Publications by authors named "Robert W Neumar"

119 Publications

Rapid Treatment with Intramuscular Magnesium Sulfate During Cardiopulmonary Resuscitation Does Not Provide Neuroprotection Following Cardiac Arrest.

Mol Neurobiol 2022 Jan 14. Epub 2022 Jan 14.

Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.

Brain injury is the most common cause of death for patients resuscitated from cardiac arrest. Magnesium is an attractive neuroprotective compound which protects neurons from ischemic injury by reducing neuronal calcium overload via NMDA receptor modulation and preventing calcium-induced mitochondrial permeability transition. Intramuscular (IM) delivery of MgSO during CPR has the potential to target these mechanisms within an early therapeutic window. We hypothesize that IM MgSO administrated during CPR could achieve therapeutic serum magnesium levels within 15 min after ROSC and improve neurologic outcomes in a rat model of asphyxial cardiac arrest. Male Long Evans rats were subjected to 8-min asphyxial cardiac arrest and block randomized to receive placebo, 107 mg/kg, 215 mg/kg, or 430 mg/kg MgSO IM at the onset of CPR. Serum magnesium concentrations increased rapidly with IM delivery during CPR, achieving twofold to fourfold increase by 15 min after ROSC in all magnesium dose groups. Rats subjected to cardiac arrest or sham surgery were block randomized to treatment groups for assessment of neurological outcomes. We found that IM MgSO during CPR had no effect on ROSC rate (p > 0.05). IM MgSO treatment had no statistically significant effect on 10-day survival with good neurologic function or hippocampal CA1 pyramidal neuron survival compared to placebo treatment. In conclusion, a single dose IM MgSO during CPR achieves up to fourfold baseline serum magnesium levels within 15 min after ROSC; however, this treatment strategy did not improve survival, recovery of neurologic function, or neuron survival. Future studies with repeated dosing or in combination with hypothermic targeted temperature management may be indicated.
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http://dx.doi.org/10.1007/s12035-021-02645-xDOI Listing
January 2022

2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Neonatal Life Support; Education, Implementation, and Teams; First Aid Task Forces; and the COVID-19 Working Group.

Resuscitation 2021 12 11;169:229-311. Epub 2021 Nov 11.

The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research.
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http://dx.doi.org/10.1016/j.resuscitation.2021.10.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8581280PMC
December 2021

2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Neonatal Life Support; Education, Implementation, and Teams; First Aid Task Forces; and the COVID-19 Working Group.

Circulation 2021 Nov 11:CIR0000000000001017. Epub 2021 Nov 11.

The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research.
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http://dx.doi.org/10.1161/CIR.0000000000001017DOI Listing
November 2021

Brain injury after cardiac arrest.

Lancet 2021 10 26;398(10307):1269-1278. Epub 2021 Aug 26.

Warwick Medical School, University of Warwick, Coventry, UK; Anaesthesia and Intensive Care Medicine, Royal United Hospital, Bath, UK.

As more people are surviving cardiac arrest, focus needs to shift towards improving neurological outcomes and quality of life in survivors. Brain injury after resuscitation, a common sequela following cardiac arrest, ranges in severity from mild impairment to devastating brain injury and brainstem death. Effective strategies to minimise brain injury after resuscitation include early intervention with cardiopulmonary resuscitation and defibrillation, restoration of normal physiology, and targeted temperature management. It is important to identify people who might have a poor outcome, to enable informed choices about continuation or withdrawal of life-sustaining treatments. Multimodal prediction guidelines seek to avoid premature withdrawal in those who might survive with a good neurological outcome, or prolonging treatment that might result in survival with severe disability. Approximately one in three admitted to intensive care will survive, many of whom will need intensive, tailored rehabilitation after discharge to have the best outcomes.
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http://dx.doi.org/10.1016/S0140-6736(21)00953-3DOI Listing
October 2021

Integration of social media with targeted emails and in-person outreach for exception from informed consent community consultation.

Acad Emerg Med 2021 Aug 20. Epub 2021 Aug 20.

Department of Emergency Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Background: Exception from informed consent (EFIC) enables the enrollment of research subjects with emergent conditions to clinical trials without prior consent. EFIC study approval requires community consultation and public disclosure. We hypothesized that the integration of social media with targeted emails and in-person outreach is an effective community consultation strategy.

Methods: We utilized social media with targeted emails and in-person outreach for the community consultation of the ACCESS cardiac arrest trial. Study advertisements were disseminated using Facebook and Instagram, and targeted emails were sent to emergency medicine, prehospital, and cardiology providers. We also interviewed at-risk individuals with cardiac conditions, their caretakers, and patient advocacy groups. Participants were asked to complete a survey about their opinions about the study.

