Tony WhitehouseOct 26, 2023

Having promised that #STRESS-L would be announced here first, the other place (Twitter / X) took of on its own!

So here are some thoughts not found elsewhere. Thread.

STRESS-L was published yesterday: https://jamanetwork.com/journals/jama/fullarticle/2811213

Landiolol and Organ Failure in Patients With Septic Shock

This clinical trial assesses whether landiolol for patients with tachycardia and established septic shock requiring prolonged vasopressor support reduces the risk of organ failure.

Show threadTony WhitehouseOct 26, 2023

We recruited patients with established septic shock defined by being treated with noradrenaline for at least 24 hours. At the time of randomisation, patients had to be on 0.1 mcg/kg/min noradrenaline and tachycardic (HR>=95 bpm).

We treated 63 patients with standard care and 63 patients with standard care and landiolol to control the heart rate between 80 and 94.

Our primary outcome was Mean SOFA Score over 14 days whilst in ICU. There was no difference between groups in our primary outcome.

Show threadTony Whitehouse

The study was halted early after 126 of an expected 340 participants as the intervention was unlikely to display benefit and could be harmful.

This last bit has been widely shared.

Oct 26, 2023 at 1:56pmWeb
Show threadTony WhitehouseOct 26, 2023

Similar trials in the field are Morelli (JAMA 2013) https://jamanetwork.com/journals/jama/fullarticle/1752246 and J-Land 3S (Kakihana, Lancet Resp Med, 2020) https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30037-0.

Morelli used esmolol but added levosimendan to patients who had a significant fall in cardiac output. J-Land 3S used landiolol but earlier than 24 hours (whereas STRESS-L treated AFTER 24 hours of noradrenaline).

Esmolol and Heart Rate Control in Septic Shock

To determine whether treating critically ill patients with severe septic shock with esmolol, a short-acting β-blocker, to reduce their heart rates, Morelli and coauthors conducted an open-label, randomized phase 2 study, involving 154 qualifying patients treated at a university hospital intensive...

Show threadTony WhitehouseOct 26, 2023

I suppose I wonder what would make a difference (if any).

Positive inotropy? With Levosimendan? Does it matter??

Earlier application of the intervention?

Less Beta1 specificity?

It's sometimes frustrating when researchers say "we need more studies" but...

ENDS

Show threadLars Mølgaard SaxhaugOct 26, 2023
@whitehouse_ICU Thank you Tony, what a wonderful and fascinating trial! I think many have been wondering if Morelli was a fluke (extreme mortality in the control group), and strengthened in that belief now.
Show threadTony WhitehouseOct 30, 2023
@load_dependent Thank you for your interest.
I have to admit that when we visited (and rejected) mortality as the primary outcome for STRESS-L, we expected the mortality for the standard care group to be much high (about 50%) given that patients were included if noradr >0.1 mcg/kg/min.
At 25.4%, it may be that there was a fluke in the standard care group!
In the end we did not feel that there was enough existing data to power for a mortality primary outcome and so we chose Mean SOFA.
Show threadMathieu DesgroseilliersOct 27, 2023
@whitehouse_ICU thank you Tony for sharing your amazing work !!