Chinese Head Trauma Data Bank: Effect of Gender on the Outcome of Patients With Acute Traumatic Brain Injury

Introduction

Anumber of factors may influence the outcome of patients with acute severe traumatic brain injury (TBI), including age, gender, Glasgow Coma Scale (GCS), intracranial pressure, pupillary size and response, hypoxia, and computed tomography (CT) findings. ^{1 –9} It has been reported that female sex may be an independent risk factor for poor or better outcome post-TBI.. ^{10 –14} However, other reports show that there is no difference of outcome between males and females post-TBI. ^{15 –18} In this study, we assessed sex differences in the outcome of 1626 patients with severe TBI.

Methods

Results

Effects of gender on the outcome of 7145 patients with acute traumatic brain injury

Mortality of 7145 patients with acute TBI in males and females was 7.48% and 7.22%, respectively, with corresponding unfavorable outcomes of 16.05% and 17.23%, respectively (p > 0.05 in both cases; Fig. 1).

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FIG. 1.

Effect of gender on mortality and morbidity of 7145 patients with severe traumatic brain injury. There is no statistical difference on the outcome of severe traumatic brain injury.

Effects of gender on the outcome of 1626 patients with severe traumatic brain injury

Mortality of 1626 patients with severe TBI in males and females was 19.68% and 20.72%, respectively, with corresponding unfavorable outcomes of 46.96% and 48.85%, respectively (p > 0.05 in both cases; Fig. 2).

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FIG. 2.

Effect of gender on the mortality and morbidity of 1626 patients with severe traumatic brain injury. There is no statistical difference on the outcome of severe traumatic brain injury.

Discussion

We have found that there is no significant difference of the outcome of patients with acute TBI injury between males and females, which indicates that sex may not play a role in the outcome of patients with severe TBI.

Whether sex plays a role in the outcome of severe TBI is still controversial. Berry and colleagues have made a retrospective review of all patients with isolated moderate-to-severe TBI using data from the National Trauma Database (version 6.2; 2000–2005). Logistic regression analysis was used to determine the relationship among female sex, mortality, and development of complications after moderate-to-severe TBI. A total of 72,294 patients with moderate-to-severe TBI were evaluated. Females showed a significantly lower risk in both mortality and in developing any type of complications than the male population after adjusting for differences in patient characteristics. They concluded that female sex is independently associated with reduced mortality and decreased complications post-TBI. ¹⁰ Groswasser and colleagues have reported the effect of sex on the outcome of 334 consecutive TBI patients, including 72 females and 262 males (age range, 5–65 years). They have also found that female TBI patients had a better predicted outcome. ¹² However, Ng and colleagues investigated whether there are possible sex differences in relation to outcome after closed severe TBI in a predominantly Asian population. A study has been conducted using our prospectively maintained TBI database of 672 patients with severe TBI admitted into our neurosurgical intensive care unit. Females have a significantly higher mortality and poorer outcome compared to males. ¹⁴ Kraus and colleagues have examined sex as an independent predictor of survival post-TBI. A prospective cohort of severe and moderate TBI individuals is identified from two trauma centers over a period of 3.5 years. Patients enrolled in the cohort are followed for as long as 18 months postdischarge. Overall, mortality is 1.28 times higher in females than males, with the greatest difference of 2.14 found in deaths postdischarge. Controlling for age, admission GCS, penetrating as compared with blunt injury, and the presence of multiple trauma, females are 1.75 times more likely than males to die of their TBI. Further, females are 1.57 times more likely to experience poor outcomes (i.e., severe disability or persistent vegetative state) than males. ¹³ Coimbra and colleagues have performed a retrospective, case-controlled study matching female patients to male counterparts for overall injury severity; hemodynamic status at admission, and head, chest, and abdomen Abbreviated Injury Scale score. An overall comparison between women (n = 914) and their male matched counterparts (n = 916) was performed. Patients were then stratified according to severity of TBI on the basis of admission GCS score into three groups: group 1, GCS score of 13–15 (788 female patients, 769 male patients); group 2, GCS score of 9–12 (40 female patients, 42 male patients); and group 3, GCS score <9 (63 female patients, 87 male patients). There was no statistically significant difference in outcome overall or in subset analysis of mild (group 1), moderate (group 2), or severe (group 3) TBI. They concluded that sex does not play a role in post-traumatic mortality or in the incidence of acute complications after any degree of TBI. ¹⁵ Leitqeb and colleagues have reported that 17 Austrian centers prospectively enrolled 863 patients with moderate and severe TBI, including 134 female and 305 male patients. Hospital mortality was 39.6% for females and 32.5% for males. Rates of unfavorable outcome were 58.7% for females and 53.4% for males. There were no significant mortality differences between females and males for factors such as age groups, trauma mechanisms, GCS scores, lesions on CT scan, or treatment factors. Logistic regression revealed that sex had no significant influence on mortality of unfavorable outcome. The differences in outcome were owing to the higher mean age of females (61.4 vs. 50.4; p < 0.001) and, possibly, because of small differences in GCS scores and in CT scores. They conclude that female sex is not an independent risk factor for in-hospital mortality post-TBI. ¹⁶

The mechanisms for different effect of sex on outcome of TBI is not clear. Arellano-Orden and colleagues assessed the role of sex as an independent factor in cerebral oxygenation variations after red blood cell transfusion (RBCT). They found differences in age, weight, mean arterial pressure, Injury Severity Score, and cerebral perfusion pressure between groups. After adjusting for these covariables, they observed that sex and age are related to increase in PbrO₂. The data suggest that the effect of RBCT on cerebral oxygenation, as measured by PbrO₂, is greater in women than in men. ⁶ Ost and colleagues have demonstrated a connection between apolipoprotein E (APOE) genotype and outcome post-TBI. A total of 96 patients with GCS < or =8 were prospectively and consecutively included. Twenty-six patients expressed APOE epsilon 4, whereas 70 patients did not. Outcome demonstrated that patients with APOE epsilon 4 had a worse outcome vs. those lacking this allele. When subdividing patients into sex, males with APOE epsilon 4 were worse, a difference not observed among female patients. The data show that APOE epsilon 4 correlates to worse outcome in TBI patients, and males with APOE epsilon 4 had a poor outcome whereas females did not. They concluded that genetic polymorphism may influence outcome post-TBI. ⁷ Wagner and colleagues have found that a significant sex effect is observed with F2-isoprostane/lactate/pyruvate. Females had a significant inverse relationship between day 1 F2-isoprostane/glutamate ratios and GOS scores as well as day 1 F2-isoprostane/lactate/pyruvate ratio and GOS scores. These results indicate that females had smaller oxidative damage loads than males for a given excitotoxic or ischemic insult, and female gonadal hormones may play a role in mediating this neuroprotective effect. ²⁵ Bayir and colleagues have evaluated the effect of gender on lipid peroxidation (LPO), as assessed by cerebrospinal fluid (CSF) levels of F2-isoprostane, after severe TBI in humans. LPO was assessed in CSF from 68 adults after severe TBI. F2-isoprostane was approximately 2-fold higher in males than females. They suggest that LPO occurs early after severe TBI in adults and is more prominent in males versus females. ²⁶

In summary, although some previous reports show different effects of sex on the outcome of acute moderate-to-severe TBI, our data strongly suggest that sex does not play a role in the outcome of patients with acute TBI.