n = 72), we induced a 8 or 12-min asystolic cardiac arrest with KCl, followed by initiation of CPR and blinded randomized administration of TAT-PHLPP (7.5 mg/kg) or saline placebo. The primary outcomes were 4-h and 5-day survival, mean arterial blood pressure (MAP) and cerebral blood flow (CBF). We assessed PHLPP-NHERF1 binding and glucose utilization (via pyruvate dehydrogenase (PDH) phosphorylation and ATP generation). In 16 swine, we induced 5 min of VF followed by ACLS with vest CPR and administered two doses of TAT-PHLPP or saline. Survival (24 h) and neurological function were assessed. Plasma biomarkers taurine and glutamate levels in mice were measured and validated in CA patients (n=68) with a shockable rhythm at the time of hospital arrival, 6, 24, 48, and 72 h post-hospital arrival. Results: In mice, compared to saline, TAT-PHLPP significantly improved 4-h and 5-day survival, increased post-ROSC MAP and CBF, inhibited PHLPP-NHERF1 binding, increased p-Akt, decreased p-PDH (increased activity) at 15 min post-ROSC, enhanced ATP generation in both heart and brain, and reduced plasma taurine and glutamate levels. In swine, TAT-PHLPP improved 24 h neurologically intact survival (1/9 in control vs. 6/7 with peptide, p < 0.01). In patients, taurine levels were higher in non-survivors (n=44) than survivors (n=24) at 6 h of post-hospital arrival (65.9 ± 34.8 vs. 45.6 ±23.7, p< 0.001). Conclusions: TAT-PHLPP has high translational potential as a first-of-class biologic treatment to reproduce critical outcomes of therapeutic hypothermia and improve cardiac arrest survival.

Abstract 48: Neurological Outcomes of Inpatient Cardiopulmonary Resuscitation in a University Hospital

2013 ◽  
Vol 6 (suppl_1) ◽  
Author(s):  
Lia M Thomas ◽  
Miguel Benavides ◽  
Pierre Kory ◽  
Samuel Acquah ◽  
Steven Bergmann
Keyword(s):  
Cardiac Arrest ◽  
Critical Care ◽  
Cardiopulmonary Resuscitation ◽  
Therapeutic Hypothermia ◽  
Cardiopulmonary Arrest ◽  
University Hospital ◽  
Neurological Dysfunction ◽  
Neurological Outcomes ◽  
Shockable Rhythm ◽  
Neurologically Intact

Background: Despite advances in out- of- hospital resuscitation practices, the prognosis of most patients after a cardiac arrest remains poor. The long term outcomes of patients successfully resuscitated from cardiac arrest are often complicated by neurological dysfunction. Therapeutic hypothermia has significantly improved neurological outcomes in patients successfully resuscitated from out- of- hospital cardiac arrests. The objective of this study was to look into the neurological outcomes in inpatients after successful cardiopulmonary resuscitation (CPR) in a university hospital setting. Methods: This was a retrospective observational study of 68 adult patients who experienced cardiac or respiratory arrest over an 18 month period at a metropolitan teaching hospital with dedicated, trained code teams. Arrests that occurred in the Emergency Department, Critical Care Units or Operating Rooms were excluded. Results: Of the 68 consecutive patients included in this study, 53% were resuscitated successfully. However, only 12 (18%) survived to discharge from the hospital and only 6 (10%) were discharged with intact neurological status. The initial survival was better in patients who received prompt CPR and in those with less co - morbidities. Pulseless electrical activity (PEA) or asystole were the most common rhythms (47% of the arrests). Most patients who survived and were neurologically intact had PEA (67%). We believe that most PEA arrests were more likely severe hypotension with the inability to palpate a pulse rather than true PEA. The mean time to defibrillation for all patients with an initial shockable rhythm (n=5) was 8.2 minutes. Patients who had an initial shockable rhythm and survived to discharge were shocked within 1 minute (n=2). Conclusion: Despite advances in critical care, survival from inpatient cardiopulmonary arrest to neurologically intact discharge remains poor. Therapeutic hypothermia should be expanded to those resuscitated from in - hospital cardiopulmonary arrest to determine if neurological outcomes would improve.

P1703Impact of prehospital epinephrine administration and quality of cardiopulmonary resuscitation on neurologically intact survival in out-of-hospital cardiac arrest patients with non-shockable rhythm

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Funada ◽  
Y Goto ◽  
H Okada ◽  
T Maeda ◽  
M Takamura
Keyword(s):  
Cardiac Arrest ◽  
Multivariate Logistic Regression Analysis ◽  
Multivariate Logistic Regression ◽  
High Quality ◽  
Epinephrine Administration ◽  
Hospital Arrival ◽  
Shockable Rhythm ◽  
Neurologically Intact ◽  
Hospital Cardiac Arrest

Abstract Background The effects of prehospital epinephrine administration in combination with the quality of cardiopulmonary resuscitation (CPR) on neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients with non-shockable rhythm remains unclear. Purpose This study aimed to elucidate the effects of prehospital epinephrine administration in combination with the quality of CPR on neurologically intact survival in OHCA patients with non-shockable rhythm. Methods We analysed 118,732 adult OHCA patients with non-shockable rhythm from the All-Japan OHCA registry between 2011 and 2016 (29,989 emergency medical service [EMS]-witnessed arrests with EMS-initiated CPR [high-quality CPR] and 88,743 bystander-witnessed arrests with bystander-initiated CPR continued by EMS providers [low-quality CPR]). Patients who achieved prehospital return of spontaneous circulation without prehospital epinephrine administration were excluded. The primary outcome measure was 1-month neurologically intact survival (cerebral performance category 1 or 2; CPC 1–2). Time from collapse to prehospital epinephrine administration for patients with prehospital epinephrine administration, or to hospital arrival for patients without prehospital epinephrine administration was calculated and adjusted collectively in multivariate logistic regression analysis for 1-month CPC 1–2. Results Multivariate logistic regression analysis revealed that the time from collapse to prehospital epinephrine administration or to hospital arrival was negatively associated with 1-month CPC 1–2 (adjusted odds ratio [OR] 0.95 per 1-minute increment, 95% confidence interval [CI] 0.94–0.96). Compared with bystander-witnessed arrests without prehospital epinephrine administration, EMS-witnessed arrests with or without prehospital epinephrine administration were significantly associated with increased chances of 1-month CPC 1–2 (adjusted OR 2.04, 95% CI 1.50–2.75 and adjusted OR 1.97, 95% CI 1.57–2.48, respectively). Prehospital epinephrine administration was significantly associated with an increased chance of 1-month CPC 1–2 among bystander-witnessed arrests (adjusted OR 1.57, 95% CI 1.24–1.98), but not among EMS-witnessed arrests. EMS-witnessed arrests without prehospital epinephrine administration were significantly associated with an increased chance of 1-month CPC 1–2 compared with bystander-witnessed arrests with prehospital epinephrine administration (adjusted OR 1.26, 95% CI 1.01–1.56). Conclusions High-quality CPR is crucial for increasing neurologically intact survival in OHCA patients with non-shockable rhythm. The additional beneficial effects of prehospital epinephrine administration were observed only among OHCA patients with low-quality CPR.

scholarly journals Higher achieved mean arterial pressure during therapeutic hypothermia is not associated with neurologically intact survival following cardiac arrest

Resuscitation ◽  
2015 ◽  
Vol 88 ◽  
pp. 158-164 ◽  
Author(s):  
Michael N. Young ◽  
Ryan D. Hollenbeck ◽  
Jeremy S. Pollock ◽  
Jennifer L. Giuseffi ◽  
Li Wang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Therapeutic Hypothermia ◽  
Neurologically Intact

Abstract 173: The Neuroprotective Effect Of JZL184 is Comparable With Therapeutic Hypothermia in a Rat Model of Cardiac Arrest

