Neurological Intact Survival Research Articles

Survival and Neurologic Outcomes From Pharmacologic Peptide Administration During Cardiopulmonary Resuscitation of Pulseless Electrical Activity.

Outcomes from cardiopulmonary resuscitation (CPR) following sudden cardiac arrest are suboptimal. Postresuscitation targeted temperature management has been shown to have benefit in subjects with sudden cardiac arrest due to ventricular fibrillation, but there are few data for outcomes from sudden cardiac arrest due to pulseless electrical activity. In addition, intra-CPR cooling is more effective than postresuscitation cooling. Physical cooling is associated with increased protein kinase B activity. Therefore, our group developed a novel peptide, TAT-PHLPP9c, which regulates protein kinase B. We hypothesized that when given during CPR, TAT-PHLPP9c would improve survival and neurologic outcomes following pulseless electrical activity arrest. In 24 female pigs, pulseless electrical activity was induced by inflating balloon catheters in the right coronary and left anterior descending arteries for ≈7 minutes. Advanced life support was initiated. In 12 control animals, epinephrine was given after 1 and 3 minutes. In 12 peptide-treated animals, 7.5 mg/kg TAT-PHLPP9c was also administered at 1 and 3 minutes of CPR. The balloons were removed after 2 minutes of support. Animals were recovered and neurologically scored 24 hours after return of spontaneous circulation. Return of spontaneous circulation was more common in the peptide group, but this difference was not significant (8/12 control versus 12/12 peptide; P=0.093), while fully intact neurologic survival was significantly more common in the peptide group (0/12 control versus 11/12 peptide; P<0.00001). TAT-PHLPP9c significantly increased myocardial nicotinamide adenine dinucleotide levels. TAT-PHLPP9c resulted in improved survival with full neurologic function after sudden cardiac arrest in a swine model of pulseless electrical activity, and the peptide shows potential as an intra-CPR pharmacologic agent.

Recurrence of ventricular fibrillation in out-of-hospital cardiac arrest: Clinical evidence and underlying ionic mechanisms.

Defibrillation remains the optimal therapy for terminating ventricular fibrillation (VF) in out-of-hospital cardiac arrest (OHCA) patients, with reported shock success rates of ∼90%. A key persistent challenge, however, is the high rate of VF recurrence (∼50-80%) seen during post-shock cardiopulmonary resuscitation (CPR). Studies have shown that the incidence and time spent in recurrent VF are negatively associated with neurologically-intact survival. Recurrent VF also results in the administration of extra shocks at escalating energy levels, which can cause cardiac dysfunction. Unfortunately, the mechanisms underlying recurrent VF remain poorly understood. In particular, the role of chest-compressions (CC) administered during CPR in mediating recurrent VF remains controversial. In this review, we first summarize the available clinical evidence for refibrillation occurring during CPR in OHCA patients, including the postulated contribution of CC and non-CC related pathways. Next, we examine experimental studies highlighting how CC can re-induce VF via direct mechano-electric feedback. We postulate the ionic mechanisms involved by comparison with similar phenomena seen in commotio cordis. Subsequently, the hypothesized contribution of partial cardiac reperfusion (either as a result of CC or CC independent organized rhythm) in re-initiating VF in a globally ischaemic heart is examined. An overview of the proposed ionic mechanisms contributing to VF recurrence in OHCA during CPR from a cellular level to the whole heart is outlined. Possible therapeutic implications of the proposed mechanistic theories for VF recurrence in OHCA are briefly discussed.

Thrombolytics in Cardiac Arrest from Pulmonary Embolism: A Systematic Review and Meta Analysis.

