• Jilske A Huijben, Abhishek Dixit, Nino Stocchetti, MaasAndrew I RAIRDepartment of Neurosurgery, Antwerp University Hospital and University of Antwerp, Edegem, Belgium., Hester F Lingsma, Mathieu van der Jagt, David Nelson, Giuseppe Citerio, Lindsay Wilson, David K Menon, Ari Ercole, and CENTER-TBI investigators and participants.
• Center for Medical Decision Sciences, Department of Public Health, Erasmus MC- University Medical Center Rotterdam, Rotterdam, The Netherlands. j.a.huijben@erasmusmc.nl.
• Crit Care. 2021 Feb 23; 25 (1): 7878.

PurposeTo study variation in, and clinical impact of high Therapy Intensity Level (TIL) treatments for elevated intracranial pressure (ICP) in patients with traumatic brain injury (TBI) across European Intensive Care Units (ICUs).MethodsWe studied high TIL treatments (metabolic suppression, hypothermia (< 35 °C), intensive hyperventilation (PaCO2 < 4 kPa), and secondary decompressive craniectomy) in patients receiving ICP monitoring in the ICU stratum of the CENTER-TBI study. A random effect logistic regression model was used to determine between-centre variation in their use. A propensity score-matched model was used to study the impact on outcome (6-months Glasgow Outcome Score-extended (GOSE)), whilst adjusting for case-mix severity, signs of brain herniation on imaging, and ICP.Results313 of 758 patients from 52 European centres (41%) received at least one high TIL treatment with significant variation between centres (median odds ratio = 2.26). Patients often transiently received high TIL therapies without escalation from lower tier treatments. 38% of patients with high TIL treatment had favourable outcomes (GOSE ≥ 5). The use of high TIL treatment was not significantly associated with worse outcome (285 matched pairs, OR 1.4, 95% CI [1.0-2.0]). However, a sensitivity analysis excluding high TIL treatments at day 1 or use of metabolic suppression at any day did reveal a statistically significant association with worse outcome.ConclusionSubstantial between-centre variation in use of high TIL treatments for TBI was found and treatment escalation to higher TIL treatments were often not preceded by more conventional lower TIL treatments. The significant association between high TIL treatments after day 1 and worse outcomes may reflect aggressive use or unmeasured confounders or inappropriate escalation strategies.Take Home MessageSubstantial variation was found in the use of highly intensive ICP-lowering treatments across European ICUs and a stepwise escalation strategy from lower to higher intensity level therapy is often lacking. Further research is necessary to study the impact of high therapy intensity treatments.Trial RegistrationThe core study was registered with ClinicalTrials.gov, number NCT02210221, registered 08/06/2014, https://clinicaltrials.gov/ct2/show/NCT02210221?id=NCT02210221&draw=1&rank=1 and with Resource Identification Portal (RRID: SCR_015582).

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