Impact of Glasgow Coma Scale score and pupil parameters on ...€¦ · multicenter cohort study *Pedram Emami, MD,1 Patrick Czorlich, MD,1 Friederike S. Fritzsche, MD, 1 Manfred Westphal,

CLINICAL ARTICLEJ Neurosurg 126:760–767, 2017

ABBREVIATIONS AIS = Abbreviated Injury Scale; CPR = cardiopulmonary resuscitation; ECS = Eppendorf-Cologne Scale; GCS = Glasgow Coma Scale; GOS = Glasgow Outcome Scale; ICU = intensive care unit; ISS = Injury Severity Score; RISC II = Revised Injury Severity Classification II; TBI = traumatic brain injury; TR-DGU = Trau-maRegister DGU of the German Trauma Society.SUBMITTED October 15, 2015. ACCEPTED January 14, 2016.INCLUDE WHEN CITING Published online April 1, 2016; DOI: 10.3171/2016.1.JNS152385.* Drs. Emami and Czorlich contributed equally to this work.

Impact of Glasgow Coma Scale score and pupil parameters on mortality rate and outcome in pediatric and adult severe traumatic brain injury: a retrospective, multicenter cohort study*Pedram Emami, MD,1 Patrick Czorlich, MD,1 Friederike S. Fritzsche, MD,1 Manfred Westphal, MD,1 Johannes M. Rueger, MD,2 Rolf Lefering, PhD,3 and Michael Hoffmann, MD2

Departments of 1Neurosurgery and 2Trauma, Hand, and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf, Hamburg; and 3Institute for Research in Operative Medicine, Witten/Herdecke University, Cologne, Germany

OBJECTIVE Prediction of death and functional outcome is essential for determining treatment strategies and allocation of resources for patients with severe traumatic brain injury (TBI). The aim of this study was to evaluate, by using pupillary status and Glasgow Coma Scale (GCS) score, if patients with severe TBI who are ≤ 15 years old have a lower mortality rate and better outcome than adults with severe TBI.METHODS A retrospective cohort analysis of patients suffering from severe TBI registered in the Trauma Registry of the German Society for Trauma Surgery between 2002 and 2013 was undertaken. Severe TBI was defined as an Ab-breviated Injury Scale of the head (AIShead) score of ≥ 3 and an AIS score for any other part of the body that does not exceed the AIShead score. Only patients with complete data (GCS score, age, and pupil parameters) were included. To assess the impact of GCS score and pupil parameters, the authors also used the recently introduced Eppendorf-Co-logne Scale and divided the study population into 2 groups: children (0–15 years old) and adults (16–55 years old). Each patient’s outcome was measured at discharge from the trauma center by using the Glasgow Outcome Scale.RESULTS A total of 9959 patients fulfilled the study inclusion criteria; 888 (8.9%) patients were ≤ 15 years old (median 10 years). The overall mortality rate and the mortality rate for patients with a GCS of 3 and bilaterally fixed and dilated pupils (19.9% and 16.3%, respectively) were higher for the adults than for the pediatric patients (85% vs 80.9%, respec-tively), although cardiopulmonary resuscitation rates were significantly higher in the pediatric patients (5.6% vs 8.8%, respectively). In the multivariate logistic regression analysis, no motor response (OR 3.490, 95% CI 2.240–5.435) and fixed pupils (OR 4.197, 95% CI 3.271–5.386) and bilateral dilated pupils (OR 2.848, 95% CI 2.282–3.556) were as-sociated with a higher mortality rate. Patients ≤ 15 years old had a statistically lower mortality rate (OR 0.536, 95% CI 0.421–0.814; p = 0.001). The rate of good functional outcomes (Glasgow Outcome Scale Score 4 or 5) was higher in pediatric patients than in the adults (72.2% vs 63.1%, respectively).CONCLUSIONS This study found that severe TBI in children aged ≤ 15 years is associated with a lower mortality rate and superior functional outcome than in adults. Also, children admitted with a missing motor response or fixed and bilaterally dilated pupils also have a lower mortality rate and higher functional outcome than adults with the same initial presentation. Therefore, patients suffering from severe TBI, especially pediatric patients, could benefit from early and aggressive treatment.https://thejns.org/doi/abs/10.3171/2016.1.JNS152385KEY WORDS traumatic brain injury; mortality; outcome; pediatrics

