Cardiac Arrest Protocol Research Articles

Carbon monoxide as a cellular protective agent in a swine model of cardiac arrest protocol.

Out-of-hospital cardiac arrest (OHCA) affects over 360,000 adults in the United States each year with a 50-80% mortality prior to reaching medical care. Despite aggressive supportive care and targeted temperature management (TTM), half of adults do not live to hospital discharge and nearly one-third of survivors have significant neurologic injury. The current treatment approach following cardiac arrest resuscitation consists primarily of supportive care and possible TTM. While these current treatments are commonly used, mortality remains high, and survivors often develop lasting neurologic and cardiac sequela well after resuscitation. Hence, there is a critical need for further therapeutic development of adjunctive therapies. While select therapeutics have been experimentally investigated, one promising agent that has shown benefit is CO. While CO has traditionally been thought of as a cellular poison, there is both experimental and clinical evidence that demonstrate benefit and safety in ischemia with lower doses related to improved cardiac/neurologic outcomes. While CO is well known for its poisonous effects, CO is a generated physiologically in cells through the breakdown of heme oxygenase (HO) enzymes and has potent antioxidant and anti-inflammatory activities. While CO has been studied in myocardial infarction itself, the role of CO in cardiac arrest and post-arrest care as a therapeutic is less defined. Currently, the standard of care for post-arrest patients consists primarily of supportive care and TTM. Despite current standard of care, the neurological prognosis following cardiac arrest and return of spontaneous circulation (ROSC) remains poor with patients often left with severe disability due to brain injury primarily affecting the cortex and hippocampus. Thus, investigations of novel therapies to mitigate post-arrest injury are clearly warranted. The primary objective of this proposed study is to combine our expertise in swine models of CO and cardiac arrest for future investigations on the cellular protective effects of low dose CO. We will combine our innovative multi-modal diagnostic platform to assess cerebral metabolism and changes in mitochondrial function in swine that undergo cardiac arrest with therapeutic application of CO.

Lower versus higher blood pressure targets in comatose patients resuscitated from out-of-hospital cardiac arrest-Protocol for a secondary Bayesian analysis of the box trial.

The management of blood pressure targets during intensive care after out-of-hospital cardiac arrest (OHCA) remains a topic of debate. The blood Pressure and Oxygenation Targets After OHCA (BOX) trial explored the efficacy of two different blood pressure targets in 789 patients during intensive care after OHCA. In the primary frequentist analysis, no statistically significant differences were found for neurological outcome after 90 days. This protocol outlines secondary Bayesian analyses of 365-day all-cause mortality and two secondary outcomes: neurological outcome after 365 days, and plasma neuron-specific enolase, a biomarker of brain injury, after 48 h. We will employ adjusted Bayesian logistic and linear regressions, presenting results as relative and absolute differences with 95% confidence intervals. We will use weakly informative priors for the primary analyses, and skeptical and evidence-based priors (where available) in sensitivity analyses. Exact probabilities for any benefit/harm will be presented for all outcomes, along with probabilities of clinically important benefit/harm (risk differences larger than 2%-points absolute) and no clinically important differences for the binary outcomes. We will assess whether heterogeneity of treatment effects on mortality is present according to lactate at admission, time to return of spontaneous circulation, primary shockable rhythm, age, hypertension, and presence of ST-elevation myocardial infarction. This secondary analysis of the BOX trial aim to complement the primary frequentist analysis by quantifying the probabilities of beneficial or harmful effects of different blood pressure targets. This approach seeks to provide clearer insights for researchers and clinicians into the effectiveness of these blood pressure management strategies in acute medical conditions, particularly focusing on mortality, neurological outcomes, and neuron-specific enolase.

Abstract 331: Whether the Compliance of Target Temperature Management Protocol Affects Outcomes in Cardiac Arrest Survivors?

