Authors: Rob Hirst, Becky Maxwell, Chris Connolly, Dave McCreary, Andy Neill / Codes: ObC19, RP6, SLO10, SLO11, SLO3, XC3 / Published: 08/04/2025
Title - Landiolol for heart rate control in patientswith septic shock and persistent tachycardia. Amulticenter randomized clinical trial (Landi-SEP)
Author - Rehberg, ICM, 2024
Background - Sepsis is really common and kills lots of people, so that's the epidemiology and public health bit covered. In terms of patho phys, we know there are lots of "dysregulated" reactions in the body to sepsis. There have been many drugs trialled to see if we can dampen down that dysregulated response and so far they've not panned out. Beta blockers are next up. This paper comes on the background of a prior small paper that suggested given beta blockers may improve mortality. The obvious biologic plausibility one is tachycardia, if you're going too fast then you've no time in the cardiac cycle to fill well and this might impair cardiac output and perfusion of the coronary arteries. Well, that is the theory at least. There may be many other reasons why beta blockers might be good for what ails you too. To avoid the negative inotropic properties for most beta blockers they use super selective beta 1 antagonists in these papers like esmolol that we've likely heard of or landilol that, like me, you probably haven't
Methods - MCRCT aross 7 countries in Europe - septic shock with HR >95 as inclusion (95 chosen as it was a previous increment point for mortality in observational work). There was an allowance for "compensatory tachycardia" to be excluded but that sounds like a good point for fudging. - open label with no good reason that I can see. (they say "due to an absence of a specific treatment in the control group" but I was always of the opinion that was perfect for placebo? - Lanidilol had infusion dose varied to keep HR<95 till pressors stopped. - The outcome was "multi component" as a wat of combining physiological outcomes of HR control and pressor requirement. Hardly ideal. - I did noy see a power calculation.
Results - 200 pts - 40% primary outcome in landilol group vs 24% in the control group - no changes in mortality -65% adverse event rate reported in both groups.
Thoughts - not sure this adds much. It seems relatively safe but what's the point simply to correct a number? - as they highlight it would be helpful to have cardiac output data as the putative rationale here is largely haemodynamic and it's not clear if beta blocker actually changed the haemodynamics here.