p.12 抽出テキスト

Circulation. 2025;152(suppl 2):S538–S577. DOI: 10.1161/CIR.0000000000001376 October 21, 2025 S549

Wigginton et al Advanced Life Support: 2025 AHA Guidelines for CPR and ECC

Synopsis The potent vasopressor effects of epinephrine have been recognized for nearly 150 years. Vasopressors increase coronary perfusion pressure and increase the likelihood of ROSC. Epinephrine has been shown to increase ROSC and survival to hospital admission in placebo-controlled RCTs, cohort studies, and registry studies, but there is limited evidence to support improvement in survival to hospital discharge or functional neurologic outcome. Studies comparing different dosing intervals, high-dose epinephrine, and low-dose epinephrine against standard-dose epinephrine (1 mg every 3–5 minutes) have not demonstrated an advantage in survival outcomes. Defining the optimal number of doses or maximum dose of epinephrine is a critical knowledge gap and more research is needed. Vasopressin, a naturally occurring antidiuretic hormone, has been studied as an alternative to epinephrine during cardiac resuscitation. In high doses, vasopressin acts as a potent vasoconstrictor and, like epinephrine, increases systemic vascular resistance and raises coronary perfusion pressure. However, there have been no clinical trials demonstrating an advantage to using vasopressin alone or vasopressin in addition epinephrine over standard-dose epinephrine alone.

Recommendation-Specific Supportive Text

1 There have been no new RCTs comparing epineph-

rine to placebo since the publication of the 2020 ALS guidelines. There is consistent and compelling evidence from previous RCTs, cohort, and registry studies to support a potent effect of epinephrine on ROSC, survival to hospital admission, and survival to hospital discharge.1,2 However, studies have failed to show an increase in survival with functional neurologic outcome.2–5 A secondary analysis of the PARAMEDIC2 (Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration in Cardiac Arrest) trial found 12-month survival favored epinephrine, whereas there was no significance difference in 6-month survival with functional neurologic outcome between arms.6 While there is no evidence supporting improvement in neurologic outcome, epinephrine does improve short- term survival, a prerequisite to meaningful recovery. In the absence of a feasible, intra-arrest method of determining the likelihood of favorable neurological outcome, epinephrine remains standard therapy to treat cardiac arrest. 2.	 Existing clinical trials have used a protocol of 1

mg of epinephrine administered every 3 to 5 minutes.3–6 Operationally, administering epinephrine every second cycle of CPR, after the initial dose, meets this recommendation. 3 Multiple observational studies have demonstrated

an association between earlier epinephrine administration and ROSC.2 A post-hoc analysis of the PARAMEDIC2 trial found that the effectiveness of epinephrine, compared to placebo, converges at approximately 20 minutes of pulselessness where there is no difference in survival to hospital discharge, 30-day survival, or functional neurologic outcome with longer times to initial epinephrine administration.7

4 Systematic reviews and meta-analyses of RCTs

and cohort studies have found that epinephrine is associated with improved ROSC in all rhythms, but the benefit in shockable rhythms is less than in nonshockable rhythms.2–4,8 One observational study of IHCA demonstrated 10% lower riskadjusted survival in hospitals with the highest rates of epinephrine administration prior to initial defibrillation when compared with those hospitals with the lowest rates.9 The optimal timing for epinephrine in relation to defibrillation is unknown. In patients with shockable rhythms, this literature supports prioritizing rapid defibrillation and administering epinephrine after initial attempts with CPR and defibrillation are not successful. 5.	 When compared to placebo, administration of vaso-

pressin improves ROSC regardless of presenting rhythms and increases survival to hospital admission and discharge in nonshockable rhythms.10 However, multiple systematic reviews and meta-analyses of RCTs and observational studies have found no difference in survival outcomes when comparing vasopressin alone or vasopressin combined with epinephrine versus epinephrine alone.2,10–12

6 Multiple RCTs have compared administration of

high-dose epinephrine with standard-dose, but the definition of high-dose epinephrine varies widely by study. There were no new RCTs published since the 2020 Guidelines comparing standarddose epinephrine to any high-dose epinephrine. Systematic reviews and meta-analysis of RCTs have yielded mixed results.10,12 One registry-based study found dosing epinephrine more frequently than the standard interval may be potentially harmful.13 High-dose intramuscular (IM) epinephrine for the treatment of OHCA, with a different pharmacokinetic profile than traditional IV administration, has also been evaluated. One single-center, beforeafter study of 1405 OHCA patients receiving an initial IM dose of epinephrine followed by standard IV/IO administration shortened time to epinephrine administration and improved survival to hospital admission, hospital survival, and favorable neurologic status at hospital discharge. However, the study design could not account for multiple

Downloaded from http://ahajournals.org by on October 7, 2026