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GCS score and pupil parameters in severe traumatic brain injury

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TraumaTic brain injury (TBI) is the second most common cause of death in children aged 0 to 15 years in Germany and the United States.9,12 Besides

its high mortality rate, TBI is also a leading cause of severe disability.19 Many prognostic factors for predicting death and functional outcome after TBI, such as the Glasgow Coma Scale (GCS) (with special regard to the motor com-ponent) and the presence of other injuries or hypotension and hypoxia, have been identified.1,10,16,18,25,26,32 A recently published study found that the Eppendorf-Cologne Scale (ECS) score,20 a novel trauma score that combines pupil reactivity, pupil size, and a modified GCS motor compo-nent, exceeds the predictive value of the GCS score. Fur-ther studies have reported that eye and verbal responses add only a little power to the predictive accuracy of the GCS.18–20 However, additional pupil evaluation is useful, because neuromuscular-blocking agents do not affect pu-pillary function.14,31

Age at the time of TBI is known to be one of the most important independent predictors of death and functional outcome.12,24 Recent studies have found that patients with an initial GCS score of 3 and with bilateral fixed and dilat-ed pupils face a poor prognosis.23,27,30 Still, it is generally accepted that pediatric TBI is associated with a mortality rate that is lower than adult TBI, even when the patient presents on admission with unilaterally or bilaterally fixed pupils.4,16,24 Some studies that compared the outcome of pediatric and adult TBI had a certain selection bias ac-cording to the study design used, that is, the definition of TBI severity used or whether they were single-center or regional-center analyses, with most studies focusing on ei-ther pediatric or adult TBI including elderly patients aged 65 years or older.7,12,20,29,30

The purpose of this study was to evaluate, by analyzing a large registry database, the impact of pupillary status and GCS score on death and functional outcome in pedi-atric and adult patients.

MethodsTraumaRegister DGU of the German Trauma Society

The TraumaRegister of the German Trauma Society (TR-DGU) was founded in 1993. The aim of building this multicenter database was to create anonymous standard-ized documentation of data from severely injured patients.

Data are collected prospectively in 4 consecutive time phases from the site of the accident until discharge from the hospital: 1) prehospital phase, 2) emergency depart-ment and initial surgery, 3) intensive care unit (ICU) stay, and 4) discharge. The documentation includes detailed in-formation on demographics, injury pattern, any comorbid-ities, prehospital and in-hospital management, course of treatment in the ICU, relevant laboratory findings (includ-ing data on transfusion), and the outcome of each patient. The inclusion criterion is admission to the hospital via the emergency department with subsequent ICU/ICM (inten-sive care medicine unit) care or arrival at the hospital with vital signs and death before admission to the ICU.

The infrastructure for documentation, data manage-ment, and data analysis is provided by the Akademie der Unfallchirurgie GmbH (Academy for Trauma Surgery),

a company affiliated with the German Trauma Society. The scientific leadership is provided by the Committee on Emergency Medicine, Intensive Care and Trauma Man-agement (Sektion NIS) of the German Trauma Society. The participating hospitals submit their data anonymously to a central database via a Web-based application. As a compulsory tool for quality assessment, no informed con-sent is necessary for data collection. In accordance with the local data regulations, no institutional review board approval is necessary when anonymous data are used. Scientific data analysis is approved according to a peer-review procedure established by Sektion NIS. The study was registered at the TR-DGU (TR-DGU 2014-048).

All the participating hospitals are located in Germany. Participation in the TR-DGU is voluntary. For hospitals associated with TraumaNetzwerk DGU, however, the en-try of at least a basic data set is obligatory for quality as-surance.

Study Population and Inclusion CriteriaAlthough the TR-DGU database comprises a wide va-

riety of information for each case, only patients with se-vere TBI (defined as an Abbreviated Injury Scale of the head [AIShead] score of ≥ 3) treated between 2002 and 2013 with complete status documentation of GCS and ECS scores recorded at the scene before resuscitation and on hospital admission were included in this study.2 Other in-clusion criteria were complete outcome documentation in terms of survival to hospital discharge or death. Patients with missing data were excluded from this study. Patients documented in the TR-DGU qualified for this analysis if their Injury Severity Score (ISS)3 was ≥ 9 and if they were admitted from the scene of the injury directly to the participating hospital (i.e., patients transferred from one hospital to another were excluded).

