
==== Front
Eur J Phys Rehabil Med
Eur J Phys Rehabil Med
EJPRM
European Journal of Physical and Rehabilitation Medicine
1973-9087
1973-9095
Edizioni Minerva Medica

38888736
8430
10.23736/S1973-9087.24.08430-2
Article
Survival and predictive factors of clinical outcome in patients with severe acquired brain injury
TYLL Tomáš 1
BUBENÍKOVÁ Adéla 2 3
VOTAVA Jan 1
POCHOP Martin 1
SOTÁK Michal 1 *
1Department of Anesthesiology and Intensive Care, First Faculty of Medicine, Military University Hospital of Prague, Charles University, Prague, Czech Republic; 2Department of Neurosurgery and Neurooncology, First Faculty of Medicine, Military University Hospital of Prague, Charles University, Prague, Czech Republic; 3Department of Neurosurgery, Second Faculty of Medicine, Motol University Hospital of Prague, Charles University, Prague, Czech Republic
* Corresponding author: Michal Soták, Department of Anesthesiology and Intensive Care, First Faculty of Medicine, Military University Hospital of Prague, Charles University, U Vojenské nemocnice 1200, Prague, 169 02, Czech Republic. E-mail: michal.sotak@uvn.cz
Authors’ contributions: Tomáš Tyll was consultant of the study, contributed to data interpretation and wrote the manuscript; Adéla Bubeníková contributed to data analysis and statistics and contributed to data interpretation; Jan Votava and Martin Pochop revised and edited the manuscript critically for important intellectual consent; Michal Soták supervised, edited, prepared and drafted the manuscript. All authors read and approved the final version of the manuscript.

18 6 2024
8 2024
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03 6 2024
16 4 2024
19 1 2024
2024 THE AUTHORS
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND) 4.0 License.
BACKGROUND

Despite the many tools available to modern medicine, predicting the neurological and functional status of patients after severe brain injury remains difficult.

AIM

This analysis evaluates the outcomes of patients with the most severe degree of cerebral function impairment.

DESIGN

Retrospective cohort study.

SETTING

Patients hospitalized in the long-term Intensive Care Unit (ICU) department in the Military University Hospital in Prague between 2015-2022.

POPULATION

We analyzed patients with severe acquired brain damage from five distinct etiologies whose initial Glasgow Coma Scale (GCS) score was eight or less upon admission to ICU due to neurological damage.

METHODS

Several parameters reflecting the patients’ clinical status were evaluated. Overall survival after discharge from the ICU was calculated according to the Kaplan-Meier model with comparison between traumatic (TR) and non-traumatic (non-TR) etiologies.

RESULTS

The analyzed cohort of 221 patients consisted of 116 patients of TR and 105 of non-TR etiology. There was no significant difference in overall survival between TR and non-TR groups. The length of hospitalization in the ICU was similar in both groups with a median of 94 days. The majority of patients had an improvement of GCS during the hospitalization with a median improvement of five points. GCS improvement occurred in the vast majority of patients regardless of TR or non-TR etiology.

CONCLUSIONS

We did not observe a statistically significant difference in mortality or log-term neurological status between patients with severe brain injury of traumatic or non-traumatic etiology for the duration of our follow-up. The majority of patients had improved GCS, were successfully decannulated, but remained disabled with severe limitations of functional independence.

CLINICAL REHABILITATION IMPACT

The return of the patient to normal life is a rehabilitation challenge, regardless of the etiology of brain injury, and is extremely influenced by the level of development of neurorehabilitation programs in individual institutions, the severity of brain injury, and the individual motivation of the patient.