Results: We collected 559 surveys over an 8-week period, and 70.5% of the surveys were obtained using social media. The median (IQR) age of survey respondents was 44 (33-57) years; 89.9% were White and 60.1% were women. A total of 91.3% believed ACCESS was an important study. Compared to the in-person group, more from social media (81.8% vs. 63.3%, p < 0.05) and targeted email (77.4% vs. 63.3%, p < 0.05) groups said they would include their loved ones in the study. More from the in-person group believed that their opinion would be considered seriously compared to the social media (75.9% vs. 62.6%, p < 0.05) and targeted email (75.9% vs. 54.5%, p < 0.05) groups. The incorporation of social media and targeted emails for community consultation reduced the cost per survey by fourfold compared to an in-person-only strategy.

Conclusions: The integration of social media with targeted emails and in-person outreach was a feasible and cost-saving approach for EFIC community consultation. Future work is necessary to determine the perception and best utilization of social media for community consultation.
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http://dx.doi.org/10.1111/acem.14377DOI Listing
August 2021

Emergency medicine research: 2030 strategic goals.

Acad Emerg Med 2021 Aug 7. Epub 2021 Aug 7.

Department of Emergency Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.

All academic medical specialties have the obligation to continuously create new knowledge that will improve patient care and outcomes. Emergency medicine (EM) is no exception. Since its origins over 50 years ago, EM has struggled to fulfill its research mission. EM ranks last among clinical specialties in the percentage of medical school faculty who are National Institutes of Health (NIH)-funded principal investigators (PIs; 1.7%) and the percentage of medical school departments with NIH-funded PIs (33%). Although there has been a steady increase in the number of NIH-funded projects and total NIH dollars, the slowing growth in the number of NIH-funded PIs and lack of growth in the number of EM departments with NIH-funded PIs is cause for concern. In response, the Association of Academic Chairs of Emergency Medicine (AACEM) Research Task Force proposes a set of 2030 strategic goals for the EM research enterprise that are based on sustaining historic growth rates in NIH funding. These goals have been endorsed by the AACEM Executive Committee and the boards of Society for Academic Emergency Medicine (SAEM), American College of Emergency Physicians (ACEP), and American Academy of Emergency Medicine (AAEM). The 2030 strategic goals include 200 NIH-funded projects led by 150 EM PIs in at least 50 EM departments with over $100M in annual funding resulting in over 3% of EM faculty being NIH-funded PIs. Achieving these goals will require a targeted series of focused strategies to increase the number of EM faculty who are competitive for NIH funding. This requires a coordinated, intentional effort with investments at the national, departmental, and individual levels. These efforts are ideally led by medical school department chairs, who can create the culture and provide the resources needed to be successful. The specialty of EM has the obligation to improve the health of the public and to fulfill its research mission.
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http://dx.doi.org/10.1111/acem.14367DOI Listing
August 2021

Prehospital Tibial Intraosseous Drug Administration is Associated with Reduced Survival Following Out of Hospital Cardiac Arrest: A study for the CARES Surveillance Group.

Resuscitation 2021 10 5;167:261-266. Epub 2021 Jul 5.

Department of Emergency Medicine, Henry Ford Hospital, Detroit, MI, USA.

Background: Recent reports have questioned the efficacy of intraosseous (IO) drug administration for out-of-hospital cardiac arrest (OHCA) resuscitation. Our aim was to determine whether prehospital administration of resuscitative medications via the IO route was associated with lower rates of return of spontaneous circulation (ROSC) and survival to hospital discharge than peripheral intravenous (IV) infusion in the setting of OHCA.

Methods: We obtained data on all OHCA patients receiving prehospital IV or IO drug administration from the three most populous counties in Michigan over three years. Data was from the Michigan Cardiac Arrest Registry to Enhance Survival (CARES) database. The association between route of drug administration and outcomes was tested using a matched propensity score analysis.

Results: From a total of 10,626 OHCA patients, 6869 received parenteral drugs during their prehospital resuscitation (37.8% by IO) and were included in analysis. Unadjusted outcomes were lower in patients with IO vs. IV access: 18.3% vs. 23.8% for ROSC (p < 0.001), 3.2% vs. 7.6% for survival to hospital discharge (p < 0.001), and 2.0% vs. 5.8% for favorable neurological function (p < 0.001). After adjustment, IO route remained associated with lower odds of sustained ROSC (OR 0.72, 95% CI 0.63-0.81, p < 0.001), hospital survival (OR 0.48, 95% CI 0.37-0.62, p < 0.001), and favorable neurological outcomes (OR 0.42, 95% CI 0.30-0.57, p < 0.001).

Conclusion: In this cohort of OHCA patients, the use of prehospital IO drug administration was associated with unfavorable clinical outcomes.
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http://dx.doi.org/10.1016/j.resuscitation.2021.06.016DOI Listing
October 2021

Dose optimization of early high-dose valproic acid for neuroprotection in a swine cardiac arrest model.

Resusc Plus 2020 Mar-Jun;1-2:100007. Epub 2020 Jun 1.

Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.

