Influence of multiple trauma on the effect of transfusion strategies in patients with traumatic brain injury: a sub-study of the HEMOTION trial

Abstract

Purpose: In moderate-to-severe traumatic brain injury (TBI), anemia may exacerbate secondary cerebral injury, and patients with multiple trauma may be especially vulnerable to cerebral hypoxia. We conducted a secondary analysis of the HEMOTION trial (liberal transfusion strategy > 10 g/dL vs. restrictive > 7 g/dL), to assess whether multiple trauma modifies the effect of transfusion strategy after moderate-to-severe TBI.

Methods: We included all HEMOTION trial participants (n = 742) and defined multiple trauma using three definitions: (1) extracranial injury with Injury Severity Score (ISS) > 15; (2) extracranial injury requiring emergency extracranial surgery; (3) spinal injury with neurological deficit. The primary outcome was the 6-month Glasgow Outcome Scale Extended (GOS-E). We tested interactions between transfusion strategy and multiple trauma status using sliding dichotomy and hierarchical Poisson regression, with sensitivity analyses using classical dichotomy (GOS-E ≤ 4) and proportional odds models. Secondary outcomes included mortality, quality of life (EQ-5D-5L, QOLIBRI), functional independence (FIM), and depression (PHQ-9).

Results: We found no interaction between multiple trauma status and transfusion strategies on the 6-month GOS-E across all three definitions. The adjusted relative risk (RR) of an unfavourable outcome with the liberal strategy was 0.87 (95% CI 0.71-1.07) for patients with ISS > 15, 0.79 (0.59-1.05) for emergency extracranial surgery, and 0.99 (0.42-2.33) for spinal cord injury. Sensitivity analyses suggested a potential interaction for patients undergoing emergency extracranial surgery (p-interaction = 0.02 for proportional odds analysis; 0.05 for classical dichotomy). A liberal strategy was associated with better FIM, EQ-5D-5L, and Qolibri scores for definitions 1 and 2, but not 3, with no consistent interaction. Mortality and PHQ-9 did not differ.

Conclusion: Multiple trauma status was not associated with the effect of liberal vs. restrictive transfusion strategies on the GOS-E. Patients requiring emergency extracranial surgery may warrant further investigation.

Keywords: Anemia; Extracranial surgery; Glasgow outcome scale extended; Multiple trauma; Transfusion strategy; Traumatic brain injury.

Fig. 1

Flow chart

Fig. 2

Neurological, functional, and quality-of-life outcomes in TBI patients with multiple trauma. A Definition 1: extracranial injury with ISS > 15. B Definition 2: emergency extracranial surgery. C Definition 3: spinal injury with neurological deficit. ^a The primary outcome was assessed at 6 months by trained personnel blinded to group assignment. ^b The Glasgow Outcome Scale–Extended (GOS-E) ranges from 1 (death) to 8 (upper good recovery). A sliding dichotomy classified outcomes as favorable or unfavorable based on each patient’s baseline prognosis, with adjustments for site and sex. The TBI-IMPACT prognostic model, incorporating factors such as age, GCS motor score, pupil reactivity, hypoxemia, hypotension, CT findings, and blood parameters, guided this process. Missing data were imputed as needed. Patients were divided into thirds by predicted risk: those with the worst prognosis were considered to have an unfavorable outcome if their GOS-E score was ≤ 3 (death, vegetative state, or lower severe disability); those with intermediate prognosis if the score was ≤ 4 (death, vegetative state, or severe disability); and those with the best prognosis if the score was ≤ 5 (death, vegetative state, severe disability, or lower moderate disability). ^c The regression model was adjusted for sex and covariates included in the TBI-IMPACT prognostic model, with a random intercept for center. ^d In this category, the treatment effect is an odds ratio. The regression model was adjusted for sex and covariates included in the TBI-IMPACT prognostic model, with a random intercept for center. ^e Secondary outcomes were centrally assessed at 6 months by trained personnel who were unaware of the group assignments. All analyses were adjusted for center (random intercept), sex, and admission covariates used in the TBI-IMPACT prognostic model. ^f The Functional Independence Measure assesses the level of assistance needed for 18 daily activities (13 physical and 5 cognitive), with each scored on a 7-point scale. The total score ranges from 18 (complete dependence) to 126 (complete independence). Data were missing for 14 of 270 patients in the liberal group and 20 of 271 in the restrictive group who survived to 6 months. ^g The EuroQol visual analogue scale measures health-related quality of life, with scores ranging from 0 (worst imaginable health) to 100 (best imaginable health). Data were missing for 23 of 270 patients in the liberal group and 29 of 271 in the restrictive group who survived to 6 months. ^hThe Quality of Life after Brain Injury (Qolibri) scale assesses health-related quality of life and is specific to persons with traumatic brain injury. Scores range from 0 (the worst imaginable state of health) to 100 (the best imaginable state of health). Data were missing for 41 of the 270 patients in the liberal-strategy group and for 52 of 271 in the restrictive-strategy group who survived to 6 months. ⁱ The nine-item Patient Health Questionnaire (PHQ-9) assesses the frequency of depressive symptoms within the past 2 weeks. Scores range from 0 to 27, with higher numbers indicating greater frequency of symptoms. Data were missing for 43 of the 270 patients in the liberal-strategy group and for 49 of 271 in the restrictive-strategy group who survived to 6 months. The “p value global interaction” refers to the interaction between transfusion strategy (liberal vs. restrictive) and the presence/absence of multiple trauma for each specific outcome

