Epinephrine Delivery Research Articles

The Route to ROSC: Evaluating the Impact of Route and Timing of Epinephrine Administration in Out-of-Hospital Cardiac Arrest Outcomes

Objectives Previous investigations comparing intraosseous (IO) and intravenous (IV) epinephrine delivery in out-of-hospital cardiac arrest (OHCA) suggest that epinephrine is oftentimes more expeditiously administered via the IO route, but this temporal benefit doesn’t always translate to clinical benefit. However, very few studies adequately controlled for indication and resuscitation time biases, making the influence of first epinephrine route on OHCA outcomes unclear. To determine the association between first epinephrine route and return of spontaneous circulation (ROSC) while controlling for resuscitation time bias and other potential confounders. Methods We conducted a retrospective analysis using the 2020 ESO Data Collaborative dataset. Adult patients with a witnessed, non-traumatic OHCA prior to EMS arrival were included. Logistic regression was used to determine the association between medication route and ROSC. Linear regression was then used to calculate the probability of ROSC for each route across all call receipt-to-drug delivery intervals. Using these linear equations, the call receipt-to-drug delivery intervals were calculated that would yield equivalent probabilities of ROSC between the IV and IO routes. Results Data were available for 10,350 patients, of which 27.4% presented with a shockable rhythm, 29.7% received bystander CPR, and 39.6% experienced ROSC. After controlling for confounders, IO epinephrine was associated with decreased likelihood of ROSC (OR = 0.77, p < 0.001). The linear regression models provided differing slope coefficients for ROSC between each route, with the IV route associated with a higher likelihood of ROSC for any given call receipt-to-drug-delivery interval. From these equations, the additional time allowed to establish an IV and administer epinephrine intravenously beyond the time required for IO delivery, yet with an equivalent predicted probability of ROSC via the IO route, was calculated. This additional time interval for intravenous administration declined linearly from 9 min at a call receipt-to-intraosseous epinephrine interval of 4 min to no additional time at a call receipt-to-intraosseous epinephrine interval of 29 min. Conclusions This retrospective analysis of a national EMS database revealed that IO epinephrine was negatively associated with ROSC. Additionally, there appears to be a finite time window during which intravenous epinephrine remains superior to the intraosseous route even if there are brief initial delays in IV drug delivery.

Evidence based use of epinephrine in anaphylaxis.

Epinephrine is the first line treatment for anaphylaxis, however, there are limited data to support this. This review examines data surrounding evidence for the use of epinephrine in anaphylaxis, data on prescription for and use of epinephrine autoinjectors, and data examining newer routes of delivery of epinephrine; with a focus on recent publications over the past few years. With recent epidemiologic studies of anaphylaxis and new forms of epinephrine being studied, new data on the effects of epinephrine are aiding in the understanding of epinephrine's effects and the shortcomings of epinephrine both in its effect and utility in the real world. Epinephrine is still considered the first line therapy for anaphylaxis, and we are starting to have a better understanding of its effects in both healthy patients and those with anaphylaxis.

Intracoronary adenosine compared with adrenaline and verapamil in the treatment of no-reflow phenomenon following primary PCI in STEMI patients

Backgroundno-reflow can complicate up to 25% of pPCI and is associated with significant morbidity and mortality. We aimed to compare the outcomes of intracoronary epinephrine and verapamil with intracoronary adenosine in the treatment of no-reflow after primary percutaneous coronary intervention (pPCI). Methods108 STEMI patients had no-reflow during pPCI were assigned into four groups. Group 1, in which epinephrine and verapamil were injected through a well-cannulated guiding catheter. Group 2, in which same drugs were injected in the distal coronary bed through a microcatheter or perfusion catheter. Group 3, in which adenosine was injected through a guiding catheter. Group 4, in which adenosine was injected in distal coronary bed. Primary end point was the achievement of TIMI III flow and MBG II or III. Secondary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during hospital stay. ResultsThe study groups did not differ in their baseline characteristics. Primary end point was achieved in 15 (27.8%) patients in the guide-delivery arm compared with 34 (63%) patients in the local-delivery arm, p < 0.01. However, the primary end point did not differ between the epinephrine/verapamil group and the adenosine group (27 (50%) vs 22 (40.7%), p = 0.334). The secondary end points were similar between the study groups. ConclusionLocal delivery of epinephrine, verapamil and adenosine in the distal coronary bed is more effective in achieving TIMI III flow with MBG II or III compared with their guide-delivery in patients who suffered no-reflow during pPCI. There was no difference between epinephrine/verapamil Vs. adenosine.

