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October 21, 2025 Circulation. 2025;152(suppl 2):S538–S577. DOI: 10.1161/CIR.0000000000001376 S548

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

initial IV access in adult OHCA and found no differences in clinical outcomes.9–11 Each RCT used a superiority design; therefore, the absence of outcome differences between the two groups does not indicate equivalence. An ILCOR systematic review, including data from these RCTs, found that the use of IO access compared with IV access did not result in a statistically significant improvement in outcomes, including survival to discharge, survival with favorable neurological outcome, or health-related quality of life.12 This systematic review noted lower odds of achieving sustained ROSC for the IO route compared with the IV route (odds ratio [OR] 0.89; 95% CI, 0.80–0.99).12 Patient, EMS professional, or circumstantial characteristics may limit successful IV access or make IV access infeasible. In these cases, the available evidence supports IO access as an alternative. The optimal anatomical location for IO access (ie, tibial or humeral) remains a knowledge gap. 3.	Drug administration through central venous

access can achieve faster circulation times and higher plasma concentrations in adults in cardiac arrest when compared with peripheral IV administration.13–15 However, data comparing clinical outcomes from cardiac arrest based on different access routes, including central venous access, remain limited. A small, single- center study reported higher rates of ROSC among participants who were randomized to femoral or internal jugular vein access compared to those with peripheral IV access, although with a high risk of bias.16 If central venous access is attempted by appropriately trained professionals, special attention is required to avoid delays in chest compressions or defibrillation.

REFERENCES

1 Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Car-

diovascular Care. Part 6: advanced cardiovascular life support: section 2: defibrillation. The American Heart Association in collaboration with the International Liaison Committee on Resuscitation. Circulation. 2000;102:I90–I94. 2.	 Panchal AR, Bartos JA, Cabanas JG, Donnino MW, Drennan IR, Hirsch KG, Kudenchuk PJ, Kurz MC, Lavonas EJ, Morley PT, et al; Adult Basic and Advanced Life Support Writing Group. Part 3: Adult Basic and Advanced Life Support: 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020;142:S366–S468. doi: 10.1161/CIR.0000000000000916 3.	 Riva E, Gerna M, Latini R, Giani P, Volpi A, Maggioni A. Pharmacokinetics of amiodaron in man. J Cardiovasc Pharmacol. 1982;4:264–269. doi: 10.1097/00005344-198203000-00015 4.	 Orlowski JP, Porembka DT, Gallagher JM, Lockrem JD, VanLente F. Comparison study of intraosseous, central intravenous, and peripheral intravenous infusions of emergency drugs. Am J Dis Child. 1990;144:112–117. doi: 10.1001/archpedi.1990.02150250124049 5.	 Greenblatt DJ, Bolognini V, Koch-Weser J, Harmatz JS. Pharmacokinetic approach to the clinical use of lidocaine intravenously. JAMA. 1976;236:273–277. 6.	 Collinsworth KA, Kalman SM, Harrison DC. The clinical pharmacology of

lidocaine as an antiarrhythymic drug. Circulation. 1974;50:1217–1230. doi: 10.1161/01.cir.50.6.1217 7.	 Vadeyar S, Buckle A, Hooper A, Booth S, Deakin CD, Fothergill R, Ji C,

Nolan JP, Brown M, Cowley A, et al. Trends in use of intraosseous and intravenous access in out-of-hospital cardiac arrest across English ambulance services: A registry-based, cohort study. Resuscitation. 2023;191:109951. doi: 10.1016/j.resuscitation.2023.109951 8.	 Agostinucci JM, Alheritiere A, Metzger J, Nadiras P, Martineau L, Bertrand P, Gentilhomme A, Petrovic T, Adnet F, Lapostolle F. Evolution of the use of intraosseous vascular access in prehospital advanced cardiopulmonary resuscitation: The IOVA-CPR study. Int J Nurs Pract. 2024;30:e13244. doi: 10.1111/ijn.13244 9.	 Vallentin MF, Granfeldt A, Klitgaard TL, Mikkelsen S, Folke F, Christensen HC, Povlsen AL, Petersen AH, Winther S, Frilund LW, et al. Intraosseous or Intravenous Vascular Access for Out-of-Hospital Cardiac Arrest. N Engl J Med. 2025;392:349–360. doi: 10.1056/NEJMoa2407616 10.	 Ko YC, Lin HY, Huang EP, Lee AF, Hsieh MJ, Yang CW, Lee BC, Wang YC, Yang WS, Chien YC, et al. Intraosseous versus intravenous vascular access in upper extremity among adults with out-of-hospital cardiac arrest: cluster randomised clinical trial (VICTOR trial). BMJ. 2024;386:e079878. doi: 10.1136/bmj-2024-079878 11.	 Couper K, Ji C, Deakin CD, Fothergill RT, Nolan JP, Long JB, Mason JM, Michelet F, Norman C, Nwankwo H, et al. A randomized trial of drug route in out-of-hospital cardiac arrest. N Engl J Med. 2024;392:336–348. doi: 10.1056/NEJMoa2407780 12.	 Couper K, Drennan IR, Garrett JS, Grunau BE, Vallentin MF. Intraosseous and intravenous vascular access during adult cardiac arrest: a systematic review update. Resuscitation. 2025;209:110564. doi: 10.1016/j.resuscitation.2025.110564 13.	 Kuhn GJ, White BC, Swetnam RE, Mumey JF, Rydesky MF, Tintinalli JE, Krome RL, Hoehner PJ. Peripheral vs central circulation times during CPR: a pilot study. Ann Emerg Med. 1981;10:417–419. doi: 10.1016/s0196-0644(81)80308-3 14.	 Emerman CL, Pinchak AC, Hancock D, Hagen JF. Effect of injection site on circulation times during cardiac arrest. Crit Care Med. 1988;16:1138–1141. doi: 10.1097/00003246-198811000-00011 15.	 Barsan WG, Levy RC, Weir H. Lidocaine levels during CPR: differences after peripheral venous, central venous, and intracardiac injections. Ann Emerg Med. 1981;10:73–78. doi: 10.1016/s0196-0644(81)80339-3 16.	 Qin H, Wang L, Yu B, Xing D, Su J, Bai Z. Effect of other venous access

on cardiopulmonary resuscitation quality: A prospective, randomized, controlled trial. Biotechnol Genet Eng Rev. 2024;40:2262–2272. doi: 10.1080/02648725.2023.2199239

RECOMMENDATIONS FOR VASOPRESSOR MEDICATIONS IN ADULT CARDIAC ARREST

Recommendations for Vasopressor Management in Cardiac Arrest COR LOE Recommendations

1 B-R 1.  Administration of epinephrine is recommended for adult patients in cardiac arrest. 2a B-R 2.  It is reasonable to administer epinephrine (1 mg) every 3 to 5 min for adult patients in cardiac arrest.

2a B-NR 3.  With respect to timing, for adult patients in cardiac arrest with a nonshockable rhythm, it is reasonable to administer epinephrine as soon as feasible.

2a B-NR 4.  With respect to timing, for adult patients in cardiac arrest with a shockable rhythm, it is reasonable to administer epinephrine after initial defibrillation attempts have failed.

3: No Benefit B-R 5.  Vasopressin alone or vasopressin in combination with epinephrine offers no advantage as a substitute for epinephrine for adult patients in cardiac arrest. 3: No Benefit B-R 6.  High-dose epinephrine is not recommended for routine use for adult patients in cardiac arrest.

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