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

Background We 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 Results A 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). Conclusions Despite 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.

Antithrombin use during pediatric cardiac extracorporeal membrane oxygenation admission: insights from a national database.

INTRODUCTION: The frequency of extracorporeal membrane oxygenation in pediatric patients continues to increase, especially in patients with complex congenital heart disease. Providing adequate anticoagulation is necessary for patients on extracorporeal membrane oxygenation and is achieved with adequate heparin administration. Antithrombin is administered to potentiate heparin's effects. However, the efficacy of antithrombin supplementation is unclear and a clear clinical benefit has not been established. We present a large retrospective study examining the effects of antithrombin on pediatric patients receiving extracorporeal membrane oxygenation. METHODS: Data for this study were obtained from the Pediatric Health Information System and Pediatric Health Information System+ databases from 2004 to 2015. Pediatric patients receiving extracorporeal membrane oxygenation with a congenital heart disease diagnosis were included and divided into groups that did or did not utilize antithrombin. For all admissions, the following were captured: age of admission, gender, year of admission, length of stay, billed charges, inpatient mortality, the presence of specific congenital malformations of the heart, specific cardiac surgeries, and comorbidities. RESULTS: A total of 9,193 admissions were included and 865 (9.4%) utilized antithrombin. Between groups, there were significantly different frequencies of co-morbidities, cardiac lesion types and antithrombin usage over the study period. There were significantly lower odds in the antithrombin group of venous thrombosis. Antithrombin was not significantly associated with hemorrhage; however, antithrombin was associated with increased inpatient mortality and a decrease in length of stay and billed charges. CONCLUSION: Antithrombin administration is associated with increased mortality, a shorter length of stay, and decreased billing cost. Recently, antithrombin usage has been decreasing-potentially due to the reported lack of clinical benefit. Together, these results reinforce that antithrombin may not be indicated for all pediatric extracorporeal membrane oxygenation patients.

The effect of air exposure on leucocyte and cytokine activation in an in-vitro model of cardiotomy suction.

INTRODUCTION: Cardiopulmonary bypass (CPB) is known to cause a systemic inflammatory and immune response. OBJECTIVE: An in-vitro model of cardiotomy suction was designed to quantify the effects of incrementally increased air-blood exposure on leucocyte marker CD11b and cytokine activation in two common anticoagulants, heparin and citrate. METHODS: Fresh human blood was exposed to increasing amounts of air flow for ten minutes. Leucocyte and cytokine levels were measured prior to and after ten minutes of air flow. Cytokine levels were also measured after air exposure when incubated for 24 hours at 37oC. RESULTS: Leucocyte activation, measured by CD11b, was elevated between baseline and air flow rates up to 50 mL/min. After 10 minutes of air exposure, no measured cytokine levels were elevated. After 24 hours of incubation, cytokine levels of TNFα, IL-10, IL-6, and IL-8 were elevated. However, only IL-8 was significantly elevated in citrated blood, but not in heparinized blood, when compared to baseline samples that were also incubated for 24 hours. CONCLUSION: This study investigates CD11b levels in response to an air stimulus in blood that was anticoagulated with citrate or heparin. Exposure to an air stimulus activates leucocytes. Activation of CD11b was less when using heparin as an anticoagulant compared to citrate. Cytokine activation occurs with air stimulation, but levels do not immediately rise, indicating that time is required to generate free cytokines.