Background: Targeted temperature management (TTM) improves neurological recovery in cardiac arrest survivors and protocols have been established during the implementation of high quality TTM with recommended about cooling rate, duration of maintenance, and rewarming speed. Research question Whether fitting TTM protocols results in better survival and neurological recovery remains un-investigated. Aim: To evaluate the benefit of TTM protocol compliance on the outcomes in cardiac arrest survivors. Methods: The retrospective cohort study enrolled 1141 non-traumatic adult cardiac arrest survivors and pre-arrest Cerebral Performance Category (CPC) score=1-2 during 2015-2020 at a tertiary medical center. Patients who underwent TTM (n=305) were further selected. Patients with spontaneous hypothermia (<35°C) at ROSC (n=107) and those without TTM completion (n=21) were excluded. A total of 202 patients were finally enrolled in the study. As the protocol was divided into three categories: cooling rate, duration of maintenance, and rewarming speed, there were 110 patients in the protocol-fit group and 92 patients in the protocol non-fit group. The favorable neurological recovery was considered as CPC=1-2 at hospital discharge. Results: There were 42 patients (38.2%) in the protocol-fit group had favorable neurological recovery, while 32 patients (34.8%) in the protocol non-fit group. After adjusting age, initial shockable rhythm, witnessed collapse and CPR duration, the protocol non-fit group was associated to the poor neurological outcome (adjusted odds ratio [aOR] 2.44, 95% confidence interval [CI]= 2.23-5.35) but not the in-hospital mortality (aOR 2.31, 95% CI= 0.70-2.47). In the protocol non-fit group, the most common non-fitting reason was the prolong time-to-target temperature (n=33, 58.7%). Twenty-four patients who failed to fit the 2 categories. The number of non-fitting category was not significantly associated with in-hospital mortality and poor neurological recovery due to limited sample number. Conclusion: Among cardiac arrest survivors undergoing TTM, patients who did not fit the TTM protocols were associated with poor neurological recovery than those who completely fit the protocols.

Influence of cardioplegic solution on incidence of delirium after CABG surgery: Use of Calafiore blood cardioplegia versusHTK-Bretschneider-solution in a single-center retrospective analysis from 2017 to 2021.

Purpose of the present study is an evaluation of postoperative incidence for delirium after coronary artery bypass surgery (CABG). Study addressed whether application of Histidine-Tryptophan-Ketoglutarate (HTK) solution (Bretschneider) or blood cardioplegia (Calafiore) is associated with increased of postoperative delirium cases. In a retrospective, single center evaluation a total number of 273 patients were enrolled in the study from January 2017 to October 2021. There were 124 patients assigned to the Calafiore groupblood cardioplegic solution (BCC) and 149 patients were included in the Bretschneider group (HTK). The primary endpoint was the postoperative delirium rate in its frequency of occurrence. Definition of the dilirium status was performed using the Confusion Assessment Method in the Intensive Care Unit (CAM-ICU) score during the first three postoperative days. Secondary endpoints were the time intervals of intensive care duration of stay, mechanical ventilation, total extracorporeal circulation, ischemia and reperfusion. Serum levels of the electrolytes Sodium, Potassium, ionized Calcium, and Chloride were monitored. Although no significant difference in delirium status between the groups were noticed, on third postoperative day, delirium rate dependent on cardioplegia solution used (HTK 12.0%; BCC 3.0%; p = .024) and duration of intensive care stay differed (HTK 4.5 vs. BCC 3.0 days; p = .001). Although Ischemic time (HTK 73.0 vs. BCC 83.0 min; p < .001) and reperfusion time (HTK 35.0 vs. Calafiore 24.0 min; p < .001) were extended in the BCC group less cases of delirium were diagnosed. Serum sodium levels after HTK cardioplegic infusion were decreased (HTK 129.68 vs. BCC 138.96 mmol/l; p < .001). The significant difference persists up to the hundredth extracorporeal circulation circuit min(p = .005). The present data suggest an impact of the cardioplegic solution used upon postoperative delirium rates. Optimization of cardiac arrest protocols is needed. Present data encourage further prospective studies regarding the impact of cardioplegic solutions on electrolyte imbalance for postoperative delirium rates in CABG surgery.

Temporal Changes in Epinephrine Dosing in Out-of-Hospital Cardiac Arrest: A Review of EMS Protocols across the United States.

Administration of epinephrine has been associated with worse neurological outcomes for survivors of out-of-hospital cardiac arrest. The publication of the 2018 PARAMEDIC-2 trial, a randomized and double-blind study of epinephrine in out-of-hospital cardiac arrest, provides the strongest evidence to date that epinephrine increases return of spontaneous circulation (ROSC) but not neurologically intact survival. This study aims to determine if Emergency Medical Services (EMS) cardiac arrest protocols have changed since the publication of PARAMEDIC-2. States in the US utilizing mandatory or model state-wide EMS protocols, including Washington DC, were included in this study. The nontraumatic cardiac arrest protocol as of January 1, 2018 was compared to the protocol in effect on January 1, 2021 to determine if there was a change in the administration of epinephrine. Protocols were downloaded from the relevant state EMS website. If a protocol could not be obtained, the state medical director was contacted. A 2021 state-wide protocol was found for 32/51 (62.7%) states. Data from 2018 were available for 21/51 (41.2%) states. Of the 11 states without data from 2018, all follow Advanced Cardiac Life Support (ACLS) guidelines in the 2021 protocol. Five (15.6%) of the states with a state-wide protocol made a change in the cardiac arrest protocols. Maximum cumulative epinephrine dose was limited to 4mg in Maryland and 3mg in Vermont. Rhode Island changed epinephrine in shockable rhythms to be administered after three cycles of cardiopulmonary resuscitation (CPR) and an anti-arrhythmic. Rhode Island also added an epinephrine infusion as an option. No states removed epinephrine administration from their cardiac arrest protocol. Simple statistical analysis was performed with Microsoft Excel. Several states have adjusted cardiac arrest protocols since 2018. The most frequent change was limiting the maximum cumulative dosage of epinephrine. One state changed timing of epinephrine dosing depending on the rhythm and also provided an option of an epinephrine infusion in place of bolus dosing. While the sample size is small, these changes may reflect the future direction of prehospital cardiac arrest protocols. Significant limitations apply, including the exclusion of local and regional protocols which are more capable of quickly adjusting to new research. Additionally, this study is only focused on EMS in the United States.

