The effect of time to neurosurgical or neuroradiological intervention therapy on outcomes and quality of care after traumatic brain injury, a registry-based observational study

Abstract

Background

Evidence regarding the effect of time to neurosurgical and neuroradiological intervention on outcomes in traumatic brain injury (TBI) across Asia-Pacific region is limited. This study evaluates the quality of care and outcomes for TBI patients undergoing neurosurgical and neuroradiological procedures at different timings.

Methods

Adult TBI patients who received any neurosurgical or neuroradiological interventions during the year 2015–2022 in the Pan-Asian Trauma Outcome Study database were analyzed. The time to intervention, as the main exposure, was classified into three groups (Early, Intermediate, and Delayed) using Restricted Cubic Spline (RCS) analysis. The outcomes were in-hospital mortality and unfavorable neurological outcomes. W score was utilized to compare the quality of care among exposure groups. Multivariable logistic regression analysis and interaction analysis were performed to identify the association between the exposure groups and outcomes, reported as adjusted odds ratios (AOR) with 95% confidence intervals (CI).

Results

A total of 1,780 patients were included. From the RCS analysis, patients were classified into three groups according to time to intervention: Early (< 1.9 h), Intermediate (1.9–4.1 h), and Delayed (> 4.1 h). According to the time to intervention, W score was − 8.6 in the early group, -1.1 in the intermediate group, and + 0.4 in the delayed group. Patients receiving intermediate and delayed intervention showed significantly lower mortality (AOR 0.64, 95% CI 0.47–0.86 and AOR 0.66, 95%CI 0.48–0.90, respectively).

Conclusion

Early neurosurgical and neuroradiological interventions in TBI patients in the Asia-Pacific region were associated with lower quality of care and higher mortality. The quality of care should be focused and improved during the early hours of TBI.

Background

Trauma is among the leading causes of death and disability. Globally, 4.4 million annual deaths are attributed to traumatic injuries [1]. With the advancement in trauma care and emergency response systems, the relative contribution of death due to multiple organ dysfunction, acute respiratory distress syndrome, and sepsis has been decreasing dramatically over the past few decades. Traumatic brain injury (TBI) has become the leading cause of trauma-related death instead [2]. TBI accounted for 37% of all trauma-related deaths across European countries [3].

Timely definitive care is of the essence in TBI patients. Early craniotomy or hematoma drainage within 4 h of emergency department (ED) arrival significantly reduced mortality in TBI patients, according to a nationwide registry-based study [4]. A study also reported lower mortality when the time to craniectomy was within 5.3 h of injury in combat-related brain injury [5]. However, a recent meta-analysis questioned the universal efficacy of early surgical intervention in TBI patients [6]. It found that brain surgeries performed in the early period were unexpectedly linked to adverse outcomes, specifically in developing countries. Patients requiring immediate intervention were typically more complicated and higher in severity. Rushing to surgery might impede the resuscitation process, affecting the ‘quality of care’ in a real-life situation. This highlights the complexity of balancing timely care with the need for comprehensive treatment. Variations in EMS systems and healthcare disparities further complicate efforts to optimize TBI management and care quality. Evidence regarding the impact of prompt interventions on regional outcomes and various healthcare settings across the Asia-Pacific region remains limited.

Therefore, this study aimed to evaluate the quality of care and outcomes among TBI patients receiving neurosurgical and neuroradiological intervention at different timings across the Asia-Pacific region. Furthermore, the study examined how prehospital and interhospital transport settings might differently affect outcomes in TBI patients, emphasizing the need for tailored strategies to optimize TBI management in diverse systems.

Methods

Study design

This is a registry-based observational study using the Pan-Asian Trauma Outcome Study (PATOS) database. The manuscript adheres to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines [7].

Study setting

PATOS is a large multinational emergency medical services (EMS)-based trauma registry network across the Asia-Pacific region, initiating data collection in 2015 [8]. The main purposes of PATOS were to benchmark emergency trauma care and improve survival outcomes in the Asia-Pacific region. The registry collected standardized data from 10 countries: India, Japan, Malaysia, Philippines, South Korea, Singapore, Taiwan, Thailand, United Arab Emirates, and Vietnam [9]. Trauma care systems, especially EMS systems, in Asia-Pacific countries were relatively new and underdeveloped compared to the systems in European countries and the United States.

The EMS systems varied among countries. Most of the countries had both Advanced Life Support (ALS) and Basic Life Support (BLS) teams [10]. Fire departments typically provided prehospital trauma care in countries like Korea, Japan, and Singapore, while hospital-based or community-based teams were common in Thailand, Malaysia, and the Philippines [11, 12]. The EMS team leaders were physicians in more than half of the participating sites. Nurses, emergency medical technicians (EMT), and paramedics were team leaders in Korea, Malaysia, Philippines, Singapore, and Taiwan [12].

