Unexpected contribution of moderate traumatic brain injury to death after major trauma

BACKGROUND: The cardiovascular reflex responses to injury and simple hemorrhage are coordinated in the central nervous system. Coincidental brain injury, which is present in 64% of trauma patients who die, could impair these homeostatic responses. The occurrence of hemorrhagic shock in the patient with head injury is also known to increase mortality. Therefore, there is a potential bidirectional interaction between traumatic brain injury and peripheral injury, which would result in an increased mortality when these two injuries coexist. Our objective was to test the hypothesis that moderate traumatic brain injury is an independent predictor of outcome in patients with multisystem trauma. METHODS: We carried out an analysis of the UK Trauma Audit and Research Network Database. Moderate traumatic brain injury was defined as an Abbreviated Injury Scale score of 3. The study population included 2,717 patients with multisystem injury: 378 patients had a moderate brain injury with peripheral injury, and 2,339 patients had extracranial injury alone. Mortality rates for both groups were compared at increasing injury severity. RESULTS: Moderate brain injury alone was associated with a mortality rate of 4.2%. However, when combined with extracranial injury, the risk of death was double that attributable to extracranial injury alone (odds ratio, 2.08; 95% confidence interval, 1.57-2.77). CONCLUSION: This study confirms that the coexistence of moderate traumatic brain injury with extracranial injury is associated with a doubling of the predicted mortality rate throughout the injury severity ranges studied.     

Long-term neuropsychological outcome after traumatic brain injury.

OBJECTIVE: To describe neuropsychological outcome 5 years after injury in persons with traumatic brain injury (TBI) who received inpatient medical rehabilitation. To determine the magnitude and pattern neuropsychological recovery from 1 year to 5 years after injury. DESIGN: Longitudinal cohort study with inclusion based on the availability of neuropsychological data at 1 year and 5 years after injury. SETTING: National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems of Care. PARTICIPANTS: One hundred eighty-two persons with complicated mild to severe traumatic brain injury. PRIMARY OUTCOME MEASURES: Digits Forward and Backward, Logical Memory I and II, Token Test, Controlled Oral Word Association Test, Symbol Digit Modalities Test, Trail Making Test, Rey Auditory Verbal Learning Test, Visual Form Discrimination, Block Design, Wisconsin Card Sorting Test, and Grooved Pegboard. RESULTS: Significant variability in outcome was found 5 years after TBI, ranging from no measurable impairment to severe impairment on neuropsychological tests. Improvement from 1 year after injury to 5 years was also variable. Using the Reliable Change Index, 22.2% improved, 15.2% declined, and 62.6% were unchanged on test measures. CONCLUSIONS: Neuropsychological recovery after TBI is not uniform across individuals and neuropsychological domains. For a subset of persons with moderate to severe TBI, neuropsychological recovery may continue several years after injury with substantial recovery. For other persons, measurable impairment remains 5 years after injury. Improvement was most apparent on measures of cognitive speed, visuoconstruction, and verbal memory.     

Functional outcome after violence related traumatic brain injury

Violent injuries have become an increasingly prevalent cause of traumatic brain injury TBI . These injuries can be classified as either penetrating or non penetrating in nature. While much of the research on violence has been within a military population, there exists a marked difference between military and civilian injuries. Prior work has reported relatively poor outcomes for those individuals who have suffered penetrating TBIs, but little has been done to assess specific functional outcome parameters in survivors. We examined 25 subjects that had sustained blunt injuries and 25 cases with penetrating injuries as a result of a violent act. Cases were matched by initial Glasgow Coma Scale GCS , age and educational level. Mean GCS for this study sample was 8.8. The following outcome variables were assessed at rehabilitation admission and discharge and at 1 year post injury: Disability Rating Scale DRS , Rancho Los Amigos Scale LCFS , Functional Independence Measure FIM ambulation, expression items , length of stay, and cost of care. Student s t tests were performed to assess for differences between the two groups. No significant differences were noted between the groups for any of the outcome variables. Although penetrating injuries may have a higher initial mortality, those who survive to come to rehabilitation appear to have similar outcomes to those patients with non penetrating violence related injuries.     