Aim: High-dose valproic acid (VPA) improves the survival and neurologic outcomes after asphyxial cardiac arrest (CA) in rats. We characterized the pharmacokinetics, pharmacodynamics, and safety of high-dose VPA in a swine CA model to advance clinical translation.

Methods: After 8 ​min of untreated ventricular fibrillation CA, 20 male Yorkshire swine were resuscitated until return of spontaneous circulation (ROSC). They were block randomized to receive placebo, 75 ​mg/kg, 150 ​mg/kg, or 300 ​mg/kg VPA as 90-min intravenous infusion (n ​= ​5/group) beginning at ROSC. Animals were monitored for 2 additional hours then euthanized. Experimental operators were blinded to treatments.

Results: The mean(SD) total CA duration was 14.8(1.2) minutes. 300 ​mg/kg VPA animals required more adrenaline to maintain mean arterial pressure ≥80 ​mmHg and had worse lactic acidosis. There was a strong linear correlation between plasma free VPA C and brain total VPA (r ​= ​0.9494; p ​< ​0.0001). VPA induced dose-dependent increases in pan- and site-specific histone H3 and H4 acetylation in the brain. Plasma free VPA C is a better predictor than peripheral blood mononuclear cell histone acetylation for brain H3 and H4 acetylation (r ​= ​0.7189 for H3K27ac, r ​= ​0.7189 for pan-H3ac, and r ​= ​0.7554 for pan-H4ac; p ​< ​0.0001).

Conclusions: Up to 150 ​mg/kg VPA can be safely tolerated as 90-min intravenous infusion in a swine CA model. High-dose VPA induced dose-dependent increases in brain histone H3 and H4 acetylation, which can be predicted by plasma free VPA C as the pharmacodynamics biomarker for VPA target engagement after CA.
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http://dx.doi.org/10.1016/j.resplu.2020.100007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244526PMC
June 2020

Mitochondrial fission and mitophagy are independent mechanisms regulating ischemia/reperfusion injury in primary neurons.

Cell Death Dis 2021 05 12;12(5):475. Epub 2021 May 12.

Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.

Mitochondrial dynamics and mitophagy are constitutive and complex systems that ensure a healthy mitochondrial network through the segregation and subsequent degradation of damaged mitochondria. Disruption of these systems can lead to mitochondrial dysfunction and has been established as a central mechanism of ischemia/reperfusion (I/R) injury. Emerging evidence suggests that mitochondrial dynamics and mitophagy are integrated systems; however, the role of this relationship in the context of I/R injury remains unclear. To investigate this concept, we utilized primary cortical neurons isolated from the novel dual-reporter mitochondrial quality control knockin mice (C57BL/6-Gt(ROSA)26Sortm1(CAG-mCherry/GFP)Ganl/J) with conditional knockout (KO) of Drp1 to investigate changes in mitochondrial dynamics and mitophagic flux during in vitro I/R injury. Mitochondrial dynamics was quantitatively measured in an unbiased manner using a machine learning mitochondrial morphology classification system, which consisted of four different classifications: network, unbranched, swollen, and punctate. Evaluation of mitochondrial morphology and mitophagic flux in primary neurons exposed to oxygen-glucose deprivation (OGD) and reoxygenation (OGD/R) revealed extensive mitochondrial fragmentation and swelling, together with a significant upregulation in mitophagic flux. Furthermore, the primary morphology of mitochondria undergoing mitophagy was classified as punctate. Colocalization using immunofluorescence as well as western blot analysis revealed that the PINK1/Parkin pathway of mitophagy was activated following OGD/R. Conditional KO of Drp1 prevented mitochondrial fragmentation and swelling following OGD/R but did not alter mitophagic flux. These data provide novel evidence that Drp1 plays a causal role in the progression of I/R injury, but mitophagy does not require Drp1-mediated mitochondrial fission.
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http://dx.doi.org/10.1038/s41419-021-03752-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8115279PMC
May 2021

Machine learning-based classification of mitochondrial morphology in primary neurons and brain.

Sci Rep 2021 03 4;11(1):5133. Epub 2021 Mar 4.

Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI, 48109, USA.

The mitochondrial network continually undergoes events of fission and fusion. Under physiologic conditions, the network is in equilibrium and is characterized by the presence of both elongated and punctate mitochondria. However, this balanced, homeostatic mitochondrial profile can change morphologic distribution in response to various stressors. Therefore, it is imperative to develop a method that robustly measures mitochondrial morphology with high accuracy. Here, we developed a semi-automated image analysis pipeline for the quantitation of mitochondrial morphology for both in vitro and in vivo applications. The image analysis pipeline was generated and validated utilizing images of primary cortical neurons from transgenic mice, allowing genetic ablation of key components of mitochondrial dynamics. This analysis pipeline was further extended to evaluate mitochondrial morphology in vivo through immunolabeling of brain sections as well as serial block-face scanning electron microscopy. These data demonstrate a highly specific and sensitive method that accurately classifies distinct physiological and pathological mitochondrial morphologies. Furthermore, this workflow employs the use of readily available, free open-source software designed for high throughput image processing, segmentation, and analysis that is customizable to various biological models.
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http://dx.doi.org/10.1038/s41598-021-84528-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933342PMC
March 2021

Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest (EROCA): Results of a Randomized Feasibility Trial of Expedited Out-of-Hospital Transport.