The impact of anaphylaxis on the absorption of intranasal epinephrine in anaesthetized non-naive beagle dogs.

Epinephrine delivery via an intranasal spray (neffy) is being evaluated as an additional option to treat severe allergic reaction and may provide clinical benefit by reducing the time to dosing in community settings by avoiding needles. Given that hypotension is a hallmark symptom of severe allergic reactions, a preclinical study was conducted to evaluate the impact of this factor on epinephrine absorption via neffy. The objective of this study was to evaluate the absorption of epinephrine via neffy in a dog model of anaphylaxis with severe hypotension. Epinephrine absorption via neffy was evaluated in anesthetized beagle dogs under both normal conditions and hypotension associated with anaphylaxis. Atotal of 14 dogs (10 males and 4 females) were dosed with neffy, 1.0 mg, under normal conditions, followed by neffy, 1.0 mg, under conditions of anaphylaxis. The mean maximum concentration of epinephrine was higher during anaphylaxis than under normal conditions (2,670± 2,150 pg/mL and 1,330± 739 pg/mL [P< .05]). Relative to normal conditions, anaphylaxis resulted in higher overall epinephrine exposure (area under the curve from 0 to 45 minutes= 54,400± 18,100 min×pg/mL and 34,300± 21,500 minutes×pg/mL [P< .05]), which is likely due to the increase in vascular permeability commonly observed during severe allergic reactions. Taken together with real-world evidence from nasal naloxone treatment for opioid overdose demonstrating that the reduced blood flow or hypotension associated with overdose does not appear to suppress naloxone's efficacy, the current findings demonstrate that epinephrine is well absorbed following neffy delivery during the hypotension associated with severe anaphylaxis reactions.

Pharmacokinetics/pharmacodynamics of epinephrine after single and repeat administration of neffy, EpiPen, and manual intramuscular injection

Epinephrine is the first-line treatment for severe allergic reactions, and rapid treatment is associated with lower rates of hospitalization and death. Current treatment options (epinephrine auto-injectors and manual intramuscular injection) are considered cumbersome, and most patients/caregivers fail to use them, even during severe reactions. An intranasal epinephrine delivery device, neffy, has been designed to provide an additional option for patients/caregivers. We sought to assess the comparative pharmacokinetics and pharmacodynamics of neffy 2.0 mg, EpiPen 0.3 mg, and manual intramuscular injection 0.3 mg. This was a phase 1, randomized, 6-treatment, 6-period, 2-part crossover study in 59 healthy subjects. Pharmacokinetic and pharmacodynamic parameters following single and repeat doses of epinephrine were assessed before dosing and at various postdose intervals. The pharmacokinetic profile of neffy was bracketed by approved injection products, with a mean peak plasma level of 481 pg/mL, which fell between EpiPen (753 pg/mL) and epinephrine manual intramuscular injection (339 pg/mL). When dosed both once and twice, neffy resulted in more pronounced increases in pharmacodynamic parameters relative to EpiPen or manual injection. neffy's pharmacokinetic profile was bracketed by approved injection products, with pharmacodynamic responses that were comparable to or better than approved injection products. neffy is expected to be a safe and effective option, particularly for patients/caregivers who are reluctant to carry and use injection devices.

Epinephrine Dosing Use During Extracorporeal Cardiopulmonary Resuscitation: Single-Center Retrospective Cohort.

