In 2010, over 56,000 deaths in the USA and 57,000 in the European Union were related to traumatic brain injury (TBI) [
TBI not only causes mortality, but can also lead to severe functional impairment. Unresponsive wakefulness syndrome (UWS) is a dreaded outcome, in which the patient does not demonstrate any sign of consciousness [
The Ethicus study [
Therefore, the aim of this study was to investigate WLST rates in patients with moderate to severe isolated TBI and to assess outcome data of the survivors.
A local institutional review board (IRB) waiver was formally obtained.
A retrospective cohort study was conducted including all consecutive patients who sustained isolated moderate or severe traumatic brain injury and were admitted to ICU of the University Medical Center Utrecht (UMCU, a level-1 trauma center) between 2011 and 2015. Isolated moderate or severe brain injury was defined as an Abbreviated Injury Score head & neck (AIShead) of more than three and no significant injury in other regions (defined as AIS of more than two). Patients under 18 years of age, patients with isolated spinal injury without TBI, and referrals to and from other hospitals were excluded. If first CT head showed only subdural and/or parenchymal hemorrhage, patients’ records were checked and patients were excluded from analysis, if there was any doubt on whether the brain injury was the consequence or the cause of trauma.
Patients who passed away without WLST were only analyzed for cause of death. This decision was based on the hypothesis that this excluded group will be relatively small, and our main interest was in WLST.
Data were collected from medical records and the local trauma database. This database includes several baseline characteristics such as age, sex, ISS, and the AIS of the head region. The trauma mechanism was collected from the medical records. Collected variables included: the Glasgow Coma Scale (GCS) as assessed by the neurologist during the primary survey; pupillary light reflexes and corneal reflexes during primary survey; the need for sedation before arrival or during the stay in the Emergency Department (ED), the concurrent use of a low molecular weight heparin (LMWH); and coumarin or a novel oral anticoagulant (NOAC).
The Charlson Comorbidity Index score was calculated for every patient. This is a widely used score for comorbidity, which comprises 22 comorbidities and each is assigned a weight, according to its impact on the prognosis of the patient [
In each patient, a noncontrast CT of the head was acquired within 30 minutes after arrival to ED. An experienced neuroradiologist, blinded to the outcome data, revaluated the CT in every patient for the presence of epidural, subdural and/or subarachnoid hemorrhage, compression of the basal cisterns, and midline shift retrospectively.
Cause of death and WLST data were collected from the medical records. For patients who received WLST, length of stay in ICU was noted. Functional outcome data, measured by the Glasgow Outcome Scale (GOS), were collected at three months (+one month) from records of outpatient clinic visits or correspondence from a neurological rehabilitation center. In case of missing data at three months, the first available GOS was used. If this was before three months’ time, it was assessed with the three-month follow-up data, since further deterioration was not expected. If follow-up data were only available after the four-month mark, they were separately analyzed. The GOS allows for objective assessment of the recovery of patients with brain damage in five categories [
All statistical analyses were performed using IBM SPSS Statistics, version 21.0.0 (Armonk, NY, USA). Group differences between survivors and patients who died due to WLST were calculated using a Mann–Whitney U test in case of continuous, nonnormally distributed, variables. In case of a different shape of distributions in each group, mean ranks were compared for analysis of significant differences between groups, and medians were only shown. Differences in distribution of categorical or ordinal variables between groups were calculated with the chi-square test of homogeneity. Fisher’s exact test instead of a chi-square test was used if the expected cell count was less than five. Statistical significance was defined as
The search in the trauma registry generated a total of 367 patients with isolated moderate or severe TBI admitted between 2011 and 2015 to the ICU. After applying our exclusion criteria, 179 patients were included in this study (Figure
Baseline characteristics and mortality.