During cardiopulmonary resuscitation, intravenous thrombolytics are commonly used for patients whose underlying etiology of cardiac arrest is presumed to be related to pulmonary embolism (PE). We performed a systematic review and meta-analysis of the existing literature that focused on the use of thrombolytics for cardiac arrest due to presumed or confirmed PE. Outcomes of interest were return of spontaneous circulation (ROSC), survival to hospital discharge, neurologically-intact survival, and bleeding complications. Thirteen studies with a total of 803 patients were included in this review. Most studies included were single-armed and retrospective. Thrombolytic agent and dose were heterogeneous between studies. Among those with control groups, intravenous thrombolysis was associated with higher rates of ROSC (OR 2.55, 95% CI = 1.50-4.34), but without a significant difference in survival to hospital discharge (OR 1.41, 95% CI = 0.79-2.41) or bleeding complications (OR 2.21, 0.95-5.17). Use of intravenous thrombolytics in cardiac arrest due to confirmed or presumed PE is associated with increased ROSC but not survival to hospital discharge or change in bleeding complications. Larger randomized studies are needed. Currently, we recommend continuing to follow existing consensus guidelines which support use of thrombolytics for this indication.

Impact of Heavy Snowfall on Emergency Transport and Prognosis of Out-of-Hospital Cardiac Arrest Patients: A Nation-Wide Cohort Study.

Out-of-hospital cardiac arrest (OHCA) is a significant global cause of mortality, and Emergency Medical Services (EMS) response interval is critical for survival and a neurologically-favorable outcome. Currently, it is unclear whether EMS response interval, neurologically-intact survival, and overall survival differ between snowy and non-snowy periods at heavy snowfall areas. A nation-wide population-based cohort of OHCA patients, registered from 2017 through 2019 in the All-Japan Utstein Registry, was divided into four groups according to areas (heavy snowfall area or other area) and seasons (winter or non-winter): heavy snowfall-winter, heavy snowfall-non-winter, other area-winter, and other area-non-winter. The first coprimary outcome was EMS response interval, and the secondary coprimary outcome was one-month survival and a neurologically-favorable outcome at one month. A total of 337,781 OHCA patients were divided into four groups: heavy snowfall-winter (N = 15,627), heavy snowfall-non-winter (N = 97,441), other area-winter (N = 32,955), and other area-non-winter (N = 191,758). Longer EMS response intervals (>13 minutes) were most likely in the heavy snowfall-winter group (OR = 1.86; 95% CI, 1.76 to 1.97), and also more likely in heavy snowfall areas in non-winter (OR = 1.44; 95% CI, 1.38 to 1.50). One-month survival in winter was worse not only in the heavy snowfall area (OR = 0.86; 95% CI, 0.78 to 0.94) but also in other areas (OR = 0.91; 95% CI, 0.87 to 0.94). One-month neurologically-favorable outcomes were also comparable between heavy snowfall-winter and other area-non-winter groups. This study showed OHCA in heavy snowfall areas in winter resulted in longer EMS response intervals. However, heavy snowfall had little effect on one-month survival or neurologically-favorable outcome at one month.

Abstract 210: Norepinephrine Versus Epinephrine For Post-Cardiac Arrest Shock In The Prehospital Setting: A Retrospective Analysis

Introduction: Shock after out-of-hospital cardiac arrest (OHCA) is common and often treated with vasopressors. Compared with norepinephrine (NOR), infusion of epinephrine (EPI) is associated with higher mortality and morbidity among hospitalized patients; but the optimal prehospital approach is unknown. We sought to examine whether infusion of EPI versus NOR is associated with neurologically-intact survival among OHCA patients. Methods: This retrospective cohort study included transported OHCA cases in Seattle, WA from 2014-2021 who received advanced life support. Our primary exposure was infusion of EPI or NOR. Our primary outcome was neurologically-favorable survival (Cerebral Performance Category score of 1 or 2) to hospital discharge. Key secondary outcomes were prehospital rearrest, survival to hospital admission, and hospital mortality. We conducted multivariable logistic regression adjusting for baseline patient and OHCA characteristics. Results: Of 1784 OHCA patients, 263 (15%) received NOR and 201 (11%) received EPI infusions, 18 received both, and 1298 received neither. Those who received EPI were older (median 65 [IQR 52-78] vs 62 [IQR 47-75] years), but otherwise had similar baseline characteristics, including initial arrest rhythm (Table 1). Patients who received EPI were over twice as likely to have rearrested in the prehospital setting (53% vs 24%). After adjustment, there was no difference in neurologically-favorable survival (OR 0.91, 95% CI 0.47-1.78). We found no difference in survival to hospital admission or discharge. Conclusion: Neurologically-favorable survival was similar among patients who received NOR or EPI infusions for post-OHCA shock, though patients who received EPI had prehospital rearrests more often. Future trials should examine the optimal approach to hemodynamic management for post-OHCA shock.

