Clinical trial NCT04651803: Outcome in Traumatic Brain Injury Elderly Patients
Official title: Factors Associated With Unfavorable Outcome in Traumatic Brain Injury Elderly Patients. A Retrospective Multicenter Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Traumatic Brain Injury
Lead sponsor: Association pour la Recherche en Aanesthésie Réanimation Digestive
Sponsor class: OTHER
First posted: 2020-12-03
Enrollment: 1633
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Traumatic brain injury

Brief summary: In patients suffering from traumatic brain injury (TBI), the study's purpose was to determinate factors associated with mortality and poor functional outcome at 3 months in patients aged ≥ 65 hospitalized in ICU and to compare outcome at 3 months between younger patients (18-64 years) vs older patients (≥65 years).

Traumatic brain injury is a common cause of hospitalization for trauma and accounting for roughly 37% of all injury-related death in Europe. This was particularly true for patients ≥ 65 years old and in the most severe case(Glasgow coma score ≤ 8) with mortality rates between 31 to 51%. Over time, epidemiological patterns of TBI are changing. Indeed, in high-income countries, overall incidence is steadily decreasing, but increasing in elderly population with falls becoming the leading cause of TBI. In parallel, the World Population Ageing 2019 report of the Population Division of the United Nations Department of Economic and Social Affairs reported 703 (9%) million persons aged ≥65 years in the global population and that this proportion is projected to rise further to 16 % in 2050. Accordingly, we could expect that TBI in elderly would be increasing and could explain why mortality did not improved in the latest decades.

In a study performed in three neuro-intensive care unit (ICUs) from 1997 to 2007, 6-month mortality in patients aged of 70-79 and ≥ 80 years was 59% and 79%, respectively. In severe elderly (≥ 65 years) TBI patients admitted in ICU, hospital and 6-month mortality was 64.6% and 72.9%, respectively. Beyond mortality, TBI can lead to poor functional neurologic outcome and elderly patients are more prone to survive with disabilities according to a higher rate of comorbidities, frequent use of oral anticoagulants and/or antiplatelet and/or previous brain disorders. In patients hospitalized in ICU, age (\> 59 years) was the strongest parameter associated with an unfavorable outcome including death, vegetative state and severe disability, at 6 month. Moreover, TBI elderly patients (≥ 65 years) had worse functional outcome at discharge than younger patients. Identifying elderly patients who may benefit from ICU remained challenging, since there is no consensual guideline of triage. Traumatic brain-injured patients are particularly concerned by this issue. Nevertheless, few data are available related to outcome in elderly TBI patients requiring ICU.

Detailed description: The investigators conducted a multicentre, retrospective, observational study from April 2013 to February 2019 in the surgical ICUs of 5 level 1 Trauma centers in France. The investigators collected data from the "regional intensive care network of the great west of france" (AtlanRéa) database. The AtlanRéa database registers prospectively and consecutively numerous informations about brain injury and trauma patients hospitalized in ICUs, in order to provide epidemiologic informations for this population. Data were collected by clinical research assistants in each participating ICU, using an electronic case report form. The investigators assessed data regarding outcomes after discharge from ICUs through phone interview led by dedicated clinical research assistants.

The following data were entered in the database: Age, gender and body mass index, previous medical history, and more specifically the presence of cardiac insufficiency, chronic renal failure defined as an estimated glomerular filtration rate less than 60 ml/min.1.73 m-1, chronic respiratory illness, neurologic background, diabetes, neoplasia history, previous TBI, active smoking and chronic alcoholism. Mechanism of injury (domestic accident, road traffic crash, fall from heights or others). The Glasgow Coma Score (GCS) score determinates in the prehospital setting or at admission at hospital before intubation and/or sedation, and the presence of at least one nonreactive and dilated pupil at the initial management. Severity of illness according to the Simplified Acute Physiology Score II (SAPS II) the Sequential Organ Failure Assessment (SOFA) score, and the Injury Severity Score (ISS). The investigators also specified the severity of TBI by the abbreviated Injury Score (AIS) and reported the associated injuries from 5 territories (face, chest, abdomen, extremity (including pelvis) and external). Initial CT-scan was classified according to the Marshall classification in six categories (Diffuse injury I, II, III, IV, evacuated mass (V) and non-evacuated mass lesion (VI)).

The following data during the patients' hospitalization are also entered in the database: use of an intracranial pressure (ICP) catheter, occurrence of intracranial hypertension (defined as an ICP above 20 mmHg in absence of confounding factors), and use of barbiturates and/or osmotherapy, decompressive craniectomy, and other neurosurgical procedure. The occurrence of intercurrent events occurring during ICU stay, including infections, Acute Respiratory Distress Syndrome (ARDS), need of vasopressor drugs, acute renal failure, thrombophlebitis, pulmonary embolism, hemorrhage, infection and tracheostomy. The investigators specified the need for intubation and durations of mechanical ventilation, central venous catheterism and vasopressor. The investigators also recorded the decision in ICU to withdraw or withhold life support.

The length of stay in ICU, ICU and 3-month mortalities and patient outcome were assessed using the Glasgow Outcome Scale Extended (GOSE) score at 3 months. The investigators dichotomized the GOSE score between the four lower values (corresponding to unfavorable outcome- GOSE 1 to 4) and the four upper values (corresponding to favorable outcome- GOSE 5 to 8).

Statistical Analysis All statistical analysis will be performed using R software 3.3.1 (package pROC) and SAS 9.1 Statistical Software (SAS Institute, Cary, NC, USA). For quantitative continuous variables, position and dispersion parameters (mean, standard deviation, median, interquartile range) will be calculated. For qualitative variables, proportion rates will be calculated. For groups' comparison, we used independent-samples t-tests for normally distributed continuous variables, and Mann-Whitney U-tests for non-normally distributed continuous variables. Χ² tests will be performed for categorical variables. To build the model for multivariate analysis, the investigators selected among the variables with a p ≤ 0.20 according to the univariate analysis. The investigators performed logistic regression model to identify factors associated with in-ICU mortality and dichotomized GOSE score at 3 months. The Odds Ratios (ORs) and 95% confidence intervals (CI) will be calculated. For continuous variables, diagnosis of log linear behavior was established, and if not confirmed, the variable will be divided into categories and treated as categorical variables. Model's fit will be assessed by checking residual plots and Cook's distance. The calibration of the model will be tested by Goodness of Fit Hosmer-Lemeshow test. A p ≤0.05 will be considered statistically significant for all the comparisons.

Eligibility criteria: Inclusion Criteria:

* Traumatic brain injury
* Aged at least 18 years,
* Hospitalized in intensive care unit

Exclusion Criteria:

* Patients who die within 24h of hospitalization
* Patients initially resuscitated awaiting for organ donation
* Refusal for study participation expressed by the patient or relatives.
* Missing data related to the main objective of the study (outcome at 3 months)

Primary outcomes:
measure: Outcome was assessed using the Glasgow Outcome Scale Extended (GOSE) score
timeFrame: GOSE score at 3 months.
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: AtlanRéa
name: Philippe Seguin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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