Typically, septic shock treatment involves vasopressor agents, with norepinephrine being preferred. β-blockers, usually seen as counterintuitive in this context, have been explored for their potential benefits in sepsis treatment.
Animal and Early Human Studies
Some animal models showed improved survival with β-blockers in septic shock, suggesting better myocardial energy efficiency. However, results varied, with some models indicating potential harm, such as impaired kidney and microvascular perfusion.
Clinical Trials with β-Blockers
Early human studies found that short-acting β-blockers like esmolol could be administered without significant hemodynamic deterioration. The largest trial showed promising results with esmolol, increasing stroke volume without changing cardiac output, and suggesting lower mortality rates.
The STRESS-L Randomized Clinical Trial
This study evaluated the effectiveness of landiolol, a β-blocker, in patients with tachycardia and septic shock who were already receiving norepinephrine. Conducted across 40 UK National Health Service intensive care units, it involved 126 adult participants, randomized into two groups: one receiving standard care and the other, landiolol. The primary measurement was the change in the Sequential Organ Failure Assessment (SOFA) score over 14 days, with secondary outcomes including 28-day and 90-day mortality rates and the incidence of adverse events. The trial was prematurely halted due to a lack of demonstrable benefit and potential harm.
The results indicated no significant reduction in organ failure as measured by the SOFA score in the landiolol group compared to the standard care group. Additionally, there was a non-significant trend towards higher mortality rates at both 28 and 90 days in the landiolol group. These findings suggest that landiolol does not provide a benefit in managing tachycardia in patients with established septic shock treated with norepinephrine, and thus its use is not supported in this context.
Challenges and Limitations
The study faced challenges like the timing of β-blockade initiation and lack of uniform cardiac output monitoring. The variability in patient responses and the complex nature of sepsis made it difficult to draw definitive conclusions.
This study highlights the intricate balance required in sepsis treatment, where interventions like β-blockers might have both beneficial and harmful effects, varying among patients and conditions. Further research is needed to understand these mechanisms better and identify patient subsets that could benefit from β-blockade. This underscores the need for personalized medicine approaches in sepsis management.
This study contributes to the broader understanding of septic shock's pathophysiology and the potential role of β-blockers, not just as cardiovascular agents but also in modulating immune and metabolic responses in critical illnesses. The rigor of this trial, despite its early termination, emphasizes the necessity of well-designed studies to evaluate the safety and efficacy of treatments, especially in complex conditions like sepsis.
Whitehouse T, Hossain A, Perkins GD, et al; for the STRESS-L Collaborators. Landiolol and organ failure in patients with septic shock: the STRESS-L randomized clinical trial. JAMA. Published online October 25, 2023.