Long-term neurological intact survival and quality of life after refractory out-of-hospital cardiac arrest treated with rescue mechanical circulatory support

Abstract Background Mechanical circulatory support (MCS) with either veno-arterial extracorporeal membrane oxygenation (V-A ECMO) or Impella has emerged as a rescue therapy for refractory out-of-hospital cardiac arrest (OHCA). However, only short-term outcome is specified and most studies do not report follow-up beyond six months. Long-term survival and quality of life in this high-risk population remains unknown. Purpose To determine long-term neurological intact survival and quality of life in patients with refractory OHCA treated with MCS. Methods This was an observational, single-centre study of OHCA-patients from January 2015 to December 2019. Patients treated with MCS for OHCA were compared with patients receiving conventional cardiopulmonary resuscitation (CPR). A follow-up of long-term survivors in the MCS group was conducted (&amp;gt;1 year after arrest). This included health related quality of life questionaries (Short Form-36 [SF-36]) and assessment of neurological function with Cerebral Performance Category (CPC). Good neurological outcome was defined as CPC 1 and CPC 2. Results A total of 1015 with OHCA were included; 101 received MCS for refractory cardiac arrest. Among these V-A ECMO was deployed in 97 patients and Impella in 4 patients. The MCS group had significantly longer low-flow times compared to the conventional group (105 [IQR, 94–123] minutes versus 18 [IQR 10–39] minutes) and were more metabolically deranged upon arrival at hospital (Table 1). In patients receiving MCS, the hospital discharge rate was 27% and good neurological outcome was seen in 93% among patients discharged. At follow-up, 15 out of 21 long-term survivors participated. Median follow-up time was 4.8±1.6 (range 2.8–6.1 years). Mean age at follow-up was 61±7.3 years, 11 (73%) were men. Neurological outcome with CPC 1 was found in 12 patients (80%), with CPC 2 in 2 patients (13%), and with CPC 3 in 1 patient (7%). Two had improved neurological status from CPC 2 to CPC 1 since discharge. Mean scores of the SF-36 revealed an overall high level of psychical and mental health in long-term survivors (Figure 1). Conclusion Long-term survival with good neurological outcome was high in patients with refractory OHCA treated with MCS despite prolonged resuscitation and severe metabolic derangement. These patients may expect a reasonable quality of life after discharge. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Department of Cardiology, Aarhus University HospitalSnedkermester Sophus Jacobsen og hustru Astrid Jacobsens Fond

Mountain Emergency Medicine Review, 1st edition

Mountain Emergency Medicine Review, 1st edition

Neurological intact survival with rescue mechanical circulatory support for refractory out-of-hospital cardiac arrest despite long low-flow times