Ann Emerg Med 2021 07 1;78(1):92-101. Epub 2021 Feb 1.

Department of Emergency Medicine, University of Michigan Medical School, Ann Arbor, MI; Michigan Center for Integrative Research in Critical Care, University of Michigan Medical School, Ann Arbor, MI; Extracorporeal Life Support Laboratory, University of Michigan Medical School, Ann Arbor, MI.

Study Objective: Outcomes of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest depend on time to therapy initiation. We hypothesize that it would be feasible to select refractory out-of-hospital cardiac arrest patients for expedited transport based on real-time estimates of the 911 call to the emergency department (ED) arrival interval, and for emergency physicians to rapidly initiate ECPR in eligible patients.

Methods: In a 2-tiered emergency medical service with an ECPR-capable primary destination hospital, adults with refractory shockable or witnessed out-of-hospital cardiac arrest were randomized 4:1 to expedited transport or standard care if the predicted 911 call to ED arrival interval was less than or equal to 30 minutes. The primary outcomes were the proportion of subjects with 911 call to ED arrival less than or equal to 30 minutes and ED arrival to ECPR flow less than or equal to 30 minutes.

Results: Of 151 out-of-hospital cardiac arrest 911 calls, 15 subjects (10%) were enrolled. Five of 12 subjects randomized to expedited transport had an ED arrival time of less than or equal to 30 minutes (overall mean 32.5 minutes [SD 7.1]), and 5 were eligible for and treated with ECPR. Three of 5 ECPR-treated subjects had flow initiated in less than or equal to 30 minutes of ED arrival (overall mean 32.4 minutes [SD 10.9]). No subject in either group survived with a good neurologic outcome.

Conclusion: The Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest trial did not meet predefined feasibility outcomes for selecting out-of-hospital cardiac arrest patients for expedited transport and initiating ECPR in the ED. Additional research is needed to improve the accuracy of predicting the 911 call to ED arrival interval, optimize patient selection, and reduce the ED arrival to ECPR flow interval.
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http://dx.doi.org/10.1016/j.annemergmed.2020.11.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238799PMC
July 2021

Aerosol generation during chest compression and defibrillation in a swine cardiac arrest model.

Resuscitation 2021 02 15;159:28-34. Epub 2020 Dec 15.

Department of Emergency Medicine, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA; Michigan Center for Integrative Research in Critical Care, University of Michigan Medical School, 2800 Plymouth Road, Ann Arbor, MI, 48109, USA. Electronic address:

Aim: It remains unclear whether cardiac arrest (CA) resuscitation generates aerosols that can transmit respiratory pathogens. We hypothesize that chest compression and defibrillation generate aerosols that could contain the SARS-CoV-2 virus in a swine CA model.

Methods: To simulate witnessed CA with bystander-initiated cardiopulmonary resuscitation, 3 female non-intubated swine underwent 4 min of ventricular fibrillation without chest compression or defibrillation (no-flow) followed by ten 2-min cycles of mechanical chest compression and defibrillation without ventilation. The diameter (0.3-10 μm) and quantity of aerosols generated during 45-s intervals of no-flow and chest compression before and after defibrillation were analyzed by a particle analyzer. Aerosols generated from the coughs of 4 healthy human subjects were also compared to aerosols generated by swine.

Results: There was no significant difference between the total aerosols generated during chest compression before defibrillation compared to no-flow. In contrast, chest compression after defibrillation generated significantly more aerosols than chest compression before defibrillation or no-flow (72.4 ± 41.6 × 10 vs 12.3 ± 8.3 × 10 vs 10.5 ± 11.2 × 10; p < 0.05), with a shift in particle size toward larger aerosols. Two consecutive human coughs generated 54.7 ± 33.9 × 10 aerosols with a size distribution smaller than post-defibrillation chest compression.

Conclusions: Chest compressions alone did not cause significant aerosol generation in this swine model. However, increased aerosol generation was detected during chest compression immediately following defibrillation. Additional research is needed to elucidate the clinical significance and mechanisms by which aerosol generation during chest compression is modified by defibrillation.
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http://dx.doi.org/10.1016/j.resuscitation.2020.12.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833865PMC
February 2021

Variation in pre-hospital outcomes after out-of-hospital cardiac arrest in Michigan.

Resuscitation 2021 01 8;158:201-207. Epub 2020 Dec 8.

University of Michigan, Michigan Medicine, Ann Arbor, MI, United States; Division of Cardiovascular Diseases and The Department of Internal Medicine, United States.

