Soup to nuts: A review of Pharmacotherapy Considerations for Inpatient ACLS (Noble, Posgai, & Hochstetler, 2025)

Summary: "Pharmacotherapy Considerations for Inpatient Advanced Cardiac Life Support" (Posgai & Hochstetler, AACN Advanced Critical Care, 2025)

This review addresses medication management in adult cardiac arrest, emphasizing that despite decades of use, no drug has been proven to improve survival with favorable neurologic outcome. Survival to discharge remains low—9.1% for out-of-hospital and 18.8% for in-hospital arrest—with high-quality CPR and early defibrillation of shockable rhythms remaining the most effective interventions. Medication administration should never delay CPR or defibrillation. Modern resuscitation research has shifted toward patient-centered core outcomes (survival, neurologic function, health-related quality of life) rather than return of spontaneous circulation (ROSC) alone.

Guideline-recommended medications (AHA adult algorithm):

• Epinephrine — The only drug recommended in every AHA ACLS iteration. Acts via α-adrenergic vasoconstriction to boost coronary/cerebral perfusion, though β-adrenergic effects may be harmful (increased myocardial oxygen demand, proarrhythmia). The landmark PARAMEDIC-2 trial (n=8007) showed improved 30-day survival with epinephrine vs placebo (3.2% vs 2.4%) but no benefit in survival with favorable neurologic outcome, and more severe neurologic impairment in survivors. Benefit was significant only in nonshockable rhythms. Thus, epinephrine should be given as soon as feasible in nonshockable rhythms but delayed in shockable rhythms until defibrillation attempts fail (ERC: after 3 shocks). Observational data (Javaudin et al) link cumulative doses ≥5 mg to worse outcomes; the ongoing Epi-DOSE trial is evaluating low vs standard cumulative dosing. Capping doses at 3–5 is common practice. The article also details bedside dilution techniques (using 0.9% saline bags or flush syringes) to reproduce the 1 mg/10 mL concentration, stressing clear labeling and closed-loop communication.

• Antiarrhythmics (lidocaine and amiodarone) — Both are first-line, co-equal options for shockable rhythms (VF/pulseless VT), used to help maintain a perfusing rhythm alongside defibrillation rather than for direct conversion. Key trials: ARREST (amiodarone improved survival to admission vs placebo), ALIVE (amiodarone > lidocaine for survival to admission, no difference at discharge), and ROC-ALPS (no significant survival-to-discharge difference vs placebo except benefit in witnessed arrests), which drove the 2018 AHA recommendation for either agent. A retrospective in-hospital study (Wagner et al) suggested lidocaine may yield better 24-hour survival, survival to discharge, and neurologic outcomes than amiodarone, raising the question of preferential inpatient use. Logistical trade-offs: lidocaine comes prefilled (faster) but is weight-based; amiodarone has fixed dosing (300 mg, then 150 mg) but must be drawn from a vial.

Adjunctive medications (removed from or outside the algorithm):

• Sodium bicarbonate — Not recommended routinely; meta-analysis linked it to worse ROSC and neurologic outcomes. Reserved for hyperkalemia or drug overdose.

• Calcium — 2023 AHA guidelines recommend against routine use; the Vallentin et al RCT was stopped early for harm (worse 30-day and neurologic outcomes).

• Magnesium — No proven benefit for ROSC/survival; reasonable for torsades de pointes (prevents reinitiation).

• β-blockers (esmolol) — May counteract detrimental catecholamine/β-adrenergic effects in refractory VF. Small studies (Driver, Lee) showed improved ROSC and, in one, better survival/neurologic outcomes (500 µg/kg load + infusion). Not yet guideline-recommended but a potential option for refractory VF.

Conclusion: Drug therapy remains integral to ACLS despite limited evidence for long-term benefit. The authors anticipate a shift toward individualized, cause- and setting-specific arrest algorithms, making pharmacotherapy expertise increasingly important.