Key words:

Brain injuries
Tracheostomy
Recovery of function
Neurological rehabilitation
Mortality
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pmcSevere acquired brain injury (sABI) refers to any damage to the brain that occurs after birth as a result of a traumatic event, medical condition or other external factor and is characterized by the onset of variably prolonged coma (Glasgow Coma Scale [GCS] <8) with simultaneous motor, sensory, cognitive and/or behavioral impairment.1 There are two main classifications of sABI: traumatic brain injury (TBI), caused by an external force such as a blow to the head, and non-traumatic brain injury, resulting from internal factors like stroke, tumor, or anoxia (lack of oxygen to the brain). TBIs can range from mild, with brief changes in mental status, to severe, causing prolonged unconsciousness or memory loss.2 Non-TBI encompasses a wide range of conditions, including brain tumors, infections, cerebral hemorrhage and toxic-metabolic encephalopathy, each of which presents unique challenges and outcomes.1 Understanding and addressing the specific type and severity of acquired brain injury is essential for proper diagnosis, treatment, and rehabilitation since these conditions are the leading causes of long-term disability worldwide.2-4 Mortality in severely impaired patients might be as high as 44% during acute inpatient care and the vast majority of these mortalities are connected to the withdrawal of life-sustaining therapy.5-8 The longer the disorder of consciousness disturbance persist, the higher risk of permanent cognitive and functional deficits that influence not only the patient, but the whole family.9

While there seems to be a common perception among physicians that functional recovery after severe brain injury is very unfavorable with poor quality of life, many published reports question this with their results showing a relevant number of patients who acquire good, long-term outcomes in terms of regaining good cognitive function, functional independence and mobility.10-13 However, the most important factor in the evaluation of functional recovery in these patients is the time elapsed between the sABI and the time of evaluation. The majority of deaths following withdrawal of life-sustaining therapy occur in the ICU within seven days of brain injury.2, 3, 5 However, a phenomenon of delayed functional recovery (DFR) is of great importance, showing progress in functional recovery for up to six months after injury, mainly reported in cases of TBI,2, 11, 13 and also in severe stroke.3

Despite several studies evaluating DFR in these patients,14, 15 the literature remains sparse and the understanding of the differences in functional outcomes between traumatic and non-traumatic etiology groups remains weak.

This study evaluates survival and functional outcomes in both groups and reviews the differences and determinants of favorable functional outcomes.

Materials and methods

Study population

Patients admitted to the long-term intensive care unit (ICU) department in the Military University Hospital in Prague with TBI, subarachnoid hemorrhage (SAH), acute ischemic stroke, intracerebral hemorrhage (ICH), and anoxic damage over a 7-year period (2015-2022) were included in the database. The inclusion criteria for the analyses were the following: (1) initial GCS ≤ 8 at the admission to intensive care (IC); (2) requiring a tracheostomy due to neurologic disability or impaired consciousness (Figure 1).

Figure 1 —Diagram of patient selection along with the characteristics of exclusion and inclusion criteria.

The minimum length of hospital stay required for inclusion in the study was 12 days. Data collection for the follow-up period was completed from admission to discharge from the IC. The survival data following discharge from the IC were analyzed at 1, 3, and 5-year intervals using the National Health Insurance database. Patients, who received tracheostomy exclusively for respiratory dysfunction with GCS>8 were excluded. Patients discharged from the IC with the absence of follow-up data were also excluded. The study complies with ethics standards.

Parameters evaluated

Several clinical parameters were evaluated to reflect outcome following brain injury. These were the following:

GCS was recorded on admission and on discharge from IC;

classification of Disorders of Consciousness (DoC) (coma, vegetative state, minimally conscious state, locked-in syndrome)16 on discharge from IC;

motor disability (bedridden, able to sit, able to stand, able to walk);

functional independence (evaluated according to the Barthel score);

ability to receive nutrition per os;

successful decannulation rate;

length of hospitalization in the IC;

mortality in the IC and after discharge from the IC;

length of survival after discharge from the IC.

