Abstract 246: Therapeutic Hypothermia Mimicking Peptide Administration During Cardiopulmonary Resuscitation Improved Cardiac Arrest Survival in Swine

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Matt Oberdier ◽  
Jing Li ◽  
Dan Ambinder ◽  
Xiangdong Zhu ◽  
Sarah Fink ◽  
...  

Background: Out-of-hospital sudden cardiac arrest is a leading cause of death in the United States, affecting over 350,000 people per year with an overall survival rate around 10%. CPR, defibrillation, and therapeutic hypothermia are common resuscitation strategies, but hypothermia is difficult to implement timely to achieve survival benefit. A cell-permeable peptide TAT-PHLPP9c has been shown to alter metabolic pathways similar to hypothermia, and decreases the release of two biomarkers, taurine and glutamate, during the high osmotic stress of heart stunning and brain injury in a mouse arrest model. Hypothesis: TAT-PHLPP9c, given during CPR, enhances 24-hour survival in a swine ventricular fibrillation (VF) model. Methods: In 14 (8 controls and 6 treated) sedated, intubated, and mechanically ventilated swine, after 5 min of VF, ACLS with vest CPR and periodic defibrillations was performed. Venous blood samples were collected at baseline, after 2 min of CPR, and at 2 and 30 min after return of spontaneous circulation (ROSC). The animals were survived up to 24 hrs and plasma samples were analyzed for glutamate and taurine in 2 controls and 1 animal given peptide. Results: Three of the control animals had ROSC, but none survived for 24 hrs, while 4 of 6 treated animals achieved neurologically intact survival at 24 hrs (p < 0.02). Compared to baseline, both taurine and glutamate plasma concentrations increased in the control group, but the increase was reduced substantially by the peptide treatment at 30 min after ROSC (Figure). Conclusion: The use of the cooling mimicking peptide TAT-PHLPP9c administered during CPR significantly improved 24-hour survival in this swine model of cardiac arrest. It reduced the increase of cerebral and myocardial metabolic biomarkers, which encourages utilizing a strategy of cell-permeable peptides for intravenous administration for more rapid onset of hypothermia-like salutary effects than are possible with current CPR cooling devices.

2006 ◽  
Vol 21 (6) ◽  
pp. 445-450 ◽  
Author(s):  
Corita Grudzen

AbstractAmericans are living longer and are more likely to be chronically or terminally ill at the time of death. Although surveys indicate that most people prefer to die at home, the majority of people in the United States die in acute care hospitals. Each year, approximately 400,000 persons suffer sudden cardiac arrest in the US, the majority occurring in the out-of-hospital setting. Mortality rates are high and reach almost 100% when prehospital care has failed to restore spontaneous circulation. Nonetheless, patients who receive little benefit or may wish to forgo life-sustaining treatment often are resuscitated. Risk versus harm of resuscitation efforts can be differentiated by various factors, including cardiac rhythm. Emergency medical services policy regarding resuscitation should consider its utility in various clinical scenarios. Patients, family members, emergency medical providers, and physicians all are important stakeholders to consider in decisions about out-of-hospital cardiac arrest. Ideally, future policy will place greater emphasis on patient preferences and quality of life by including all of these viewpoints.


2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yuan-Zhuo Chen ◽  
Shu-Qin Zhou ◽  
Yan-Qing Chen ◽  
Hu Peng ◽  
Yu-Gang Zhuang

Background. Adipokines are a group of cytokines or peptides secreted by adipose tissue to exert numerous biological functions. In the present study, we measured the plasma levels of four adipokines (adiponectin, leptin, fatty acid-binding protein 4 (FABP4), and visfatin) in cardiac arrest patients following return of spontaneous circulation (ROSC). Methods. Totally, 21 patients who experienced cardiac arrest and successful ROSC with expected survival of at least 48 hours (from January 2016 to December 2017) were consecutively enrolled into this prospective observational clinical study. Of the 21 enrolled patients, ten survived, and other eleven died between 2 days and 6 months post ROSC. Venous blood was drawn at three time points: baseline (<1 hour post ROSC), 2 days post ROSC, and 7 days post ROSC. Plasma concentrations of adiponectin, leptin, FABP4, and visfatin were determined using commercial enzyme-linked immunosorbent assays. Results. The plasma visfatin levels at 2 or 7 days post ROSC increased significantly compared with the baseline (P<0.01), while plasma levels of adiponectin, leptin, and FABP4 did not change. Moreover, plasma visfatin levels in survivors at 2 or 7 days post ROSC were higher than those in nonsurvivors (P<0.01). Plasma visfatin levels at 2 or 7 days post ROSC were negatively correlated with Acute Physiology and Chronic Health Evaluation (APACHE) II score and time to ROSC. Moreover, receiver operating characteristic curve analysis showed that the plasma visfatin levels at 2 or 7 days post ROSC were good predictors for survival of the patients. Conclusion. Elevated plasma visfatin levels may be a marker for better outcome of cardiac arrest patients post ROSC.