DefinitionsTraumatic brain injury was defined as an AIShead score

of 3 or higher. Severe injuries were defined as an AIS score for any body region of 3 or higher. Patients were subclassified as pediatric (0–15 years of age) or adult (16–55 years of age) patients. Patients older than 55 years were excluded from further analysis, because previous studies have shown that the mortality rate rapidly increases in el-derly patients.7,13,25,27

The severity of TBI and alteration of consciousness were scored using the GCS (motor scores of 1–6, verbal scores of 1–5, and eye scores of 1–4). Unconsciousness was defined as a GCS score of ≤ 8. In addition, the re-cently introduced ECS score was recorded (details are presented in Table 1).20 The GCS parameters and bilateral pupil size and reactivity were evaluated before resuscita-tion at the scene and on admission to the hospital. Death was defined as any patient who did not survive to the time of hospital discharge.

Neurological outcomes were categorized into 1 of 5 lev-els using the Glasgow Outcome Scale (GOS): 1, death; 2, vegetative state (unable to interact with environment, un-responsive); 3, severe disability (able to follow commands, unable to live independently); 4, moderate disability (able to live independently, unable to return to work or school);


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and 5, good recovery (able to return to work or school).22 A GOS score of 4 or 5 indicated a good outcome.

Statistical AnalysisStatistical analyses were performed using SPSS 18.0

statistical software. Data are presented as means (± stan-dard deviation) for continuous variables, as medians with the interquartile range for time to death and for ISS and GCS scores, and as numbers (percentage) for categorical variables.

To assess the relative importance of GCS score, pupil parameters, and TBI, a multivariable logistic regression analysis that included only the variables under investiga-tion was performed. Hospital death was used as the de-pendent variable. Coefficients are presented together with their respective odds ratio (OR) and corresponding 95% confidence interval (CI).

Presentation of multiple p values from pairwise com-parisons was avoided, and statistical significance is men-tioned only in select situations. All tests were 2-tailed, and p values of < 0.05 were considered statistically significant.

ResultsAfter excluding transferred patients and those who did

not fulfill the inclusion criteria, 13,413 potential patients were available for analysis. Patients with missing or in-complete data for pupil size (n = 1332 [9.9%]) and pupil reactivity (n = 3355 [25.0%]) were excluded, which left 9959 patients, some of whom had more than 1 missing pa-rameter, for analysis. Complete GCS status and outcome documentation of all the patients were available. Patient and core injury characteristics are provided in Table 2.

Pediatric patients were more likely than adult patients to be transferred to a Level 1 trauma center (790 [89.0%] vs 7842 [86.5%] patients, respectively), and there was an asso-ciated higher rate of airborne transports (40.6% vs 33.1%, respectively) and significantly (p < 0.001) decreased trans-fer times from the scene to the hospital. The leading cause of injury in the adults was motor vehicle collision. Most of the pediatric patients were injured as pedestrians. The female/male ratio was higher in adult patients, as was the rate of penetrating trauma. Pediatric patients were more likely than the adults to have suffered from an isolated TBI (37.3% vs 25.3%, respectively), which was associated with a significantly (p = 0.02) decreased median GCS score. In both groups, unconscious patients with a GCS score of 8 or lower were recorded to have a 1.5-fold-higher mortal-ity rate than those who presented with a GCS score of 15 (Table 3). Additional thorax, abdominal, extremity, pelvic, and spinal injuries were more common in adult patients. The median ISS score was significantly (p < 0.001) higher in adult patients than in the pediatric patients (25 vs 21, respectively). Increases in the AIShead score were associ-ated with increases in the risk of death. The mortality risk for patients who presented with an AIShead score of 6 was 55-fold higher than for patients with an AIShead score of 3.