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Jing Xu ◽  
Guanghui Zheng ◽  
Juntao Hu ◽  
Weiwei Ge ◽  
Jennifer Bradley ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Therapeutic Hypothermia ◽  
Rat Model ◽  
Neuroprotective Effect ◽  
Experimental Studies ◽  
Flow Index ◽  
Protective Effects ◽  
Cerebral Microcirculation ◽  
Sprague Dawley ◽  
Neuroprotective Effects

Introduction: JZL184 is a synthetic monoacylglycerol lipase inhibitor that reduces brain edema, infarct size and alleviates inflammation following cerebral ischemia in experimental studies. In this study, we compared its cerebral protective effects with therapeutic hypothermia following cardiopulmonary resuscitation (CPR) in a rat model. Hypothesis: JZL184 will have similar neuroprotective effects to therapeutic hypothermia after cardiac arrest (CA) by reducing brain and blood brain barrier (BBB) injury and preserving cerebral microcirculation following CPR. Methods: Thirty six male Sprague-Dawley rats weighing between 450-550 g were randomized: 1) control 2) hypothermia 3) JZL184. Ventricular fibrillation was induced and untreated for 6 min for all rats. Resuscitation was attempted with a 4 Joule defibrillation after 8 min of CPR. Immediately following resuscitation, either hypothermia (33+0.5 o C) or JZL184 (16 mg/k, IP) was administered. Cerebral microcirculation, S-100β, NSE and Evan’s Blue (EB) concentrations were analyzed at 6hrs after resuscitation. Results: NSE and S-100β levels were higher in control compared to hypothermia and JZL18 at 6hr post ROSC (p < 0.001) (Fig. 1). Compared with control, there was a significant decrease in brain permeability to EB in Hypothermia and JZL184 after 6hr post ROSC (p<0.001) (Fig. 2). Microvascular flow index (MFI) was reduced in control compared with hypothermia and JZL184 6hr post ROSC (p <0.01). Conclusions: JZL184 administered following resuscitation reduced brain and BBB injury and preserved cerebral microcirculation at 6 hr post arrest to the same extent as hypothermia in a rat model of cardiac arrest.

Abstract 264: The Association of Chest Compression Fraction and Clinical Outcomes from Shockable Out-of-Hospital Cardiac Arrest During the Resuscitation Outcomes Consortium Primed Trial

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Sheldon Cheskes ◽  
Robert H Schmicker ◽  
Tom Rea ◽  
Judy Powell ◽  
Ian R Drennan ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Clinical Outcomes ◽  
Chest Compression ◽  
Reference Group ◽  
Secondary Analysis ◽  
Process Data ◽  
Shockable Rhythm ◽  
The Relationship ◽  
Neurologically Intact ◽  
Hospital Cardiac Arrest

INTRODUCTION: The role of chest compression fraction (CCF) in resuscitation of shockable out-of-hospital cardiac arrest (OHCA) is uncertain. We evaluated the relationship between CCF and clinical outcomes in a secondary analysis of the Resuscitation Outcomes Consortium (ROC) PRIMED trial. METHODS: We included OHCA patients from the ROC PRIMED trial who suffered cardiac arrest prior to EMS arrival, presented with a shockable rhythm, and had cardiopulmonary resuscitation (CPR) process data for at least one shock. We used multivariable logistic regression adjusting for Utstein variables, CPR metrics of compression rate and perishock pause, and ROC site to determine the relationship between CCF and survival to hospital discharge, return of spontaneous circulation (ROSC), and neurologically intact survival defined with Modified Rankin Score (MRS) ≤ 3. Due to potential confounding between CCF and cases that achieved early ROSC, we also performed an analysis restricted to patients without ROSC in the first 10 minutes of EMS resuscitation. RESULTS: Among the 2,558 eligible patients, median (IQR) age was 65 (54, 76) years, 76.9% were male, and mean (SD) CCF was 0.70 (0.15). Compared to the reference group (CCF < 0.60), the odds ratio (OR) for survival was 0.57 (95%CI: 0.42, 0.78) for CCF 0.60-0.79 and 0.32 (95%CI: 0.22, 0.48) for CCF ≥0.80. Results were similar for outcomes of ROSC and neurologically intact survival. Conversely, when restricted to the cohort who did not achieve ROSC during the first 10 minutes (n=1,660), the relationship between CCF and survival was no longer significant. Compared to the reference group (CCF < 0.60), the OR for survival was 0.85 (95 %CI: 0.58, 1.26) for CCF 0.60-0.79 and OR 0.87 (95%CI: 0.58, 1.36) for CCF ≥0.80. CONCLUSIONS: In this observational cohort study of OHCA patients presenting in a shockable rhythm, CCF when adjusted for Utstein predictors, CPR metrics and ROC site was paradoxically associated with lower odds of survival. The relationship between CCF and clinical outcomes was null in a sensitivity analysis restricted to patients without ROSC in the first 10 minutes. CCF is a complex measure and taken by itself may not be a consistent predictor of clinical outcome.