Defining age-related differences in outcome after traumatic spinal cord injury: analysis of a combined,multicenter dataset

Background contextThe existing evidence suggests that, although older spinal cord injury (SCI) patients experience a similar degree of neurologic recovery to younger patients, older patients experience diminished functional outcomes at follow-up. However, all studies have assumed that the impact of age on functional outcome is the same across the spectrum of injury severity.PurposeTo test this assumption, we evaluated age as a potential effect moderator governing the relationship between acute neurologic status and long-term functional outcome.Study design/settingCombined analysis of two prospective SCI datasets enrolling patients from North American trauma centers over the last decade.Patient sampleAdult patients (≥16 years old) with traumatic SCI and a standardized American Spinal Injury Association (ASIA) neurologic examination performed within 3 days of injury.Outcome measuresFunctional independence measure (FIM) motor score at the 1-year follow-up was the primary outcome of interest.MethodsTo define older and younger age groups, age was dichotomized at a threshold of 65 years old. A sensitivity analysis was also performed by dichotomizing age at 60 years. Multivariable linear regression was used to investigate the moderating effects of age on the relationship between acute ASIA Impairment Scale (AIS) grade and follow-up FIM motor score. An interaction plot was generated to understand how the effect of age on functional outcome changed depending on the acute AIS grade. A second linear regression model investigating the moderating effects of age was produced that adjusted for additional relevant predictor variables.ResultsOf 729 patients, 376 met the eligibility criteria. The mean age was 43.2 (±16.9), with a total of 41 patients (10.9%) older than 65 years. In the univariable analysis there was no age-related difference in motor recovery or AIS grade conversion at follow-up; however, there was a significantly lower mean FIM motor score observed among the older group at 1 year (p=.03). In the multivariable analysis, age was found to have a significant moderating effect on the relationship between acute AIS grade and future functional status (p<.05). The interaction plot revealed that, although older patients had decreased follow-up FIM motor scores overall, this effect was greatest for AIS B and AIS C patients and lesser for AIS A and AIS D patients. After adjustment for additional covariates in the second linear model, these results remained unchanged.ConclusionsOverall, advanced age is associated with worse functional outcome after SCI; however, this effect varies across the spectrum of injury severity. These results will help to facilitate enhanced clinical communication as well as potentially aid in the development of customized treatment and rehabilitation protocols.     

The contribution of hypoxia to postischemic renal dysfunction

Renal ischemia is a multifactorial insult consisting of both hypoxia and stagnation of blood flow. This study compared the renal response with hypoxia alone versus ischemia (hypoxia and stagnation of flow). Isolated rat kidneys were perfused at 90 to 110 mm Hg and 37 degrees C with an asanguinous modified Krebs' buffer. Perfusate flow rate, vascular resistance, urine flow rate, glomerular filtration rate (GFR), percent sodium reabsorption, and oxygen consumption were measured. Five groups were examined: 10-minute hypoxia (HYP10), 30-minute hypoxia (HYP30), 10-minute ischemia (ISC10), 30-minute ischemia (ISC30), and time-matched controls. HYP10 resulted in isolated tubular dysfunction, as evidenced by an increase in urine flow rate and a decrease in percent sodium reabsorption. ISC10 caused decreased GFR, oliguria, and more severe tubular dysfunction. The pattern of glomerular and tubular dysfunction after HYP30 was similar to that after ISC30. Glomerular dysfunction was associated with a decrease in perfusate flow rate and an increase in vascular resistance only after ISC30. This suggests that the decrease in GFR seen with postischemic renal dysfunction is not a primary result of decreased flow. Furthermore, hypoxia does not account for the entire reduction in renal function after ischemia of similar duration. The more severe dysfunction after ischemia may be a consequence of the stagnation of renal flow (anaerobic waste product accumulation and inadequate nutrient supply).     

脑外伤后神经细胞功能障碍的机制

创伤性脑损伤后受损区的神经元细胞常可发生继发性损伤,其机制包括细胞凋亡、兴奋性氨基酸的作用、钙离子的作用等,并且在动物模型上都得到了证实。     

Blood pressure and outcome after severe pediatric traumatic brain injury

BACKGROUND: The relationship between systolic blood pressure and outcome in children after severe traumatic brain injury (TBI) is unclear. We examined the relationship between age-appropriate systolic blood pressure (AASBP) percentile and outcome after severe pediatric TBI. METHODS: We examined the association between AASBP percentiles and outcome in 172 children younger than 14 years of age with a Glasgow Coma Scale score < 9. Outcome was evaluated using discharge Glasgow Outcome Scale score. Poor outcome was defined as a Glasgow Outcome Scale score < 4. RESULTS: Poor outcome was associated with AASBP < 75th percentile (odds ratio, 4.2; 95% confidence interval, 2.1-8.3). Patients with systolic blood pressure (SBP) > or = 90 mm Hg and AASBP < 75th percentile had a higher odds for poor outcome compared with patients with SBP > or = 90 mm Hg and AASBP > or = 75th percentile (odds ratio, 3.5; 95% confidence interval, 1.7-7.3). CONCLUSION AASBP < 75th percentile was associated with poor outcome after severe pediatric TBI, even when SBP was > or = 90 mm Hg.     

Serum biomarker concentrations and outcome after pediatric traumatic brain injury

Predicting outcome after pediatric traumatic brain injury (TBI) is important for providing information to families and prescribing rehabilitation services. The study objective was to assess whether biomarkers concentrations obtained at the time of injury are associated with outcome. Serial serum concentrations of neuron-specific enolase (NSE), S100B and myelin basic protein (MBP) were measured in 152 children with acute TBI. Outcome was assessed with the Glasgow Outcome Scale (GOS) score and/or GOS-Extended Pediatric (GOS-E Peds). Spearman's rank correlation and binary logistic regression assessed the relationship between biomarker concentrations and outcome. For all biomarkers and time points, higher biomarker concentrations were associated with worse outcome. Initial and peak NSE concentrations and initial MBP concentrations were more strongly correlated with outcome in children < or =4 years compared with those >4 years of age. Using binary logistic regression to evaluate the simultaneous affect of all biomarkers on outcome, there was significant overall model fit predicting a dichotomous GOS from biomarker concentrations with a 77% correct classification rate and a negative and positive predictive value of 97% and 75%, respectively. We conclude that NSE, S100B, and MBP concentrations obtained at the time of TBI may be useful in predicting outcome. Future studies should focus on assessing the differential benefit of biomarkers compared with clinical variables and in assessing a continuous rather than categorical outcome variable.     

卡巴胆碱对烧创伤后肠道功能障碍影响的研究

目的观察肠道内给予卡巴胆碱对兔肠部分缺血再灌注(I/R)损伤及重度烧伤患者肠道功能障碍的影响。方法将50只大白兔制成肠部分I/R损伤模型后,随机分为肠部分I/R损伤组(25只)、卡巴胆碱组[25只,于肠系膜上动脉(SMA)阻断后1h肠内注入3g/L卡巴胆碱(3μg/kg)]；另取25只设为假手术组,仅分离SMA,不阻断；取5只作为正常对照组,不致伤,处死后留取标本待测。检测兔SMA阻断前后及肠道内给予卡巴胆碱后肠黏膜的血流量。各致伤组均在处理后2、4、6、8、24、48、72h留取静脉血测定其血浆二胺氧化酶(DAO)活性及D-乳酸和D-木糖含量。并行葡聚糖蓝排出实验,以检测胃肠道吸收功能。同时选择大面积烧伤[烧伤总面积(84±12)%TBSA]患者8例,在患者肠呜音＜2次/min或腹胀明显时,口服1g/L卡巴胆碱(15μg/kg),观察给药后每分钟肠鸣音次数及腹胀情况。结果SMA阻断后肠部分I/R损伤组肠黏膜血流量为(48±6)PU,较正常对照组[(102±5)PU]明显减少,而肠道内注入卡巴胆碱后1h血流量增至(77±3)PU。肠缺血后肠部分I/R损伤组血浆DAO活性及D-乳酸含量开始升高,处理后24h达峰值[(4．63±0．27)U/ml、(7．9±2．4)mg/L],以后逐渐下降,但仍高于正常对照组[(0．89±0．14)U/ml、(2．0±1．1)mg/L,P＜0．05]。卡巴胆碱组的变化基本同肠部分I/R损伤组,但变化幅度较小；而假手术组则无明显变化(P＞0．05)。在给予D-木糖后2h,肠部分I/R损伤组血浆D-木糖含量显著降低,但处理后6h肠部分I/R损伤组及卡巴胆碱组明显升高,以后逐渐下降；假手术组略有波动。SMA处理后2h肠部分I/R损伤组葡聚糖蓝未见排出,处理后6h其运动距离逐渐增加,但处理后24h其运动距离仍明显短于正常值(P＜0．05),48～72h基本恢复正常；卡巴胆碱组注入葡聚糖蓝后即可见其排出,其运动距离明显增加,处理后6h达峰值(43±6)cm,以后逐渐缩短接近正常(28±3)cm。给药前患者肠呜音较弱(1．6±1．1)次/min,给药后10 min明显增强为(6．9±1．7)次/min,30 min时为(8．3±2．4)次/min,给药后1h患者肠鸣音仍较活跃,为(6．1±1．3)次/min。给药后2h患者腹胀明显减轻,其中有6例患者开始排便。结论肠内给予卡巴胆碱可增加兔肠黏膜血流量,改善其肠道运动、吸收、屏障功能；大面积烧伤患者口服卡巴胆碱,可改善其肠道功能障碍。     