CJEM ◽  
2017 ◽  
Vol 19 (S1) ◽  
pp. S97-S98
Author(s):  
J.M. Goodloe ◽  
L.D. Vinson ◽  
M.L. Cox ◽  
B.D. Burns

Introduction: Patient co-morbidities contribute to survivability from out-of-hospital sudden cardiac arrest. Many studies have been conducted regarding contributing factors to sudden cardiac arrest survival, though very few studies have been published detailing specific analysis of morbid obesity association with return of spontaneous circulation (ROSC) in adults treated by paramedics. Methods: Adults in sudden cardiac arrest with resuscitation initiated, including at least one defibrillation, between July 1, 2016 and December 1, 2016 were enrolled. Due to an increasing prevalence of morbid obesity in the United States adult population, a novel defibrillation strategy, involving weight-based joule settings and double sequential external defibrillation (DSED) was initiated in June 2016. As exact body weight is logistically difficult to obtain in the EMS care environment, a paramedic-estimated weight at the time of resuscitation to be 100 kg or greater was deemed representative of “morbid obesity” for this analysis. All resuscitations were reviewed from electronic medical records (EMRs) completed by treating paramedics, alongside telemetry and defibrillation events recorded, transmitted, and analyzed in proprietary software (CODE-STAT, Physio-Control Corporation, Redmond, WA). ROSC was determined from both paramedic and hospital clinician EMRs reviewed by a paramedic researcher. Results: During the 5 month study period, paramedics involved treated 133 adults in sudden cardiac arrest involving perceived ventricular fibrillation that was treated with at least one defibrillation. 49/90 (54.4%) with weight &lt;100 kg as estimated by paramedics at the time of resuscitative care achieved at least transient ROSC. Only 17/43 (39.5%) with estimated weight ≥100 kg achieved any ROSC, despite paramedics authorized to perform defibrillations at higher joule energy settings for such weight. The OR for ROSC if &lt;100 kg estimated weight is 1.83 (95% CI 0.87-3.83), though given limited sample size p=0.11. Conclusion: While survival from out-of-hospital sudden cardiac arrest in adults is multi-factorial, the presence of morbid obesity, defined as estimated weight ≥100 kg, trends towards less ROSC. Continued community health efforts to decrease the prevalence of morbid obesity in the adult population may confer improved ability to survive out-of-hospital sudden cardiac arrest.


2016 ◽  
Vol 11 (4) ◽  
pp. 237-242 ◽  
Author(s):  
Mark H. Wimmer, BSN ◽  
Kenneth Heffner, BSN ◽  
Michael Smithers, BSN ◽  
Richard Culley, BSN ◽  
Jennifer Coyner, PhD, CRNA ◽  
...  

Introduction: The American Heart Association (AHA) recommends intravenous (IV) or intraosseous (IO) vasopressin in Advanced Cardiac Life Support (ACLS). Obtaining IV access in hypovolemic cardiac arrest patients can be difficult, and IO access is often obtained in these life threatening situations. No studies have been conducted to determine the effects of humeral IO (HIO) access with vasopressin in the return of spontaneous circulation (ROSC). Our study compared the kinetics of vasopressin and ROSC with HIO with IV access in the hypovolemic swine model.Methods: Twenty-two Yorkshire swine were divided into three groups: HIO (n = 7), IV (n = 8), and a control group (n = 7). The IV and HIO group received vasopressin and cardiopulmonary resuscitation (CPR), while the control group received only CPR. All subjects were exsanguinated 31 percent of their blood volume, placed in cardiac arrest, and resuscitated per ACLS. Subjects that achieved ROSC were then monitored for 20 minutes. Blood samples (10 mL) collected at 0.5, 1, 1.5, 2, 2.5, 3, and 4 minutes after vasopressin injection and analyzed for maximum concentration (Cmax) and time to maximum concentration (Tmax). Data were analyzed using a multivariate analysis of variance (MANOVA) and a Fisher's Exact Test.Results: ROSC was achieved in every subject that received vasopressin via the HIO route. Data analysis using a MANOVA pairwise comparison revealed no difference between mean Cmax (p = 0.601) and Tmax (p = 0.771) of vasopressin administered IV versus HIO routes. Analysis of the mean serum concentrations at time intervals using a repeated measures analysis of variance found no difference (p 0.05). A Fisher's Exact Test revealed no difference in rate of ROSC between HIO and IV groups (p 0.05). Odds ratio determined that there was a 33 times higher chance of survival among HIO subjects versus control (CPR and Defibrillation; p = 0.03) and no difference in the survivability of the HIO or IV groups (p = 0.52). Conclusion: The data from this study strongly suggest that there is no significant difference in ROSC, time to ROSC, hemodynamics, or pharmacokinetics between HIO vasopressin and IV vasopressin. This research reinforces current AHA guidelines recommending the use of HIO route early over delaying care awaiting IV access.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Haifang Yu ◽  
Lu Yin ◽  
Ping Gong ◽  
Jiangang Wang ◽  
Zhengfei Yang ◽  
...  

