Outcomes of Patients with Severe Traumatic Brain Injury Who Have Glasgow Coma Scale Scores of 3 or 4 and Are Over 65 Years Old

Abstract

The goal of this study was to investigate the outcomes of patients with traumatic brain injury (TBI) who had Glasgow Coma Scale (GCS) scores of 3 or 4, and were aged 66 years or older. Between January 2001 and December 2005, 13 European centers enrolled patients with severe brain trauma. Data sets of all patients who had a GCS score of 3 or 4 and were 66 years of age or older were analyzed. Outcomes were classified according to the Glasgow Outcome Scale (GOS) 12 months post-trauma as “favorable” (GOS score of 4 or 5), or “unfavorable“ (GOS score of 1–3); relevant data for patients of the two groups were compared. Variables were analyzed by univariate analyses (chi-square, Wilcoxon-Mann-Whitney, and Fisher's exact tests), and a p value of <0.05 was considered significant. We analyzed 100 patients identified from the database as having GCS scores of 3 or 4 and age over 65 years. Factors having significant effects on outcomes were worse results of the Injury Severity Score (ISS), Trauma and Injury Severity Score (TRISS), and Abbreviated Injury Scale (AIS) for the head. Closed or partially closed basal cisterns and/or midline shift >15 mm were also associated with unfavorable outcomes, as was subarachnoid hemorrhage (SAH). Patients with GCS scores of 3 or 4 who are older than 65 years have a poor, but not hopeless, prognosis. Confirmed factors predicting poor prognosis for this group of patients were closed basal cisterns and midline shift >15 mm on the first CT scan. Factors possibly related to favorable outcomes were female gender, lower trauma severity, open or partially open basal cisterns, and no midline shift on the first CT scan.

Introduction

T raumatic brain injury (TBI) has been called “the silent epidemic” (Pascrell, 2001). It has been estimated that TBI accounts for one million hospital admissions in the European Union (EU) each year (Hyder et al., 2007). During the last 10 years, the International Neurotrauma Research Organization (INRO) has coordinated projects in different European countries. An EU-funded project in the Balkan countries addressed issues of TBI guidelines and their implementation, and subsequent development of national policies. Another project was done in Austria (Leitgeb et al., 2007; Lenartova et al., 2007; Mauritz et al., 2007; Rosso et al., 2007; Rusnak et al., 2007a, 2007b), and smaller projects included centers from Slovakia. Purely observational data were collected for all of these projects, and the same database was used everywhere. Thus the INRO now has data for over 1000 patients with severe TBI that have already been used for various analyses (Mauritz et al., 2009).

Glasgow Coma Scale score (GCS) and age are important prognostic indicators in patients with severe TBI (Hukkelhoven et al., 2003; Maas et al., 2007a). In all trials that were designed to investigate the effects of new medications for the treatment of severe TBI, patients aged over 65 years, as well as patients who had GCS scores <5, were excluded (Guha, 2004; Slieker et al., 2008). There are some observational studies that concluded that age over 65 years and GCS scores of 3 or 4 are both associated with poor outcomes (Tokutomi et al., 2008; Utomo et al., 2009). To the best of our knowledge no study has investigated older patients who have poor GCS scores. The traditional belief seems to be that these patients have a hopeless prognosis. A quick search of our database, however, revealed that we had some survivors with favorable outcomes who were aged 66 years and older, and who had initial GCS scores of 3 or 4.

The goal of this study was to identify patients aged 66 years or older who had initial GCS scores of 3 or 4, and to compare those who had achieved favorable outcomes to those who had had unfavorable outcomes, and to identify factors that may have contributed to these outcomes.