In terms of outcome, the percentage of deaths overall (19.9% vs 16.3%, respectively; p = 0.01) and within 24 hours of admission to the hospital (11.1% vs 9.0%, respec-tively; p = 0.054) was higher in adult patients than in pedi-

atric patients. The multivariable logistic regression analy-sis revealed age of 15 years or younger as a predictor of decreased risk of death (OR 0.585, 95% CI 0.421–0.814; p = 0.001) (Table 3). No motor response and no pupillary re-action to light were associated with a higher mortality risk. Regarding GOS parameters, a good functional outcome (GOS Score 4 or 5) was more likely in pediatric patients than in the adults (72.2% vs 63.1%, respectively), just as survival was (Fig. 1), although cardiopulmonary resuscita-tion (CPR) rates were significantly (p < 0.001) higher in pe-diatric patients than in adults (8.8% vs 5.6%, respectively). Intubation rates did not vary significantly between pediat-ric and adult patients (57.0% vs 60.2%, respectively). The number of days in which ventilator use was required, the number of days in intensive care, and the overall number of in-hospital days were significantly (all p < 0.001) lower in the pediatric patients.

Prehospital shock, defined as a blood pressure of ≤ 90 mm Hg (OR 1.649, 95% CI 1.358–2.002), and prehospi-tal CPR (OR 4.569, 95% CI 3.123–6.685) were associated with an increased mortality risk, whereas the level of the trauma center, air transport, sex, and rate of intubation had no influence on risk of death in the multivariate logistic regression.

The number of patients with a GCS score of 3 who died was higher in the pediatric patients than in the adults (109 [53.4%] vs 1278 [50.7%] patients, respectively). The num-bers of patients with a GCS score of 15 who died were similar between pediatric and adult patients (33 [1.9%] vs 32 [2.1%] patients, respectively). In the middle range of GCS scores, the number of deaths was lower in pediatric patients (Fig. 2). Compared with the GCS scores, the risk of death continuously increased with rising ECS scores. In contrast to the GCS scores, fewer patients were allo-cated to the group of patients with a critical ECS score of 8 (766 adult and 89 pediatric patients). Furthermore, the risk of death in the group of patients with a critical ECS score of 8 was high in both pediatric and adult patients, predominantly in adult (85.0%) and lower in pediatric (80.9%) patients, compared with that in the patients with a critical GCS score of 3 (Fig. 3). The lowest mortality rate

TABLE 1. Definitions and subscores of the ECS*

Element Findings Score/Value

Motor response Normal 0Specific 1Nonspecific 2None 3

Pupil reactivity Brisk 0Sluggish 1Fixed 3

Pupil size Normal 0Anisocoric 1Bilaterally dilated 2

* The ECS is calculated by summing the values of each subscore. Scores are from a minimum of 0 for a patient who shows brisk, reactive, normal-sized pupils and a normal motor response to a maximum of 8 for a patient who presents with fixed and bilaterally dilated pupils and no motor response.




was found in pediatric patients who presented with an ECS score of 0 (1 patient [0.4%]).

DiscussionThe results of this study show that severe TBI in pedi-

atric patients (0–15 years of age) is associated with a lower mortality rate and superior functional outcome compared with adults (16–55 years of age) with severe TBI when they are admitted with a GCS score of 3 and a missing motor response and bilaterally fixed and dilated pupils, respec-tively. However, severe TBI remains a challenging disorder that results in a mortality rate of up to 100% for patients

who present with a GCS score of 3 in combination with bilaterally fixed and dilated pupils.24,28,32 Mortality rates for pediatric patients with severe TBI are reportedly lower than those for adults.5,17,25 However, most studies have fo-cused on either pediatric or adult TBI without allowing a direct comparison between the 2 subgroups. This study was based on a large multicenter data set, which enabled analysis of the clinical course and outcome in different age groups in a comparative way. As a result, the results of this study support those of previous ones, supposing that pedi-atric patients have a superior early functional outcome and lower mortality rate than adults. No GCS motor response in combination with bilaterally fixed and dilated pupils