Statistical analysis

The normality of the data was evaluated according to the Shapiro-Wilk’s Test. Differences of categorical variables were standardly evaluated using the Chi-square Test. Comparisons of two continuous variables were calculated using t-tests for independent samples. Multiple intergroup comparisons were performed using Analysis of Variance (ANOVA) with subsequent Fisher Least Significant Difference (LSD) post-hoc testing. Overall survival analysis was analyzed according to the Kaplan-Meier method with P values derived from the log-rank test. All calculations were performed in the open-source R environment using ggplot2 and survminer libraries (v4.1.2, R Core Team (2021). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria, https://www.R-project.org/).

Results

A total of 221 patients with a mean age of 55.87±18.32 years met the inclusion criteria. The median GCS at administration was 5 (IQR=3-6), with no significant difference between TR and non-TR group (P=0.608). Patients of non-TR were older (P<0.001) and males predominated in both groups (P=0.004). Regarding the etiology in the non-TR group was hemorrhagic stroke (27.4%), followed by ischemic stroke (25.9%), sABI of anoxic origin (24.4%) and finally SAH (22.2%). The only primary etiology of brain injury with female predominance was SAH. The length of ICU stay was similar in both groups with a median of 94 days (IQR=52-181, P=0.561). Out of all 221 patients, 209 (94.6%) improved on GCS; the median improvement on GCS during hospitalization was 5 points (IQR=3-8). GCS improvement occurred in the vast majority of patients regardless of TR or non-TR origin (P=0.859). Mortality during ICU stay was higher in the non-TR group (62% of deaths were non-TR, P=0.024), as well as during follow-up (P=0.045). See Table I for detailed demographics of included patients.

Table I —Summary of demographic data of patients included in the study.

	Overall	TR group	non-TR group	P value	
Total, N. (%)	221 (100)	116 (52.49)	105 (47.51)		
Gender	
Female, N. (%)	62 (28.05)	23 (37.10)	39 (62.90)	0.004	
Male, N. (%)	159 (71.95)	93 (58.49)	66 (41.51)	
Age, mean (SD)	55.87±18.32	52.15±19.10	59.97±16.56	0.001	
Initial GCS, median (IQR)	4 (3-6)	4 (3-6)	4 (3-6)	0.608	
Length of ICU stay in days, median (IQR)	94 (52-181)	92 (47-187)	95 (58-152)	0.561	
Barthel Score	
45-65 points, N. (%)	13 (5.94)	4 (30.77)	9 (69.23)	0.113	
<45 points, N. (%)	206 (94.06)	110 (53.40)	96 (46.60)	
GCS at discharge, median (IQR)	11 (8-14)	11 (8-13)	11 (8-14)	0.416	
Improvement at GCS, N. (%)	209 (94.57)	110 (52.63)	99 (47.37)	0.859	
Mortality at ICU, N. (%)	50 (23.81)	19 (38.00)	31 (62.00)	0.024	
Mortality overall, N. (%)	132 (59.73)	62 (46.97)	70 (53.03)	0.045	

The difference in the group of patients who improved their consciousness by communicating coherently and having adequate self-awareness was not statistically significant between the groups (P=0.135). Most of the patients were immobile after the discharge from the ICU. Up to 14% of patients were able to walk with help in both groups (P=0.776). The vast majority of patients remained fed via gastrostomy, while 35% and 38% of patients (P=0.35) managed to recover oral intake of nutrition. Younger age was associated with a higher probability of regaining the ability to walk (P=0.018), reaching successful decannulation (P<0.001), oral intake of nutrition (P<0.001), and overall higher probability of survival (P<0.001). The vast majority of patients remained significantly disabled after discharge from the ICU. Only 3% and 9% of patients in the TR and non-TR group, respectively (P=0.113) reached the maximum of the middle range of dependence (Barthel Score 45-65bb) with a slightly higher number of patients in non-TR group (69.23%). Successful decannulation was achieved in 115 patients (52.27%), with no significant difference between TR and non-TR groups (P=0.435). Otherwise, the common cause of decannulation failure was oropharyngeal dysphagia or airway obstruction above the tracheostomy.