Variable | All patients ( |
WLST ( |
Non-WLST ( |
|
---|---|---|---|---|
Mortality, |
55 (33) | 100 (45) | 0 | |
Median age in years (IQR) | 57 (32.5) | 67 (22) | 54 (35.25) | |
Mean rank age | n/a | 114.56 | 74.27 | <0.001 |
Median ISS (IQR) | 20 (9) | 25 (9) | 20 (9) | 0.01 |
Median AIShead (IQR) | 4 (1) | 5 (1) | 4 (1) | |
Mean rank AIShead | n/a | 108.47 | 76.48 | <0.001 |
Female, |
62 (37) | 16 (36) | 46 (37) | 0.854 |
Trauma mechanism, |
0.061 | |||
Fall stairs or height | 53 (32) | 19 (44) | 34 (28) | |
Fall low height/collaps or nos | 15 (24) | 8 (19) | 16 (13) | |
Traffic accident: two wheels | 60 (36) | 11 (26) | 49 (41) | |
Traffic accident: car | 12 (7) | 1 (2) | 11 (10) | |
Traffic accident: pedestrian | 4 (2) | 1 (2) | 3 (3) | |
Hit by subject | 6 (4) | 0 (0) | 6 (5) | |
Penetrating injury | 3 (2) | 2 (5) | 1 (1) | |
Hanging | 2 (1) | 1 (2) | 1 (1) | |
Missing | 5(3) | 2 (4) | 3 (2) | |
Charlson Comorbidity Index (IQR) | ||||
Median | 0 (1) | 0 (1) | ||
Mean rank | 88.37 | 81.23 | 0.302 | |
Anticoagulant users, |
||||
None or platelet aggregation inhibitors | 32 (82) | 116 (94) | 0.043 | |
Coumarins/heparines/NOAC | 7 (18) | 7 (6) | ||
Missing | 6 (13) | 1 (1) | ||
GCS in ED (IQR) | ||||
Median | 7 (8) | 8.5 (5) | ||
Mean rank | 47.54 | 64.51 | 0.030 | |
Sedated, |
20 (44) | 28 (23) | ||
Motor score in ED (IQR) | ||||
Median | 5 (4) | 5 (1) | 0.009 | |
Missing, |
20 (44) | 28 (23) | ||
Pupil reflexes in ED, |
||||
None or one eye | 21 (50) | 17 (15) | <0.001 | |
Both eyes | 21 (50) | 96 (85) | ||
Missing | 3 (7) | 11 (9) | ||
Corneal reflexes in ED, |
||||
None or one eye | 11 (58) | 4 (17) | 0.009 | |
Both eyes | 8 (42) | 20 (83) | ||
Missing | 26 (58) | 100 (81) | ||
Sedation, |
20 (44) | 28 (23) | 0.005 | |
Signs on first CT scan, |
||||
Epidural hemorrhage | 17 (38) | 42 (34) | 0.716 | |
Subdural hemorrhage | 43 (96) | 93 (75) | 0.004 | |
Subarachnoidal hemorrhage | 39 (87) | 91 (74) | 0.097 | |
Compression basal cisterns | 34 (76) | 52 (42) | <0.001 | |
Midline shift | 25 (56) | 33 (27) | 0.001 |
WLST: withdrawal of life-sustaining treatment; AIShead: Abbreviated Injury Score of the head region.
Flowchart of inclusion process. TBI: traumatic brain injury; WLST: withdrawal of life-sustaining treatment.
Patients for whom WLST was initiated were significantly older and had a median AIShead of five, whereas the AIShead of the non-WLST patients was four (
Forty five patients (82%) died following the decision to withdraw life-sustaining treatment. The decision to withdraw life-sustaining treatment was made on the day of admission in 18 cases (40%). In 33% (
10 (22%) of the WLST patients and 13 (10%) of the non-WLST patients received an ICP meter (
Neurosurgery and ICP meter.
Neurosurgery variables | WLST, |
Non-WLST, |
|
---|---|---|---|
Received ICP meter, |
10 (22) | 13 (10) | 0.049 |
Underwent neurosurgical decompression, |
17 (38) | 48 (39) | 0.912 |
WLST: withdrawal of life-sustaining treatment; ICP: intracranial pressure.
Median length of stay in ICU before the decision to withdraw life-sustaining treatment was made for patients who received WLST after the first day was 4 days. Of these 27 patients, 12 (44%) suffered from a systemic complication at some point during their admission. In 50% (
ICU parameters for patients who did not receive WLST on the first day.
ICU variables | WLST, |
Non-WLST, |
---|---|---|
Median length of stay in ICU in days (IQR) | 4 (5) | 3 (5) |
Median length of stay in hospital in days (IQR) | n/a | 17.5 (21.75) |
WLST following systemic complications |
|
n/a |
WLST: withdrawal of life-sustaining treatment; n/a: not applicable.
In-hospital mortality as a result of complications occurred in six patients (11%). In two patients, these complications were cardiovascular: These patients died due to a cardiac arrest. Two patients died due to respiratory insufficiency, and one due to a fever in combination with the TBI. One patient had a fever, complicated by respiratory insufficiency, anuria, and diarrhea. This patient had several comorbidities. Four patients (7%) progressed to death by neurological criteria (Figure
None of our patients were discharged to a hospice, since death was expected to follow relatively quickly after the decision to withdraw life-sustaining care.