Abstract Funding Acknowledgements Type of funding sources: None. Background The potential window for using mechanical circulatory support (MCS) for refractory out-of-hospital cardiac arrest (OHCA) remain unsettled. It has been proposed that a cut-off limit defined as the golden hour may produce higher survival with good neurological outcome. Purpose The present study analyzed the association of low-flow time and neurological intact survival (Cerebral Performance Categories 1-2) at discharge between patients receiving conventional cardiopulmonary resuscitation (CCPR) and MCS. Methods The present retrospective, observational, single centre study from 2015-2019 included all consecutive OHCA patients, who were treated with MCS for refractory OHCA or received CCPR. Low-flow time was defined as the time from CPR to deployment of either veno-arterial extracorporeal membrane oxygenation or Impella support for the MCS group. Time from CPR to return of spontaneous circulation or termination of treatment was recorded for the CCPR group. Rate of neurological intact survival at discharge were analyzed for both groups. Results A total of 101 patients were treated with MCS and 914 patients received CCPR. The MCS group was significantly younger with a median age of 56 (IQR, 46-62) years compared to 67 (IQR, 57-74) years, p &amp;lt; 0.001. In the CCPR group, short low-flow times (0-20 minutes) were associated with high survival with good neurological outcome at discharge. There were no survivors with low-flow times exceeding 70 minutes. All patients receiving MCS survived at low-flow times 31-60 minutes, however neurological intact survival dropped to 21% at low-flow times &amp;gt; 80 minutes. Conclusion Patients treated with MCS with low-flow time 70-80 minutes did show similar favorable neurological outcome at discharge as patients receiving CCPR with low-flow &amp;lt; 10 minutes. Despite, low-flow times exceeding 80 minutes, patients treated with MCS still presented high survival rate of 21%. Hence, the data in this study does not support a golden hour for MCS.

The role of head-up cardiopulmonary resuscitation in sudden cardiac arrest: a systematic review and meta-analysis.

BackgroundHead-up cardiopulmonary resuscitation (HU-CPR) is an experimental treatment for sudden cardiac arrest (SCA), where cardiopulmonary resuscitation (CPR) is performed in a ramped position. We evaluated whether HU-CPR improved survival and surrogate outcomes as compared to standard CPR (S-CPR).MethodsStudies reporting on HU-CPR in SCA were searched for in PubMed, Embase and Cochrane Library from inception to May 1st 2021. Outcomes included neurologically-intact survival, 24-hour-survival, intracranial pressure (ICP), cerebral perfusion pressure (CerPP) and brain blood flow (BBF). Risk of bias was assessed using the GRADE assessment tool and Newcastle Ottawa Scale. Fixed- and random-effects models were used to estimate the pooled effects of HU-CPR at 30 degrees.ResultsThirteen articles met the criteria for inclusion (11 animal-only studies, one before-and-after human-only study, one study that utilized human- and animal-cadavers). Among animal studies, the most common implementation of HU-CPR was a 30-degree upward tilt of the head and thorax (n=7), while four studies investigated controlled sequential elevation (CSE). Two animal studies reported improved cerebral performance category (CPC) scores at 24-hour. The pooled effect on 24-hour survival was not statistically significant (P=0.37). The lone human study reported doubled return of spontaneous circulation (ROSC) (17.9% versus 34.2%, P<0.0001). The pooled effect on ROSC in three porcine studies was OR =3.63 (95% CI: 0.72–18.39). Pooled effects for surrogate physiological outcomes of intracranial cranial pressure (MD −14.08, 95% CI: −23.21 to −4.95, P=0.003), CerPP (MD 14.39, 95% CI: 3.07–25.72, P=0.01) and BBF (MD 0.14, 95% CI: 0.02–0.27, P=0.03), showed statistically significant benefit.DiscussionOverall, HU-CPR improved neurologically-intact survival at 24-hour, ROSC and physiological surrogate outcomes in animal models. Despite promising preclinical data, and one human observational study, clinical equipoise remains surrounding the role of HU-CPR in SCA, necessitating clarification with future randomized human trials.

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

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

Abstract 10618: A Head up CPR Based Care Bundle Improves the Likelihood of Survival to Hospital Discharge After Out of Hospital Cardiac Arrest

