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October 21, 2025 Circulation. 2025;152(suppl 2):S538–S577. DOI: 10.1161/CIR.0000000000001376 S552 Wigginton et al Advanced Life Support: 2025 AHA Guidelines for CPR and ECC discharge in bystander-witnessed arrest, with a significant interaction between active drug effect and witnessed arrest status, as did amiodarone in EMS-witnessed arrest. When administered within 8 minutes of ALS-capable EMS arrival, amiodarone also improved survival to hospital admission, discharge, and functional survival at hospital discharge.6 This suggests the potential for a small, time-dependent therapeutic window in patients with rapidly recognized and treated cardiac arrest. Data are insufficient to definitively distinguish between the effectiveness of lidocaine and amiodarone, nor their benefit when given in combination. 2. No new evidence emerged from a 2025 ILCOR evidence update7 regarding the use of other parenteral antiarrhythmic agents in cardiac arrest. These include bretylium tosylate (which was recently reintroduced in the United States market with no new evidence on its effectiveness or safety); sotalol (which requires a slow infusion and has unknown benefit when given as a bolus in cardiac arrest8), procainamide (also requiring slow infusion, and of uncertain benefit when given by rapid infusion as a second-line agent in cardiac arrest9), and beta blockers (for which the ILCOR update found insufficient evidence to recommend for or against use).10 The effectiveness of these drugs administered in combination for cardiac arrest has not been systematically addressed and remains a knowledge gap. Nifekalant is currently unavailable in the United States and is therefore excluded from this recommendation. 3. Both the 2023 AHA focused update and ILCOR’s 2023 CoSTR summary identified no new compelling data to alter previous recommendations regarding the use of steroids bundled with a vasopressor agent in cardiac arrest.3,11 A large multicenter, blinded, placebo-controlled randomized trial of IHCA deploying this drug combination found an improved rate of ROSC but not survival to hospital discharge or neurological outcome, failing to confirm results of 2 previous single center trials.12 Observational studies combining intra-arrest corticosteroids with standard resuscitation have demonstrated mixed outcomes.13–15 An ongoing registered clinical trial (NCT06203847) may provide further clarity. 4. The 2023 AHA focused update,3 ILCOR’s 2023 CoSTR summary,11 and a systematic review including 3 RCTs,16 found routine calcium administration during cardiac arrest, including cases of refractory asystole and pulseless electrical activity, did not improve survival to hospital discharge or neurological outcome, with a cautionary trend toward potential harm. A Get With the Guidelines registry report also found no evidence of benefit from calcium administration, independent of rhythm presentation, during IHCA.17 Although the findings of registry data are confounded by temporal bias (ie, calcium administered as a last resort during prolonged resuscitations, where outcomes are already likely poor), the randomized trial data, designed to mitigate that bias, found no evidence of benefit when calcium was administered immediately after the first dose of epinephrine.18 Administration of calcium in special circumstances such as hyperkalemia and toxic ingestion is discussed elsewhere as noted above. 5. The 2023 AHA focused update found routine administration of sodium bicarbonate in cardiac arrest was of no benefit.3 However, recent observational data examining prehospital administration of sodium bicarbonate in pulseless electrical activity and asystole suggests a potential association with improved survival.19 As observed with calcium, issues of resuscitation time bias may also apply to bicarbonate, resulting in difficulty interpreting the findings.20,21 Although contemporary evidence is insufficient to change the recommendation, there may be clinical equipoise to warrant further clinical trials to assess its utility in nonshockable presenting rhythms. Use of sodium bicarbonate in special circumstances such as hyperkalemia is discussed elsewhere as noted above. 6. The 2024 ILCOR CoSTR found intra-arrest magnesium administration did not improve ROSC, survival, or neurological outcome regardless of the presenting cardiac arrest rhythm,22–25 nor was it useful for monomorphic VT.26 Magnesium’s efficacy in the treatment of torsade de pointes is addressed later in this Part (see Treatment of Adults With Polymorphic Ventricular Tachycardia). REFERENCES 1. 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 2. Cao D, Arens AM, Chow SL, Easter SR, Hoffman RS, Lagina AT, Lavonas EJ, Patil KD, Sutherland LD, Tijssen JA, et al. Part 10: Adult and pediatric special circumstances of resuscitation: 2025 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2025;152(suppl 2):S578–S672. doi: 10.1161/CIR.0000000000001378 3. Perman SM, Elmer J, Maciel CB, Uzendu A, May T, Mumma BE, Bartos JA, Rodriguez AJ, Kurz MC, Panchal AR, et al; American Heart Association. 2023 American Heart Association Focused Update on Adult Advanced Cardiovascular Life Support: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2024;149:e254–e273. doi: 10.1161/CIR.0000000000001194 4. Greif R, Bray JE, Djarv T, Drennan IR, Liley HG, Ng KC, Cheng A, Douma MJ, Scholefield BR, Smyth M, et al. 2024 International Consensus on Downloaded from http://ahajournals.org by on October 7, 2026