TABLE 2. Basic study characteristics and demographics*

ParameterValue

Patients Aged ≤15 Yrs Patients Aged 16–55 Yrs

No. of patients 888 9,071Mean age in yrs (SD) 9.24 (4.4) 34.7 (12.2)Male 545 (61.4) 6,975 (76.9)Median ISS (IQR) 21 (13) 25 (14)Blunt trauma 863 (97.2) 8,599 (94.8)Isolated TBI 331 (37.3) 2,298 (25.3)Trauma mechanism Traffic overall 528 (59.5) 5,260 (58) MVC, vehicle 102 (11.5) 2,494 (27.5) MVC, bicycle 146 (16.4) 899 (9.9) MVC, motorbike 38 (4.3) 1,111 (12.2) Pedestrian 227 (25.6) 690 (7.6) High fall (>3 m) 144 (16.2) 1,596 (17.6) Low fall (<3 m) 113 (12.7) 1,056 (11.6) Other 103 (11.6) 1,159 (12.8)Median prehospital GCS score (IQR) 9 (4) 8 (4)GCS score ≤ 8 421 (47.4) 4,562 (50.3)Intubation 506 (57.0) 5,465 (60.2)Mean transportation time from scene to hospital, mins (SD) 62.6 (27.1) 67.0 (28.9)Air transport 361 (40.7) 2,998 (33.1)Prehospital CPR 78 (8.8) 512 (5.6)BP ≤90 mm Hg 186 (20.9) 1,449 (16.0)Mean prehospital HR (SD) 97.4 (31.6) 91.0 (26.3)Mean admission SpO2 (SD) 97.1 (9.2) 96.7 (9.0)Mean resuscitation time in ED, mins (SD) 58.9 (36.7) 66.2 (42.5)Mean time from admission to CT scan, mins (SD) 20.0 (13.2) 20.5 (13.8)Whole-body CT scan 402 (45.3) 5,766 (63.6)CT scan (e.g., head only) 843 (94.9) 8,693 (95.8)Mean length of hospital stay, days (SD) 14.2 (14.0) 19.3 (21.0)Mean ventilator duration, days (SD) 3.9 (6.8) 6.6 (10.1)Mean ICU stay, days (SD) 6.9 (8.8) 10.3 (12.3)Death w/in 24 hrs after admission 80 (9.0) 1,009 (11.1)Deaths during hospital stay 145 (16.3) 1,806 (19.9)Mean RISC II prognosis (SD) 17.7 (29.8) 20.3 (30.4)

BP = blood pressure; ED = emergency department; HR = heart rate; IQR = interquartile range; MVC = motor vehicle collision; SpO2 = arterial oxygen saturation.* Values are numbers (%) of patients unless indicated otherwise.


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(ECS score of 8) was associated with a mortality rate of 85.0% in adults with severe TBI in these prospectively col-lected and retrospectively evaluated data. Reported deaths of pediatric patients with TBI in this study were signifi-cantly lower (80.9%). Although the prognosis for these se-verely injured patients is poor, our findings clearly show a lower mortality rate than that reported by other studies.24,32

Limitations such as the small number of included patients, missing data for various treatment strategies in subgroups, and differences regarding injury severity between children and adults allow for the results to be of only limited sig-nificance.24,32

Furthermore, despite a significantly higher prehospital CPR rate in the pediatric patients than in the adults, this study found a lower pediatric mortality rate and better functional outcome. Nevertheless, this may contribute to the fact that children who suffer a TBI should be resus-citated with maximum efforts. As a consequence of our findings, all patients, especially children, who suffer a severe TBI and present with a GCS score of 3 and bilat-erally fixed and dilated pupils should be treated aggres-sively with adequate allocation of medical resources. This recommendation is in accordance with other studies that described some patients suffering from severe TBI and a GCS score of 3 recovering with a good functional out-come.28

Reliable GCS and ECS evaluations as prognostic tools and monitoring parameters are likely to be biased by prehospital pharmacological paralysis for sedation and intubation, which can result in a loss of 1 or more com-ponents.14,19,34 Hypothermia, severe facial fractures, high spinal cord lesions, previous cataract surgery, and recent ophthalmological examinations might even render reliable score evaluations impossible.11,18,32,33 However, GCS score interpretation was initially defined by analyzing each component alone. Furthermore, it has been shown that be-side the motor component, evaluations of pupil size and reactivity work as stand-alone outcome-prediction tools.19 Therefore, evaluation of a nonaltered subparameter of the GCS or ECS might offer a reasonable prognostic tool.

Regarding the lower mortality rates associated with pediatric TBI, the findings of our study verify the as-sumption that these patients have a better prognosis and lower mortality rate than adults, which is in accordance with other studies.5,17,25 It is surprising that there exist few data concerning this point in the literature. One of the ma-jor studies, by Flaada et al.,13 found that mortality rates within 6 months after TBI increase with increasing age, from 10.3% for patients aged 16 years or younger to 40.3% for patients between 16 and 65 years of age. According to these findings, we also identified a hospital mortality rate for adults (19.9%) that was higher than that of pediatric

TABLE 3. Prediction of death according to stepwise multivariable logistic regression analysis*

Parameter Coefficient OR (95% CI) p Value

ECS motor response <0.001 Normal† 1 <0.001 Specific 0.523 1.687 (1.159–2.455) 0.006 Nonspecific 0.529 1.697 (1.059–2.718) 0.028 None 1.250 3.490 (2.240–5.435) <0.001Pupil reaction to light <0.001 Brisk† 1 <0.001 Sluggish 0.430 1.538 (1.231–1.921) <0.001 Fixed 1.434 4.197 (3.271–5.386) <0.001Pupil size <0.001 Normal† 1 <0.001 Anisocoric 0.121 1.128 (0.908–1.402) 0.276 Bilaterally dilated 1.047 2.848 (2.282–3.556) <0.001GCS score <0.001 15† 1 <0.001 ≤8 0.383 1.466 (1.071–2.006) 0.017AIS score w/o TBI <0.001 0–2 1 <0.001 3 0.57 1.059 (0.874–1.284) 0.559 4 0.457 1.579 (1.257–1.984) <0.001 5 0.888 2.431 (1.741–3.396) <0.001Age <0.001 16–55 yrs (adults)† 1 <0.001 ≤15 yrs (children) –0.536 0.585 (0.421–0.814) 0.001AIShead score <0.001 3† 1 <0.001 4 0.857 2.356 (1.669–3.326) <0.001 5 2.637 13.971 (10.186–19.163) <0.001 6 4.006 54.929 (31.403–96.081) <0.001BP ≤90 mm Hg <0.001 >90 mm Hg† 1 <0.001 <90 mm Hg 0.500 1.649 (1.358–2.002) <0.001Prehospital CPR <0.001 No† 1 <0.001 Yes 1.519 4.569 (3.123–6.685) <0.001Trauma mechanism Other† 1 Traffic overall –0.219 0.803 (0.676–0.954) 0.013

* Hospital level of care, air transport, sex, and rate of intubation had no statis-tically significant impact (data not shown).† Reference category.

FIG. 1. Functional outcomes according to GOS score.




patients with TBI (16.3%) at the time of hospital discharge. It is interesting to note that mortality rates for pediatric patients are higher and for adult patients are lower than those described by Flaada et al.13 but lower than those cal-culated by using the Revised Injury Severity Classification II (RISC II). Age was identified as a RISC II predictor and accounted for a significant difference between pediatric and adult prognoses according to RISC II scores (Table 2).23 To investigate this effect further, a multivariate logis-tic regression analysis was performed; age was identified as an independent predictor of death (Table 3). These di-verging results may be a result of the different definitions of severe TBI, the age spectrum of the included patients (because we excluded patients aged 55 years or older to reduce bias caused by their multicausal higher mortality rates, as shown in the literature), and the use of diverse treatment allocations in different countries.4,13,25 For this reason, we chose to define severe TBI as an AIShead score of ≥ 3.

The association of age and different statistical methods for evaluating the impact of age on outcome in patients with severe TBI was described in detail by Hukkelhoven et al.21 in 2003. Nevertheless, despite the well-conducted study design, their study evaluated only patients 15 years of age or older and thus did not include children. For this reason, we conducted our study to compare the mortality rate and outcome of children and adults while focusing on GCS scores and pupil parameters.

Another relevant study that investigated the impact of age on patients with severe TBI was published in 1988 by

Luerssen et al.25 Likewise, the Flaada et al.13 study and our study revealed a statistically significant difference in the mortality rate between pediatric and adult patients (28.4% vs 47.7%, respectively).25 However, the validity of the find-ings in this study is underlined by the size of the study population, which included almost 10,000 patients.