During pediatric cardiac arrest, contemporary guidelines recommend dosing epinephrine at regular intervals, including in patients requiring extracorporeal membrane oxygenation (ECMO). The impact of epinephrine-induced vasoconstriction on systemic afterload and venoarterial ECMO support is not well-defined. Nested retrospective observational study within a single center. The primary exposure was time from last dose of epinephrine to initiation of ECMO flow; secondary exposures included cumulative epinephrine dose and arrest time. Systemic afterload was assessed by mean arterial pressure and use of systemic vasodilator therapy; ECMO pump flow and Vasoactive-Inotrope Score (VIS) were used as measures of ECMO support. Clearance of lactate was followed post-cannulation as a marker of systemic perfusion. PICU and cardiac ICU in a quaternary-care center. Patients 0-18 years old who required ECMO cannulation during resuscitation over the 6 years, 2014-2020. Patients were excluded if ECMO was initiated before cardiac arrest or if the resuscitation record was incomplete. None. A total of 92 events in 87 patients, with 69 events having complete data for analysis. The median (interquartile range) of total epinephrine dosing was 65 mcg/kg (37-101 mcg/kg), with the last dose given 6 minutes (2-16 min) before the initiation of ECMO flows. Shorter interval between last epinephrine dose and ECMO initiation was associated with increased use of vasodilators within 6 hours of ECMO (p = 0.05), but not with mean arterial pressure after 1 hour of support (estimate, -0.34; p = 0.06). No other associations were identified between epinephrine delivery and mean arterial blood pressure, vasodilator use, pump speed, VIS, or lactate clearance. There is limited evidence to support the idea that regular dosing of epinephrine during cardiac arrest is associated with increased in afterload after ECMO cannulation. Additional studies are needed to validate findings against ECMO flows and clinically relevant outcomes.

Symjepi Epinephrine Injection Device Deconstruction and Residual Medication Retrieval in an Austere Environment.

Epinephrine is the primary therapy in the treatment of anaphylaxis. Epinephrine delivery devices are commonplace in out-of-hospital care of anaphylaxis because they administer a standardized dose of epinephrine, limit human error, and allow for ease of use by the operator. However, a major limitation of these devices is the single-use nature of the products. In an austere setting, the ability to obtain additional doses from an autoinjector may prevent further progression of anaphylaxis. Previous articles have demonstrated the deconstruction of spring-loaded epinephrine autoinjectors to extract additional medication doses. This article provides instruction and videography, outlining the process of deconstructing and obtaining additional doses of epinephrine from the Symjepi prefilled syringe.

Acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand management of acute disease

Transdermal drug delivery provides convenient and pain-free self-administration for personalized therapy. However, challenges remain in treating acute diseases mainly due to their inability to timely administrate therapeutics and precisely regulate pharmacokinetics within a short time window. Here we report the development of active acoustic metamaterials-driven transdermal drug delivery for rapid and on-demand acute disease management. Through the integration of active acoustic metamaterials, a compact therapeutic patch is integrated for penetration of skin stratum corneum and active percutaneous transport of therapeutics with precise control of dose and rate over time. Moreover, the patch device quantitatively regulates the dosage and release kinetics of therapeutics and achieves better delivery performance in vivo than through subcutaneous injection. As a proof-of-concept application, we show our method can reverse life-threatening acute allergic reactions in a female mouse model of anaphylaxis via a multi-burst delivery of epinephrine, showing better efficacy than a fixed dosage injection of epinephrine, which is the current gold standard ‘self-injectable epinephrine’ strategy. This innovative method may provide a promising means to manage acute disease for personalized medicine.

Efficacy of intraseptal anesthesia obtained by computer-controlled articaine with epinephrine delivery in scaling and root planing.