Contribution of functional ratings to prediction of longterm employment outcome after traumatic brain injury

The present study investigated the contribution of functional ratings to prediction of employment outcome after traumatic brain injury (TBI). Previous studies have suggested that functional ratings obtained at a significant time post-injury can supplement neurologic, pre-injury, neuropsychologic, and other post-injury variables in predicting long-term employment outcome. Functional ratings studied were patients' needs for physical, cognitive, and behavioural supervision. This investigation also addressed the issue of predicting long-term outcome for the select group of TBI patients who receive post-acute brain injury rehabilitation. Subjects were 76 patients with TBI. The mean age (25th, 50th, and 75th percentiles) was 32 (22, 28, 39) years and mean premorbid education level was 13 (12, 12, 14) years. Predictors studied were severity of injury, premorbid education level, pre-injury substance use, and needs for physical, cognitive and behavioural supervision at discharge from post-acute rehabilitation. Supervision needs ratings were obtained an average of 9.6 (4.2, 5.9, 11.2) months post-injury. Productivity status was assessed an average of 22.5 (12.6, 20.7, 30.5) months post-injury and 12.9 (4.9, 12.4, 16.6) months post-discharge from treatment. Spearman correlation coefficients revealed that premorbid educational level, pre-injury substance use, and needs for physical and behavioural supervision were related to long-term functional outcome (p < 0.05). However, multiple logistic regression analysis revealed that only level of pre-injury substance use was predictive of long-term productivity outcome once adjusted for the effects of the other predictors. Patients with no history of pre-injury substance use were more than eight times as likely to be employed at follow-up as those with a history of pre-injury substance abuse (p < 0.01).     

Evaluation of models that predict short-term outcome after traumatic brain injury

PRIMARY OBJECTIVE: This study aimed to identify models that predicted the short-term outcome after traumatic brain injury (TBI) from the literature and to evaluate their clinical significance. METHODS: Literatures from PubMED were reviewed. Regression coefficients and intercepts were extracted. A group of 229 cases was used for validation and the unfavourable rate was calculated to assess the validity of these models by the area under receiver operating. Characteristic curve (AUC), C-statistic and Brier score. MAIN RESULTS: In total, 13 studies of 18 different models were included. Data from the validation group were in accordance with the indicators of the studies reviewed. All models got an AUC value ranging from 0.644-0.890 except two (AUC value <0.6) and their Brier scores were near zero. However, the calibration of most studies was insufficient (p < 0.05). CONCLUSIONS: Most of the models included in this study have a good discriminatory power while lacking sufficient calibration. However, they all predict with relative accuracy at the level of individuals. Therefore, current models can be used to predict the survival rate of individual patients and may be useful to inform patients and relatives about the likelihood of a beneficial outcome.     

