This is a subject that has been on our backburner for a while and it’s now due for a discussion on neuroscand.com. The use of beta-blockers in traumatic brain injury is nothing new. The indications have been largely centered on targeting and preventing paroxysmal sympathetic hyperactivity (PSH) and associated post-TBI autonomic phenomena. Please see our post on PSH and especially this article by Schroeppel and colleagues.
A few recent studies have raised the question whether early, empirical administration of beta-blockers could improve overall outcomes in TBI. Most recently, Ko et al prospectively followed 440 TBI patients, 25% of whom received early administration of propranolol after TBI (EPAT – within 24 hours after admission, 1 mg q6h). It must be stressed that this was not a randomised controlled trial. Propranolol was ordered at the discretion of the treating physician in each case. The authors note some differences in patient baseline characteristics between the EPAT and non-EPAT cohorts that may have influenced outcomes, but they did perform multivariate regression analyses to address these potential confounders. The data show that EPAT was independently associated with reduced mortality (OR 0.25; p=0.012).
An earlier study by Murry and colleagues also examined the effect of propranolol on TBI outcomes and found no differences. This was, however, a tiny study (n=38) with 28 patients receiving early propranolol (<12 hrs after ICU admission) and a control group of 10 patients. The authors found no difference in hypotensive events between the groups. There was a higher incidence of bradycardia in the control group, surprisingly enough.
Zangbar et al examined the effect of metoprolol on heart rate and patient survival in a group of 914 patients with severe TBI, from which they were able to derive two propensity-matched cohorts of 178 patients each (control vs. EPAT). They found an association between beta-blockade and improved survival that did not seem to be related to the heart rate lowering effect. Again, this was not an RCT and the results must be interpreted with that limitation in mind.
Then there’s the retrospective Schroeppel study from 2014, which is the largest to date. This Memphis-based group performed a comprehensive search of their trauma registry and extracted data for 1755 TBI patients, of whom 427 received more than one dose of (any) beta-blocker. They identified propranolol as the superior drug in reducing mortality, while there was no discernible positive effect from beta-blockade overall.
The cumulative body of evidence does suggest a tendency toward better outcomes in those who receive early beta-blockers, predominantly propranolol. Indeed, many centres use beta-blockers in TBI regularly. There is, till now, no indication of increased risk of adverse effects, even if EPAT patients in the Ko study stayed longer in ICU/hospital and required longer periods on a ventilator. The use of beta blockade may not have been demonstrated to confer harm, but a more robust prospective trial is needed to fully clarify this issue before routine empirical use can be advocated. Furthermore, patient selection, optimal dose regimens and timing are all matters that need consideration. Till then administration should probably be on a patient-by-patient basis.
All that said, beta blockade in TBI remains a very alluring low-cost and (probably) low-risk option with a significant potential upside for this vulnerable patient group.