Aim: Care by emergency medical service (EMS) agencies is critical for optimizing prehospital outcomes following out-of-hospital cardiac arrest (OHCA). We explored whether substantial differences exist in prehospital outcomes across EMS agencies in Michigan-specifically focusing on rates of sustained return of spontaneous circulation (ROSC) upon emergency department (ED) arrival.

Methods: Using data from Michigan Cardiac Arrest Registry to Enhance Survival (MI-CARES) for years 2014-2017, we calculated rates of sustained ROSC upon ED arrival across EMS agencies in Michigan. We used hierarchical logistic regression models that accounted for patient, arrest-, community-, and response-level characteristics to determine adjusted rates of sustained ROSC among EMS agencies.

Results: A total of 103 EMS agencies and 20,897 OHCA cases were included. Average age of the cohort was 62.5 years (SD = 19.6), 39.7% were female, and 17.9% had an initial shockable rhythm due to ventricular fibrillation or pulseless ventricular tachycardia. The adjusted rate of sustained ROSC upon ED arrival across all EMS agencies was 23.8% with notable variation across EMS agencies (interquartile range [IQR], 20.5-29.2%). The top five EMS agencies had mean adjusted rates of sustained ROSC upon ED arrival of 42.7% (95% CI: 34.6-51.1%) while the bottom five had mean adjusted rates of 9.8% (95% CI: 7.6-12.7%).

Conclusions: Substantial variation in sustained ROSC upon ED arrival exists across EMS agencies in Michigan after adjusting for patient-, arrest, community-, and response-level features. Such differences suggest opportunities to identify and improve best practices in EMS agencies to advance OHCA care.
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http://dx.doi.org/10.1016/j.resuscitation.2020.11.034DOI Listing
January 2021

Enhancing Prehospital Outcomes for Cardiac Arrest (EPOC) study: sequential mixed-methods study protocol in Michigan, USA.

BMJ Open 2020 11 27;10(11):e041277. Epub 2020 Nov 27.

Acute Care Research Unit, Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, Michigan, USA

Introduction: Out-of-hospital cardiac arrest (OHCA) is a common, life-threatening event encountered routinely by first responders, including police, fire and emergency medical services (EMS). Current literature suggests that there is significant regional variation in outcomes, some of which may be related to modifiable factors. Yet, there is a persistent knowledge gap regarding strategies to guide quality improvement efforts in OHCA care and, by extension, survival. The Enhancing Prehospital Outcomes for Cardiac Arrest (EPOC) study aims to fill these gaps and to improve outcomes.

Methods And Analysis: This mixed-methods study includes three aims. In aim I, we will define variation in OHCA survival to the emergency department (ED) among EMS agencies that participate in the Michigan Cardiac Arrest Registry to Enhance Survival (CARES) in order to sample EMS agencies with high-survival and low-survival outcomes. In aim II, we will conduct site visits to emergency medical systems-including 911/dispatch, police, non-transport fire, and EMS agencies-in approximately eight high-survival and low-survival communities identified in aim I. At each site, key informant interviews and a multidisciplinary focus group will identify themes associated with high OHCA survival. Transcripts will be coded using a structured codebook and analysed through thematic analysis. Results from aims I and II will inform the development of a survey instrument in aim III that will be administered to all EMS agencies in Michigan. This survey will test the generalisability of factors associated with increased OHCA survival in the qualitative work to ultimately build an EPOC Toolkit which will be distributed to a broad range of stakeholders as a practical 'how-to' guide to improve outcomes.

Ethics And Dissemination: The EPOC study was deemed exempt by the University of Michigan Institutional Review Board. Findings will be compiled in an 'EPOC Toolkit' and disseminated in the USA through partnerships including, but not limited to, policymakers, EMS leadership and health departments.
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http://dx.doi.org/10.1136/bmjopen-2020-041277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703417PMC
November 2020

The Design of an Adaptive Clinical Trial to Evaluate the Efficacy of Extra-Corporeal Membrane Oxygenation for Out-of-Hospital Cardiac Arrest.

Resuscitation 2021 01 19;158:185-192. Epub 2020 Nov 19.

Department of Emergency Medicine, University of Michigan, Ann Arbor, MI, United States.

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) is a promising therapy for out-of-hospital cardiac arrest (OHCA) that is refractory to standard therapy, but no multicenter randomized clinical trials have been conducted to establish its efficacy. We report the design and operating characteristics of a proposed randomized Bayesian adaptive "enrichment" clinical trial designed to determine whether ECPR is effective for refractory OHCA and, if effective, to define the interval after arrest during which patients derive benefit.

