Effect of Epinephrine on outcomes in OutofHospital Cardiac

Effect of Epinephrine on outcomes in Out-of-Hospital Cardiac Arrest Ian Lumsden, MMS (c) Faculty Advisor: Lisa Murphy, PA-C, MSPAS Department of Medical Science Abstract Epinephrine administration during cardiac arrest has been the standard of in the United States since the AHA published the first cardiac arrest guidelines in 1974. However, epinephrine use became the standard of care with strong medical rational but with limited data on outcomes. The intent of this research is to review available literature and determine if in (P) an adult population in non-traumatic out-of-hospital cardiac arrest (I) treatment with epinephrine administration (C) compared to cardiac care without the administration of epinephrine (O) results in improved survival with good neurologic outcomes. Introduction Sudden Cardiac Death Overview ◊ The American Heart Association reported that a 2014 estimate found that SCD resulted in 2 million potential life years lost for males and 1. 3 million potential life years lost for females. ◊ Among the American male population, SCD was estimated to attribute to more deaths than any other individual cause. Current Treatment ◊ Epinephrine administration is recommended in cardiac arrest as soon as IV or IO access is obtained and every 3 -5 mins afterwards. Debate ◊ Animal models showed epinephrine administration was associated with greater brain ischemia and increased severity of post-resuscitation myocardial dysfunction ◊ These findings suggest that epinephrine may increase ROSC but worsen postresuscitation outcomes. Methods Literature search was preformed in November 2018 using the following: v Pub. Med v Ovid v Biomedical Reference Collection Of the 16 articles found in the literature search, a total of 8 articles were selected based on the strongest level of evidence, research from various countries of origin, and to provide a well-rounded picture of how epinephrine administration is being researched. Results Discussion 3 Randomized Controlled Trials were selected: Jacobs et al. , Olasveengen et al. , and Perkins et al. ◊ Perkins et al. , was a double-blind study conducted in the United Kingdom, was the largest RCT and provided the strongest level of evidence. ◊ Jacobs et al. , was a double-blind study conducted in Australia and compared ALS care without cardiac medications to only epinephrine administration and suffered from site drop-out. ◊ Olasveengen et al. , was a single blind study conducted in Oslo, Norway that compared no IV access to IV access with epinephrine administration during initial resuscitation attempts. 4 Retrospective Cohort Studies were selected: Dumas et al. , Ewy et al, Fukuda et al. , and Tanaka et al. ◊ Dumas et al. , was a singe site cohort study that investigated neurologic outcomes in patients who arrived at a Parisian cardiac-arrest receiving hospital with ROSC ◊ Ewy et al. , used the SHARE registry in Arizona to investigate the timing of epinephrine on survival and neurologic outcomes in witnessed cardiac arrests. ◊ Fukuda et al. , used a Japanese national registry of all cardiac arrests to compare outcomes when epinephrine was given vs. patients who did not receive epinephrine. ◊ Tanaka et al. , used a Japanese national registry of all cardiac arrests and included only witnessed arrests, to compare neurologic outcomes in both EPI vs non-EPI patients, and investigate neurologic outcomes based on timing of epinephrine administration. 1 Prospective Cohort study was selected: Fisk et al. ◊ Fisk et al. , conducted a prospective study that compared outcomes of cardiac arrest patients in Seattle, Washington after a protocol change reduced epinephrine dosage from 1 mg to 0. 5 mgs. Table 1. Summary of results Study Dumas et al (2014) Survival to discharge Neurologic Outcome ROSC n/a S (-) n/a Time Dependence Improved Survival of EPI in Non-Shockable Administration Subgroup S (+)1 S (-) Ewy et al (2015) S (+) NS n/a S (+) NS Fisk et al (2018)2 NS NS NS Fukuda et al (2016) Jacobs et al (2011) S (-) S (+) NS (-) S (+) n/a NS (+) NS S (+) n/a S(+)3 Olasveengen et al (2009) Perkins et al (2018) Tanaka et al (2016)4 n/a S (-) S (+) n/a 1. An overall negative effect of EPI vs non-EPI was seen, however the best outcomes in the EPI group were found when administered ≤ 9 min. 2. This study compares low dose and standard dose EPI. 3. Authors published article in July 2019 with subgroup analysis based on rhythm, improved survival in non-shockable subgroup 4. Limited analysis was done between the EPI and non-EPI groups; however, differences of statistical significance were noted. Key: S+ = significant increase, S- = significant decrease, NS = not significant Survival to discharge S = trends were of statistical significance Neurologic Outcome S = trends were of statistical significance ROSC S = trends were of statistical significance Time Dependence of EPI Administration S = trends were of statistical significance Improved Outcomes in Non-Shockable Subgroup S = trends were of statistical significance NS = trends failed to reach statistical significance NS = trends failed to reach statistical significance (+) = EPI associated with increased survival to discharge (+) = EPI associated with increased Return of Spontaneous Circulation (+) = Earlier administration of EPI associated with better outcomes (+) = EPI associated with improved survival (+) = EPI associated with good neurologic outcomes (-) = EPI associated with poor neurologic outcomes (-) = EPI associated with decreased survival to discharge (-) = EPI associated with decreased survival (-) = EPI associated with decreased Return of Spontaneous Circulation (-) = Earlier administration of EPI associated with worse outcomes 3 of the selected studies show statistically significant worsening of neurologic outcomes. However, none of the RCT’s or the prospective before and after cohort study supported worsened neurologic outcomes. None of the studies supported improved neurologic outcomes with epinephrine. Statistically significant increases in survival to discharge were found in 2 studies. However, 1 study found a significant decrease in survival to discharge. Subgroup analysis showed the best outcomes with earlier epinephrine administration. 2 studies had significant findings with improved survival in patients with initially non-shockable rhythms, and one study showed a significant decrease in survival with non-shockable rhythms. Research was limited by a lack of Randomized Controlled Trials. Ethical and logistical concerns results in few RCT’s conducted in this field. In a few studies, the small n in survivor groups caused data regarding survival and neurologic outcomes to fail to reach significance. Varying study designs conducted in countries with differing populations and Emergency Services makes direct comparisons of results and synthesis of data problematic. Conclusion The data fails to show an overall increased survival to discharge with epinephrine administration, but does show a trend towards increased survival. Data fails to show improved neurologic outcomes with epinephrine administration, with a slight trend toward worsened outcomes. Worse outcomes with increasing dose of epinephrine may not be a drug effect, but may be a marker of prolonged resuscitation efforts. However, a trend was noted in subgroups with earlier administration being associated with improved outcomes. Studies did show a consistent increase in ROSC with epinephrine administration. Increases in ROSC were balanced by an increase in deaths after arrival at hospitals. Further studies investigating the optimal timing and dosage of epinephrine are warranted. In light of the potential benefits of earlier administration, an intriguing area of research could be intramuscular epinephrine “auto-injectors” made available with AED’s or to BLS responders.

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