Point-of-Care Ultrasound Use by EMS Providers in Out-of-Hospital Cardiac Arrest.

Paramedics received training in point-of-care ultrasound (POCUS) to assess for cardiac contractility during management of medical out-of-hospital cardiac arrest (OHCA). The primary outcome was the percentage of adequate POCUS video acquisition and accurate video interpretation during OHCA resuscitations. Secondary outcomes included POCUS impact on patient management and resuscitation protocol adherence. A prospective, observational cohort study of paramedics was performed following a four-hour training session, which included a didactic lecture and hands-on POCUS instruction. The Prehospital Echocardiogram in Cardiac Arrest (PECA) protocol was developed and integrated into the resuscitation algorithm for medical non-shockable OHCA. The ultrasound (US) images were reviewed by a single POCUS expert investigator to determine the adequacy of the POCUS video acquisition and accuracy of the video interpretation. Change in patient management and resuscitation protocol adherence data, including end-tidal carbon dioxide (EtCO2) monitoring following advanced airway placement, adrenaline administration, and compression pauses under ten seconds, were queried from the prehospital electronic health record (EHR). Captured images were deemed adequate in 42/49 (85.7%) scans and paramedic interpretation of sonography was accurate in 43/49 (87.7%) scans. The POCUS results altered patient management in 14/49 (28.6%) cases. Paramedics adhered to EtCO2 monitoring in 36/36 (100.0%) patients with an advanced airway, adrenaline administration for 38/38 (100.0%) patients, and compression pauses under ten seconds for 36/38 (94.7%) patients. Paramedics were able to accurately obtain and interpret cardiac POCUS videos during medical OHCA while adhering to a resuscitation protocol. These findings suggest that POCUS can be effectively integrated into paramedic protocols for medical OHCA.

Abstract 13198: Impact of Targeted Resident Education on Perceptions of Communication and Participation in Cardiac Arrest

Introduction: Debriefing sessions after in-hospital cardiac arrest have been demonstrated to improve teamwork and survival outcomes. Though recommended in 2020 AHA Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care, implementation remains low. Hypothesis: We postulated that a didactic training session provided to code leaders would increase rates of participation of AHA-recommended post-arrest debriefing sessions. Methods: Surveys were distributed to hospital personnel who participate in code blue/ERTs at an academic, tertiary-care medical center. Questions were graded on Likert scale to assess provider-reported perceptions of teamwork, communication, and confidence in conducting and participating in Code Blues. Participants were stratified in groups depending on whether they had previously participated in debriefing sessions. Primary outcomes were quantified using a Likert-type scale ranging from 1 to 5. Surveys were compared to surveys from prior years to assess if the intervention of a code blue didactics lecture delivered to code leaders resulted in any change in overall participation rate in the debriefing protocol. Results: Among 181 participants (61% female), 32% were residents, 54% nurses, 1.7% respiratory therapists. Self-evaluated current knowledge of ACLS protocols was significantly higher in the debriefing group (p = 0.0098), while there were no differences in perceived communication (p=0.76), and confidence in leading (p = 0.2) and participating (p = 0.2). We did not find a statistically significant difference in debriefing participation rate after our intervention (57% pre vs 58% post intervention, p=0.8), even when stratified by hospital role: critical care nurses (50% vs 71%, p=0.3), non-ICU nurses (68% vs 57%, p=0.3) and residents (67% vs 50%, p=0.2). Conclusions: Our study demonstrated that participation in post-code debriefing sessions was associated with a statistically significant increase in knowledge of cardiac arrest protocols. A code blue didactics lecture did not result in a statistically significant increase in post-arrest debriefing participation. Further study to elucidate methods to enhance adoption of this crucial, guideline recommended practice is warranted.