The primary aim of this study was to compare the anesthetic efficacy of the intraseptal anesthesia (ISA) obtained with three doses of 4% articaine with 1:100,000 epinephrine (4%Ar + Ep) for scaling and root planing (SRP), using a computer-controlled local anesthetic delivery system (CCLADS). The secondary aims were to compare the clinical anesthetic parameters in relation to different jaw regions and examine the possible influence of sex and smoking habits on them. SRP under ISA obtained with different doses (0.1ml, 0.2ml, and 0.3ml) of 4%Ar + Ep was performed in 360 patients. The success rate, onset, duration of soft tissue anesthesia, and the anesthetic field widths were recorded by pinprick testing. The anesthesia success was high (90-95%). The onset was immediate. The duration and anesthetic field widths showed a dose-related significance, however, without a consistent sex-related or smoking-related significance. The multiple logistic regression analysis revealed a twofold higher chance of anesthesia success by increasing the dose and increased bleeding on probing-related and female sex-reduced probability of anesthesia success. ISA obtained with 0.3ml of 4%Ar + Ep delivered by a computer-controlled local anesthetic delivery system provided a high anesthetic success and the adequate clinical anesthetic parameters for SRP in all regions of both jaws. ISA obtained with 4%Ar + Ep provides an effective anesthesia for SRP. The anesthetic success rate may be reduced in the presence of gingival inflammation and in females as well. The study was registered in a Clinical Trials database (NCT04392804, registration date May 9, 2020).

Abstract 155: Intra-arrest Epinephrine Administration is Associated with Increased Myocardial Injury and Inflammation in a Novel Murine Model of Cardiac Arrest

Introduction: Epinephrine (EPI) is routinely administered in cardiac arrest resuscitation. Using a novel murine model of cardiac arrest, this study aims to assess the effects of epinephrine on myocardial inflammation and injury. Hypothesis: Intra-arrest epinephrine use is associated with increased myocardial injury, inflammation and fibrosis. Methods: A total of 56 mice were included in the study. Both cardiac arrest (CA) and sham (SHAM) groups received intravenous potassium chloride either as a bolus (CA) or slow infusion (SHAM), inducing ECG-confirmed asystole (CA only) for 4-minutes prior to delivery of intravenous epinephrine (250ul, 30ug/ml) or saline (250ul) and manual chest compressions (300BPM) for 4-minutes (Fig A). Mice were recovered for assessments at 24- or 72-hour timepoints. Results: Rates of successful ROSC (n=21(96%) vs. n=14(82%), P=0.18) and survival to recovery (n=11(50%) vs. n=12(71%),P=0.19) were similar in CA treated with (CA+EPI) and without (CA-Epi) EPI, respectively. Greater myocardial injury occurred in CA+EPI, compared to CA-Epi, with increased Hs-Troponin levels measured at 24- (26.0±0.9ng/mL vs. 9.4±5.3,P=0.015) and 72-hours (20.9±8.3ng/mL vs. 5.0±2.4,P=0.012) (Fig B). To examine mRNA expression in cardiac tissue, rt-PCR was performed. At 72-hours, CA+EPI, compared to CA-EPI, was associated with significantly increased expression of inflammatory (TNF-α, IL1β, IL10, F4-80 and CD68) and fibrotic (TGFβ, Col1 and Col3) genes. There was no difference between SHAM-EPI and SHAM+EPI at 72-hours (Fig C). Conclusion: In a mouse model of cardiac arrest, the use of epinephrine did not improve rates of ROSC and survival. However, epinephrine exposure was associated with increased biomarkers of myocardial injury, end-organ inflammation, and fibrosis. These findings underscore the need for further pre-clinical studies to assess alternate agents that confer protection to vital organs and improve rates of survival.

Pharmacokinetic and pharmacodynamic comparison of epinephrine, administered intranasally and intramuscularly: An integrated analysis