Abstract 165: Impact of Prehospital Epinephrine for Patients Treated With Extracorporeal Cardiopulmonary Resuscitation After Refractory Out-Of-Hospital Shockable Cardiac Arrest

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Ken Nagao ◽  
Yoshio Tahara ◽  
Hiroshi Nonogi ◽  
Naohiro Yonemoto ◽  
David Gaieski ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Neurological Outcome ◽  
Standard Dose ◽  
Rescue Therapy ◽  
Extracorporeal Cardiopulmonary Resuscitation ◽  
Hospital Arrival ◽  
Curve Estimation ◽  
Favorable Neurological Outcome ◽  
Neurologically Intact

Background: The 2015 CoSTR recommended that standard-dose epinephrine (SDE) was reasonable for patients with out-of-hospital cardiac arrest (OHCA) and extracorporeal cardiopulmonary resuscitation (ECPR) was reasonable rescue therapy for selected patients with ongoing cardiac arrest when initial conventional CPR was unsuccessful. We investigated the effect of prehospital SDE for patients who met the criteria of ECPR. Methods: From the All-Japan OHCA Utstein Registry between 2007 and 2015, we included 22,552 patients who met the criteria of ECPR of the SAVE-J study (age between 20 and 75, witnessed shockable OHCA, cardiac arrest on hospital arrival, cardiac etiology, and collapse-to-ECPR interval within 60 minutes). Study patients were divided into two groups according to prehospital SDE or not. Primary endpoint was favorable 30-day neurological outcome after OHCA. Results: Of the 22,552 study patients, 5,659 (25%) received prehospital SDE and 16,893 (75%) did not. The SDE group resulted in lower proportion of favorable 30-day neurological outcome than the no-SDE group (5.6% versus 8.4%, p<0.001) with longer collapse-to-hospital-arrival interval (36.7±9.8 min vs. 29.6±11.3 min, p<0.001). After adjustment for independent predictors of resuscitation, prehospital SDE did not impact on neurological benifit (adjusted OR,1.13; 95%CI,0.98-1.29), but the collapse-to-hospital-arrival interval was associated with neurological benefit (adjusted OR, 0.94; 95% CI, 0.93-0.95). In curve estimation of the SDE group, when collapse-to-hospital-arrival interval was delayed, proportion of the favorable neurological outcome decreased to about 25% at 1 minute and about 0% at 54 minutes (R=0.14). In the 274 patients undergoing ECPR of the SAVE-J study, however, it was about 43% at 1 minute and about 0% at 96 minutes (R=0.17). Conclusions: Prehospital SDE did not improve likelihood of favorable neurological outcome for patients who met the criteria of ECPR (age between 20 and 75, witnessed shockable OHCA, cardiac arrest on hospital arrival, cardiac etiology and collapse-to-ECPR interval within 60 minutes), because SED administration delayed the collapse-to-hospital-arrival interval which was closely related to the neurologically intact survival on ECPR.

Sign in / Sign up

Export Citation Format

Share Document