Most participating sites were urban academic tertiary care hospitals, with a quarter designated as trauma centers [9]. Trauma teams were available in half of the participating sites. Licensed trauma surgeons were available in two-thirds of the participating sites [9].

On the national level, trauma care systems varied due to differences in health care infrastructure, resources, and policy priorities. National trauma triage protocols and patient transfer protocols existed in Korea and Japan [13]. Most participating sites generally followed Advanced Trauma Life Support (ATLS), with exceptions in Korea, Singapore, and Japan where national trauma guidelines existed [13].

Study data source

The PATOS registry gathered data from 36 participating hospitals (27 tertiary, 8 secondary, and 1 primary hospital) across the Asia-Pacific region [9]. The registry collected trauma patients data of any severity who were transported by EMS ambulances in developed communities or non-EMS (non-professional) vehicles in developing communities to the emergency department of the participating hospitals [8].

To ensure data consistency and quality across participating sites, each site designated a research coordinator or principal investigator responsible for data collection, extraction, and input. The PATOS Data Quality Management Committee oversaw the central data cleaning process, conducted routine audits, and provided feedback to research teams to maintain high data quality standards. Additionally, regular meetings were held between the committee and site investigators to address inconsistencies and ensure adherence to standardized protocols [8].

Population

This study included all adult (≥ 18 years) TBI patients who received any neurosurgical or neuroradiological interventions from every participating site during January 2015 to December 2022. The International Classification of Diseases 10th Edition (ICD-10) code S06 (intracranial injury) was used as an index for TBI patients. Neurosurgical and neuroradiological interventions were defined as the first recorded neurological operative procedures performed on the patients in the PATOS database, including both neurosurgical operations (such as craniectomy, craniotomy, and hematoma evacuation) and neuroradiological intervention (such as angioembolization) in the head region.

Patients were excluded if the primary outcome was missing. We also excluded patients whose time to intervention could not be measured. We also excluded patients with unknown systolic blood pressure.

Variables and measurements

Exposure definition and measurement

The primary exposure, time to intervention, was defined as the interval between ED arrival and the initiation of the neurosurgical or neuroradiological intervention. In the latest guideline, the time of injury was used as a reference starting time [14]. However, in this study, we used ED arrival time instead for the following reasons: (1) the exact time of injury was likely inaccurate and missing in some cases, and (2) using ED arrival time as a starting point until the time of the surgery would directly reflect the effectiveness of in-hospital management.

The second exposure is the mode of transport. Prehospital transport was defined as the direct transportation of trauma patients from the scene to the ED. Interhospital transport was defined as the secondary transfer of trauma patients from another hospital.

Confounder definition and measurement

Confounder variables were categorized into 5 groups: general factors, injury factors, prehospital care, ED and hospital care, and injury severity. General factors included age, sex, and Charlson’s comorbidity index [15]. The injury factors included the intent of the injury (accidental, intentional), mechanisms of injury, place of injury, alcohol intake, and day of injury (weekday vs. weekend), and time of the injury. Prehospital care data included the top-level personnel, airway management, breathing & ventilation management, and fluid management. ED and hospital care data included vital signs, Glasgow Coma Scale (GCS), and types of intervention (neurosurgical versus neuroradiological intervention). For injury severity, we used the excess mortality ratio-based injury severity scale (EMR-ISS) which was a diagnosis-based injury severity scale for large data sets derived from the ICD-10 codes to depict injury severity [16].

Outcome measures

The primary outcome was death, defined as in-hospital mortality. The secondary outcome was unfavorable neurological outcomes at discharge, defined as Glasgow Outcome Scale (GOS) 1–3 [17]. GOS is a 5-point scale score, categorized as (1) dead, (2) vegetative state, (3) severe disability, (4) moderate disability, and (5) good recovery [18]. This scale was chosen for its wide acceptance and standardized evaluation of functional recovery in TBI research.

Statistical analyses

Confounding and outcomes variables were compared between exposure groups using median and interquartile range (IQR) for continuous variables, and numbers and percentages for categorical variables. Statistical significances were considered when the p-values were less than 0.05 using Wilcoxon sum rank test for continuous variables, and Chi-square test for categorical variables.

The categorization of time to intervention was determined using the Restricted Cubic Spline (RCS) analysis with four knots to model the non-linear relationship between time to intervention and mortality. Two key time points (1.9 and 4.1 h) were identified as knots where the relationship between time to intervention and mortality exhibited noticeable shifts, based on statistical analysis and visual inspection of the spline curve. The remaining two knots were placed at the extremes of the distribution to ensure adequate flexibility in fitting the model. Based on this analysis, patients were stratified into three groups according to time to intervention: early (< 1.9 h), intermediate (1.9–4.1 h), and delayed (> 4.1 h). These intervals not only reflect statistically significant inflection points but also aligned with practical clinical workflows in TBI management. The early group included cases requiring immediate intervention. In contrast, the delayed group represented interventions that occurred after stabilization, allowing for more comprehensive resuscitation, evaluation, or transfer. The intermediate group aligned with the critical therapeutic window frequently emphasized in TBI care, balancing timely intervention with adequate preparation.