BackgroundManual intramuscular epinephrine injection is the standard of care for treating severe allergic reactions and anaphylaxis. Epinephrine autoinjectors were approved on the basis of the assumption that their pharmacokinetic and pharmacodynamic profiles are equivalent to manual intramuscular injection; however, although there is emerging evidence for product-related differences in pharmacokinetic profiles, very little is known about the comparative pharmacodynamic profiles. ObjectiveTo compare pharmacokinetic and pharmacodynamic profiles of epinephrine delivered through manual intramuscular injection, autoinjectors, and intranasal spray. MethodsThis integrated analysis was based on data from 4 randomized cross-over phase 1 trials that compared the pharmacokinetics and pharmacodynamics of epinephrine using manual intramuscular epinephrine 0.3 mg injection, epinephrine 0.3 mg autoinjectors (Symjepi and EpiPen), and epinephrine 1 mg intranasal spray (neffy). ResultsData from 175 participants showed that although neffy (1.0 mg intranasal spray) resulted in a maximum concentration (258 pg/mL) that was lower than or comparable with manual epinephrine intramuscular injection (254 pg/mL), Symjepi (438 pg/mL) and EpiPen (503 pg/mL), it led to comparable increases in systolic blood pressure (maximum effect [Emax], 16.9, 10.9, 14.9, and 18.1 mm Hg, respectively). The effect of neffy on diastolic blood pressure was also markedly more pronounced than that of other products (Emax, 9.32, 5.51, 5.78, and 5.93 mm Hg, respectively). ConclusionIntranasal delivery of epinephrine using neffy increases systolic blood pressure more efficiently than do manual intramuscular injection and epinephrine autoinjectors, despite lower maximum plasma concentrations.

255 Delivery of Epinephrine by Metered-Dose Inhaler for the Treatment of Croup in Children

255 Delivery of Epinephrine by Metered-Dose Inhaler for the Treatment of Croup in Children

Abstract 10911: Amplitude Spectral Area to Guide Shock and Epinephrine Delivery in a Swine Model of Ventricular Fibrillation and Closed-Chest Resuscitation

Introduction: VF accounts for ~30% of all sudden cardiac arrest episodes. VF signal analysis in the frequency domain - calculating the amplitude spectral area (AMSA) - can inform on the probability that an electrical shock could terminate VF followed by return of spontaneous circulation (ROSC). BLS guidelines require delivery of shocks every 2 min and epinephrine every 4 min. Yet, shocks often do not terminate VF and may injure the myocardium. We have previously reported that guiding the timing of shock delivery based on AMSA reduces myocardial injury and improves outcome. Epinephrine is given to increase the coronary perfusion pressure (CPP) and therefore myocardial blood flow but has detrimental effects on post-resuscitation myocardial function and possibly on neurological outcome. Hypothesis: Monitoring AMSA during CPR could be used not only to guide shock delivery but also to avoid administering epinephrine when AMSA predicts a high probability of shock success, reserving epinephrine when AMSA predicts a low probability of shock success and additional CPP increase might be helpful. Methods: In a swine model of electrically induced VF and mechanical chest compressions, two resuscitation protocols were compared in 8 pigs each: (1) A guidelines-driven (GD), delivering shocks and epinephrine guided by the current BLS protocol and (2) An AMSA-driven, delivering shocks and epinephrine guided by AMSA (ADSE). VF was untreated for 10 min and pigs that achieved ROSC were monitored for 240 min. Results: Compared to GD, ADSE was associated with a shorter time to ROSC (400±80 vs 569±16 sec, p=0.034) and higher survival rate at 240 minutes with borderline statistical significance (7/8 vs 3/8, p=0.059). ADSE required fewer shocks (3±2 vs 5±2, p=0.026) and received fewer doses of epinephrine (median [interquartile range], 1[1-1] vs 2[1.3-3], p=0.038). Conclusions: Resuscitation with the ADSE protocol was superior to the GD protocol resulting in a shorter time to ROSC with improved survival requiring fewer shocks and fewer epinephrine doses. The ADSE protocol represents a more tailored approach to resuscitation enabling delivery of resuscitation interventions with higher precision and consequently minimizing their associated adverse effects.

Targeted Delivery of Electrical Shocks and Epinephrine, Guided by Ventricular Fibrillation Amplitude Spectral Area, Reduces Electrical and Adrenergic Myocardial Burden, Improving Survival in Swine.