Methods: Through iterative trial simulation and trial design modification, we developed a Bayesian adaptive trial of ECPR for adults who experience non-traumatic out-of-hospital cardiac arrest. Our proposed trial design addresses the threats to trial success identified during the design process, which were (1) the uncertainty surrounding the cardiac arrest (CA)-to-ECPR interval within which clinical benefit might be preserved (2) the difference in prognosis between patients with an initial rhythm that is non-shockable vs. shockable. Trial subjects will be randomized 1:1 to receive either standard care or expedited transport to a hospital for potential ECPR. The CA-to-ECPR interval will be estimated in real time based on the sum of the estimated paramedic response time (911 call to scene arrival), paramedic scene time, and transport time to hospital. A Bayesian decreasing step function will be used to estimate the efficacy of the treatment with an outcome of the 90-day utility-weighted Modified Rankin Scale (uwmRS) for each rhythm subgroup and estimated CA-to-ECPR interval at pre-specified interims. The trial will adaptively lengthen the estimated CA-to-ECPR eligibility window if the treatment appears effective at the upper limit of initial eligibility window. If ECPR appears ineffective at longer estimated CA-to-ECPR intervals, the upper limit of the window for enrollment eligibility will be shortened. The analysis will be stratified by rhythm subgroup.

Results: With a maximum total sample size of 400, and a cap on the maximum sample size of 300 for the non-shockable rhythm subgroup, the trial design has power ranging from 91-100% to detect a benefit from ECPR for non-shockable rhythms under the various efficacy scenarios simulated and power ranging from 69-98% for shockable rhythms under the same scenarios. The trial design also has a high probability of correctly identifying the maximum CA-to-ECPR interval within which ECPR produces a clinically significant benefit of 0.2 on the uwMRS. If ECPR is equivalent to standard CA care, the type I error is 2.5% with a 99% probability of stopping enrollment early for futility in the non-shockable subgroup and a 97% probability of stopping enrollment early for futility in the shockable subgroup.

Conclusion: This proposed adaptive trial design helps to ensure the population of patients who are most likely to benefit from treatment-as defined both by rhythm subgroup and estimated CA-to-ECPR interval-is enrolled. The design promotes early termination of the trial if continuation is likely to be futile.
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http://dx.doi.org/10.1016/j.resuscitation.2020.11.011DOI Listing
January 2021

Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations.

Resuscitation 2020 Nov 21;156:A80-A119. Epub 2020 Oct 21.

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations for advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recent interest within the resuscitation community and the amount of new evidence available since any previous review. Systematic reviews addressed higher-priority topics, and included double-sequential defibrillation, intravenous versus intraosseous route for drug administration during cardiac arrest, point-of-care echocardiography for intra-arrest prognostication, cardiac arrest caused by pulmonary embolism, postresuscitation oxygenation and ventilation, prophylactic antibiotics after resuscitation, postresuscitation seizure prophylaxis and treatment, and neuroprognostication. New or updated treatment recommendations on these topics are presented. Scoping reviews were conducted for anticipatory charging and monitoring of physiological parameters during cardiopulmonary resuscitation. Topics for which systematic reviews and new Consensuses on Science With Treatment Recommendations were completed since 2015 are also summarized here. All remaining topics reviewed were addressed with evidence updates to identify any new evidence and to help determine which topics should be the highest priority for systematic reviews in the next 1 to 2 years.
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http://dx.doi.org/10.1016/j.resuscitation.2020.09.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576326PMC
November 2020

Adult Advanced Life Support: International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

Resuscitation 2020 Sep 21. Epub 2020 Sep 21.

This 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations for advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recent interest within the resuscitation community and the amount of new evidence available since any previous review. Systematic reviews addressed higher-priority topics, and included double-sequential defibrillation, intravenous versus intraosseous route for drug administration during cardiac arrest, point-of-care echocardiography for intra-arrest prognostication, cardiac arrest caused by pulmonary embolism, postresuscitation oxygenation and ventilation, prophylactic antibiotics after resuscitation, postresuscitation seizure prophylaxis and treatment, and neuroprognostication. New or updated treatment recommendations on these topics are presented. Scoping reviews were conducted for anticipatory charging and monitoring of physiological parameters during cardiopulmonary resuscitation. Topics for which systematic reviews and new Consensuses on Science With Treatment Recommendations were completed since 2015 are also summarized here. All remaining topics reviewed were addressed with evidence updates to identify any new evidence and to help determine which topics should be the highest priority for systematic reviews in the next 1 to 2 years.
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http://dx.doi.org/10.1016/j.resuscitation.2020.09.012DOI Listing
September 2020

Adult Advanced Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

Circulation 2020 10 21;142(16_suppl_1):S92-S139. Epub 2020 Oct 21.