Introduction: Survival rates after out-of-hospital cardiac arrest (OHCA) remain poor with widespread use of conventional (C) CPR. Based on pre-clinical studies showing improved cerebral flow and neurologically-intact survival, a FDA approved automated Head Up Positioning (AHUP) device for CPR was developed for use with an impedance threshold device (ITD), and manual and/or automated suction cup-based CPR. A prospective observational IRB approved registry was created to track use and clinical outcomes with this AHUP device based bundle. Hypothesis: Faster time to use of an AHUP CPR bundle improves survival to hospital discharge after OHCA versus historical controls treated with C-CPR. Methods: Registry patients from sites routinely recording time from 911 call to AHUP device placement (T 911 ) were included. C-CPR controls were from 3 prior randomized prospective CPR trials: 1) Resuscitation Outcomes Consortium Prehospital Resuscitation using an IMpedance valve and Early versus Delayed (ROC PRIMED) Study, 2) Resuscitation Outcomes Consortium Amiodarone, Lidocaine, or Placebo Study (ROC-ALPS), 3) The ResQTrial. Propensity score analysis was performed using logistic regression for baseline characteristics including age, sex, witnessed arrest, bystander CPR, shockable rhythm, and time to first responder CPR. Each AHUP patient was matched with up to 4 C-CPR patients. Results: Of 11 U.S. sites reporting AHUP CPR outcomes, 6 had time from 911 call to AHUP device placement recorded (n = 227). The model yielded a c-statistic of 0.76. Stratified by T 911 , the odds of survival with AHUP CPR were significantly higher than with C-CPR between T 911 &lt; 7 minutes (OR 4.57, 95% CI 1.3-16.0) and T 911 &lt; 15 minutes (OR 2.01, 95% CI 1.1-3.8). There was a time dependent effect of AHUP device placement on survival (See Figure). Conclusions: More rapid initiation of an AHUP CPR bundle resulted in improved survival to hospital discharge versus historical controls treated with C-CPR in OHCA.

Extracorporeal Membrane Oxygenation (ECMO) for Refractory Cardiac Arrest.

Extracorporeal Membrane Oxygenation (ECMO) for Refractory Cardiac Arrest.

Impact of Lung Compliance on Neurological Outcome in Patients with Acute Respiratory Distress Syndrome Following Out-of-Hospital Cardiac Arrest.

(1) Background: Acute respiratory distress syndrome (ARDS) following cardiac arrest is common and associated with in-hospital mortality. We aim to investigate whether lung compliance during targeted temperature management is associated with neurological outcome in patients with ARDS after out-of-hospital cardiac arrest (OHCA). (2) Methods: This observational study is conducted in the emergency intensive care unit from January 2011 to April 2019 using data from a prospective patient registry. Adult patients (age ≥18 years) who survived non-traumatic OHCA and subsequently developed ARDS based on the Berlin definition are included. Mechanical ventilator parameters such as plateau pressure, tidal volume, minute ventilation, positive end expiratory pressure, and compliance are recorded for 7 days or until death, and categorized as maximum, median, and minimum. The primary outcome is a favorable neurological outcome defined as a Cerebral Performance Category score of 1 or 2 at hospital discharge. (3) Results: Regarding 246 OHCA survivors, 119 (48.4%) patients developed ARDS. A favorable neurologic outcome was observed in 23 (19.3%). Patients with a favorable outcome have a significantly higher lung compliance (38.6 mL/cm H2O versus 27.5 mL/cm H2O), lower inspiratory pressure (12.0 cm H2O versus 16.0 cm H2O), and lower plateau pressure (17.0 cm H2O versus 21.0 cm H2O) than those with a poor neurologic outcome (all p < 0.01). Concerning time-dependent cox regression models, all maximum (adjusted hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.02–1.09), minimum (HR 1.08, 95% CI 1.03–1.13), and median (HR 1.06, 95% CI 1.02–1.09) compliances are independently associated with a good neurologic outcome. Maximum compliance, >32.5 mL/cm H2O at day 1, has the highest area under the receiver operating characteristic curve (0.745) with a positive predictive value of 90.4%. (4) Conclusions: Lung compliance may be an early predictor of intact neurologic survival in patients with ARDS following cardiac arrest.