BackgroundWe previously reported that resuscitation delivering electrical shocks guided by real‐time ventricular fibrillation amplitude spectral area (AMSA) enabled return of spontaneous circulation (ROSC) with fewer shocks, resulting in less myocardial dysfunction. We now hypothesized that AMSA could also guide delivery of epinephrine, expecting further outcome improvement consequent to less electrical and adrenergic burdens.Methods and ResultsA swine model of ventricular fibrillation was used to compare after 10 minutes of untreated ventricular fibrillation a guidelines‐driven (n=8) resuscitation protocol, delivering shocks every 2 minutes and epinephrine every 4 minutes, with an AMSA‐driven shocks (n=8) protocol, delivering epinephrine every 4 minutes, and with an AMSA‐driven shocks and epinephrine (ADSE; n=8) protocol. For guidelines‐driven, AMSA‐driven shocks, and ADSE protocols, the time to ROSC (mean±SD) was 569±164, 410±111, and 400±80 seconds (P=0.045); the number of shocks (mean±SD) was 5±2, 3±1, and 3±2 (P=0.024) with ADSE fewer than guidelines‐driven (P=0.03); and the doses of epinephrine (median [interquartile range]) were 2.0 (1.3–3.0), 1.0 (1.0–2.8), and 1.0 (0.3–3.0) (P=0.419). The ROSC rate was similar, yet survival after ROSC favored AMSA‐driven protocols (guidelines‐driven, 3/6; AMSA‐driven shocks, 6/6; and ADSE, 7/7; P=0.019 by log‐rank test). Left ventricular function and survival after ROSC correlated inversely with electrical burden (ie, cumulative unsuccessful shocks, J/kg; P=0.020 and P=0.046) and adrenergic burden (ie, total epinephrine doses, mg/kg; P=0.042 and P=0.002).ConclusionsDespite similar ROSC rates achieved with all 3 protocols, AMSA‐driven shocks and ADSE resulted in less postresuscitation myocardial dysfunction and better survival, attributed to attaining ROSC with less electrical and adrenergic myocardial burdens.

Distal Intracoronary Delivery of Epinephrine versus Verapamil to Prevent No-Reflow During Primary Percutaneous Coronary Intervention: A Randomized, Open-Label, Trial

Background: Previous trials showed a promising potential use of epinephrine in the treatment of no-reflow phenomenon (the no-reflow phenomenon is multiple pathogenetic processes, which may be attributed to ischemic injuries, distal atherothrombotic embolization, coronary-microcirculation susceptibility to injury, and reperfusion injuries (6)). This study aimed to compare the safety and efficacy of distal intracoronary delivery of epinephrine versus verapamil to prevent no-reflow during primary percutaneous coronary intervention (PPCI). Materials and Methods: We conducted a randomized, open-label, trial on patients undergoing PPCI. Patients were randomized to one of three groups: group I who received distal intracoronary administration of epinephrine; group II who received verapamil; and group III who served as a control group. The primary endpoint in our study was the incidence of no-reflow, defined as a post-procedural (Thrombolysis in Myocardial Infarction) TIMI flow grade (TFG) is &lt; 3 or, in the case of a TFG of 3, when TIMI myocardial perfusion grade (TMPG) is 0 or 1. Results: A total of 120 patients were randomized. The angiographic flow and perfusion parameters were significantly improved in group I and II versus the control group, with better results in epinephrine group only TMPG3 was significantly higher with epinephrine (77.5%) than verapamil (55%) (p = 0.037) and TMPG2 was higher in verapamil (32.5%) than epinephrine (7.5%) (p = 0.003). No reflow is lower with epinephrine than verapamil (25% vs 27.5%); however, with no statistically significant difference (P=0.785). Patients in the three groups has no statistical significant difference in (MACE) or heart failure hospitalization. Conclusion: Epinephrine and verapamil are safe and effective in managing patients with no-reflow during PPCIs. Further studies with a larger sample and a longer duration of follow-up are required to confirm these findings

Intravenous vs intraosseous adrenaline administration in cardiac arrest: A protocol for systematic review and meta-analysis.