Long-term physical and psychological outcomes after out-of-hospital cardiac arrest—protocol for a national cross-sectional survey of survivors and their relatives (the DANCAS survey)

IntroductionThe number of out-of-hospital cardiac arrest (OHCA) survivors is increasing. However, there remains limited knowledge on the long-term physical and psychological problems suffered by survivors and their relatives. The aims...

P0250COLD DIURESIS DURING TARGETED TEMPERATURE MANAGEMENT AFTER CARDIAC ARREST, MYTH OR FACT?

Abstract Background and Aims Therapeutic hypothermia or targeted temperature management (TTM) has been standard treatment for cardiac arrest survivors with suspected hypoxic ischemic brain injury for improvement in both survival and neurological outcomes. TTM is consisted of an induction phase of quickly lowering the temperature to target temperature (ranging from 32°C -36°C) as soon as possible, a hypothermia maintenance phase of keeping the body temperature at target temperature for at least 24 hours, a rewarming phase of slowly rewarming the temperature to normothermia, and a normothermia phase of keeping the body temperature at normothermia. During the dynamic changes in body temperature, cold-diuresis is a commonly described phenomenon. However, limited studies have characterized cold-induced diuresis during TTM. In this study, we sought to determine urine output changes during post cardiac arrest therapeutic hypothermia. Method This retrospective cohort study included adult patients who underwent TTM after out-of-hospital cardiac arrest and were admitted to the intensive care unit for post cardiac arrest care between January 2012 and August 2018. The exclusion criteria of this study were as follows: 1) deceased status before the completion of all phase of TTM; 2) previous end stage kidney disease patients, 3) undergoing renal replacement therapy due to AKI within 48 hours of TTM termination; 4) terminal cancer less than 6 months of life expectancy or previously cerebral performance category (CPC) 3 or more. The neurologic outcome was assessed using the CPC score after 1 month. Good neurologic outcome was defined as a CPC score of 1, 2 and poor neurologic outcome as a CPC score of 3 to 5. The post cardiac arrest protocol recommends a target temperature of 33°C unless the patient is hemodynamically unstable or has a bleeding tendency or severe infection. Rewarming rate was 0.15°C/hr or 0.25°C/hr. TTM was conducted with the use of temperature managing devices with a feedback loop system (Artic Sun Energy Transfer Pads, Medivance Corp., Louisville, CO, USA; Cool Guard Alsius Icy Heat Exchange Catheter, Alsius Corporation, Irvine, CA, USA). We calculated the hourly IV fluid input and urine output rates for each TTM phase. To compare the mean of urine volume between each TTM phase, we used repeated measure analysis of variance (ANOVA). Results 178 Patients included in the analysis. We observed a increase in urine output rates during hypothermia induction. This effect persisted even after adjustment for variable clinical confounders, including intravenous fluid input rate, mean arterial pressure (MAP), initial shockable rhythm, SOFA score, body mass index, and IV furosemide use. However, we did not detect any evidence of urine output increases or decreases during the hypothermia maintenance or rewarming phases. By repeating measures ANOVA and a linear mixed model, it was confirmed that there is a difference in urine output for each TTM phase. Even after the post hoc analysis was calibrated with several variables, only the hypotheria induction phase differed significantly from the urine output of the phase. Conclusion Although our results are some limitations, the findings support the potential presence of cold-induced dieresis, but not rewarm anti-diuresis during TTM. Our study may not fully capture the extent of renal impairment in post cardiac arrest undergoing TTM. However, our objective was to characterize urine output during TTM in post cardiac arrest patients. This has important implications for fluid management in patients undergoing TTM.

Preventing Harm: Testing and Implementing Health Care Protocols Using Systems Integration and Learner-Focused Simulations: A Case Study of a New Postcardiac Surgery, Cardiac Arrest Protocol

Systems integration (SIS) simulation and system-focused debriefing is an approach to test new processes with health care teams to inform its design and utility and identify systems issues proactively. Learner-focused simulations support team training with a focus on individual knowledge and skills. These strategies combined provide a highly effective quality improvement approach to test and implement new processes. This article will describe how we used SIS followed by learner-focused simulations and debriefings to introduce, test, refine, and train our team on a new, locally adapted cardiac arrest protocol after cardiac surgery (early chest opening).