Methods

The data for this study were collected prospectively in 13 centers located in Austria, Bosnia and Herzegovina, Croatia, Macedonia, and Slovakia. All centers were of tertiary care level; they included six university departments of neurosurgery (Graz, Osijek, Rijeka, Sarajevo, Skopje, and Zagreb), five large city hospitals (Banska Bystrica, Klagenfurt, Martin, Michalovce, and Salzburg), one Center for neurosurgery and neurology (Linz), and one free-standing trauma center (Vienna). The data were collected between January 2001 and December 2005, but none of the centers enrolled patients for more than 3 years. This reflects the fact that the centers collected data for different projects.

Inclusion criteria

Patients were included if they had “severe TBI” according to the criteria defined by the U.S. National Traumatic Coma Database (Marshall et al., 1983), such as a GCS score of 8 or less.

Treatment process

Treatment in the field was provided by emergency physicians or paramedics. All patients had a rapid examination, which included documentation of vital signs (GCS score, pupillary status, blood pressure, heart rate, and oxygen saturation). Rapid sequence intubation, ventilation, treatment of hemorrhage, and fluid resuscitation were done as appropriate. Each patient was again examined by the local trauma team (surgeons, anesthesiologists, and/or neurosurgeons) upon admission to the study center, and a computed tomography (CT) scan was done as soon as possible. The patients then underwent surgery as appropriate and/or were admitted to the intensive care unit (ICU). The whole treatment process in each center was supposed to be based on the guidelines for the management of patients with severe TBI published by the Brain Trauma Foundation (Bullock et al., 1996), and introduced at the start of the project in each center.

Data collection was done using the International Traumatic Coma Project (ITCP) database (Rusnak et al., 2007a). This database allowed for data collection over the Internet; it recorded basic demographic data of the patient, cause and location of trauma, pre-hospital status and treatment, mechanism and severity of trauma, results of CT scans, results of lab testing, and data on surgical procedures and outcomes. Pre-hospital data were recorded by paramedics and included in the patient files by local researchers. The GCS score was taken prior to analgesia, sedation, or intubation. Information on status and treatment was recorded in detail for the first 10 days. In addition, data on the duration of various treatments, on complications, and on outcomes were collected at discharge from the ICU. Information on status and location were recorded at 3, 6, and 12 months post-injury. In most centers data were collected by a local researcher. In the Austrian centers the data were extracted from the records by a single researcher who visited the centers at regular intervals. Personal data protection was maintained, and the identifiers were kept separately from the data.

Data analysis

Data sets of all patients who were aged 66 years and older, and who had initial (pre-hospital) GCS scores of 3 or 4, were selected for this analysis. According to the Glasgow Outcome Scale (GOS) score at 12 months after trauma, the patients were assigned to two groups: patients with a GOS score of 4 or 5 were classified as having a “favorable outcome,” and patients with a GOS score of 1–3 were classified as having an “unfavorable outcome.” Demographic data (e.g., age, gender, and trauma mechanism), data on trauma severity (e.g., Abbreviated Injury Scale [AIS] score, and Injury Severity Score [ISS]), probability of survival (Ps, calculated by the Trauma and Injury Severity Score [TRISS] method; Boyd et al., 1987), characteristics of the first CT scan, data on treatment (e.g., pre-hospital resuscitation and surgery), and data on outcomes were retrieved from the ITCP files. Data from the “favorable” group of patients were then compared to those from the “unfavorable” group.

Statistical methods

Statistical analysis was performed with the open source statistical package “R” (Dessau and Pipper, 2008). We did univariate analyses to identify differences between the two groups of patients using the chi-square test, Wilcoxon-Mann-Whitney two-sample rank sum test, and Fisher's exact test, as appropriate. We also did multivariate analyses, including those factors that contributed to favorable outcomes in the univariate analyses, but due to the low number of patients with favorable outcomes, we were unable to create valid models for multivariate analyses, and logistic regressions could therefore not be calculated. Quantitative data are presented as median range or as proportions. A p value of <0.05 was considered statistically significant.

Results

A total of 1172 patient records were available for analysis. Of these, 231 were aged 66 years or older, and 485 had an initial GCS score of 3 or 4. We identified 100 patients (8.5%) who fulfilled both criteria (age > 65 years and poor GCS scores). Out of this 100, seventy-six died at the ICU (76%, all “unfavorable”), and 24 were discharged alive from the ICU (24%; 11 “favorable” and 13 “unfavorable” patients). At 12 months after trauma, 20 patients (20%) were still alive; 11 of them had favorable outcomes (11%), and 9 had unfavorable outcomes (9%). Relevant data for the 11 “favorable” patients were compared to those for the 89 “unfavorable” patients.

In the group of 100 patients, significantly more (71%) had a GCS score of 3, than a GCS score of 4 (29%). Of those patients that had a GCS score of 4, 27 had a Motor score of 2 (“Extension to pain”), and 2 had an Eye score of 2 (“Opening to pain”).

Out of 100 patients, 29 were female and 71 male, and we found an effect of gender upon outcomes: 21% of the female, but only 7% of the male patients had favorable outcomes. Age had no significant effect on outcomes in this group. Mean age was slightly higher in the group with unfavorable outcomes (74.8 versus 73.6 years), but this was not significant. The oldest survivor was 88 years old. With regard to trauma mechanisms, none of the patients with injuries due to assault, gunshot, fall from more than 3 meters of height, or bicycle or motorcycle accident had a favorable outcome.

Data on trauma severity are presented in Table 1. ISS was significantly lower in patients with favorable outcomes. Only one of the patients with favorable outcomes had an AIS “head” score >4, whereas half of the patients with unfavorable outcomes had an AIS “head” score of 5, and 11% had an AIS “head” score of 6. None of the patients with an ISS score of 41 or more achieved a favorable outcome. With regard to additional injuries there were no significant differences between the groups.

Table 1.

Gender and Trauma Severity of the Patients from Both Groups (Favorable or Unfavorable Long-Term Outcome), as Defined by Injury Severity Score (ISS), Trauma and Injury Severity Score (TRISS), and Abbreviated Injury Scale (AIS) Score ^a

		Long Term outcome
		Favorable			Unfavorable
		GCS 3 (n)	GCS 4 (n)	total GCS 3 and 4 n (%)	GCS 3 (n)	GCS 4 (n)	Total GCS 3 and 4 n (%)	Favorable versus unfavorable difference
Gender	Female	3	3	6 (54)	16	17	23 (26)	n.s.
	Male	4	1	5 (46)	48	18	66 (74)	n.s.
Total patients		7	4	11 (100)	64	25	89 (100)
ISS median		20	16	20	25	26	26	p < 0.05
TRISS median		25	56	38	18	37.5	23	p < 0.05
AIS head median		4	4	4	5	5	5	p < 0.05
AIS head	<4	0	1	1 (9)	4	2	6 (7)	n.s.
	4	6	3	9 (82)	22	7	29 (33)	p < 0.05
	5	1	0	1 (9)	30	14	44 (49)	p < 0.05
	6	0	0	0	8	2	10 (11)	n.s.
No. of additional regions injured	0	6	4	10 (91)	48	19	67 (75)	n.s.
	1	0	0	0	7	4	11 (12)	n.s.
	2	0	0	0	6	2	8 (9)	n.s.
	3	1	0	1 (9)	3	0	3 (3)	n.s.
Total patients		7	4	11 (100)	64	25	89 (100)

Injuries to region “external” not included in statistics.

GCS, Glasgow Coma Scale score; n.s., not significant.

With regard to pre-hospital status, mean values for first breathing rate, first heart rate, and lowest systolic blood pressure, were not significantly different between the groups. However, none of the patients with an initial breathing rate <6/min had a favorable outcome. Pre-hospital hypoxia (defined as oxygen saturation <90%) was more frequently observed in patients with unfavorable outcome (36% versus 27%).

Table 2 gives relevant results from the first CT scans. No patient with basal cisterns classified as “closed,” and no patient with a midline shift >15 mm on the first CT scan had a favorable outcome. With regard to intracranial pathology, patients with unfavorable outcomes had the more severe lesions; 66% of patients with unfavorable outcomes had subdural hematoma as the main diagnosis on the first CT scan, and 13% had intraventricular hemorrhage, which was the second most common main diagnosis for this group. For the group of patients with favorable outcomes, 55% had subdural hematoma and 27% had subarachnoid hemorrhage (SAH) as the main diagnosis. Significantly more patients with favorable outcomes had SAH than those with unfavorable outcomes. Having SAH as a main diagnosis was therefore a predictor of good prognosis.

Table 2.

Results of the First CT Scan of the Patients from Both Groups

		Long-term outcome
		Favorable			Unfavorable
		GCS 3 (n)	GCS 4 (n)	Total GCS 3 and 4 n (%)	GCS 3 n (%)	GCS 4 n (%)	Total GCS 3 and 4 n (%)	Favorable versus unfavorable difference
Basal cisterns	Closed	0	0	0	20	6	26 (29)	n.s.
	Open	5	1	6 (55)	21	3	24 (27)	n.s.
	Partially open	2	2	4 (36)	14	8	22 (25)	n.s.
	Missing data	0	1	1 (9)	9	8	17 (19)
	Total patients	7	4	11 (100)	64	25	89 (100)
Midline shift	<0.5 cm	1	0	1 (9)	6	3	9 (10)	n.s.
	0.5–1.5 cm	2	3	5 (45)	29	6	35 (39)	n.s.
	≥1.5 cm	0	0	0	9	5	14 (16)	n.s.
	No shift	4	0	4 (36)	9	2	11 (12)	n.s.
	Missing data	0	1	1 (9)	11	9	20 (22)
	Total patients	7	4	11 (100)	64	25	89 (100)
Main diagnosis	Contusion	0	1	1 (9)	6	3	9 (10)	n.s.
	EDH	0	1	1 (9)	5	0	5 (6)	n.s.
	IVH	0	0	0	6	6	12 (13)	n.s.
	SAH	3	0	3 (27)	2	0	2 (2)	p < 0.01
	SDH	4	2	6 (55)	43	16	59 (66)	n.s.
	unknown	0	0	0	1	0	1 (1)	n.s.
	normal CT	0	0	0	1	0	1 (1)	n.s.
	Total patients	7	4	11 (100)	64	25	89 (100)

CT, computed tomography; EDH, epidural hematoma; IVH, intraventricular hemorrhage; SAH, subarachnoid hemorrhage; SDH, subdural hematoma; n.s., not significant; GCS, Glasgow Coma Scale score.

Treatment factors are presented in Table 3. Patients with favorable outcomes were more frequently transported by helicopter to the treatment center. They also had a higher rate of intracranial pressure (ICP) monitoring, and had a higher rate of cranial surgery. Patients with unfavorable outcomes received higher doses of mannitol during the first 48 h in the ICU (382 versus 244 mL). However, neither of these differences was statistically significant.

Table 3.

Management of Patients during the First 10 Days after Trauma

	Long-term outcome
	Favorable			Unfavorable
	GCS 3 (n)	GCS 4 (n)	Total GCS 3 and 4 n (%)	GCS 3 (n)	GCS 4 (n)	Total GCS 3 and 4 n (%)	Favorable versus unfavorable difference
	7	4	11 (100)	64	25	89 (100)
Transport by helicopter	1	1	2 (18)	11	0	11 (12)	n.s.
Direct transfer	2	1	3 (27)	16	9	25 (28)	n.s.
Pre-hospital airway management with ET	6	3	9 (82)	44	12	56 (63)	n.s.
Pre-hospital airway management with LMA	1	1	2 (18)	8	7	15 (17)	n.s.
Neurosurgery	5	4	9 (82)	50	11	61 (68)	n.s.
ICP monitoring	4	2	6 (55)	32	3	35 (39)	n.s.
Pre-hospital fluid (mL, median)	1000	500	500	750	500	500	n.s.

