Landi-SEP — Landiolol for Heart Rate Control in Septic Shock

TL;DR: 🟢 Positive — landiolol significantly controlled persistent tachycardia in septic shock (39.8% vs 23.5% achieving HR target, P=0.013) without increasing vasopressor need or adverse events.

1. Publication

• Title: Landiolol for heart rate control in patients with septic shock and persistent tachycardia. A multicenter randomized clinical trial
• Acronym: Landi-SEP
• Year & Journal: Intensive Care Medicine, published March 18, 2024 (50(10):1622-1634)
• Citation: Rehberg S, Frank S, Černý V, et al. Intensive Care Med. 2024;50(10):1622-1634. doi:10.1007/s00134-024-07587-1

2. Context & Rationale

Background: Excessive tachycardia in resuscitated septic shock impairs hemodynamics and worsens outcomes. Beta-blockade could theoretically help, but concern about further reducing cardiac output/vasopressor tolerance limited use; landiolol's ultra-short half-life makes it uniquely titratable for this population.

Research Question/Hypothesis: In septic shock patients with persistent tachycardia (HR≥95 bpm), does titrated landiolol reduce and maintain heart rate (80-94 bpm) within 24h without increasing vasopressor requirements, compared with standard treatment alone?

3. Design & Methods

• Study Type: Multicenter, open-label, controlled, phase IV RCT
• Setting & Centers: 20 sites, 7 European countries; 2018–2022
• Population: Adult septic shock patients with persistent tachycardia (HR≥95 bpm)
• Intervention: Titrated landiolol plus standard treatment (n=98)
• Comparator: Standard treatment alone (n=98)
• Randomization: 196 patients
• Statistical Power & Follow-Up: Combined primary endpoint: HR response (80-94 bpm) and maintenance without increased vasopressor requirement, first 24h. Secondary: 28-day mortality, adverse events.

4. Key Results

196 patients randomized (98/98).

5. Internal Validity Assessment

Multicenter, adequately sized (196-patient) RCT with an Independent Data Monitoring Committee. Overall: Moderate-to-strong — clear, statistically significant primary result (P=0.013) with no safety penalty; open-label design is a limitation for a hemodynamic-titration trial.

6. External Validity Assessment

International (7-country) septic shock population with persistent tachycardia — broadly representative of this specific, clinically identifiable subgroup.

7. Strengths & Limitations

Strengths: International, multicenter design; clear, clinically meaningful primary endpoint combining efficacy and safety; no adverse safety signal.

Limitations: Open-label; secondary outcomes (mortality) not powered to detect a difference; builds on but is distinct from the STRESS-L trial (landiolol, JAMA 2023), reflecting an active area of beta-blockade-in-sepsis research.

8. Interpretation & Practice Impact

Supports landiolol as an effective, titratable option for controlling persistent tachycardia in septic shock without compromising vasopressor requirements — a targeted hemodynamic intervention for a specific, identifiable subgroup.

9. Controversies & Subsequent Evidence

Builds on and complements the STRESS-L trial (Whitehouse et al., JAMA 2023, "Landiolol and organ failure in patients with septic shock") — together these trials represent an active, evolving body of evidence on beta-blockade for tachycardia control in septic shock, distinct from the broader (and more mixed) esmolol literature.

10. Summary & Executive Takeaway

Summary: Landi-SEP randomized 196 septic shock patients with persistent tachycardia across 20 European sites to titrated landiolol plus standard treatment or standard treatment alone. The combined primary endpoint (HR control without increased vasopressor need) was met significantly more often with landiolol (39.8% vs 23.5%, P=0.013), with no difference in mortality or adverse events.

Overall Takeaway: Landiolol effectively controls persistent tachycardia in septic shock without increasing vasopressor requirements or adverse events — a useful, titratable hemodynamic tool for this specific, identifiable clinical scenario, complementing the STRESS-L trial evidence base.

11. Bibliography

• Whitehouse T, Hossain A, Perkins GD, et al. Landiolol and organ failure in patients with septic shock: the STRESS-L randomized clinical trial. JAMA. 2023;330:1641-1652.