This for advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recent interest within the resuscitation community and the amount of new evidence available since any previous review. Systematic reviews addressed higher-priority topics, and included double-sequential defibrillation, intravenous versus intraosseous route for drug administration during cardiac arrest, point-of-care echocardiography for intra-arrest prognostication, cardiac arrest caused by pulmonary embolism, postresuscitation oxygenation and ventilation, prophylactic antibiotics after resuscitation, postresuscitation seizure prophylaxis and treatment, and neuroprognostication. New or updated treatment recommendations on these topics are presented. Scoping reviews were conducted for anticipatory charging and monitoring of physiological parameters during cardiopulmonary resuscitation. Topics for which systematic reviews and new Consensuses on Science With Treatment Recommendations were completed since 2015 are also summarized here. All remaining topics reviewed were addressed with evidence updates to identify any new evidence and to help determine which topics should be the highest priority for systematic reviews in the next 1 to 2 years.
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http://dx.doi.org/10.1161/CIR.0000000000000893DOI Listing
October 2020

Up to 206 Million People Reached and Over 5.4 Million Trained in Cardiopulmonary Resuscitation Worldwide: The 2019 International Liaison Committee on Resuscitation World Restart a Heart Initiative.

J Am Heart Assoc 2020 08 30;9(15):e017230. Epub 2020 Jul 30.

Heart and Stroke Foundation of Canada Vancouver British Columbia Canada.

Sudden out-of-hospital cardiac arrest is the third leading cause of death in industrialized nations. Many of these lives could be saved if bystander cardiopulmonary resuscitation rates were better. "All citizens of the world can save a life-CHECK-CALL-COMPRESS." With these words, the International Liaison Committee on Resuscitation launched the 2019 global "World Restart a Heart" initiative to increase public awareness and improve the rates of bystander cardiopulmonary resuscitation and overall survival for millions of victims of cardiac arrest globally. All participating organizations were asked to train and to report the numbers of people trained and reached. Overall, social media impact and awareness reached up to 206 million people, and >5.4 million people were trained in cardiopulmonary resuscitation worldwide in 2019. Tool kits and information packs were circulated to 194 countries worldwide. Our simple and unified global message, "CHECK-CALL-COMPRESS," will save hundreds of thousands of lives worldwide and will further enable many policy makers around the world to take immediate and sustainable action in this most important healthcare issue and initiative.
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http://dx.doi.org/10.1161/JAHA.120.017230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7792236PMC
August 2020

Intravenous vs. intraosseous administration of drugs during cardiac arrest: A systematic review.

Resuscitation 2020 04 3;149:150-157. Epub 2020 Mar 3.

Department of Anaesthesiology and Intensive Care, Randers Regional Hospital, Randers, Denmark; Research Center for Emergency Medicine, Department of Clinical Medicine, Aarhus University Hospital and Aarhus University, Aarhus, Denmark; Center for Resuscitation Science, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA. Electronic address:

Aim: To perform a systematic review of the literature on intravenous (IV) vs. intraosseous (IO) administration of drugs during cardiac arrest in order to inform an update of international guidelines.

Methods: The review was performed according to PRISMA guidelines and registered on PROSPERO. Medline, Embase and Evidence-Based Medicine Reviews were searched on December 17, 2019 for studies comparing IV to IO administration of drugs. The population included neonatal, paediatric, and adult patients with cardiac arrest. Two investigators reviewed each search for study relevance, extracted data, and assessed the risk of bias of individual studies. Meta-analyses were performed for studies without a critical risk of bias. Certainty of evidence was evaluated using GRADE.

Results: We included six observational studies comparing IV to IO administration of drugs and two randomized trials assessing the effect of specific drugs in subgroups related to IV vs. IO administration. All studies included adult out-of-hospital cardiac arrest patients. No studies were identified in neonatal or paediatric patients. The risk of bias for the observational studies was overall assessed as critical or serious, with confounding and selection bias being the primary sources of bias. The meta-analyses excluding studies with a critical risk of bias favoured IV access for all outcomes. Using GRADE, the certainty of evidence was judged at very low. Subgroup analyses of the two randomized trials demonstrated no statistically significant interactions between the route of access and study drugs on outcomes. However, these trials were underpowered to assess such interactions.

Conclusions: We identified a limited number of studies comparing IV vs. IO administration of drugs during cardiac arrest. Pooled results from four observational studies favoured IV access with very low certainty of evidence. From the subgroup analyses of two randomized clinical trials, there was no statistically significant interaction between the route of access and study drug on outcomes.
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http://dx.doi.org/10.1016/j.resuscitation.2020.02.025DOI Listing
April 2020

2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

Resuscitation 2019 12 14;145:95-150. Epub 2019 Nov 14.

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research.
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http://dx.doi.org/10.1016/j.resuscitation.2019.10.016DOI Listing
December 2019

2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces.

Circulation 2019 12 14;140(24):e826-e880. Epub 2019 Nov 14.

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research.
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http://dx.doi.org/10.1161/CIR.0000000000000734DOI Listing
December 2019

Association of an Emergency Department-Based Intensive Care Unit With Survival and Inpatient Intensive Care Unit Admissions.

JAMA Netw Open 2019 07 3;2(7):e197584. Epub 2019 Jul 3.