Introduction:Cardiac arrest refers to the sudden termination of cardiac ejection function due to various causes. Adrenaline is an important component of resuscitation among individuals experiencing cardiac arrest. The adrenaline delivery method chiefly involved intraosseous infusion and intravenous access. However, the impact of different adrenaline delivery methods on cardiac arrest has been unclear in previous research. Thus, the present study aimed to synthesize the available evidence regarding intravenous vs intraosseous adrenaline administration in cardiac arrest.Methods and analysis:We will search PubMed, EMBASE, Cochrane Library, Wanfang, and China National Knowledge Infrastructure. As per the inclusion criteria, randomized controlled trials (RCTs) on adrenaline administration in cardiac arrest were selected. The primary outcome was prehospital restoration of spontaneous circulation (ROSC); the secondary endpoints were survival, favorable neurological outcome at discharge, and poor neurological outcome at ≥3 mon.We plan to use the Cochrane Collaboration's tool for assessing the bias risk for RCTs. The Grading of Recommendations Assessment, Development and Evaluation approach will grade the certainty of the evidence for all the outcome measures across studies. RevMan 5.3.5 will be used for meta-analysis. If the heterogeneity tests show slight or no statistical heterogeneity, the fixed effects model will be used, in other cases, the random effect model will be used for data synthesis.Results and conclusion:This protocol will determine which epinephrine delivery method is the optimal in the management of cardiac arrest. Our findings will help clinicians and health professionals in making accurate clinical decisions about adrenaline administrations in cardiac arrest.Ethics and dissemination:Ethical approval was not required because this study was planned as a secondary analysis. The results will be disseminated in peer-reviewed publications, journals, and academic.INPLASY registration number:INPLASY202090100 (DOI:10.37766/inplasy2020.9.0100).

Association Between Hospital Debriefing Practices With Adherence to Resuscitation Process Measures and Outcomes for In-Hospital Cardiac Arrest.

Background Identifying actionable resuscitation practices that vary across hospitals could improve adherence to process measures or outcomes after in-hospital cardiac arrest (IHCA). We sought to examine whether hospital debriefing frequency after IHCA varies across hospitals and whether hospitals which routinely perform debriefing have higher rates of process-of-care compliance or survival. Methods We conducted a nationwide survey of hospital resuscitation practices in April of 2018, which were then linked to data from the Get With The Guidelines-Resuscitation national registry for IHCA. Hospitals were categorized according to their reported frequency of debriefing immediately after IHCA; rarely (0%-20% of all IHCA cases), occasionally (21%-80%), and frequently (81%-100%). Hospital-level rates of timely defibrillation (≤2 minutes), epinephrine administration (≤5 minutes), survival to discharge, return of spontaneous circulation, and neurologically intact survival were comparted for patients with IHCA from 2015 to 2017. Results Overall, there were 193 hospitals comprising 44 477 IHCA events. Mean patient age was 65±16, 41% were females, and 68% were of White race. Across hospitals, 84 (43.5%) rarely performed debriefings immediately after an IHCA, 82 (42.5%) performed debriefing sessions occasionally, and 27 (14.0%) performed debriefing frequently. There was no association between higher reported debriefing frequency and hospital rates of timely defibrillation and epinephrine administration. Mean hospital rates of risk-standardized survival to discharge were similar across debriefing frequency groups (rarely 25.6%; occasionally 26.0%; frequently 25.2%, P=0.72), as were hospital rates of risk-adjusted return of spontaneous circulation (rarely 72.2%; occasionally 73.0%; frequently 70.0%, P=0.06) and neurologically intact survival (rarely 21.9%, occasionally 22.2%, frequently 21.1%, P=0.75). Conclusions In a large contemporary nationwide quality improvement registry, hospitals varied widely in how often they conducted debriefings immediately after IHCA. However, hospital debriefing frequency was not associated with better adherence to timely delivery of epinephrine or defibrillation or higher rates of IHCA survival.

Interim Guidance for Basic and Advanced Life Support in Adults, Children, and Neonates With Suspected or Confirmed COVID-19: From the Emergency Cardiovascular Care Committee and Get With The Guidelines-Resuscitation Adult and Pediatric Task Forces of the American Heart Association.

Interim Guidance for Basic and Advanced Life Support in Adults, Children, and Neonates With Suspected or Confirmed COVID-19: From the Emergency Cardiovascular Care Committee and Get With The Guidelines-Resuscitation Adult and Pediatric Task Forces of the American Heart Association.