71% (
GOS score and destination after discharge of the survivor group. The GOS score at three to four months or less of patients who were alive at discharge, expressed in percentage per GOS score.
Glasgow Outcome Scale | Patients assessed at three months, |
Patients assessed after three months, |
All assessed patients, |
Discharged to | Patients, |
---|---|---|---|---|---|
1 | 1 (1) | 0 (0) | 1 (0) | Home | 50 (40) |
2 | 0 (0) | 0 (0) | 0 (0) | Rehab | 69 (56) |
3 | 31 (31) | 0 (0) | 31 (28) | Home against medical advice | 3 (2) |
4 | 52 (51) | 5 (56) | 57 (52) | ||
5 | 17 (17) | 4 (44) | 21 (19) | Psychiatry ward | 2 (2) |
Missing | 23 (19) | 14 (61) | 14 (11) | 0 (0) |
The individual values are rounded to the nearest percent and may not total 100%. Score 1 is defined as death and score 2 is unresponsive wakefulness syndrome. Score 3 is defined as severe injury with permanent need for help with daily living, and score 4 is moderate disability; no need for assistance in everyday life, employment is possible, but may require special equipment. When a patient scores a 5, he or she has only minor deficits in the physical, social, or psychological domain [
We have performed a single-center retrospective analysis on mortality rates, causes of death, WLST, and neurological outcome in patients who were admitted to the ICU with isolated moderate or severe TBI. The mortality rate was 33%, which is comparable to that found in other developed countries (30–40%) [
There are only four studies that have published rates of WLST in this group of patients. In-hospital mortality rates amongst patients with moderate to severe TBI varied between 10.8% and 44.1%, whilst the WLST rates ranged between 45.0% and 86.6% in these studies: likely due to geographical and cultural differences [
Our WLST rates are at the higher end of the spectrum, when compared to the aforementioned studies; however, they are in range with the earlier published Dutch data [
Patient wishes were always taken into account. If medical practitioners believe there is no chance of a decent outcome, they will inform the family that medical treatment would be futile. There are no cases in our database where families have doubted or opposed this statement. Unfortunately, due to the retrospective nature of our study, we are not able to trace preexistent patient documents, which might have influenced the decision.
WLST can be appropriate after severe traumatic brain injury to prevent a patient from staying alive at the cost of being left in a state of disability that might be against his or her wishes. However, WLST should not deny patients their chance of a good recovery. Numerous studies have identified several factors with a predictive relationship with outcome after TBI. So far, no model has proven to be perfect, but two widely used prognostication models are the IMPACT score and the CRASH score [
In our study, the decision to withdraw life-sustaining treatment was made in the very acute stage of the disease. Our findings are similar to those of Turgeon et al. [
The Neurocritical Care Society therefore suggests delaying withdrawal of treatment and treatment limitations for at least 72 hours in cases of devastating brain injury to give the patient the chance to recover and reduce the risk of prematurely forgoing treatments that could provide clinical benefit [
In addition, the amount of patients who received ICP monitoring was relatively low, when compared to other studies [
This study has several limitations. Firstly, due to the retrospective nature of this study, we encountered several missing data. One example is the agent and dosage used to sedate the patient. Therefore, we were only able to tell whether the patient was sedated before completion of the primary survey and not if and how this could have affected prognosis. The most important of missing data is that the GOS was not available for all of our patients. Furthermore, at the three-month mark, many patients were still in rehabilitation clinics, but expected to be able to return to an independent life. As such, there is a broad range of neurological outcomes amongst those with a GOS of three, ranging from patients requiring a tracheostomy to those who are on the verge of discharge from the rehabilitation clinic. Patients are not likely to have made their full recovery yet at three months; however, most follow-up data were available until three months. Therefore, future research including a longer follow-up period of these patients is necessary to determine the definite neurological outcome. Using the eight-point GOS scale (the extended GOS) can also specify functional outcome even more and has been recommended in the literature [
The vast majority of in-hospital deaths after moderate or severe TBI occur following a decision to withdraw life-sustaining treatments. Functional outcome of TBI survivors is generally good.
The data from the medical records used to support the findings of this study are restricted by the Medisch Ethische Toetsingscommissie (Medical Ethical Committee) in order to protect patient privacy. Pseudonymized data are available from the corresponding author for researchers who meet the criteria for access to confidential data.
The authors declare that they have no conflicts of interest.