Introduction: Therapeutic hypothermia improves the outcomes of cerebral function after resuscitation from cardiac arrest (CA). The effect of therapeutic hypothermia on post resuscitation pulmonary function, however, is less known. In the present study, we investigated the effect of therapeutic hypothermia on oxygenation index, a sensitive index of pulmonary function,in a rat model of cardiac arrest and resuscitation. Hypothesis: We hypothesize that during therapeutic mild hypothermia in a rat model of cardiac arrest, the pulmonary function following resuscitation is less impaired when compare to normothermia. Methods: Twenty-one male Sprague-Dawley rats were randomized into three groups: 1) control group (control, n=5): the normothermic rats only received anesthesia and the surgical procedure as the other groups without ventricular fibrillation (VF); 2) normothermia group (NT, n=7): the normothermic rats were subjected to induced VF for 8 mins followed by 8 mins of cardiopulmonary resuscitation (CPR); 3) Mild hypothermia group (HT, n=9): the rats were subjected to induced VF for 8 mins followed by 8 mins of CPR. Mild hypothermia of 33±0.5°C was started 5 mins after return of spontaneous circulation (ROSC) and maintained for 8 hrs. The oxygenation indexes were measured at baseline, 2, 4 or 8 hours after ROSC with a conventional blood gas analyzer (PHOX plus L; Nova Biomedical Corporation, Waltham, MA, USA). Results: Compared to the control group, the oxygenation indexes of both the NT and HT groups were significantly decreased at 2 hrs after ROSC. However, more significant reduction in oxygenation index was observed in the NT group (Figure). Conclusions: There is an early pulmonary dysfunction after successful resuscitation from cardiac arrest. Hypothermia reduces the impairment of pulmonary function.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiffany S. Ko ◽  
Constantine D. Mavroudis ◽  
Ryan W. Morgan ◽  
Wesley B. Baker ◽  
Alexandra M. Marquez ◽  
...  

AbstractNeurologic injury is a leading cause of morbidity and mortality following pediatric cardiac arrest. In this study, we assess the feasibility of quantitative, non-invasive, frequency-domain diffuse optical spectroscopy (FD-DOS) neuromonitoring during cardiopulmonary resuscitation (CPR), and its predictive utility for return of spontaneous circulation (ROSC) in an established pediatric swine model of cardiac arrest. Cerebral tissue optical properties, oxy- and deoxy-hemoglobin concentration ([HbO2], [Hb]), oxygen saturation (StO2) and total hemoglobin concentration (THC) were measured by a FD-DOS probe placed on the forehead in 1-month-old swine (8–11 kg; n = 52) during seven minutes of asphyxiation followed by twenty minutes of CPR. ROSC prediction and time-dependent performance of prediction throughout early CPR (< 10 min), were assessed by the weighted Youden index (Jw, w = 0.1) with tenfold cross-validation. FD-DOS CPR data was successfully acquired in 48/52 animals; 37/48 achieved ROSC. Changes in scattering coefficient (785 nm), [HbO2], StO2 and THC from baseline were significantly different in ROSC versus No-ROSC subjects (p < 0.01) after 10 min of CPR. Change in [HbO2] of + 1.3 µmol/L from 1-min of CPR achieved the highest weighted Youden index (0.96) for ROSC prediction. We demonstrate feasibility of quantitative, non-invasive FD-DOS neuromonitoring, and stable, specific, early ROSC prediction from the third minute of CPR.


Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Joseph M Wider ◽  
Erin Gruley ◽  
Jennifer Mathieu ◽  
Emma Murphy ◽  
Rachel Mount ◽  
...  

Background: Mitochondrial dysfunction contributes to cardiac arrest induced brain injury and has been a target for neuroprotective therapies. An emerging concept suggests that hyperactivation of neuronal mitochondria following resuscitation results in hyperpolarization of the mitochondrial membrane during reperfusion, which drives generation of excess reactive oxygen species. Previous studies from our group demonstrated that limiting mitochondrial hyperactivity by non-invasively modulating mitochondrial function with specific near infrared light (NIR) wavelengths can reduce brain injury in small animal models of global and focal ischemia. Hypothesis: Inhibitory wavelengths of NIR will reduce neuronal injury and improve neurocognitive outcome in a clinically relevant swine model of cardiac arrest. Methods: Twenty-eight male and female adult swine were enrolled (3 groups: Sham, CA/CPR, and CA/CPR + NIR). Cardiac arrest (8 minutes) was induced with a ventricular pacing wire and followed by manual CPR with defibrillation and epinephrine every 30 seconds until return of spontaneous circulation (ROSC), 2 of the 20 swine that underwent CA did not achieve ROSC and were not enrolled. Treatment groups were randomized prior to arrest and blinded to the CPR team. Treatment was applied at onset of ROSC by irradiating the scalp with 750 nm and 950 nm LEDs (5W) for 2 hours. Results: Sham-operated animals all survived (8/8), whereas 22% of untreated animals subjected to cardiac arrest died within 45 min of ROSC (CA/CPR, n= 7/9). All swine treated with NIR survived the duration of the study (CA/CPR + NIR, n=9/9). Four days following cardiac arrest, neurological deficit score was improved in the NIR treatment group (50 ± 21 CA/CPR vs. 0.8 ± 0.8 CA/CPR + NIR, p < 0.05). Additionally, neuronal death in the CA1/CA3 regions of the hippocampus, assessed by counting surviving neurons with stereology, was attenuated by treatment with NIR (17917 ± 5534 neurons/mm 3 CA/CPR vs. 44655 ± 5637 neurons/mm 3 CA/CPR + NIR, p < 0.05). All data is reported as mean ± SEM. Conclusions: These data provide evidence that noninvasive modulation of mitochondria, achieved by transcranial irradiation of the brain with NIR, mitigates post-cardiac arrest brain injury.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Shuichi Hagiwara ◽  
Kiyohiro Oshima ◽  
Masato Murata ◽  
Makoto Aoki ◽  
Kei Hayashida ◽  
...  

Aim: To evaluate the priority of coronary angiography (CAG) and therapeutic hypothermia therapy (TH) after return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA). Patients and Methods: SOS-KANTO 2012 study is a prospective, multicenter (69 emergency hospitals) and observational study and includes 16,452 patients with OHCA. Among the cases with ROSC in that study, we intended for patients treated with both CAG and TH within 24 hours after arrival. Those patients were divided into two groups; patients in whom TH was firstly performed (TH group), and the others in whom CAG was firstly done (CAG group). We statistically compared the prognosis between the two groups. SPSS Statistics 22 (IBM, Tokyo, Japan) was used for the statistical analysis. Statistical significance was assumed to be present at a p value of less than 0.05. Result: 233 patients were applied in this study. There were 86 patients in the TH group (M/F: 74/12, mean age; 60.0±15.2 y/o) and 147 in the CAG group (M/F: 126/21, mean age: 63.4±11.1 y/o) respectively, and no significant differences were found in the mean age and M/F ratio between the two groups. The overall performance categories (OPC) one month after ROSC in the both groups were as follows; in the TH group, OPC1: 21 (24.4%), OPC2: 3 (3.5%), OPC3: 7 (8.1%), OPC4: 8 (9.3%), OPC5: 43 (50.0%), unknown: 4 (4.7%), and in the CAG group, OPC1: 38 (25.9%), OPC2: 13 (8.8%), OPC3: 15 (10.2%), OPC4: 18 (12.2%), OPC5: 57 (38.8%), unknown: 6 (4.1%). There were no significant differences in the prognosis one month after ROSC between the two groups. Conclusion: The results which of TH and CAG you give priority to over do not affect the prognosis in patients with OHCA.


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