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Early Intravenous Beta-Blockade with Esmolol in Adults with Severe Traumatic Brain Injury: A Phase 2a Intervention Design Study.
Thomas, Matt; Hayes, Kati; White, Paul; Baumer, Thomas; Beattie, Clodagh; Ramesh, Aravind; Culliford, Lucy; Ackland, Gareth L; Pickering, Anthony E.
Afiliación
  • Thomas M; Intensive Care Unit, North Bristol NHS Trust, Bristol, UK. matt.thomas@nbt.nhs.uk.
  • Hayes K; Research and Development, North Bristol NHS Trust, Bristol, UK.
  • White P; School of Data Science and Mathematics, University of the West of England, Bristol, UK.
  • Baumer T; Severn Deanery, Bristol, UK.
  • Beattie C; Research and Development, North Bristol NHS Trust, Bristol, UK.
  • Ramesh A; Faculty of Health Sciences, University of Bristol, Bristol, UK.
  • Culliford L; Bristol Medical School (PHS), Bristol Trials Centre, University of Bristol, Bristol, UK.
  • Ackland GL; William Harvey Research Institute, Queen Mary University of London, London, UK.
  • Pickering AE; School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK.
Neurocrit Care ; 2024 Jun 28.
Article en En | MEDLINE | ID: mdl-38951446
ABSTRACT

BACKGROUND:

Targeted beta-blockade after severe traumatic brain injury may reduce secondary brain injury by attenuating the sympathoadrenal response. The potential role and optimal dosage for esmolol, a selective, short-acting, titratable beta-1 beta-blocker, as a safe, putative early therapy after major traumatic brain injury has not been assessed.

METHODS:

We conducted a single-center, open-label dose-finding study using an adaptive model-based design. Adults (18 years or older) with severe traumatic brain injury and intracranial pressure monitoring received esmolol within 24 h of injury to reduce their heart rate by 15% from baseline of the preceding 4 h while ensuring cerebral perfusion pressure was maintained above 60 mm Hg. In cohorts of three, the starting dosage and dosage increments were escalated according to a prespecified plan in the absence of dose-limiting toxicity. Dose-limiting toxicity was defined as failure to maintain cerebral perfusion pressure, triggering cessation of esmolol infusion. The primary outcome was the maximum tolerated dosage schedule of esmolol, defined as that associated with less than 10% probability of dose-limiting toxicity. Secondary outcomes include 6-month mortality and 6-month extended Glasgow Outcome Scale score.

RESULTS:

Sixteen patients (6 [37.5%] female patients; mean age 36 years [standard deviation 13 years]) with a median Glasgow Coma Scale score of 6.5 (interquartile range 5-7) received esmolol. The optimal starting dosage of esmolol was 10 µg/kg/min, with increments every 30 min of 5 µg/kg/min, as it was the highest dosage with less than 10% estimated probability of dose-limiting toxicity (7%). All-cause mortality was 12.5% at 6 months (corresponding to a standardized mortality ratio of 0.63). One dose-limiting toxicity event and no serious adverse hemodynamic effects were seen.

CONCLUSIONS:

Esmolol administration, titrated to a heart rate reduction of 15%, is feasible within 24 h of severe traumatic brain injury. The probability of dose-limiting toxicity requiring withdrawal of esmolol when using the optimized schedule is low. Trial registrationI SRCTN, ISRCTN11038397, registered retrospectively January 7, 2021 ( https//www.isrctn.com/ISRCTN11038397 ).
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Neurocrit Care Asunto de la revista: NEUROLOGIA / TERAPIA INTENSIVA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Neurocrit Care Asunto de la revista: NEUROLOGIA / TERAPIA INTENSIVA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos