Patients suffering traumatic brain injury: characteristics, primary referral and mortality – A population-based follow-up study

doi:10.21203/rs.3.rs-3344688/v1

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Patients suffering traumatic brain injury: characteristics, primary referral and mortality – A population-based follow-up study

https://doi.org/10.21203/rs.3.rs-3344688/v1

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Background

Traumatic brain injury is a potential high-risk condition. Appropriate care pathways, including prehospital triage and primary referral to a specialized neurosurgical center, improves neurological outcome and survival. The aim of this study was to examine TBI patient and injury characteristics, the way of entering into the health care system, place of primary referral and the associated 30-day and 1-year mortality rates in TBI patients with confirmed intracranial lesions.

Methods

This was a retrospective observational population-based follow-up study conducted in Central Denmark Region from 1 February 2017 to 31 January 2019. We included all hospital contacts of patients ascribed a predefined TBI ICD-10 diagnosis code in the Danish National Patient Register. The obtained TBI cohort was merged with prehospital data from the Prehospital Emergency Medical Services, Central Denmark Region, and vital status from the Danish Civil Registration System. Binary logistic regression analysis of mortality was applied.

Results

A total of 5,257 first TBI hospital contacts were included in the cohort. Of these, 1,430 (27.2%) entered the health care system by 112-call. TBI patients triaged by 112-call were more likely to receive the highest level of emergency response, second-tier resources and were more frequently referred directly to a specialized center than patients entering through general practioner or other health care personnel. In the subgroup of 1188/5257 (22.4%) patients with confirmed intracranial lesions, we found no difference in risk ratio of 30-day (RR 1.04 (95%CI 0.65 − 1.63)) or 1-year (RR 0.96 (95%CI 0.72–1.25)) all-cause mortality between patients primarily referred to a regional hospital or specialized center when adjusting for age, sex, comorbidities, antiplatelet/-coagulant treatment and type of intracranial lesions.

Conclusion

TBI patients mainly enter the health system by contact to general practitioner or other health care professionals, but patients entering through 112-call are more frequently triaged directly to specialized center. We were unable to demonstrate any significant difference in adjusted 30-day and 1-year mortality according to primary referral to a specialized center or not.

Traumatic brain injury (TBI) is the leading cause of death and disability in young people worldwide, and an increasing cause in the European elderly(1–3). Severe TBI is a high-risk condition and the primary injury to the brain can be detrimental to neurological function and survival(4, 5). In severe TBI, hypotension and hypoxia may induce secondary insults to brain tissue, and are associated with a worsened patient outcome (5–7). Primary referral to a specialized neurosurgical centre is associated with improved neurological outcome and survival(8–10). Thus, accurate and timely identification of TBI patients expected to benefit from prehospital critical care, and direct triage to a specialized center are considered essential elements to ensure optimal patient outcome(11). In Scandinavia, prehospital emergency medical service (EMS) dispatch is performed by health care professionals upon medical emergency calls (e.g., 1-1-2 in Denmark). Contact to general practitioner (GP) or the out-of-hours physician service is another major way of entering into the health care system for patients suffering subacute and urgent conditions(11, 12). In this study on TBI patients, we aimed to 1) describe patient characteristics and their way of entrance into the health care system, 2) examine the association between way of entrance into the health care system and primary referral to specialized center, and 3) examine the association between primary referral to specialized center and 30-day and 1-year mortality in patients with confirmed intracranial lesions.

Study design

This was a register-based retrospective, observational population-based follow-up study conducted in the Central Denmark Region during a 2-year period from 1 February 2017 to 31 January 2019. The results are reported according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline(13).

Setting

The study was conducted in the Central Denmark Region with a catchment population of 1.3 million people accounting for 23% of the total Danish population. The Danish National Health Service is a tax-supported system and health care services are free of charge. It provides health care facilities such as GPs and prehospital EMS, as well as hospital services. The Central Demark Region is one of five administrative health care regions of Denmark. The region houses five hospitals with emergency departments with trauma care functions; four regional hospitals without neurosurgical capacity (Randers, Viborg, Horsens and Herning) and one specialized center with an emergency department with major trauma center facilities and neurosurgical facilities (Aarhus University Hospital). In addition, daytime emergency clinics attending minor injuries are placed in Grenaa, Holstebro, Silkeborg, Skive and Ringkøbing(14).

Prehospital triage, coordination and incident management

The Danish EMS is a two-tiered system of 1) ambulances staffed by emergency medical technicians and paramedics, and 2) physician staffed critical care teams deployed as rapid response vehicles and/or helicopters available day and night. All units respond to both trauma and medical emergencies, the second-tier to suspected critical illness. Dispatch of all EMS responses, ground-based as well as airborne, are centrally coordinated from five regional Emergency Medical Communication Centers (EMCCs). Resources can be dispatched following either GP request or layman 112-call to the EMCC.

Placement Fig. 1

Figure 1 Way of entrance

Illustration of way if entrance to the health care system and Emergency Medical Communication Centre triage.

In case of GPs requesting prehospital dispatch, the level of emergency and type of response is determined by the GP. Following a layman 112-call, specially trained emergency medical technicians, paramedics, nurses and physicians in the EMCC perform criteria-based dispatch using the criteria-based decision support tool “Danish Index for Emergency Care” (Fig. 2) (12).

The level of emergency ranges from A to E (A is lights and sirens and E is no ambulance, but oral advice or other form of service offered). Based on this classification and geography, the necessary response (ambulance and/or ground based critical care team and/or helicopter) is dispatched(12). EMCC personnel are allowed to decline ambulance dispatch if the 112-caller is better served with another health care service. All patients must be referred by GPs or prehospital personnel in the EMCC prior to hospital visits, but occasionally patients show up unreferred. Secondary referrals from regional hospitals to Aarhus University Hospital occurs when specialized treatment is need.

Study population

Patients were identified through the Danish National Patient Register and comprised all patient contacts ascribed a predefined TBI ICD-10 diagnose code (list of diagnosis in Additional file 1, Table 4) following a hospital contact in the Central Denmark Region during the 2-year study period(15). Contacts were then linked to prehospital data, if such occurred within 24 hours before the TBI hospital contact. Only the first TBI hospital contact for each patient during the study period was included. Foreigners and citizens migrating within 30 days of admission were considered lost to follow-up. Follow-up was terminated on 4 April 2020.

Data sources

All Danish citizens have a unique social security number (CPR number), which makes it possible to link Danish registers on an individual level. Using CPR numbers, the TBI cohort identified through the Danish National Patient Register was merged with prehospital patient medical records and the proprietary operational dispatch database at the Prehospital EMS, Central Denmark Region. This database contains incident log numbers, dispatch criteria, response levels, timestamps, operational and patient descriptors, and general log data. Vital status at follow-up was obtained from the Danish Civil Registration System. Data on index hospital admission and existing comorbidities were obtained from the Danish National Patient Register. Data on antiplatelet/-coagulant treatment were obtained from The Register of Pharmaceutical Sales. These Danish health registries are administered by The Danish Health Data Authority and were previously validated for research(15, 16).

Variables

Charlson Comorbidity Index (CCI), was calculated based on ICD-10 codes from the Danish National Patient Register from a 10-year period prior to the index contact as originally described by Charlson et al. and validated by Thygesen et al.(17, 18). Antiplatelet/-coagulant treatment was reported categorical defined by redeemed prescriptions of one of all B01 Anatomical Therapeutic Chemical Classification system codes (ATC codes) prior to index contact: 1) Acetylsalicylic acid, 2) ADP-receptor antagonist, 3) Vitamin K antagonist, 4) Non-vitamin K Antagonist Oral Anticoagulant (NOAC), and 5) Other. The way of entering the health care system was categorized as 1) “GP/Health Care Professional (HCP)” if the hospital contact or the prehospital dispatch leading to the hospital contact was requested by a general practitioner or another health care professional such as nurses in nursing homes, or home care nurses, 2) “112-call” if the prehospital dispatch was based on an emergency medical 112-call by a layman or as 3) “Unreferred” if the patient had neither prehospital nor GP contact prior to hospitalisation.

Variables describing prehospital triage and dispatch are reported as: 1) Assigned levels of initial prehospital emergency “A-E”, 2) Use of ambulance transport “yes/no” and 3) Additional second-tier resources “Rapid response vehicle” and/or “Helicopter”. Place of primary referral was categorized as “Regional hospital” if the patient was initially admitted to one of the regional hospitals in Randers, Viborg, Horsens, or Herning and the emergency daytime clinics in Grenaa, Holstebro, Silkeborg, Skive and Ringkøbing, and as “Specialized Center” if the patient was admitted to Aarhus University Hospital. The type of TBI was dichotomized 1) “Concussion” or 2) “Intracranial lesion”. The specific type of intracranial lesion (epidural hemorrhage, subdural hemorrhage, subarachnoid hemorrhage, cerebral contusion and other injuries) was also reported.

Exposures and outcomes

The primary outcome was a primary referral of TBI patients to the specialized center. For this primary analysis, the way of entering (“GP/HCP”, “112-call” or “Unreferred”) the health care system was regarded as exposure.

In the subgroup of patients with confirmed intracranial lesions (all concussion ICD-10 codes excluded), the secondary outcomes of crude all-cause mortality and relative risks of death at days 1, 7, 30, 90 and 365 are presented. To describe the association between direct admission to a specialized center and survival in this subgroup of patients, we performed an analysis using the place of primary referral (regional hospital or specialized center) as exposure and mortality as outcome.

Statistical methods

Continuous data are presented as means with 95% confidence intervals (95% CI) or medians with interquartile ranges [IQR] according to distribution. Categorical data are presented as numbers and proportions. For comparison between groups, the Chi-square test was applied for categorical data, while the two-sample t-test and Kruskal-Wallis test were used for continuous data.

Adjusted risk ratios were calculated by binary regression analysis. The primary analysis on all TBI cases investigated the association between the way of entrance (GP/HCP, 112-call or unreferred) and primary referral to the specialized center. Secondary analyses investigated the association between the place of primary referral and mortality in TBI cases with confirmed intracranial lesion. In both analyses, the following covariates were adjusted for: age as a continuous variable, sex as a dichotomous variable (male/female); and as categorical variables: CCI score, antiplatelet/-coagulant treatment and type of intracranial lesion (epidural hemorrhage, subdural hemorrhage, subarachnoid hemorrhage, cerebral contusion and other injuries). In the sensitivity analysis, GCS score was introduced at a categorical variable according to the stratification in mild, moderate and severe TBI.

Unadjusted and adjusted mortality curves are presented using Kaplan-Meier and Cox regression curves truncated at 30 days and 1 year.

All calculations were two-sided, and p-values < 0.05 were considered statistically significant. Missing data were considered missing at random and therefore not imputed. All statistical analysis was performed using STATA© intercooled, version 17 (StataCorp LP, College Station, Texas).

Way of entrance

Figure 2 displays inclusion and exclusion to the cohort as well as primary referral to either a regional hospital or the specialized center. Of the 5,664 TBI hospital contacts in the Central Denmark Region within the study period, 5,257 first contacts of TBI patients were included in the cohort. Of these, 3,417/5,257 (65.0%) entered the health care system either through GP or other health care professional, whereas 1,430/5,257 (27.2%) entered by 112-call and 410/5,257 (7.8%) showed up unreferred.

Placement Fig. 2

Figure 2 Flow diagram of TBI patients in the cohort. Inclusion, exclusion and flow of emergent TBI patients through the health care system stratified by way of entrance. Proportions are presented as total numbers in subgroups by type of TBI (concussion or intracranial lesion).

Baseline characteristics according to the way of entrance into the health care system are presented in Table 1. In general, patients entering by 112-call were older, had more comorbidities, were more often transported by ambulance, were regarded as higher levels of emergency, and more often received second-tier resources than patients entering by GP or other health care personnel. The proportion of patients with an intracranial lesion was higher in patients entering through 112-call (366/1,430 (25.6%)) than through GP/HCP (760/3,417 (22.3%)), p = 0.01 (Fig. 1). In patients with confirmed intracranial lesions 1/3 (366/1,180 (31.0%) entered by 112-call.

Table 1

Baseline characteristics, prehospital triage and direct referral of TBI patients stratified by the way of entrance into the health care system: General practitioner or other health care professional (GP/HCP), 112-call by layman (112-call) or unreferred, N = 5,257.
Variable	GP/HCP n = 3,417 (65.0%)	112-call n = 1,430 (27.2%)	Unreferred n = 410 (7.8%)	p-value
Sex, male, n (%)	1,788 (52.3)	814 (56.9)	242 (59.0)	0.008*
Age, median years [IQR]	44 [18–71]	50 [24–68]	28 [20–52]	< 0.001*
Charlson Comorbidity Index, n (%)
- No	1,691 (49.9)	640 (44.8)	270 (65.9)	< 0.001*
- Low	582 (17.0)	339 (23.7)	68 (16.7)
- Medium	580 (17.0)	272 19.0)	38 (9.3)
- High	564 (16.5)	179 (12.5)	34 (8.3)
Antiplatelet/-coagulant treatment, n (%)
- Acetylsalicylic acid	327 (9.6)	152 (10.6)	26 (6.3)
- ADP-receptor antagonist	146 (4.3)	48 (3.4)	3 (0.73)
- Vitamin K antagonist	167 (4.9)	45 (3.2)	9 (2.2)
- NOAC	158 (4.6)	68 (4.8)	16 (3.9)
- Other	31 (0.9)	6 (0.4)	2 (0.49)
Prehospital triage and dispatch, n (%)
Ambulance, yes	1,665 (48.7)	1,299 (90.8)	0 (0.0%)
Level of emergency
- A	533 (15.6)	720 (50.3)	-	< 0.001*
- B	843 (24.7)	583 (40.7)	-
- C	141 (4.1)	2 (0.1)	-
- D	121 (3.5)	0 (0.0)	-
- E	5 (0.2)	3 (0.2)	-
- NA	1,774 (51.9)	122 (8.5)
Second-tier resources, yes
- Rapid response vehicle (Physician)	334 (9.8)	656 (39.5)	-	< 0.001*
- Rapid response vehicle (Nurse)	36 (1.1)	31 (2.2)	-
- Helicopter	26 (0.8)	48 (3.4)	-
Type of TBI, n (%)
- Concussion	2,657 (77.7)	1,064 (74.4)	356 (86.8)
- Intracranial lesion	760 (22.3)	366 (25.6)	54 (13.2)
Direct referral to the specialized center, n (%)	1,248 (36.5)	951 (66.5)	296 (72.2)	< 0.001*
*Kruskal-Wallis equality-of-populations rank test

Place of primary referral

Direct referral to the specialized center was observed in 951/1430 (66.5%) of all patients entering by 112-call and in 1248/3417 (36.2%) of all patients entering through GP/HCP (risk ratio (RR) 1.65 (95%CI 1.56–1.74). In the subgroup of patients with confirmed intracranial lesions, 220/366 (60.1%) patients entering through 112-call and 201/760 (26.4%) entering through GP/HCP were triaged directly to specialized center (RR = 2.01 (95%CI 1.76–2.30)). In the subgroup of patients with concussions, 731/1064 (68.7%) of patients entering through 112-call and 1047/2657 (39.4%) of patients entering through GP/HCP were triaged directly to specialized center (RR = 1.59 (95%CI 1.50–1.68)).

Primary referral and mortality in patients with confirmed intracranial lesions

Baseline characteristics and specific types of intracranial lesions in the subgroup of patients with intracranial lesions by place of primary referral to a regional hospital and the specialized center are given in Table 2. Crude mortality rates, and unadjusted and adjusted risk ratios are presented in Table 3. Unadjusted overall 1-year mortality is presented as Kaplan-Meier cumulative mortality curves in Fig. 3. In Fig. 4, unadjusted (Kaplan-Meier curves) and adjusted (Cox regression curves) mortality from day 0–30 and 30–365 by place of primary admission is displayed.

Among patients with intracranial lesions, patients referred to the specialized center were younger and had less comorbidity than patients referred to the regional hospitals (Table 2).

We observed a higher crude early mortality in patients referred to the specialized center compared to patients referred to the regional hospitals; day 1 RR 4.65 (95%CI 1.26–17.06) and day 7 RR 1.46 (95%CI 0.94–2.29). The number of events (death) was insufficient for valid adjusted analysis of mortality on day 1 and day 7 (Table 3).

We observed no difference in crude 30-day mortality between patients initially referred to a regional hospital at 11.4 (95%CI 9.2–13.9) and patients directly referred to the specialized center at 11.2 (95%CI 8.5–15.5), (RR 0.98 (95%CI 0.70–1.36)). The result remained unchanged in binary regression analysis when adjusting for age, sex, comorbidity, use of antiplatelet/-coagulant treatment, and type of intracranial lesion with RR 1.04 (95%CI 0.65 − 1.63) (Table 3).