Abstract 01: The Importance of Time to Cooling in Out-Of-Hospital Cardiac Arrest Patients to Influence Neurologically Intact Survival: A Sub-Analysis of the Princess Trial

Background: Early initiation of hypothermia has shown to be important to reduce brain injuries in experimental cardiac arrest models. The aim of this study was to investigate the association between time to initiate cooling and neurological intact survival in patients with out-of-hospital cardiac arrest (OHCA). Methods: A secondary analysis of prospectively collected data from the PRINCESS trial (NCT01400373) including 677 OHCA patients randomized to transnasal evaporative intra-arrest cooling or standard advanced life support and cooling started subsequent to hospital arrival. Time to randomization was used a proxy measurement for time to initiate cooling. An early treatment group was defined as patients randomized by the EMS &lt;20 minutes from the time of the cardiac arrest. Propensity scores were used to find matching patients in the control group. Patients with initial shockable rhythms were analyzed as a predefined subgroup. The primary outcome was good neurologic outcome, Cerebral Performance Category (CPC) 1-2 at 90 days. Secondary outcome was complete recovery (CPC 1). Results: In total 406 patients were randomized &lt;20 minutes from the cardiac arrest and were propensity score matched (1:1). In the propensity score matched analysis the proportion of patients with CPC 1-2 was 21.7% in the intervention and 17.2% in the control group, odds ratio (OR) 1.33, 95% confidence interval (CI) 0.80-2.21, p=0.273. In patients with initial shockable rhythm (79 intervention, 79 control) the difference in CPC 1-2 was 48.1% versus 32.0%, OR 2.05, 95%CI 1.00-4.21, p=0.0498. The proportion of patients with complete neurologic recovery, CPC 1, was 19.7% in the intervention and 13.3% in the control group, OR 1.60, 95% CI 0.92-2.79, p=0.097. In patients with initial shockable rhythm the proportion with CPC 1 was 45.6% versus 24.6%, OR 2.81, 95% CI 1.23-6.42, p=0.014. Conclusions: In this ancillary study of OHCA patients receiving intra-arrest cooling, there were differences in survival with good neurologic outcome and in complete neurological recovery in favor of early intra-arrest cooling patient group compared to standard care. These differences were statistically significant in the subgroup of patients with initial shockable rhythms.

Abstract 30: Targeted Temperature Management at 33 versus 36 Degrees: Outcomes After Real-World Implementation

Objective: To determine the association between targeted temperature management (TTM) goal temperature of 33 versus 36°C and neurologic outcome after out-of-hospital cardiac arrest (OHCA). Methods: This was a retrospective, before-and-after, cohort study conducted at an urban, academic, Level 1 trauma center from 2010-2017. We included adults with non-traumatic OHCA who received TTM. Our primary exposure was TTM goal temperature, which was changed from 33 to 36°C in April of 2014 at the study hospital. Primary outcome was neurologically-intact survival to discharge. Secondary outcomes included hospital mortality and care processes. We used univariate analysis and multivariate logistic regression to examined the association between TTM goal and outcome. Results: Of 782 OHCA patients transported to the study hospital, 453 (58%) received TTM. Of these, 258 (57%) were treated during the 33°C period (TTM33) and 195 (43%) were treated during the 36°C period (TTM36). Patients treated during TTM33 were older (57 vs. 52 years, p&lt;0.05) and had more arrests of cardiac etiology (45 vs. 35%, p &lt;0.05), but otherwise had similar baseline characteristics, including initial rhythm. 40% of patients treated during TTM33 survived with favorable neurologic outcome, compared with 30% in the TTM36 group (p&lt;0.05). After adjustment for demographic and cardiac arrest characteristics, TTM33 was associated with increased odds of neurologically-intact survival to discharge (OR 1.79, 95% CI 1.09-2.94). TTM33 was not associated with significantly improved hospital mortality. TTM was implemented faster (1.9 vs 3.5 hours from 911 call, p&lt;0.001) and more frequently in the emergency department during the TTM33 period. (87 vs. 55%, p&lt;0.001) Conclusion: Comatose, adult OHCA patients treated during the TTM33 period had higher odds of neurologically-intact survival to hospital discharge compared with those treated during the TTM36 period. Our findings may be explained by earlier and more aggressive TTM implementation during the TTM33 period, secular changes in patient characteristics or care, or a biological effect of lower temperature not detected in recent trials.

