Pharmaceutical Venous Thrombosis Prophylaxis in Critically Ill Traumatic Brain Injury Patients

Jilske A Huijben, Dana Pisica, Iris Ceyisakar, Nino Stocchetti, Giuseppe Citerio, Andrew I R Maas, Ewout W Steyerberg, David K Menon, Mathieu van der Jagt, Hester F Lingsma, Jilske A Huijben, Dana Pisica, Iris Ceyisakar, Nino Stocchetti, Giuseppe Citerio, Andrew I R Maas, Ewout W Steyerberg, David K Menon, Mathieu van der Jagt, Hester F Lingsma

Abstract

The aims of this study are to describe the use of pharmaceutical venous thromboembolism (pVTE) prophylaxis in patients with traumatic brain injury (TBI) in Europe and study the association of pVTE prophylaxis with outcome. We included 2006 patients ≥18 years of age admitted to the intensive care unit from the CENTER-TBI study. VTE events were recorded based on clinical symptoms. Variation between 54 centers in pVTE prophylaxis use was assessed with a multi-variate random-effect model and quantified with the median odds ratio (MOR). The association between pVTE prophylaxis and outcome (Glasgow Outcome Scale-Extended at 6 months) was assessed at center level with an instrumental variable analysis and at patient level with a multi-variate proportional odds regression analysis and a propensity-matched analysis. A time-dependent Cox survival regression analysis was conducted to determine the effect of pVTE prophylaxis on survival during hospital stay. The association between VTE prophylaxis and computed tomography (CT) progression was assessed with a logistic regression analysis. Overall, 56 patients (2%) had a VTE during hospital stay. The majority, 1279 patients (64%), received pVTE prophylaxis, with substantial between-center variation (MOR, 2.7; p < 0.001). A moderate association with improved outcome was found at center level (odds ratio [OR], 1.2 [0.7-2.1]) and patient level (multi-variate adjusted OR, 1.4 [1.1-1.7], and propensity adjusted OR, 1.5 [1.1-2.0]), with similar results in subgroup analyses. Survival was higher with the use of pVTE prophylaxis (p < 0.001). We found no clear effect on CT progression (OR, 0.9; CI [0.6-1.2]). Overall, practice policies for pVTE prophylaxis vary substantially between European centers, whereas pVTE prophylaxis may contribute to improved outcome. Trial registration number is NCT02210221 at ClinicalTrials.gov, registered on August 6, 2014 (first patient enrollment on December 19, 2014).

Keywords: intensive care units; traumatic brain injuries; venous thrombosis.

Conflict of interest statement

A.I.R.M. declares consulting fees from PresSura Neuro, Integra Life Sciences, and NeuroTrauma Sciences. D.K.M. reports grants from the UK National Institute for Health Research, during the conduct of the study; grants, personal fees, and non-financial support from GlaxoSmithKline; and personal fees from Neurotrauma Sciences, Lantmaanen AB, Pressura, and Pfizer, outside of the submitted work. E.S. reports personal fees from Springer, during the conduct of the study. All other authors declare no competing interests.

© Jilske A. Huijben et al., 2021; Published by Mary Ann Liebert, Inc.

Figures

FIG. 1.
FIG. 1.
Flowchart patient inclusion in current study. Flowchart of the use of pVTE prophylaxis at ICU stay or not, including missing values. CENTER-TBI, Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury; ICU, intensive care unit; VTE, venous thrombotic event.
FIG. 2.
FIG. 2.
Random effects per country of pharmaceutical VTE prophylaxis use. This figure shows the variation at country level in the use of pVTE prophylaxis. This variation is corrected for case-mix severity and random variation (adjusted random effects per center). A higher random-effect estimate (darker green) represents a higher use of pVTE prophylaxis than average in that specific country, after adjustment for case-mix severity and random variation, whereas a lower random-effect estimate (white) represents a lower use of pVTE prophylaxis. pVTE, pharmaceutical VTE; VTE, venous thrombotic event.
FIG. 3.
FIG. 3.
Adjusted random effects per center: use of pharmaceutical prophylaxis in patients admitted to the ICU. Variation in pVTE prophylaxis between centers in Europe. These center effects are corrected for case-mix severity per center and random variation (to show variation beyond chance). The random-effect estimates represent the use of pharmaceutical VTE prophylaxis at center level beyond case-mix severity and random variation (chance). The median odds ratio (MOR) represents the odds ratio for receiving of pharmaceutical VTE prophylaxis when comparing two randomly selected centers. An MOR of 1 indicates no differences between ICUs, whereas a larger MOR indicates higher variation between ICUs in the use of pharmaceutical VTE prophylaxis. ICU, intensive care unit; pVTE, pharmaceutical VTE; VTE, venous thrombotic event.
FIG. 4.
FIG. 4.
Time-dependent Cox survival curve. This figure shows the time-dependent Cox survival curve for the use of pVTE prophylaxis. The difference in survival is significant (p < 0.001), favoring the use of VTE prophylaxis. The y-axis of survival starts at 0.5. Time is in days. pVTE, pharmaceutical VTE; VTE, venous thrombotic event.

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