In patients referred directly to the specialized center, crude 1-year all-cause mortality was lower at 17.9 (95%CI 14.6–21.8) than in patients initially referred to a regional hospital at 22.7 (95% CI 19.8–26.1) with a RR of 0.79 (0.62-1.00). When adjusting for age, sex, comorbidity, use of antiplatelet/-coagulant treatment, and type of intracranial lesion, there was no difference with an adjusted RR of 0.96 (95%CI 0.72–1.25) (Table 3).

We did a sensitivity analysis on 1-year mortality including only patients with available GCS (i.e., those transported by ambulance, n = 729) adjusting for GCS instead of type of intracranial lesion (Additional file 2, Table 5). This did not change the results of no difference.

Placement Fig. 3

Figure 3 Kaplan-Meier cumulative mortality curve of long-term (1-year) all-cause mortality in TBI patients suffering from intracranial lesions stratified by primary referral to a regional hospital or the specialized centre.

Placement Fig. 4

Figure 4 Unadjusted (Kaplan-Meier curves) and adjusted (Cox regression curves) mortality curves of short-term (30-days) and long-term (1-year) all-cause mortality in TBI patients suffering from intracranial lesions stratified by primary referral to a regional hospital or the specialized centre.

Placement Table 1

Table 2

Baseline characteristics and type of intracranial lesions in TBI patients with confirmed intracranial lesions stratified by primary referral to a regional or specialized centre, N = 1,180.
Variable	Regional Hospital n = 717 (60.8)	Specialized Centre n = 463 (39.2)	p- value
Sex, male, n (%)	449 (62.6)	309 (66.7)
Age, median years [IQR]	72 [56–81]	65 [45–76]	< 0.001*
Charlson Comorbidity Index, n (%)
- No	117 (15.9)	122 (26.4)
- Low	137 (19.1)	98 (21.2)
- Medium	228 (31.8)	143 (30.9)
- High	238 (33.2)	100 (21.6)
Antiplatelet/-coagulant treatment, n (%)
- Acetylsalicylic acid	137 (19.1)	76 (16.4)
- ADP-receptor antagonist	59 (8.2)	26 (5.6)
- Vitamin K antagonist	79 (11.0)	26 (5.6)
- NOAC	50 (7.0)	33 (7.1)
- Other	15 (2.1)	7 (1.5)
Type of intracranial lesion, n (%)
- Epidural haemorrhage	24 (3.4)	21 (4.5)
- Subdural haemorrhage	401 (55.9)	263 (56.8)
- Subarachnoid haemorrhage	93 (13.0)	78 (16.9)
- Cerebral Contusion	85 (11.9)	27 (5.8)
- Other	114 (15.0)	74 (16.0)
*Two-sample T-test

Table 3

Crude mortality rates and risk ratios of TBI patients with confirmed intracranial lesions by primary referral to a regional or specialized centre, N = 1,180.
	Crude mortality rates, % (95% CI)			Risk ratios, RR (95% CI)*
Variable	Deaths, n	Regional Hospital n = 717 (60.8%)	Specialized Center n = 463 (39.2%)	Unadjusted	p-value	Adjusted	p- value
- 1-day	12	0.42 (0.09–1.2)	1.9 (0.9–3.7)	4.65 (1.26–17.06)	0.01	**	**
- 7-day	72	5.2 (3.7-7.0)	7.6 (5.3–10.4)	1.46 (0.94–2.29)	0.09	**	**
- 30-day	134	11.4 (9.2–13.9)	11.2 (8.5–15.5)	0.98 (0.70–1.36)	0.91	1.04 (0.65–1.63)	0.87
- 90-day	171	15.3 (12.8–18.2)	13.2 (10.2–16.6)	0.86 (0.64–1.15)	0.29	1.05 (0.73–1.5)	0.79
- 1-year	246	22.7 (19.8–26.1)	17.9 (14.6–21.8)	0.79 (0.62-1.00)	0.05	0.96 (0.72–1.25)	0.72
* Binary regression analysis, ** Insufficient number of events for adjustment

In this large, retrospective population-based cohort study of TBI patients, we found that the majority of patients (65%) enter the health care system through contact to a GP or other health care professional. TBI patients triaged by 112-call are more likely to receive the highest level of emergency response and second-tier resources, and are more frequently directly referred to a specialized center. Among TBI patients with confirmed intracranial lesions, we found no difference in neither crude nor adjusted 30-day all-cause mortality rates between patients primarily referred to a regional hospital compared to a specialized center. At 1 year, we found a significantly lower crude mortality in patients transported to a specialized center. However, these patients were also younger and had less comorbidity, and in the adjusted analysis, there was no differences in 1-year mortality.