One-year survival was similar to both groups - 82.60% (95% CI, 74.68-91.40%) for the TR group, and 84.60% (95% CI, 75.09-95.30%) for the non-TR group. Survival at five years was 33.20% (95% CI, 22.53-49.00%) for the TR group and 40.86% (95% CI, 26.61-62.70%) for the non-TR group. The anoxic origin of sABI had the highest prevalence of non-survivals (78.8%, P=0.040).

See Figure 2 and Table II for detailed survival probabilities during follow-up.

Figure 2 —Kaplan-Meier curve for overall survival of included patients when divided into TR and non-TR groups (P=0.951).

Table II —Overview of survival probabilities for TR and non-TR groups at several endpoints during follow-up period (6-months, 1-, 3-, and 5-years).

	TR	non-TR	
6 months	86.00% (95% CI, 78.97-93.6%)	94.00% (95% CI,88.62-99.70%)	
1 year	82.60% (95% CI, 74.68-91.40%)	84.60% (95% CI, 75.09-95.30%)	
3 years	60.20% (95% CI, 48.92-74.10%)	66.91% (95% CI, 53.49-83.70%)	
5 years	33.20% (95% CI, 22.53-49.00%)	41.27% (95% CI, 26.94-63.20%)	

Discussion

This study evaluated the survival and clinical outcome differences of sABI with both non-TR and TR etiologies. Until now, there has been a limited amount of data in the literature regarding the long-term outcome of patients with severe brain injury. Nevertheless, this study focused particularly on the functional outcome of patients who were successfully discharged from ICU. Among patients with severe brain injury with GCS≤8 at admission to ICU and, requiring tracheostomy, 52.27% were successfully decannulated, and 14% of the included patients had regained the ability to walk within the mean follow-up time of 18 months. In addition, up to 38.46% of patients were able to either sit, stand and/or walk. As proposed in the study by Wabl et al. in 20183 who found no statistically significant differences between TR and non-TR etiologies, we found similar outcome as we did not find any significant difference in survival between TR and non-TR groups (P=0.951). There are several things to consider in this regard. First, differences between sABI groups may become more apparent over the long term. Secondarily, there is an underlying heterogeneity regarding both sample sizes and included sABI etiologies among studies, making a clear distinction harder to conclude.17, 18

Clinical outcomes

In our study, successful decannulation was achieved in the majority of patients (52.27%) which is in line with previously published data on the topic. Generally, factors that are associated with a higher probability of successful decannulation are the absence of pulmonary infections (P<0.001), sepsis (P=0.001), or tracheal alteration during fibrobronchoscopy (P=0.004) in addition to better neurological status at admission (P=0.001) as proposed by recent study evaluating patients with a mean initial GCS of 10.2±3.7 points after tracheostomy following the brain injury.19 While we did not find any significant correlation between successful decannulation rate and initial GCS (P=0.965), it is worth noting that we studied a specific group of patients which had a lower probability of successful decannulation than those with higher GCS. Similar findings to ours were reported in similar populations of patients with a GCS below eight points. In addition, diabetes, craniotomy, acute kidney injury, greater age, days spent on mechanical ventilation, reintubation or aspiration are associated with higher risk of decannulation failure.20

Regaining of normal gait after either TR or non-TR brain injury is very challenging and is influenced by the level of development of neurorehabilitation programs in individual institutes, the type of brain injury and the patient’s individual motivation.21, 22 In the current study, only 14% of included patients had regained the ability to walk, which is a number supported by similar results previously published.17 While another study has reported recovery of gait in up to 50% of patients in a three-year follow-up.3 These rates are highly individual not only among cohorts, but also among individual patients. The majority of providers caring for patients with TBI and cerebrovascular diseases including stroke in the ICU support rehabilitation efforts, but the extent and type of neurorehabilitation program differ and thus outcomes are hardly comparable between studies. Moreover, most rehabilitation studies focus on severe TBI and stroke23 but more detailed guidelines are lacking for the evaluation of mild TBI cohorts, older populations and non-TR brain injury etiologies. Such guidelines, with an emphasis on continuity of care and peer-support help to decision-making and improve standardization of care among neurorehabilitation programs.24