Fig. 2

Neurological, functional, and quality-of-life outcomes in TBI patients with multiple trauma. A Definition 1: extracranial injury with ISS > 15. B Definition 2: emergency extracranial surgery. C Definition 3: spinal injury with neurological deficit. ^a The primary outcome was assessed at 6 months by trained personnel blinded to group assignment. ^b The Glasgow Outcome Scale–Extended (GOS-E) ranges from 1 (death) to 8 (upper good recovery). A sliding dichotomy classified outcomes as favorable or unfavorable based on each patient’s baseline prognosis, with adjustments for site and sex. The TBI-IMPACT prognostic model, incorporating factors such as age, GCS motor score, pupil reactivity, hypoxemia, hypotension, CT findings, and blood parameters, guided this process. Missing data were imputed as needed. Patients were divided into thirds by predicted risk: those with the worst prognosis were considered to have an unfavorable outcome if their GOS-E score was ≤ 3 (death, vegetative state, or lower severe disability); those with intermediate prognosis if the score was ≤ 4 (death, vegetative state, or severe disability); and those with the best prognosis if the score was ≤ 5 (death, vegetative state, severe disability, or lower moderate disability). ^c The regression model was adjusted for sex and covariates included in the TBI-IMPACT prognostic model, with a random intercept for center. ^d In this category, the treatment effect is an odds ratio. The regression model was adjusted for sex and covariates included in the TBI-IMPACT prognostic model, with a random intercept for center. ^e Secondary outcomes were centrally assessed at 6 months by trained personnel who were unaware of the group assignments. All analyses were adjusted for center (random intercept), sex, and admission covariates used in the TBI-IMPACT prognostic model. ^f The Functional Independence Measure assesses the level of assistance needed for 18 daily activities (13 physical and 5 cognitive), with each scored on a 7-point scale. The total score ranges from 18 (complete dependence) to 126 (complete independence). Data were missing for 14 of 270 patients in the liberal group and 20 of 271 in the restrictive group who survived to 6 months. ^g The EuroQol visual analogue scale measures health-related quality of life, with scores ranging from 0 (worst imaginable health) to 100 (best imaginable health). Data were missing for 23 of 270 patients in the liberal group and 29 of 271 in the restrictive group who survived to 6 months. ^hThe Quality of Life after Brain Injury (Qolibri) scale assesses health-related quality of life and is specific to persons with traumatic brain injury. Scores range from 0 (the worst imaginable state of health) to 100 (the best imaginable state of health). Data were missing for 41 of the 270 patients in the liberal-strategy group and for 52 of 271 in the restrictive-strategy group who survived to 6 months. ⁱ The nine-item Patient Health Questionnaire (PHQ-9) assesses the frequency of depressive symptoms within the past 2 weeks. Scores range from 0 to 27, with higher numbers indicating greater frequency of symptoms. Data were missing for 43 of the 270 patients in the liberal-strategy group and for 49 of 271 in the restrictive-strategy group who survived to 6 months. The “p value global interaction” refers to the interaction between transfusion strategy (liberal vs. restrictive) and the presence/absence of multiple trauma for each specific outcome

Fig. 3

Scores on the Glasgow Outcome Scale–Extended at 6 Months. A Definition 1: extracranial injury with Injury Severity Score > 15. B Definition 2: emergency extracranial surgery. C Definition 3: spinal injury with neurological deficit