For the main analysis, W score was also used to compare the difference in survival outcomes among three groups of patients: early, intermediate, and delayed interventions. W score is the difference between observed survivors and expected survivors per 100 patients [19]. The formula of the W score is (A-B)/(C/100). A is the actual number of survivors. B is the expected number of survivors based on the probability of survival (PS) from the Trauma and Injury Severity Score (TRISS) model which was derived from the Major Trauma Outcome Study (MTOS) in 1995 to predict survival and disabilities with coefficient revision in 2009 [20]. C is the total numbers of patients used for calculation of the PS. For example, a positive W score of + 2 indicates that there are 2 more survivors than predicted per 100 patients. Thus, W score represents the quality of the TBI care system within each group of patients. A positive W score indicates more survivors than predicted, reflecting superior care quality. A negative W score suggests fewer survivors than expected, potentially highlighting areas for improvement.

An additional analysis was performed using the multivariable logistic regression model. Potential confounding factors were tested and selected as confounders for the model when the p-value was less than 0.2 in univariate analysis between the exposures and factors. The association between exposure groups and outcomes was tested using multivariable logistic regression analysis and adjusted odds ratios (AOR) and 95% confidence interval (95% CI) were calculated from the model. We also compared the effect size of the time to intervention on the outcomes across the mode of transport in the final model as interaction terms.

Handling of missing data

Monotone logistic regression imputation was used to address missing data for key covariates, ensuring that the analysis included as many cases as possible while maintaining data integrity. The imputation model included patient demographics, injury severities and injury mechanisms as predictors to account for relationships among variables.

Critical variables such as primary outcomes and time-to-intervention were not imputed. Cases with missing values for these variables were excluded from the analysis to preserve the reliability and robustness of the results.

Results

Baseline characteristics

From 23,328 adult TBI patients during the study period, 2,356 (10.1%) patients received neurosurgical and neuroradiological interventions. A total of 576 patients were excluded; 311 for unknown mortality outcomes, 238 for unknown time to intervention, and 27 for unknown SBP. Ultimately, 1,780 patients were included in the final analyses (Fig. 1).

Fig. 1

Study population

TBI, traumatic brain injury

SBP, systolic blood pressure

From the RCS analysis, the knots of 1.9 and 4.1 h were derived as cut-off time points. The median [IQR] time to intervention in each group was as follows: early 1.3 [1.0-1.6] hours, intermediate 2.7 [2.3–3.2] hours, and delayed 9.2 [5.7–25.3] hours after ED arrival.

Table 1 illustrates the baseline characteristics of patients according to time to intervention. There were 532 patients (29.9%) receiving early intervention, 541 patients (30.4%) receiving intermediate intervention, and 707 patients (39.7%) receiving delayed intervention. Most patients (98.5%) received neurosurgical operation, while a small number of patients (2.3%) received neuroradiological intervention. Regarding mortality, 36.1% of patients in the early group, 24.8% of patients in the intermediate group, and 18.3% of patients in the delayed intervention group died, respectively. Unfavorable neurological outcomes occurred in 65.2% of patients in the early group, 53.4% of patients in the intermediate group, and 43.6% of patients in the delayed intervention group.

Table 1 Demographic data according to time to neurosurgical and neuroradiological intervention

Baseline characteristics of patients according to the mode of transport was illustrated in Supplementary Table S1. There were 982 patients (55.2%) in the prehospital group and 798 patients (44.8%) in the interhospital group. A significantly higher mortality in the prehospital group (29.4% vs. 20.8%, p < 0.001) was observed. Unfavorable neurological outcomes were comparable between groups (53.9% vs. 52.0%, p = 0.241).

Main analysis (W score analysis)

W score was − 2.7 for overall patients, -5.0 for the subgroup of patients receiving prehospital transport, and + 0.1 for the subgroup of patients receiving interhospital transport, as shown in Table 2. According to the time to intervention, W score was lowest in patients receiving early intervention (early − 8.6, intermediate − 1.1, and delayed + 0.4).

Table 2 W score for overall patients and subgroups according to the mode of transport

In the subgroup of patients receiving prehospital transport, W score was lowest among patients receiving early intervention (early − 15.3, intermediate − 4.5, and delayed + 1.0). In the subgroup of patients receiving interhospital transport, W score was also lowest among patients receiving early intervention (early − 2.3, intermediate + 3.3, delayed − 0.30).