Strengths and limitations

The main strength of this study is the register-based design, which improves precision of findings. The unique Danish system of social security numbers provides the possibility of linking validated registers and patient records on an individual level. Also, the risk of selection bias is limited due to a tax-based health care system, which ensures a genuine cohort. The completeness of data on the included covariates in the adjusted analysis is also a strength. Lastly, TBI patients are often reported as a subgroup in general trauma research, but this study presents epidemiological data on a cohort consisting trauma patients with main ICD-10 TBI diagnosis.

However, this study has some limitations. First, we were not able to adjust for initial GCS for the entire cohort, as only patients transported by ambulance were GCS scored. This could cause residual confounding in the mortality analysis. A sensitivity analysis on 1-year mortality in GCS scored patients (i.e., those transported by ambulance) including GCS in the regression instead of type of intracranial lesion confirmed the result of no difference. In addition, we were not able to adjust for injury severity score either.

Second, TBI is a potentially fatal condition already in the prehospital setting and not all patients reach the hospital and get an ICD-10 diagnosis indicative of TBI. TBI patients dying before hospital admission will not enter the cohort, and a possible selection of patients destined to do well may underestimate mortality of the unselected TBI population. Last, the external validity of the current study is limited to prehospital EMS systems operated under similar conditions to the Danish system with the same level of prehospital critical care.

Comparison to other studies

Baseline patient characteristics reported in this current study are in concordance with previous studies, finding demographics of median age in the range 40–60 years, male predominance and subdural haemorrhage being the most frequent intracranial lesion following head trauma (2, 19, 20).

In a living systematic review of 66 studies from 23 European countries by Brazinova et al., epidemiological patterns in TBI patients from the full severity spectrum (mild, moderate and severe) based on ICD-8, 9 and 10 diagnoses as well as clinical definitions was examined (21). Sundstrøm et al. reported the mortality rate per 100.000 inhabitants per year from 27 individual studies, ranging from 3.3 to 28.4. In the Nordic countries, mortality in the range 10.4–21.2 per 100.000 inhabitants per year in cases of TBI identified from ICD8-10 diagnoses including those patients who died at the scene or before arrival at the hospital. The death rate in the Danish population was 11.5 per 100.000 inhabitants per year(22). In this current study, we found comparable mortalities with a crude 30-day mortality of 11.2–11.4% regardless of place of primary referral, and a crude 1-year mortality of 22.7% (95%CI 19.8–26.1) in regional hospitals and 17.9% (95%CI 14.6–21.8) at the specialized center.

We found that the proportion of patients entering by 112-call and GP/HCP actually suffering from confirmed intracranial lesions was quite similar with 25.6% versus 22.3%. To our knowledge, no previous studies reported way of entrance to the health care system in TBI patients comprising of both GP, HCP, 112-call to the prehospital EMS and unreferred. However, Søvsø and colleagues together with Huibers et al. found, that patients using the EMS as an entrance to heath care services are usually more severely ill, but patients suffering time-critical conditions still use GP/out-of-hours physician service as an entrance(23, 24). These studies were conducted on a heterogenic patient cohort and not solely TBI patents.

Our findings of no difference in long-term mortality according to initial transfer to different types of hospitals are compliant to the recent findings on primary referral and mortality by Sewalt and the CENTER-TBI research group. Even though we report crude 1-year mortality to be significantly lower in patients directly referred to a specialized center, the findings seemed to be caused by demographic variations (i.e., younger patients with less comorbidity) rather than place of primary referral. The difference in 1-year all-cause mortality was obliterated in the adjusted analysis (adjusted RR of 0.96 (95%CI 0.77–1.20). Sewalt and colleagues found no association between primary vs. early secondary referral to a specialized neurotrauma center and occurrence of secondary insults (hypoxia and hypotension) nor long-term clinical outcomes(25). Furthermore, our results are in line with the results of a meta-analysis by Pickering et al., who demonstrated no difference in mortality for direct transport to a trauma center versus initial triage to a local hospital in a review of 11 studies on head injury patients(26).