Epinephrine delivery via EpiPen\xae Auto-Injector or manual syringe across participants with a wide range of skin-to-muscle distances

BackgroundIntramuscular (IM) injection of epinephrine (adrenaline) at the mid-anterolateral (AL) thigh is the international standard therapy for acute anaphylaxis. Concerns exist regarding implications of epinephrine auto-injector needles not penetrating the muscle in patients with greater skin-to-muscle-distances (STMD).MethodsThis open-label, randomized, crossover study investigated pharmacokinetics and pharmacodynamics following injection of epinephrine in healthy volunteers. Individuals were stratified by maximally compressed STMD (low, < 15 mm; moderate, 15–20 mm; high, > 20 mm). Participants received epinephrine injections via EpiPen® Auto-Injector (EpiPen; 0.3 mg/0.3 mL) or IM syringe (0.3 mg/0.3 mL) at mid-AL thigh or received saline by IM syringe in a randomized order. Eligible participants received a fourth treatment (EpiPen [0.3 mg/0.3 mL] at distal-AL thigh). Model-independent pharmacokinetic parameters and pharmacodynamics were assessed.ResultsThere were numerical trends toward higher peak epinephrine concentrations (0.52 vs 0.35 ng/mL; geometric mean ratio, 1.40; 90% CI 117.6–164.6%) and more rapid exposure (time to peak concentration, 20 vs 50 min) for EpiPen vs IM syringe at mid-AL thigh across STMD groups. Absorption was faster over the first 30 min for EpiPen vs IM syringe (partial area under curve [AUC] over first 30 min: geometric mean ratio, 2.13; 90% CI 159.0–285.0%). Overall exposure based on AUC to the last measurable concentration was similar for EpiPen vs IM syringe (geometric mean ratio, 1.13; 90% CI 98.8–129.8%). Epinephrine pharmacokinetics after EpiPen injection were similar across STMD groups. Treatments were well tolerated.ConclusionsEpinephrine delivery via EpiPen resulted in greater early systemic exposure to epinephrine vs IM syringe as assessed by epinephrine plasma levels. Delivery via EpiPen was consistent across participants with a wide range of STMD, even when the needle may not have penetrated the muscle.Trial registrationsThis trial was registered with the German Clinical Trials Register (DRKS-ID: DRKS00011263; secondary ID, EudraCT 2016-000104-29) on 23 March 2017.

Epinephrine auto-injector needle length

BackgroundEpinephrine auto-injectors are expected to deliver the drug intramuscularly.ObjectiveTo study whether injection through clothing influences the frequency of subcutaneous and intraosseous/periosteal deposition of epinephrine.MethodsSkin to muscle and skin to bone distances were measured for 303 children and adolescents and 99 adults. Distance was determined by ultrasound, with high or low pressure on the ultrasound probe. The risk/percentage of subcutaneous and intraosseous/periosteal injections was calculated using the lower and upper limits for the authority-approved length of EAI needles as provided by two high pressure EAI manufacturers and one low pressure EAI manufacturer. The addition winter clothing on the delivery of epinephrine was illustrated by comparing drug delivery fissue depth with no clothes. Furthermore, the riof non-intramuscular delivery for the shortest and longest approved needle length was calculated.ResultsWhen using EpipenJr® in children < 15 kg the risk of intraosseous/periostal injection was reduced from 1% and 59% for the shortest and longest approved needle length to 0 and 15% with winter clothes. The Auvi-Q® 0.1 mg had no risk of intraosseous/periosteal injection. However, the subcutaneous deposition risk increased from 94% and 28% to 100% and 99% with winter clothes. The risk of subcutaneous injection using EpipenJr® in the youngest children increased from 13% and 0% to 81% and 1% with winter clothes, and with Epipen® in adults from 45% and 17% to 60% and 38%. Emerade®, had a risk of subcutaneous injection in adults increasing from 14% and 10% to 28% and 21% adding winter clothes.ConclusionThe risk of intraosseous/periosteal injections decreases and the risk of subcutaneous injection increases when injecting through winter clothes for all EAIs.