Recent advances in personalizing cardiac arrest resuscitation

Cardiac arrest remains a significant cause of death and disability throughout the world. However, as our understanding of cardiac arrest and resuscitation physiology has developed, new technologies are fundamentally altering our potential to improve survival and neurologic sequela. Some advances are relatively simple, requiring only alterations in current basic life support measures or integration with pre-hospital organization, whereas others, such as extra-corporeal membrane oxygenation, require significant time and resource investments. When combined with consistent rescuer and patient-physiologic monitoring, these innovations allow an unprecedented capacity to personalize cardiac arrest resuscitation to patient-specific pathophysiology. However, as more extensive options are established, it can be difficult for providers to incorporate novel resuscitation techniques into a cardiac arrest protocol which can fit a wide variety of cases with varying complexity. This article will explore recent advances in our understanding of cardiac arrest physiology and resuscitation sciences, with particular focus on the metabolic phase after significant ischemia has been induced. To this end, we establish a practical consideration for providers seeking to integrate novel advances in cardiac arrest resuscitation into daily practice.

Out-of-Hospital Cardiac Arrest Protocol Comparison

Background Early identification of out-of-hospital cardiac arrest (OHCA) has been proven to increase survival rates. Toward this goal, emergency medical dispatchers commonly use one of two types of emergency medical dispatcher systems, each with a unique OHCA protocol. The criteria-based dispatch (CBD) protocol is a set of guidelines and prompts intended for dispatchers with clinical background and experience, while the medical priority dispatch (MPD) is a scripted caller interrogation protocol intended for non-healthcare dispatchers. The objective of this study was to compare CBD and MPD protocols in terms of accuracy and duration of the identification process. Methods To compare the two protocols we conducted an OHCA simulation of an emergency phone call by a bystander. Two groups participated in the simulation: 1) emergency medical technicians during paramedic vocational training, in the role of CBD dispatchers, and 2) non-healthcare personnel in the role of MPD dispatchers. Dispatchers were asked to identify whether a patient was having a cardiac arrest based on the information they received from the bystander. Results Duration of the OHCA identification process was significantly shorter for participants using MPD (CBD 50 seconds vs. MPD 33 seconds, p=0.003). The OHCA accuracy was 86.49% for the CBD and 82.86% for MPD, but this difference was not statistically significant (p=0.60). Conclusion The advantages of each protocol suggest that some combination of the two protocols may optimise the OHCA identification process, leading to increased accuracy and shorter duration of the identification process.

Drugs in Out-of-Hospital Cardiac Arrest.

Managing out-of-hospital cardiac arrest involves unique challenges, including delays in the initiation of advanced interventions and a limited number of trained personnel on scene. Recent out-of-hospital randomized controlled trials, systematic reviews, and metaanalyses provide key insights into what interventions are best proven to positively impact patient outcomes from out-of-hospital cardiac arrest. We review the literature on medications used in out-of-hospital cardiac arrest and summarize evidence-based guidelines from the American Heart Association that form the basis for most emergency medical services cardiac arrest protocols across the United States.

In-hospital sudden cardiac arrest protocol analysis.

In-hospital sudden cardiac arrest (SCA) is an event that is linked to high mortality. Data analysis of SCA and the course of in-hospital cardiopulmonary resuscitation (CPR) allows for its better understanding and improvement. Analysis of cases of SCA and the procedures taken by the medical staff of University Hospital. A retrospective analysis of 104 protocols of SCA, from May 2014 to December 2015. Actions taken by medical staff before the arrival of the resuscitation team (RT) and RT proceedings. Data are presented as median and mean ± standard deviation. 52.88% of cases were women, and their mean age was 70.82 ± 13.32 years. Resuscitation activities (basic life support: 48.08%, advance life support: 42.31%) were performed before the RT arrival, and no action was taken in 5.77% of cases. The cardiac arrest occurred most commonly in the afternoons hours, and the Emergency Room was the place of CPR in 41.35% of cases. The waiting time for RT was on average 4.47 ± 5.85 min. Non-defibrillation rhythms occurred in 79.80%, and the efficacy of resuscitation was 40%. Resuscitation protocols should be registered not only as an important part of medical records, but also as a source of information during the CPR training of staff. The lack of rescue activities before the arrival of the RT indicates the urgent need to identify the cause of the problem and eliminate these negative behaviours.

What's New in Obstetric Anesthesia: The 2016 Gerard W. Ostheimer Lecture.