Additional analyses

Table 3 shows the results from the multivariable logistic regression analyses. After adjustment for confounders, patients receiving intermediate and delayed intervention had a significantly lower mortality compared to patients receiving early intervention (AOR 0.64, 95%CI 0.47–0.86 and AOR 0.66 95%CI 0.48–0.90, respectively). There was no significant difference in unfavorable neurological outcomes in the intermediate and delayed intervention groups (AOR 0.78, 95%CI 0.58–1.05 and AOR 0.86 95%CI 0.64–1.16, respectively). There was no difference in the rate of mortality (AOR 0.54, 95%CI 0.22–1.33) and unfavorable neurological outcome (AOR 1.17, 95%CI 0.52–2.64) between patients receiving prehospital transport and patients receiving interhospital transport.

Table 3 Multivariable logistic regression analysis for outcomes by time to neurosurgical and neuroradiological intervention and the mode of transport

The interaction analysis showed marginally significant lower mortality only in patients in the intermediate intervention group receiving interhospital transport (AOR 0.84, 95%CI 0.70-1.00) (see Supplementary Table S2). There was no difference in mortality and unfavorable neurological outcomes according to time to intervention across the mode of transport in the other groups.

Discussion

This study evaluated the quality of care for TBI patients undergoing neurosurgical and neuroradiological interventions at different timings and transport modes in the Asia-Pacific region. The highest mortality and excess mortality were observed in the early intervention group, while unfavorable neurological outcomes showed no significant variation across intervention timings or modes of transport. Notably, a marginal but significant lower mortality was identified in patients in the intermediate intervention group receiving interhospital transport.

The appropriate time to intervention and its impact on outcomes in TBI patients remains debated. Intensity and duration of elevated intracranial pressure were linked to poor outcomes, suggesting that prompt intervention should improve neurological recovery [21]. However, the recent meta-analysis proved otherwise, and aligned with the results of this study [6]. The higher mortality observed in the early intervention group was probably multifactorial. This group predominantly comprised patients with severe injuries necessitating immediate intervention, often presenting with critical conditions that limit the opportunity for thorough resuscitation and stabilization. In contrast, patients who survived long enough to receive intermediate or delayed interventions likely benefited from stabilization or might reflect a survival bias [22].

Systemic and logistical factors within the trauma care pathway may also contribute to these outcomes. Delivering high-quality emergency care within the critical early hours is particularly challenging in resource-variable settings. In parts of the Asia-Pacific region, limited prehospital stabilization, delays in imaging or surgical readiness, and resource constraints further exacerbate these challenges, leading to suboptimal outcomes for critically ill patients [12]. These findings emphasize the need for system improvements, rather than suggesting that immediate life-saving interventions should be avoided or delayed.

The W score analysis provides additional insight into the quality of trauma care. A negative W score, most prominent in the early intervention group, indicated ‘preventable deaths’ and reflected systemic deficiencies in prehospital and early in-hospital care [19]. These results underscore the urgency of measures to improve trauma care during the early hours of TBI care, especially in the prehospital setting where the W score was far more negative. Standardizing prehospital triage and resuscitation protocols across regions, enhancing the readiness of trauma teams, and streamlining in-hospital workflows, such as rapid imaging and operating room availability, may help mitigate early-phase care deficiencies [23,24,25]. Additionally, training programs for emergency care providers focused on managing high-severity TBI cases could improve care quality and outcomes for patients in the early intervention period. These measures should be endorsed internationally and adapted to the local EMS protocol.

Limitation

This study has several limitations. First, despite rigorous quality control measures, data standardization inconsistencies across a multicenter registry persisted. For instance, variability in data sources—ranging from electronic medical records to direct patient surveillance—might affect the accuracy of neurological outcomes. Additionally, variables such as ED wait times and delays in surgical preparation were not captured, limiting the ability to fully assess in-hospital factors contributing to intervention timing and outcomes. Future studies should incorporate detailed prehospital and in-hospital metrics to better elucidate these relationships. Second, while logistic regression imputation was applied to handle missing data, this method did not account for potential unmeasured confounders. Alternative statistical approaches, such as propensity score matching or stratified analyses, could enhance comparability among intervention groups and should be considered in future studies. Lastly, the study utilized data from EMS systems in the Asia-Pacific region, which might differ significantly from those in other parts of the world. Variations in trauma care protocols and healthcare system capacities across regions may limit the generalizability of these findings to other settings.

Conclusion

Early neurosurgical and neuroradiological interventions for the adult TBI patients in the Asia-Pacific region were associated with lower quality of care and higher mortality. Quality of care in the early hours of TBI should be focused and urgently improved. Risk factors related to higher mortality and disability should be investigated in the future study.