Abstract 297: Mitochondrial Cyclophilin D as a Target for Cardiac Arrest Resuscitation: Insight From Knockout Mice

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&lt;0.05). CA-induced myocardial dysfunction and increase in plasma levels of troponin were both attenuated by CypD deletion (p&lt;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&lt;0.05 versus WT). Short-term survival (24 hours) was significantly higher in CypD -/- than WT mice (p&lt;0.05). Only therapeutic hypothermia significantly improved both short-term and neurological intact survival at day 7 after CA compared to WT (p&lt;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.

Early On-Scene Management of Pediatric Out-of-Hospital Cardiac Arrest Can Result in Improved Likelihood for Neurologically-Intact Survival

AimTo evaluate the frequency of neurologically-intact survival (SURV) following pediatric out-of-hospital cardiac arrest (POHCA) when comparing traditional early evacuation strategies to those emphasizing resuscitation efforts being performed immediately on-scene. MethodsBefore 2014, emergency medical services (EMS) crews in a county-wide EMS agency provided limited treatment for POHCA on-scene and rapidly transported patients to appropriate hospitals. After 2014, training strongly concentrated upon EMS provider comfort levels with on-scene resuscitation efforts including methods to expedite protocols on-site and control positive-pressure ventilation. Frequency of SURV (hospital discharge) was compared for the two years prior to initiating the immediate on-scene care strategy to the ensuing two years following implementation. ResultsBetween 01/01/2012 and 12/31/2015, 94 children experienced POHCA. There were no significant differences before and after the on-scene focus in terms of age, sex, etiology, presenting electrocardiograph, drug infusions or bystander-performed cardiopulmonary resuscitation and total scene times actually remained similar (14.3 vs. 17.67 minutes). SURV increased significantly upon implementation of the immediate on-scene management strategy and was sustained over the next two years (0.0% to 23%; p = 0.0013). Though statistically-indeterminate in this analysis, the improvement was associated with a shorter mean time to epinephrine administration among resuscitated patients (16.6 vs. 7.65 minutes). ConclusionFacilitating immediate on-scene management of POHCA can result in improvements in life-saving. Although a historically-controlled evaluation, the compelling appearance of neurologically-intact survivors was immediate and sustained. Targeted training, more efficient, physiologically-driven procedures, and trusted encouragement from supervisors, likely played the most significant roles and not necessarily extended scene times.

Abstract 145: Efficacy of ECG Waveform to Predict Outcome in Patients With Out-of-Hospital Cardiac Arrest

Introduction: Neurological intact survival of pulseless electrical activity (PEA) has extremely poor outcome when compared with ventricular fibrillation. In Japan, the all patients with out-of-hospital cardiac arrest received CPR is transferred to emergency hospitals. To determine termination of resuscitation, it is necessary to predict their outcome. Therefore, we analyzed the relationship between ECG changes during prehospital resuscitation and outcome. Method: This study is a retrospective observational study for out-of-hospital PEA in April 2012 - April 2017 which was transported to the emergency medical center in Shizuoka General Hospital. We examined consecutive PEA cases where recorded by emergency medical services. The QRS width and RR interval were measured in ECG recording in the initial check pulse phase and arrival hospital. The primary outcome was survival admission and the secondary outcome was good neurologic outcome defined as cerebral performance score (CPC) of 1, 2. ECG changes determined as QRS width and RR interval in initial rhythm minus those at hospital arrival. Results: Eighty-four patients were analyzed and the average age was 77.3 years old, male 52.0%. There were 44 cases (52%) with survival admission (ROSC cases) and 7 (8%) with CPC 1-2. ROSC cases showed significantly narrower QRS width than non-ROSC cases in the initial waveform (139.1±61.9 vs 165.5±57.5msec, P&lt;0.05). Regarding ECG waveform changes, RR interval was significantly shortened in ROSC cases(-356.0±1256.0 vs 386.8±1258.6msec, P&lt;0.01). Comparing CPC1-2 cases and CPC3-5 cases, QRS width is significantly narrower in CPC1-2 cases(108.6±44.51 vs 155.6±60msec, P&lt;0.05), and there were no significant differences in ECG waveform changes. Multivariate analysis revealed that Initial QRS width and RR interval change are the independent factors associated with survival admission. Conclusion: Those findings suggested that analyzing QRS width and change of RR intervals during prehospital resuscitation predict survival admission in PEA cases.