This special article presents potentially important trends and issues affecting the field of obstetric anesthesia drawn from publications in 2015. Both maternal mortality and morbidity in the United States have increased in recent years because, in part, of the changing demographics of the childbearing population. Pregnant women are older and have more pre-existing conditions and complex medical histories. Cardiovascular and noncardiovascular medical diseases now account for half of maternal deaths in the United States. Several national and international organizations have developed initiatives promoting optimal obstetric and anesthetic care, including guidelines on the obstetric airway, obstetric cardiac arrest protocols, and obstetric hemorrhage bundles. To deal with the increasing burden of high-risk parturients, the national obstetric organizations have proposed a risk-based classification of delivery centers, termed as Levels of Maternal Care. The goal of this initiative is to funnel more complex obstetric patients toward high-acuity centers where they can receive more effective care. Despite the increasing obstetric complexity, anesthesia-related adverse events and morbidity are decreasing, possibly reflecting an ongoing focus on safe systems of anesthetic care. It is critical that the practice of obstetric anesthesia expand beyond the mere provision of safe analgesia and anesthesia to lead in developing and promoting comprehensive safety systems for obstetrics and team-based coordinated care.

International Federation for Emergency Medicine Consensus Statement: Sonography in hypotension and cardiac arrest (SHoC): An international consensus on the use of point of care ultrasound for undifferentiated hypotension and during cardiac arrest.

The IFEM USIG invited 24 recognized international leaders in PoCUS from emergency medicine and critical care to form an expert panel to develop the sonography in hypotension and cardiac arrest (SHoC) protocol. The panel was provided with reported disease incidence, along with a list of recommended PoCUS views from previously published protocols and guidelines. Using a modified Delphi methodology the panel was tasked with integrating the disease incidence, their clinical experience and their knowledge of the medical literature to evaluate what role each view should play in the proposed SHoC protocol. Consensus on the SHoC protocols for hypotension and cardiac arrest was reached after three rounds of the modified Delphi process. The final SHoC protocol and operator checklist received over 80% consensus approval. The IFEM-approved final protocol, recommend Core, Supplementary, and Additional PoCUS views. SHoC-hypotension core views consist of cardiac, lung, and inferior vena vaca (IVC) views, with supplementary cardiac views, and additional views when clinically indicated. Subxiphoid or parasternal cardiac views, minimizing pauses in chest compressions, are recommended as core views for SHoC-cardiac arrest; supplementary views are lung and IVC, with additional views when clinically indicated. Both protocols recommend use of the "4 F" approach: fluid, form, function, filling. An international consensus on sonography in hypotension and cardiac arrest is presented. Future prospective validation is required.

Abstract 12474: Nicotinamide Restores Tissue Nad + and Improves Outcomes in a Murine Model of Cardiac Arrest

Introduction: Metabolic suppression in the ischemic heart is characterized by reduced levels of NAD + and ATP. Hypothesis: Since NAD + is required for most metabolic processes that generate ATP, we hypothesized that nicotinamide (NAM) restore of tissue NAD + and improve cardiac function and survival in a mouse model of cardiac arrest. Methods: Cardiomyocytes isolated from 1-2-day old C57BL6 mice were exposed to 30 min ischemia and 90 min reperfusion. Contraction recovery was measured by phase contrast imaging without and with 0.1mM NAM given at reperfusion. Adult C57BL6 mice were subjected to an established KCL-induced 8 min cardiac arrest protocol, randomly assigned to receive saline or 500 mg/kg NAM after cardiopulmonary resuscitation (CPR). Survival, MAP, ETCO 2, and continuous ECG were recorded until 4 h after successful CPR. Results: We first tested the effect of NAM on NAD + recovery in heart cells exposed to the simulated ischemia and reperfusion. NAD + content was decreased from 4.51 ± 0.03 nMol/g before ischemia (equilibration) to 2.69 ± 0.42 nMol/g at the end of ischemia. Treatment with 0.01 mM NAM completely restored the cellular level of NAD + by 15 min reperfusion (4.63 ± 0.45 nMol/g), while there was no significant recovery of NAD + in untreated cells. This rescue of NAD + depletion was associated with improved contractile recovery by 10 min reperfusion (58.1 ± 7.3% return of baseline contractile velocity vs.18.5 ± 3.7% in control cells, n=5, p &lt;0.05) that could be augmented further using isoproterenol treatment (83.3 ± 3.5% vs. 58.0 ± 2.9% in control cells. p &lt;0.05). We then tested the effect of NAM (500 mg/kg) on mouse SCA 4 h survival and cardiovascular recovery. NAM administered IV after CPR resulted in a trend toward improved mouse SCA survival, with 9/10 survival at 4 h as compared to 5/10 in the saline (NS) group. Compared to saline treated mice, NAM-treated mice displayed improved NAD + content in hearts obtained at 4 h post-ROSC compared to saline treated SCA hearts (2.4 ± 0.1 nMol/g vs. 4.5 ± 0.1 nMol/g, p &lt;0.05). Conclusions: NAM is CPR medication that can rapidly restore cardiac tissue NAD + and promote contractile recovery, with improved early survival demonstrated in a mouse model of cardiac arrest.

