From Science to Guidelines: The Future for Resuscitation

The periodic development and publication of treatment guidelines is integral to the field of cardiopulmonary resuscitation and emergency cardiovascular care. The methods for guideline development have evolved over the past few decades, and the process itself has become the subject of increasing scientific investigation. An internationally validated tool for assessing the quality of clinical practice guidelines is The Appraisal of Guidelines for Research and Evaluation (AGREE) instrument. Applying this tool to the ILCOR 2010 International Consensus on CPR (cardiopulmonary resuscitation) and ECC (emergency cardiac care) Science with Treatment Recommendations (CoSTR) and the resulting member council guidelines will be a valuable initial step in evaluating both the process and the product. By doing so, important strengths can be recognized as well as opportunities for improvement moving forward. Beyond validated tools to assess and improve the quality of the traditional guidelines process, a critical reassessment of the overall strategy for improving cardiac arrest outcomes is indicated. From the lay-provider perspective, innovative approaches to facilitate performance of bystander CPR are needed. This is likely to entail more individualized instructional methods that are titrated to the provider’s capabilities for learning and performance. What the future might hold for professional providers is a more individualized treatment strategy titrated to real-time physiologic monitoring with mechanized delivery of therapies guided by real-time computer-aided medical decision-making. These individualized instructional and treatment strategies could revolutionize our approach to cardiac arrest resuscitation, and dramatically change how guidelines are developed, implemented and evaluated

National Institutes of Health–Funded Cardiac Arrest Research: A 10‐Year Trend Analysis

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142427/1/jah32314.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142427/2/jah32314_am.pd

Magnesium Depletion in Patients Treated with Therapeutic Hypothermia After Cardiac Arrest

Magnesium (Mg2+) depletion can have detrimental effects in postcardiac arrest patients through multiple potential mechanisms. Therapeutic hypothermia (TH) produces a Mg2+ diuresis, but the effects of postcardiac arrest TH on serum Mg2+ levels in patients with postcardiac arrest syndrome (PCAS) are yet to be systematically quantified. We conducted a retrospective chart review of 119 consecutive comatose PCAS patients treated with TH between 2005 and 2010 and compared them to 33 matched historic controls (HCs) seen at the same institution between 2002 and 2005 who were not treated with TH. We abstracted data from the first 96 hours postarrest, including date, time, and value of serum Mg2+ levels and date, time, and amount of Mg2+ repletion, along with outcomes at discharge. The median Mg2+ level of TH patients was 2.0?mg/dL [interquartile range (IQR), 1.9?2.2?mg/dL] (0.82 mmol/L [IQR, 0.78?0.90 mmol/L]) versus 2.2?mg/dL [IQR, 1.9?2.4?mg/dL] (0.90 mmol/L [IQR, 0.82?0.99 mmol/L]) (p=0.2) in HCs. In addition, 42.9% (520/1214) of Mg2+ levels in TH patients versus 31.9% (43/135) (p=0.014) in HC patients were below 2.0?mg/dL [0.82 mmol/L]. The average number of times the Mg2+ level was checked in TH patients was 10.2 (range 1?18) versus 4.1 (range 1?10) in HCs. The TH patients were more likely to receive supplemental Mg2+ than HCs (81.5% [97/119] vs. 27.3% [9/33] [p<0.01]). The mean supplemental Mg2+ dose was 1.9?g for TH patients versus 0.5?g for HC patients. Mortality in patients treated with TH was 53.1% (60/113) versus 78.6% (22/28) (p=0.014) in HCs. Low serum Mg2+ levels with subsequent Mg2+ supplementation were more common in comatose patients with PCAS treated with TH compared to normothermic HC patients. The effect of untreated hypomagnesemia on postcardiac arrest outcomes remains to be determined.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140255/1/ther.2014.0012.pd

Calpain mediates proteolysis of the voltage-gated sodium channel alpha-subunit

Alterations in the expression, molecular composition, and localization of voltage-gated sodium channels play major roles in a broad range of neurological disorders. Recent evidence identifies sodium channel proteolysis as a key early event after ischemia and traumatic brain injury, further expanding the role of the sodium channel in neurological diseases. In this study, we investigate the protease responsible for proteolytic cleavage of voltage-gated sodium channels (NaChs). NaCh proteolysis occurs after protease activation in rat brain homogenates, pharmacological disruption of ionic homeostasis in cortical cultures, and mechanical injury using an in vitro model of traumatic brain injury. Proteolysis requires Ca2+ and calpain activation but is not influenced by caspase-3 or cathepsin inhibition. Proteolysis results in loss of the full-length {alpha}-subunits, and the creation of fragments comprising all domains of the channel that retain interaction even after proteolysis. Cell surface biotinylation after mechanical injury indicates that proteolyzed NaChs remain in the membrane before noticeable evidence of neuronal death, providing a mechanism for altered action potential initiation, propagation, and downstream signaling events after Ca2+ elevation

Brain injury after cardiac arrest

Publisher Copyright: © 2021 Elsevier LtdAs 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.Peer reviewe

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

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 \u3c 0.001), 3.2% vs. 7.6% for survival to hospital discharge (p \u3c 0.001), and 2.0% vs. 5.8% for favorable neurological function (p \u3c 0.001). After adjustment, IO route remained associated with lower odds of sustained ROSC (OR 0.72, 95% CI 0.63-0.81, p \u3c 0.001), hospital survival (OR 0.48, 95% CI 0.37-0.62, p \u3c 0.001), and favorable neurological outcomes (OR 0.42, 95% CI 0.30-0.57, p \u3c 0.001). CONCLUSION: In this cohort of OHCA patients, the use of prehospital IO drug administration was associated with unfavorable clinical outcomes

Administration of Intranasal Insulin During Cardiopulmonary Resuscitation Improves Neurological Outcomes After Cardiac Arrest

INTRODUCTION: Over 325,000 people die from cardiac arrest each year. Prognosis is poor and survivors typically experience persistent neurologic deficits. Currently, neuroprotective treatments to reduce brain injury in cardiac arrest survivors are limited and ineffective. This study evaluates the potential neuroprotection induced by high dose intranasal insulin (HD-IN-I) in a rodent model of asphyxial cardiac arrest. METHODS: Male Long Evans rats were block randomized to sham-operated controls or 8-minute asphyxial cardiac arrest treated with placebo or HD-IN-I at the onset of CPR. To investigate mechanism of action, hippocampi were collected 30 minutes post-ROSC and analyzed by Western blot for phosphorylation of Akt. To assess long-term functional outcomes, neurobehavioral evaluation was conducted using neurologic function scores daily and Barnes maze, Rotarod, and passive avoidance on days 7-10 post-ROSC. Histologic quantification of surviving hippocampal CA1 pyramidal neurons was also conducted. RESULTS: Hippocampal phospho-Akt/total Akt ratio increased 2-fold in the placebo group and 5.7-fold in HD-IN-I group relative to shams (p \u3c 0.05). Rats treated with HD-IN-I had significantly improved performance on Rotarod, Barnes maze, and passive avoidance (p \u3c 0.05). HD-IN-I had no significant effect on ROSC rate, 10-day survival, systemic glycemic response, or on the number of surviving CA1 pyramidal neurons compared to placebo treatment. DISCUSSION: This study is the first to demonstrate that HD-IN-I administered at the onset of CPR, causes phosphorylation of brain Akt and results in significant neuroprotection. This primary work strongly suggests that intranasal insulin could be the first highly effective neuroprotective treatment for cardiac arrest patients

ACEP–SAEM response to the National Institutes of Health (NIH) proposal to simplify the review framework for research project grant applications

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