Interpretation

The present study and recent research contradict the otherwise established belief that direct transport of TBI patients to hospitals with neurosurgical facilities improves patient outcome(25). International guidelines and previous research recommend direct transport of TBI patients to hospitals with neurosurgical facilities in order to reduce time-delay to treatment and incidence of death and disability as an anticipated and documented effect of specialized neurotrauma care(9, 27, 28). We therefore expected to find improved survival rates of patients transported to the specialized center relative to transport to a regional hospital in the current study when adjusting for relevant confounders, but were unable to demonstrate this. It may be speculated that prehospital on-scene interventions and early local inhospital treatment to prevent secondary insults have improved in such degree, that the effect of primary referral to a specialized neurosurgical center have diminished(29). Especially in a region like the Central Denmark Region, where geographical distances are rather small and prehospital EMS is highly developed with a high capacity for critical care compared to other countries. In such a setting, admission to a local hospital for primary workup and CT may thus be a reasonable choice for patients where there is doubt whether or not there is a significant intracranial lesion.

The majority (65.0%) of TBI patients enter the health care system through contact to a GP/HCP. TBI patients entering the healthcare system through 112-call are more likely triaged to the highest level of prehospital response, and are more frequently primarily referred to the specialized center than patients triaged by GP/HCP. We found no difference in neither crude nor adjusted 30-day all-cause mortality between patients admitted to a regional hospital or specialized center. Crude 1-year mortality was lower in patients primarily referred to the specialized center, but the difference vanished when adjusted for age, sex, comorbidities, use of antiplatelet/-coagulant treatment, and type of intracranial lesion.

ATC: Anatomical Therapeutic Chemical Classification

CCI: Charlson Comorbidity Index

CPR: Civil Personal Number

EMCC: Emergency Medical Communication Center

EMS: Emergency Medical Services

GP: General Practitioner

HCP: Health care professional

ICD-10: International Classification of Disease 10^th edition

IQR: Interquartile Ranges

N: Number

RR: Risk Ratio

TBI: Traumatic Brain Injury

112: Emergency call number

Additional ethics, approval and consent to participate

The study was approved by The Danish Data Protection Agency, Central Denmark Region (journal no. 1-16-02-109-18) and the Danish Patient Safety Authority (journal no. 3-3013-2505/1). Approval by the local ethics committee and collection of informed consent are not required for observational cohort studies according to Danish law.

Consent for publication

Not applicable.

Availability of data and material

The data sets used and analysed during the current study is available from the corresponding author upon reasonable request and with relevant permissions from Danish authorities. The data is not publicly available due to protection of personal data.

Competing interests

The authors declare to have no competing interest. The study was entirely initiated by the research group. No commercial companies were involved in the design or initiation of the study.

Funding

This study did not receive any specific grants. Salary for primary investigator is defrayed by Prehospital Emergency Medical Services, Central Denmark Region and amounts to regular PhD-salary throughout the study period.

Author contributions

SCS, CKP, NJ, HK and MTB designed and conceived the study. SCS and CKP collected and managed the data. Statistical analysis was performed by SCS, CKP and MTB. SCS drafted the manuscript. All authors read, critically revised and approved the final manuscript.

Acknowledgement

The authors thank Kristian Friesgaard for advice on necessary approvals and vital support during the conduction of the study. We also thank Anders Christian Poulsen for assistance with data collection.

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Editorial decision: Major Revision
09 Dec, 2023
Reviewers agreed at journal
02 Oct, 2023
Reviewers invited by journal
30 Sep, 2023
Editor assigned by journal
18 Sep, 2023
First submitted to journal
15 Sep, 2023

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Patients suffering traumatic brain injury: characteristics, primary referral and mortality – A population-based follow-up study

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Abstract

Background

Methods

Results

Conclusion

Figures

BACKGROUND

METHODS

Study design

Setting

Prehospital triage, coordination and incident management

Study population

Data sources

Variables

Exposures and outcomes

Statistical methods

RESULTS

Way of entrance

Place of primary referral

Primary referral and mortality in patients with confirmed intracranial lesions

Placement Table 1

DISCUSSION

Strengths and limitations

Comparison to other studies

Interpretation

CONCLUSION

Abbreviations

Declarations

References

Supplementary Files

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Version 1