Considering the History of Interprofessional Education and Practice in the United States.

In recent years, a number of historians of nursing and have asked whether our field might more appropriately and inclusively be renamed the history of health care.1 To outsiders, history of medicine appears to reinforce conceptual and professional silos that have historically privileged the role of physicians, Western medicine, and disease over more integrative accounts of caregiving, diverse epistemologies of healing, and health. Today, the mantra that interprofessional education and practice are the future of health care offers an explicit invitation to move beyond the disciplinary and professional silos often replicated in our approach to health-care history. While nurse-physician relationships have received considerable attention from historians, this section expands on that base to explore the history of the development of interprofessional education and practice more broadly.Five of the seven papers in this special section were presented at a lunch session on the history of interprofessional education and practice at the annual meeting of the American Association for the History of Medicine (AAHM) in 2014. As the authors document, the concepts of teamwork and interprofessionalism are not new, although, as Julie Fairman points out, the term interprofessional is of more recent coinage. The case studies here help establish the range of precedents and the varied contexts across the twentieth century for both informal learning and working together and more formal interprofessional teams that arose in response to the efficient organization of care, workforce issues, and demands for health-care delivery. This timeline departs from the tendency of practitioners to locate interprofessionalism primarily as a post-World War II movement best characterized by the development of advanced practice nursing, physician assistant programs, and specialized units and teams in hospitals.2 Taken together, and supplemented by the lively discussion at the AAHM session, these articles elucidate key themes emerging from the historical examples of interprofessional education and practice and suggest an agenda for further exploration.Inherent in the appeals for interprofessional education and practice, as Fairman notes, is the assumption that changes in education and practice will be a magic bullet producing new epistemologies and increasing quality of care. This must be disaggregated into more specific questions about what interdisciplinarity and interprofessionalism mean in practice. Are there problems that require a particular combination of knowledge and skill that cannot be solved any other way, such as the physiology and diet research questions posed by Ancel Key's Laboratory of Physiological Hygiene or the treatment decisions that benefit from bringing together pharmacists and clinicians at the bedside? To what extent must members of health-care teams master the knowledge base of the other professions represented, as exemplified by the clinical pharmacist curriculum and training for nurses in a range of medical skill sets as preparation for team practice? Can interprofessional teams function purely with the combination of individual professional expertise, on the model of rehabilitation? Where and why are new hybrid professions like nurse practitioners and physician assistants required? Is there a secondary implication that interprofessional practice will also be more holistic or ecological in its approach? Daniel Brauner's article on the cardiac arrest protocol suggests that interprofessional teamwork in the hospital can also produce greater biomedical reductionism, running against the trend toward holism fostered by interprofessional teams for family and community-based patient care.The articles also engage the reciprocal, shaping relationship between interprofessional practice and sites of care-the containers for health-care delivery. Beth Linker discusses the spread of rehabilitation units in hospitals, and Jennifer Gunn looks at the rise of community health centers, as an alternative to rural hospitals, designed to accommodate the need for a different interprofessional mix in the face of scarce physician labor. …

Abstract 13483: Peptide Inhibition of PTEN Improves Metabolic Recovery and Outcomes in a Murine Cardiac Arrest Model

Introduction: Recent work shows that PTEN inhibition protects against cardiomyocyte contractile dysfunction and death following ischemia/reperfusion. To further determine whether PTEN inhibition improves metabolic recovery and survival in a mouse model of cardiac arrest, we have designed a TAT fused cell-permeable peptide (TAT-PTEN9c) based on the c-terminal PDZ binding motif of PTEN for rapid tissue delivery. We hypothesized that TAT-PTEN9c interferes with endogenous PTEN binding to cell membrane adaptors resulting in increased Akt activation, causing Akt-enhanced glucose utilization (with decreased diversion of glucose via the alternate polyol pathway to sorbitol) and improved survival. Methods: Mouse cardiomyocytes were isolated from 1-3 day old mouse pups. Western blot was used to identify concentrations of TAT-PTEN9c that enhanced Akt phosphorylation in mouse cardiomyocytes exposed to oxidant stress. C57BL6 mice were then subjected to an established KCL-induced 8 min cardiac arrest protocol. 30 mice after CPR were randomly assigned to receive saline or TAT-PTEN9c. MAP, ETCO2, and ECG were recorded until 4 h after successful cardiopulmonary resuscitation (CPR). TAT-PTEN9c (7.8 mg/kg) was given intravenously (IV) after CPR (n=10). As a measure of impaired glucose utilization, sorbitol content in heart and brain was determined by a fluorescence assay of NADH formation using sorbitol dehydrogenase and NAD+. Results: TAT-PTEN9c peptide enhanced Akt activation in neonatal mouse cardiomyoctes in a concentration-dependent manner. Survival was significantly increased in the TAT-PTEN9c treated group compared to saline controls at 2 h (14/15, 93% vs. 9/15, 60%, P &lt; 0.05) and 4 h (10/15, 67% vs. 6/15, 40%, P &lt; 0.05) after CPR. Treated mice had increased Akt phosphorylation within 30 min after CPR in heart and brain tissues with significantly decreased sorbitol content, suggesting improved metabolic recovery and glucose utilization. Conclusion: TAT-PTEN9c can be used after CPR in a mouse SCA model to rapidly enhance Akt activation and decrease glucose shunting via the polyol pathway in critical organs, preventing early cardiovascular collapse and death. Further work exploring the role of tissue sorbitol in sudden cardiac arrest injury is needed.

