PACUPod is your trusted source for AI-infused evidence-based insights tailored to advanced clinical pharmacists and physicians. Each episode dives into the latest primary literature, covering medication-focused studies across emergency medicine and critical care. We break down study designs, highlight key findings, and objectively discuss clinical implications—without the hype—so you stay informed and ready to apply new evidence in practice. Whether you’re preparing for board certification or striving for excellence in patient care, PACUPod helps you make sense of the data, one study at a time.
Britany: Welcome back to PACULit, your source for the latest clinical literature updates. Today, we’re discussing a pilot trial on landiolol for refractory ventricular fibrillation in out-of-hospital cardiac arrest. Seth, this is a hot topic given the challenge of refractory VF despite current ACLS protocols.
Seth: Absolutely, Britany. Out-of-hospital cardiac arrest with refractory VF remains a major problem. Even with defibrillation, epinephrine, and amiodarone, many patients don’t achieve return of spontaneous circulation. Mortality rates remain high, so exploring adjunct therapies like beta-blockers is warranted.
Britany: The rationale for beta-blockers, especially ultra-short-acting ones like landiolol, is to blunt the catecholamine surge during resuscitation. Excess sympathetic stimulation can worsen arrhythmias, so landiolol could reduce arrhythmogenicity and improve ROSC rates. But evidence has been sparse and conflicting.
Seth: Prior data mostly came from observational studies or small trials with esmolol, another ultra-short-acting beta-blocker. Some suggested improved ROSC and survival, but evidence quality was low. Meta-analyses haven’t confirmed survival benefits for beta-blockers or other antiarrhythmics in refractory VF.
Britany: That’s why this randomized, double-blind, placebo-controlled pilot trial by Gelbenegger et al. is important. It’s the first rigorous evaluation of landiolol’s efficacy and safety here. Let’s review the study design.
Seth: This prospective, single-center trial enrolled adults with out-of-hospital cardiac arrest presenting with recurrent or refractory VF after initial ACLS. Inclusion required refractory VF despite defibrillation, epinephrine, and amiodarone.
Britany: They excluded patients with beta-blocker contraindications, terminal illnesses, or factors limiting resuscitation. Intervention was a single 20 mg IV bolus of landiolol versus placebo infusion identical in appearance and volume. Both groups received standard ACLS care.
Seth: The primary outcome was time from drug infusion to sustained ROSC. Secondary safety outcomes included bradycardia and asystole incidence within 15 minutes post-infusion. Follow-up lasted during resuscitation until ROSC or termination.
Britany: Randomization was computer-generated and double-blinded. The sample size was small—36 patients—which limits power but is typical for a pilot. What were the results?
Seth: There was no significant difference in median time to sustained ROSC—39 minutes with landiolol versus 41 minutes with placebo. Sustained ROSC rate was lower in the landiolol group at 36.8% versus 64.7% in placebo.
Britany: That’s striking. Even more concerning was the higher incidence of asystole within 15 minutes post-infusion in the landiolol group—36.8% versus none in placebo—suggesting potential adverse cardiac effects.
Seth: Yes, increased bradycardia and asystole raise safety concerns. This challenges prior observational data suggesting beta-blockers might help. Landiolol’s ultra-short half-life of about four minutes was thought to allow rapid titration and safety, but it didn’t improve outcomes here.
Britany: This highlights the complexity of modulating sympathetic activity during cardiac arrest. Beta-blockers may reduce arrhythmogenicity but also depress myocardial contractility or conduction excessively, leading to asystole.
Seth: Exactly. The study’s strengths include randomized, double-blind design and clear refractory VF definitions. But the small sample and single-center setting limit generalizability.
Britany: Still, findings are clinically important. They suggest routine addition of landiolol to ACLS for refractory VF isn’t supported and may be harmful. Clinicians should exercise caution and closely monitor rhythm if beta-blockers are considered.
Seth: This underscores the need for larger, multicenter trials to evaluate beta-blockers’ role in refractory VF. Until then, guidelines recommending defibrillation, epinephrine, and amiodarone remain appropriate.
Britany: The international consensus recommends this sequence based on trials like ARREST and ALIVE, which showed modest survival benefits with amiodarone. Despite that, outcomes remain poor, prompting exploration of adjuncts like beta-blockers.
Seth: A 2019 systematic review found esmolol might improve ROSC and survival in refractory VF, but evidence was very low quality, mostly small retrospective studies. A feasibility study showed prehospital administration was possible, but no definitive efficacy data.
Britany: A 2021 meta-analysis of antiarrhythmics in OHCA concluded no drug class, including beta-blockers, significantly improved survival to discharge. So, Gelbenegger et al.’s trial provides the first rigorous placebo-controlled data, which do not support landiolol’s benefit.
Seth: This shows how promising observational signals need confirmation in randomized trials. The increased asystole risk with landiolol highlights safety issues previously underappreciated.
Britany: Pharmacologically, landiolol is an ultra-short-acting beta-1 selective blocker with rapid onset and offset. Its four-minute half-life theoretically allows quick reversal if adverse events occur. But in cardiac arrest, even brief bradycardia or asystole can be catastrophic.
Seth: Also, drug interactions during resuscitation matter. Combining beta-blockers with amiodarone, which has beta-blocking effects, might potentiate bradyarrhythmias. Epinephrine’s alpha and beta effects further complicate hemodynamics.
Britany: That’s a key clinical pearl. When considering beta-blockers in refractory VF, weigh the risk of conduction abnormalities or myocardial depression against the theoretical benefit of reducing catecholamine-driven arrhythmias.
Seth: Special populations need attention. Patients with conduction disease or severe heart failure may be more susceptible to beta-blocker adverse effects during resuscitation.
Britany: And in terminally ill patients or those with do-not-resuscitate orders, aggressive interventions including experimental adjuncts like landiolol may not be appropriate. The study excluded such patients, important for interpreting applicability.
Seth: To summarize, this pilot trial found no improvement in time to ROSC with landiolol and a concerning increase in asystole incidence. It challenges prior low-quality evidence suggesting beta-blockers might help in refractory VF during OHCA.
Britany: Clinicians should remain cautious about incorporating landiolol into resuscitation protocols until more robust safety and efficacy data are available. Meanwhile, adherence to established ACLS guidelines remains paramount.
Seth: Absolutely. This study reminds us that promising pharmacologic strategies require rigorous testing before widespread adoption.
Britany: Thanks for this insightful discussion, Seth. For listeners, we encourage reviewing the full study by Gelbenegger et al., published in Resuscitation, August 2024. PMID 38866231.
Seth: Thanks, Britany, and thanks to everyone tuning in to PACULit. Stay curious, stay critical, and keep advancing patient care through evidence-based practice.
Britany: That wraps up today’s episode. Until next time, keep up with the literature and keep making a difference at the bedside. Take care!