Department of Emergency Medicine, Michigan Medicine, University of Michigan, Ann Arbor.

Importance: Increased patient acuity, decreased intensive care unit (ICU) bed availability, and a shortage of intensivist physicians have led to strained ICU capacity. The resulting increase in emergency department (ED) boarding time for patients requiring ICU-level care has been associated with worse outcomes.

Objective: To determine the association of a novel ED-based ICU, the Emergency Critical Care Center (EC3), with 30-day mortality and inpatient ICU admission.

Design, Setting, And Participants: This retrospective cohort study used electronic health records of all ED visits between September 1, 2012, and July 31, 2017, with a documented clinician encounter at a large academic medical center in the United States with approximately 75 000 adult ED visits per year. The pre-EC3 cohort included ED patients from September 2, 2012, to February 15, 2015, when the EC3 opened, and the post-EC3 cohort included ED patients from February 16, 2015, to July 31, 2017. Data analyses were conducted from March 2, 2018, to May 28, 2019.

Exposures: Implementation of EC3, an ED-based ICU designed to provide rapid initiation of ICU-level care in the ED setting and seamless transition to inpatient ICUs.

Main Outcomes And Measures: The main outcomes were 30-day mortality among ED patients and rate of ED to ICU admission.

Results: A total of 349 310 visits from a consecutive sample of ED patients (mean [SD] age, 48.5 [19.7] years; 189 709 [54.3%] women) were examined; the pre-EC3 cohort included 168 877 visits and the post-EC3 cohort included 180 433 visits. Implementation of EC3 was associated with a statistically significant reduction in risk-adjusted 30-day mortality among all ED patients (pre-EC3, 2.13%; post-EC3, 1.83%; adjusted odds ratio, 0.85; 95% CI, 0.80-0.90; number needed to treat, 333 patient encounters; 95% CI, 256-476). The risk-adjusted rate of ED admission to ICU decreased with implementation of EC3 (pre-EC3, 3.2%; post-EC3, 2.7%; adjusted odds ratio, 0.80; 95% CI, 0.76-0.83; number needed to treat, 179 patient encounters; 95% CI, 149-217).

Conclusions And Relevance: Implementation of a novel ED-based ICU was associated with improved 30-day survival and reduced inpatient ICU admission. Additional research is warranted to further explore the value of this novel care delivery model in various health care systems.
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http://dx.doi.org/10.1001/jamanetworkopen.2019.7584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659143PMC
July 2019

To Breathe or Not to Breathe.

Circulation 2019 06 3;139(23):2610-2612. Epub 2019 Jun 3.

Department of Emergency Medicine (C.H.H., R.W.N.), University of Michigan Medical School, Ann Arbor.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.040370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6714578PMC
June 2019

Use of resuscitative balloon occlusion of the aorta in a swine model of prolonged cardiac arrest.

Resuscitation 2019 07 20;140:106-112. Epub 2019 May 20.

University of Michigan, Department of Emergency Medicine, United States; University of Michigan, Department of Biomedical Engineering, United States; University of Michigan, Department of Michigan Center for Integrative Research in Critical Care, United States. Electronic address:

Aim: We examined the use of a Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) catheter during cardiopulmonary resuscitation (CPR) after cardiac arrest (CA) to assess its effect on haemodynamics such as coronary perfusion pressure (CPP), common carotid artery blood flow (CCA-flow) and end-tidal CO (PetCO) which are associated with increased return of spontaneous circulation (ROSC).

Methods: Six male swine were instrumented to measure CPP, CCA-Flow, and PetCO. A 7Fr REBOA was advanced into zone-1 of the aorta through the femoral artery. Ventricular fibrillation was induced and untreated for 8 min. CPR (manual then mechanical) was initiated for 24 min. Continuous infusion of adrenaline (epinephrine) was started at minute-4 of CPR. The REBOA balloon was inflated at minute-16 for 3 min and then deflated/inflated every 3 min for 3 cycles. Animals were defibrillated up to 6 times after the final cycle. Animals achieving ROSC were monitored for 25 min.

Results: Data showed significant differences between balloon deflation and inflation periods for CPP, CCA-Flow, and PetCO (p < 0.0001) with an average difference (SD) of 13.7 (2.28) mmHg, 15.5 (14.12) mL min and -4 (2.76) mmHg respectively. Three animals achieved ROSC and had significantly higher mean CPP (54 vs. 18 mmHg), CCA-Flow (262 vs. 135 mL min) and PetCO (16 vs. 8 mmHg) (p < 0.0001) throughout inflation periods than No-ROSC animals. Aortic histology did not reveal any significant changes produced by balloon inflation.

Conclusion: REBOA significantly increased CPP and CCA-Flow in this model of prolonged CA. These increases may contribute to the ability to achieve ROSC.
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http://dx.doi.org/10.1016/j.resuscitation.2019.05.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157798PMC
July 2019
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