Is It Still Cool to Cool? Interpreting the Latest Hypothermia for Cardiac Arrest Trial: March 2014 Annals of Emergency Medicine Journal Club

1.The authors reference 2 previous trials2,3 that compared therapeutic hypothermia (32°C to 34°C [89.6F to 93.2F] for 12 to 24 hours) with standard treatment and “showed a significant improvement in neurologic function and survival with therapeutic hypothermia.”1AWhat was the treatment effect in the previous 2 studies? What percentage of patients had neurologically intact survival? How many patients would one need to treat with hypothermia to produce 1 additional neurologically intact patient?BThere is good evidence that the presence of an initial shockable rhythm greatly enhances the probability of survival from cardiac arrest. Have any randomized trials demonstrated an improvement in neurologic outcomes in patients whose initial rhythm was pulseless electrical activity or asystole?2.Previous studies have reported deleterious effects when patients recovering from an out-of-hospital cardiac arrest develop fever,1,4,5 leading authors to question whether reported benefits are due to hypothermia or prevention of hyperthermia.1 The authors conducted a multicenter, international trial that randomized unconscious adults, who had return of spontaneous circulation after out-of-hospital cardiac arrest, to either 33°C or 36°C (91.4F or 96.8F) temperature target.AThe current recommendation by many expert consensus groups is to cool out-of-hospital cardiac arrest victims to 32°C to 34°C (89.6F to 93.2F) after ventricular fibrillation and possibly other rhythms. The authors did not follow this recommendation for one of the arms of the study. Do you believe there was equipoise? Discuss the importance of equipoise in clinical research.BCould this trial have been performed in the United States? What additional requirements would the investigators have to complete to receive institutional review board approval for exception from informed consent?CThe authors note the inability to blind the critical care practitioners; however, they were able to blind the assessors providing follow-up neurologic examination. Were the methods used to eliminate the risk of critical care provider bias sufficient?3.The authors examined the primary outcome of survival time and followed patients up to the end of the trial (ie, 180 days after the enrollment of the last patient) and powered the study to this outcome.AThe trial was designed as a superiority trial to detect a 20% reduction in the hazard ratio for death with hypothermia at 33°C (91.4F) versus a control group at 36°C (96.8F). Was the study appropriately powered for this outcome?BHow would the power calculations change if the study design were a noninferiority trial of relative normothermia at 36°C (96.8F) versus hypothermia at 33°C (91.4F)?CWhat were the secondary outcomes? Discuss the advantages and disadvantages of using composite outcomes in medical research.DTherapeutic hypothermia causes many physiologic changes and potential dangers to the patient. Therefore, the authors also collected the incidence of predefined serious adverse events up to day 7 in the ICU. Which specific adverse events did they collect? Do you think these adverse events and 7-day interval were sufficient? If not, what other events or intervals might you have chosen?ETo evaluate neurologic outcomes, the authors used the Cerebral Performance Category (CPC) and the modified Rankin score (mRS). For scores to be effective, they should be already validated. Have these 2 scores been previously validated? Are there other scores that the authors could have used?4.For analysis of their results, hazard ratios were used for the analysis of the primary outcome (end-of-trial mortality), but risk ratios were used to analyze the secondary outcomes (CPC score, mRS). What are the differences between hazard ratios and risk ratios? Why did the authors use different tests to analyze their primary and secondary outcomes?5.If you were creating a cardiac arrest protocol in your hospital, what would you set for the target temperature? Do you think the temperature or the protocol is more important for survival?