LimitationsOne of the major limitations of this study is the ret-

rospective evaluation of data, although the data were col-lected prospectively in the TR-DGU. It is well known that databases bear the risk of incomplete or incorrect data, because they are provided from different trauma centers. Studies based on registry databases may have incomplete and incorrect data, which may have affected our results. Patients who died at the scene or were dead on emergen-cy department arrival were excluded from the study and therefore might have biased the study results. In addition, we have no information about the percentage of patients in whom death was associated exclusively with TBI and not other injuries, because we also included patients with mul-tiple injuries; however, severe TBI was the most serious injury according to the AIS score, disregarding the sever-ity of the concomitant injuries.

We also excluded patients who were transferred from one hospital to another to minimize bias related to a pos-sible selection of patients who were transferred from the initial institution to trauma centers that provided data for the TR-DGU. It is interesting to note that a recently pub-

FIG. 3. Left: Percentage of deaths according to ECS score. Right: Distribution of initial ECS scores.

FIG. 2. Left: Percentage of deaths according to GCS score. Right: Distribution of GCS scores.


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lished investigation was unable to demonstrate a correla-tion between death and interhospital transfer in severely injured patients.6

A final limitation is that the TR-DGU data set allows only for the evaluation of functional outcome at discharge and does not provide any data for long-term follow-up.

Nevertheless, we are convinced that our investigation reveals valid and reliable data on mortality rates and out-comes of patients with severe TBI despite the aforemen-tioned limitations.

ConclusionsSevere TBI in pediatric patients (0–15 years of age), in

contrast to severe TBI in adults (16–55 years of age), is associated with a lower mortality rate and superior early functional outcome. Even if pediatric patients with severe TBI are admitted with a missing motor response and bi-laterally fixed and dilated pupils (an ECS score of 8), the mortality rate is lower and early functional outcome is su-perior compared with those in adult patients. Therefore, patients suffering from severe TBI, especially pediatric patients, could benefit from early and aggressive treatment. Although our conclusions are based on solid data and a large study cohort of almost 10,000 patients, further pro-spective randomized trials have yet to prove these findings, conclusions, or especially the recommendation to treat in an aggressive manner all patients with a GCS score of 3 and a missing motor response in combination with bilater-ally fixed and dilated pupils.

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DisclosuresDr. Lefering was paid by the European Journal of Trauma and Emergency for statistical reviews; he is employed by the University of Witten/Herdecke, which has a service agree-ment with the Akademie der Unfallchirurgie (AUC)/German Society for Trauma Surgery for scientific assistance, annual audit reports, etc.; he has received sponsoring from the Deutsche Forschungsgemeinschaft (DFG), the Federal Highway Research Institute of the Federal Republic of Germany (BAST), the Federal Ministry of Education and Research of the Federal Republic of Germany (BMBF), and several other research foundations; and he also received payments for lectures at the KKS Düsseldorf

and Frankfurt, Mibeg, for education in statistics for study nurses, study physicians, and project managers. The TR-DGU is funded by fees from the participating hospitals. AUC GmbH, a 100% affiliate of the German Trauma Society, collects the fees and runs the registry. There is a cooperation-and-service agree-ment between the AUC and University Witten/Herdecke (Dr. Lefering), which covers statistical support for scientific analyses using the registry data.

Author ContributionsConception and design: Czorlich, Emami, Hoffmann. Acquisition of data: Lefering. Analysis and interpretation of data: Czorlich, Emami, Lefering, Hoffmann. Critically revising the article: Czorlich, Emami, Fritzsche, Westphal, Rueger, Hoffmann. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Czorlich. Statistical analysis: Lefering.

Supplemental InformationPrevious PresentationsPortions of this work were presented in poster form at the 15th Interim Meeting of the World Federation of Neurosurgical Societies held in Rome, Italy, on September 8–12, 2015; the 33rd Arbeitstagung NeuroIntensivmedizin, Berlin, Germany, January 28–30, 2016; and the Section Meeting of Neurotrauma and Neurointensive Care Medicine of the German Society of Neurosurgery (DGNC), Innsbruck, Austria, on March 11 and 12, 2016.

CorrespondencePatrick Czorlich, Department of Neurosurgery, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg 20246, Germany. email: [email protected].


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Impact of Glasgow Coma Scale score and pupil parameters on ...€¦ · multicenter cohort study *Pedram Emami, MD,1 Patrick Czorlich, MD,1 Friederike S. Fritzsche, MD, 1 Manfred Westphal,