ET, endotracheal tube; LMA, laryngeal mask airway; ICP, intracranial pressure; n.s. = not significant; GCS, Glasgow Coma Scale score.

Factors that were associated with favorable outcome were female gender, lower trauma severity (i.e., lower AIS head and lower ISS scores), basal cisterns classified as open or partially open on first CT scan, no midline shift, and SAH on first CT scan. Factors that were associated with unfavorable outcome were male gender, higher trauma severity, and closed basal cisterns on the first CT scan (this last factor was associated with 100% mortality). No other CT features, and none of the treatment factors (e.g., pre-hospital treatment, direct transfer, neurosurgery, or ICP monitoring), were associated with outcomes.

Discussion

It is well known that there is an association between patient age and outcome after severe TBI. Older patients have a higher mortality rate (some authors report 100%; Kilaru et al., 1996), and are less likely than younger adults to live or function independently after TBI. Older patients show a greater decline over the first 5 years after TBI than younger patients (Marquez de la Plata et al., 2008). Increasing age is associated with poorer outcome in patients with closed TBI (Livingston et al., 2005). There is general consensus that the probability of poor outcome increases with patient age. Older age in general worsens the impact of TBI on the brain (Schonberger et al., 2009). Hukkelhoven and associates provided a review of studies of patient outcome across age groups (Hukkelhoven et al., 2003). They concluded that some authors identified an “age threshold” for good outcome that was somewhere between 30 and 60 years (Choi et al., 1983; Signorini et al., 1999).

All of this evidence could lead to a policy not to treat older patients with severe TBI as aggressively as younger patients. This, however, could lead to a self-fulfilling prophecy. Patients older than 66 years, as well as those with GCS scores of 3 and 4, have been excluded from most clinical studies.

To the best of our knowledge this special group of patients has not been studied before. As we previously described (Mauritz et al., 2008), the treatment of patients included in our database did not differ with age. Standard policy in all participating centers was to treat all TBI patients according to guidelines.

In this study we identified patients aged 66 years or older who had initial GCS scores of 3 or 4, and compared those who had achieved favorable outcomes to those who had unfavorable outcomes. Further, we looked at the factors that may have contributed to these outcomes.

In all, 71% in our sample had a GCS score of 3, and 29% had a GCS score of 4. The GCS score used for this study was the initial one, the first one recorded in the field. We did not consider patients with a low GCS that had deteriorated from an initially better score.

Gender and increasing age do not have a clear evidence-based relationship of any influence on outcomes. There are studies showing that female gender, and in particular women aged 55 years, are factors associated with reduced mortality and decreased complications after TBI (Berry et al., 2009), while other studies show an association with increased mortality for the same age group (Ottochian et al., 2009). In our study, more females had favorable outcomes than males, but the difference was not significant.

With regard to the mechanism of the injury, none of our patients with injuries due to assault, gunshot, a fall of more than 3 meters, or bicycle or motorcycle accident, had a favorable outcome. The most common mechanism of injury in our group was a fall of less than 3 meters (73% of patients had favorable outcomes, and 41% of patients had unfavorable outcomes). This is consistent with the findings of other researchers (Gerber et al., 2009; Utomo et al., 2009).

According to Chi and associates, hypoxia in the pre-hospital setting significantly increases the odds of mortality after brain injury (Chi et al., 2006). The results of our study confirm that pre-hospital hypoxia is a strong predictor of unfavorable outcome.

Obliteration and compression of the basal cisterns, as well as midline shift, are strongly associated with unfavorable outcomes (Maas et al., 2007b), which was also confirmed by our results.