In terms of consciousness and cognitive improvement, we noted that the vast majority of analyzed patient had improved GCS median improvement during hospitalization of 5 points (IQR=3-8). Factors that influence recovery consciousness were evaluated recently in one of the most robust publications on the topic constituting 17,470 analyzed patients with TBI.2 These included the absence of intraventricular hemorrhage (P=0.002) and intracranial mass effect (P=0.030). Up to 40% of patients in this study became partially or fully independent, which is in line with our results regardless of TR or non-TR brain injury etiology. Moreover, younger age, male sex, and absence of intraventricular hemorrhage, intracranial mass effect, and subcortical contusion were associated with better functional outcome, which has also been found in non-TR groups.2, 3

Strengths and limitations of the study

Since we included patients with five unique etiologies of sABI, the results provided have a broad clinical applicability. While other publications studied only one or two etiologies without proper comparison, we tried to define differences and similarities between TR and non-TR groups which are of great clinical importance. The main limitation of our study is the retrospective nature of the functional outcome assessment, along with the limited assessments of clinical outcome. We studied the ability to walk, the process of achieving improve state of consciousness state and functional independence, which we supported by evaluation using the Barther score. However, we did not study parameters evaluating cognitive function or subjective evaluation of quality of life which are important factors influencing overall clinical and neuropsychological performance.9, 25, 26 The retrospective nature of our study also caused absence of potentially interesting findings regarding outcome prediction in sABI as we could not obtain enough high-quality data. In addition, some studies have suggested that there is a potential risk of a floor effect in the Barthel Score when used in patients with sABI compared with other scales.27 However, it is important to note that the results of studies on this topic are not consistent. While some authors recommend using Early Functional Assessment and Functional Independence Measure (FIM),28 others have found no significant difference between the Barthel Score and FIM.29 Secondarily, we did not study clinical outcomes of our population in a longer follow-up which may create a bias in interpretation of the study’s results and their potential application in towards a more accurate assessment of delayed functional recovery.

Implications of future research

Future larger prospective studies are needed for detailed elucidation of long-term and delayed clinical outcomes in patients with sABI. Clinical trials studying the need for tracheostomy in patients with severe brain injury and its influence on long term outcomes may provide insights useful in establishing guidelines for the ideal timing of the procedure based in individual patient factors, especially in mechanically ventilated stroke patients. Additionally, prospective studies evaluating not only objective clinical outcome measures, but also subjective evaluation of quality of life might be of great importance improving individualized decision-making in these patients since there is a known long-term negative impact of reduced cognitive and communication function on daily life following injury.30 Studies designed to determine optimal timing, intensity, and patient selection for early rehabilitation in order to provide higher likelihood of earlier mobilization, including evaluation of target challenges returning to work, physical, emotional and behavioral function might be of great clinical importance.31 Finally, application of virtual reality and artificial intelligence (AI) methods could be of help in enhancing patient recovery.32-34

Conclusions

In patients with severe acquired brain damage who, due to a persistent disorder of consciousness (GCS 8 or less), required tracheostomy and were admitted to long-term intensive care, we did not observe better neurological nor functional outcomes among patients with a traumatic etiology brain injury when compared to those with a non-traumatic etiology. While the traumatic etiology group had a lower mortality rate in hospital as well as after discharge, this group was on average significantly younger, and the difference in mortality was not statistically significant. Patients of both groups however were discharged from IC with persisting severe disabled per os nutritional intake, mobility and functional independence.

Conflicts of interest: The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.

Funding: The article was supported by Military University Hospital Grant MO1012.
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