STRESS-L RCT – Beta-Blockers in Septic Shock?

December 1, 2023

Written by Samuel Rouleau

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A randomized trial of patients in septic shock on norepinephrine found no benefit in those treated with an infusion of landiolol (β1-blocker). The trial was stopped early for concern of potential harm in the intervention group.

Routine use of β-blocker infusion in septic shock? Landio-LOL!
In patients with septic shock, catecholamines can potentiate adverse effects, and it has been hypothesized that β-blockers could attenuate these effects. The STRESS-L randomized clinical trial (RCT) was a multicenter, randomized, open-label trial that assessed the efficacy and safety of a continuous infusion of landiolol.

Patients included in the study were adults in the ICU with septic shock who had been receiving norepinephrine for at least 24 hours and had a heart rate ≥ 95 bpm. Patients randomized to the landiolol group received “usual care” (norepinephrine to maintain mean arterial pressure (MAP) between 65–70 mm Hg, antibiotics, fluid resuscitation) and a landiolol infusion to maintain heart rate between 80-94 bpm.

126 patients were included in the trial (63 randomized to each arm). Each group had similar baseline characteristics and acuity. The rate of atrial fibrillation in each group at randomization was similar at 11.1% (landiolol group) and 12.7% (usual care).

For the primary outcome, the mean SOFA score over 14 days for the landiolol arm was 8.8 (SD 3.9) and 8.1 (SD 3.2) for the usual care group. Sensitivity analyses confirmed no difference between the two groups. For the secondary outcomes, mortality at day 28 was 37.1% in the landiolol group and 25.4% in the usual care group: absolute difference 11.7% (95%CI -4.4 to 27.8%, p=0.16); mean heart rate was lower in the landiolol group: mean difference -6.46 bpm (95%CI -10.46 to -2.46, p=0.002); MAP was lower in the landiolol group: mean difference -2.67mm Hg (95%CI -5.06 to -0.29,p=0.03), and the average norepinephrine infusion was higher in the landiolol group: mean difference 10 ug/kg/min (95%CI 0.002 to 0.20, p=0.05). The trial was terminated based on interim analysis that showed landiolol unlikely to demonstrate benefit and a potential for causing harm.

How will this change my practice?
There is no evidence to support routinely using β-blockers in patients with septic shock. Some additional thoughts:

• I am not surprised this trial found no difference in the landiolol group. Tachycardia is, in part, helping maintain cardiac output (CO=HR*SV).
• At some point, the heart beats so fast that stroke volume and cardiac output fall off due to limited diastolic filling time. Could there be a subgroup of patients with extreme tachycardia for which an IV β-blocker infusion would be helpful?

Source
Landiolol and Organ Failure in Patients With Septic Shock: The STRESS-L Randomized Clinical Trial. JAMA. 2023 Nov 7;330(17):1641-1652. doi: 10.1001/jama.2023.20134.