Extracorporeal cardiopulmonary resuscitation in refractory intra-operative cardiac arrest: an observational study of 12-year outcomes in a single tertiary hospital.

Refractory intra-operative cardiac arrest is a challenging issue for anaesthetists. In this study, we analysed the outcomes of adult patients who received extracorporeal cardiopulmonary resuscitation for refractory intra-operative cardiac arrest between 2005 and 2016, using data from our institutional extracorporeal membrane oxygenation registry. We defined refractory intra-operative cardiac arrest as the failure of a return of spontaneous circulation after 30min of cardiopulmonary resuscitation. The primary outcome measure was neurologically intact survival with a cerebral performance category score of 1 or 2 at hospital discharge. Between 2005 and 2016, extracorporeal cardiopulmonary resuscitation was used to treat 23 patients who experienced refractory cardiac arrest in the operating room. The survival rates of neurologically-intact subjects were 9/23 (39%) and 6/23 (26%) at 24h postoperatively and at hospital discharge, respectively. The main cause of refractory-intra-operative cardiac arrest was haemorrhagic shock in 13 out of 23 (57%) patients, and the neurologically-intact survival rate in these patients was 3/13 (23%) at discharge. Our study showed that approximately a quarter of patients with refractory intra-operative cardiac arrest caused by haemorrhage would receive survival benefit from extracorporeal cardiopulmonary resuscitation. Therefore, extracorporeal cardiopulmonary resuscitation may be a possible option in this clinically-challenging situation.

Non-invasive characterization of hemodynamics in adult out-of-hospital cardiac arrest patients soon after return of spontaneous circulation

BackgroundLittle is known about hemodynamics in adult, out-of-hospital (OHCA) patients following return of spontaneous circulation (ROSC). A 1994 study when “high-dose epinephrine” use was common showed consistently elevated systemic vascular resistance (SVR) lasting ≥6 h in 49 adult patients after return of spontaneous circulation (ROSC). Study aimTo characterize hemodynamic abnormalities in adult OHCA patients soon after ROSC. Our hypothesis was that, unlike the consistently high SVR values reported when “high-dose” epinephrine was in common use, there would be a more heterogenous distribution of SVR values using current adrenergic therapy. MethodsWe included adult, OHCA patients transported by paramedics to the Emergency Department (ED) post-ROSC. Children, prisoners, pregnant women, and those with ongoing CPR or arrest due to traumatic injury were excluded. Hemodynamics were recorded non-invasively as soon as feasible after ED arrival but were not used to influence therapy, which was guided by clinical judgment of treating ED physicians. ResultsHemodynamics were recorded on 30 patients 20 [16,25] minutes after ED arrival: 50% had a normal SVR, 30% had a high SVR, and 20% had a low SVR. There was no difference in survival to admission among groups, although there was a difference among groups in survival to discharge. Comparing the low SVR group vs the combined normal and high group revealed a trend for fewer 0/6 (0%) low vs. 10/24 (42%) normal or high SVR patients surviving to hospital discharge (p = .053). ConclusionA heterogeneous range of hemodynamic states exist post-ROSC rather than consistent vasoconstriction. Adequately powered, randomized clinical trials will be needed to determine whether noninvasively-derived, hemodynamic-directed therapy can play a role in improving neurologically-intact survival following OHCA in adults.