Our patients with favorable outcomes were more frequently transported by helicopter to the treatment center. Air medical response to brain trauma was also confirmed to be a survival advantage by other studies.

With regard to other treatment factors influencing outcomes, patients with favorable outcomes had a higher rate of ICP monitoring, and a higher rate of cranial surgery. This is in agreement with the established clinical evidence of the better outcomes achieved by aggressive treatment (Stein et al., 2009). Our patients with unfavorable outcomes received higher doses of mannitol during the first 48 h in the intensive care unit.

Further investigation into the relationship between advanced age and outcomes is needed. The age threshold for increased probability of a poor outcome after TBI varies significantly in the studies that have examined this topic. We used the threshold of 65 years in our study, and we confirmed that these patients are not hopeless, as is so often presumed. Low GCS score is also a strong predictor of poor outcome.

Various studies have shown that trauma patients with very low GCS scores have poor outcomes, and despite aggressive treatment only as few as 5% of these patients make a good recovery (Nijboer et al., 2010). In our study, 11% of patients with GCS scores of 3 or 4 and age over 65 years had favorable outcomes 12 months after trauma.

To summarize our findings, favorable outcomes in our group were associated with female gender, lower trauma severity, open or partially open basal cisterns on first CT scan, and no midline shift on first CT scan. Factors significantly associated with unfavorable outcome in our group were male gender, higher trauma severity, and closed basal cisterns on first CT scan. Lemcke and associates recently confirmed that age, midline shift, and status of the basal cisterns are all factors associated with poor long-term outcome (Lemcke, 2010).

Our findings challenge the conclusions of authors who have claimed that victims of severe TBI who are older than 65 have a hopeless prognosis.

In conclusion, in this study we showed that patients with severe TBI and GCS scores of 3 or 4 who are aged over 65 years have a poor, but not hopeless, prognosis. Mortality at the ICU was 76%, and after 12 months was 80%. This is, however, still better than the mortality rate of 100% reported for these patients by most other authors. Factors confirmed to contribute to poor prognosis for this group of patients were closed basal cisterns and midline shift >15 mm on first CT scan. Factors possibly related to favorable outcomes were female gender, lower trauma severity, open or partially open basal cisterns, and no midline shift on first CT scan.

Footnotes

Acknowledgments

We are very grateful to the collaborators from the participating centers: M. Bartosova, M.D. (Michalovce, Slovakia), F. Botha, M.D. (Linz, Austria), F. Chmeliczek, M.D. (Salzburg, Austria), G. Clarici, M.D. (Graz, Austria), J. de Riggo, M.D. (St. Martin, Slovakia), K. Dizdarevic, M.D. (Sarajevo, Bosnia-Herzegovina), D. Girotto, M.D. (Rijeka, Croatia), H.-D. Gulle, M.D. (Klagenfurt, Austria), M. Kaniansky, M.D. (Banska Bystrica, Slovakia), W. Moser, M.D. (Klagenfurt, Austria), Prof. M. Soljakova, M.D. (Skopje, Former Yugoslav Republic of Macedonia), B. Splavski, M.D. (Osijek, Croatia), Prof. Z. Todorova, M.D. (Skopje, Former Yugoslav Republic of Macedonia), Ernst Trampitsch, M.D. (Klagenfurt, Austria), and Prof. M. Vukic, M.D. (Zagreb, Croatia).

The data used for this study were collected for a project funded by a European Union grant (Project “Research–Treat–TBI”; 6th Framework Program: INCO-DEV: International Cooperation with Developing Countries 1998–2002; contract number : ICA2-CT-2002-100), and for another project funded by the Austrian Worker's Compensation Board (AUVA; contract number FK 33/2003), and by the “Jubiläumsfonds” of the Austrian National Bank (project number 8987). INRO was supported by an annual grant from Mrs. Ala Auersperg-Isham and Mr. Ralph Isham, and by donations from various other sources.

Author Disclosure Statement

No competing financial interests exist.

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