The physiologic response to epinephrine and pediatric cardiopulmonary resuscitation outcomes

Abstract

Background Epinephrine is provided during cardiopulmonary resuscitation (CPR) to increase systemic vascular resistance and generate higher diastolic blood pressure (DBP) to improve coronary perfusion and attain return of spontaneous circulation (ROSC). The DBP response to epinephrine during pediatric CPR and its association with outcomes have not been well described. Thus, the objective of this study was to measure the association between change in DBP after epinephrine administration during CPR and ROSC. Methods This was a prospective multicenter study of children receiving ≥ 1 min of CPR with ≥ 1 dose of epinephrine and evaluable invasive arterial BP data in the 18 ICUs of the ICU-RESUS trial (NCT02837497). Blood pressure waveforms underwent compression-by-compression quantitative analysis. The mean DBP before first epinephrine dose was compared to mean DBP two minutes post-epinephrine. Patients with ≥ 5 mmHg increase in DBP were characterized as “responders.” Results Among 147 patients meeting inclusion criteria, 66 (45%) were characterized as responders and 81 (55%) were non-responders. The mean increase in DBP with epinephrine was 4.4 [− 1.9, 11.5] mmHg (responders: 13.6 [7.5, 29.3] mmHg versus non-responders: − 1.5 [− 5.0, 1.5] mmHg; p < 0.001). After controlling for a priori selected covariates, epinephrine response was associated with ROSC (aRR 1.60 [1.21, 2.12]; p = 0.001). Sensitivity analyses identified similar associations between DBP response thresholds of ≥ 10, 15, and 20 mmHg and ROSC; DBP responses of ≥ 10 and ≥ 15 mmHg were associated with higher aRR of survival to hospital discharge and survival with favorable neurologic outcome (Pediatric Cerebral Performance Category score of 1–3 or no worsening from baseline). Conclusions The change in DBP following epinephrine administration during pediatric in-hospital CPR was associated with return of spontaneous circulation.

Hemodynamic Effect of Repeated Epinephrine Doses Decreases With Cardiopulmonary Resuscitation Cycle Progression

“… 15 , 16 Translational and clinical studies have established wide variability in DBP responsiveness to epinephrine during CPR, including no response in many patients. 23 , 24 Our pharmacodynamics data during CPR suggested that the present epinephrine dosing and dosing intervals might not be optimal. New strategies might be necessary for optimal epinephrine administration during CPR.…”

Identification of post-cardiac arrest blood pressure thresholds associated with outcomes in children: an ICU-Resuscitation study

“…Intra-arrest invasively measured blood pressure data were prospectively collected and analyzed as a component of the ICU-RESUS trial [ 18 , 19 , 25 , 29 ]. We evaluated the association between intra-arrest mean DBP targets and post-arrest study SBP and DBP thresholds at 0–6 h post-arrest using Poisson regression with robust error estimates, controlling for illness category and pre-arrest hypotension.…”

Associations Between End-Tidal Carbon Dioxide During Pediatric Cardiopulmonary Resuscitation, Cardiopulmonary Resuscitation Quality, and Survival

“…The data collection and physiological waveform analysis methods of the parent trial, and subsequent secondary studies, have been previously published. [13][14][15] In brief, trained research coordinators collected standardized cardiopulmonary arrest data elements, 16 CPR quality mechanics data (eg, compression depth and rate), and physiological bedside monitor data (eg, electrocardiogram, invasive arterial line, and quantitative capnography) for index CPR events (ie, the first event associated with the hospitalization). Baseline Pediatric Cerebral Performance Category 17,18 and Functional Status Scale 19 scores were based on the patient's preadmission baseline and calculated on the basis of documentation review.…”