Meta-analysis of APOE4 allele and outcome after traumatic brain injury

There is conflicting evidence regarding a possible association between the apolipoprotein E4 (APOE4) allele and the consequences of traumatic brain injury (TBI). Our aim was to carry out a meta-analysis of cohort studies of sufficient rigor to determine whether the presence of the APOE4 allele contributes to initial injury severity and/or poor outcome following TBI. MEDLINE, EMBase, CBMdisc, and CNKI databases were searched for literature published from January 1993 to October 2007. Of the 100 identified studies, 14 cohort studies were selected for analysis based on comprehensive quality assessment using a standardized scale. Data from the 14 eligible cohort studies included a total of 2527 participants, 736 with and 1791 without the APOE4 allele. The APOE4 allele was not associated with initial injury severity of TBI. The pooled RR were 1.11 (95% confidence interval [CI], 0.91 to 1.35) for severe injury, 1.06 (95% CI, 0.86-1.31) for moderate injury and 0.93 (95% CI, 0.81-1.06) for mild injury. However, the APOE4 allele was significantly associated with a poor outcome of TBI at 6 months after injury (RR = 1.36; 95% CI, 1.04-1.78). The association remained significant in sensitivity tests. This meta-analysis indicates that the presence of the APOE4 allele is not associated with the initial severity of brain injury following TBI but is associated with increased risk of poor long-term outcome at 6 months after injury.     

Frequency analysis unveils cardiac autonomic dysfunction after mild traumatic brain injury

Long-term mortality is increased after mild traumatic brain injury (mTBI). Central cardiovascular-autonomic dysregulation resulting from subtle, trauma-induced brain lesions might contribute to cardiovascular events and fatalities. We investigated whether there is cardiovascular-autonomic dysregulation after mTBI. In 20 mTBI patients (37±13 years, 5-43 months post-injury) and 20 healthy persons (26±9 years), we monitored respiration, RR intervals (RRI), blood pressures (BP), while supine and upon standing. We calculated the root mean square successive RRI differences (RMSSD) reflecting cardiovagal modulation, the ratio of maximal and minimal RRIs around the 30th and 15th RRI upon standing (30:15 ratio) reflecting baroreflex sensitivity (BRS), spectral powers of parasympathetic high-frequency (HF: 0.15-0.5?Hz) RRI oscillations, of mainly sympathetic low-frequency (LF: 0.04-0.15?Hz) RRI oscillations, of sympathetic LF-BP oscillations, RRI-LF/HF-ratios reflecting sympathovagal balance, and the gain between BP and RRI oscillations as additional BRS index (BRS(gain)). We compared supine and standing parameters of patients and controls (repeated measures analysis of variance; significance: p<0.05). While supine, patients had lower RRIs (874.2±157.8 vs. 1024.3±165.4?ms), RMSSDs (30.1±23.6 vs. 56.3±31.4?ms), RRI-HF powers (298.1±309.8 vs. 1507.2±1591.4?ms(2)), and BRS(gain) (8.1±4.4 vs. 12.5±8.1?ms·mmHg(-1)), but higher RRI-LF/HF-ratios (3.0±1.9 vs. 1.2±0.7) than controls. Upon standing, RMSSDs and RRI-HF-powers decreased significantly in controls, but not in patients; patients had lower RRI-30:15-ratios (1.3±0.3 vs. 1.6±0.3) and RRI-LF-powers (2450.0±2110.3 vs. 4805.9±3453.5?ms(2)) than controls. While supine, mTBI patients had reduced cardiovagal modulation and BRS. Upon standing, their BRS was still reduced, and patients did not withdraw parasympathetic or augment sympathetic modulation adequately. Impaired autonomic modulation probably contributes to cardiovascular irregularities post-mTBI.     

A profile of outcome: 2 years after traumatic brain injury

A group of 175 traumatic brain injury (TBI) patients who had undergone intensive rehabilitation at Bethesda Hospital attended a follow-up interview 2 years after injury. The majority of patients had suffered severe TBI. Outcome was documented in ten areas: medical/physical, mobility, activities of daily living (ADLs) accommodation, marital status, leisure and recreation, employment/study, communication, cognition and behaviour. Whilst most patients were physically independent and competent in personal and domestic activities of daily living, a third of the group were still reliant on assistance with community skills and transport, and more than half of those who previously had a job, were not working at 2 years post-injury. Around two-thirds of the sample reported cognitive, behavioural and emotional changes. There is clearly a need for ongoing community-based support and assistance in dealing with practical difficulties and psychological problems as they are experienced after return to the community.