Lactate levels are commonly evaluated in acutely ill patients. Although most often used in the context of evaluating shock, lactate levels can be elevated for many reasons. While tissue hypoperfusion may be the most common cause of elevation, many other etiologies or contributing factors exist. Clinicians need to be aware of the many potential causes of lactate level elevation as the clinical and prognostic importance of an elevated lactate level varies widely by disease state. Moreover, specific therapy may need to be tailored to the underlying cause of elevation. The present review is based on a comprehensive PubMed search between the dates of January 1, 1960, to April 30, 2013, using the search term lactate or lactic acidosis combined with known associations, such as shock, sepsis, cardiac arrest, trauma, seizure, ischemia, diabetic ketoacidosis, thiamine, malignancy, liver, toxins, overdose, and medication. We provide an overview of the pathogenesis of lactate level elevation followed by an in-depth look at the varied etiologies, including medication-related causes. The strengths and weaknesses of lactate as a diagnostic/prognostic tool and its potential use as a clinical end point of resuscitation are discussed. The review ends with some general recommendations on the management of patients with elevated lactate levels.

https://www.mayoclinicproceedings.org/article/S0025-6196(13)00555-7/pdf

Etiology and Therapeutic Approach to Elevated Lactate Levels

Mild traumatic brain injury (mTBI) remains a challenge to accurately assess with conventional neuroimaging. Recent research holds out the promise that diffusion tensor imaging (DTI) can be used to predict recovery in mTBI patients. Unlike computed tomography or conventional magnetic resonance imaging, DTI is sensitive to microstructural axonal injury, the neuropathology that is thought to be most responsible for the persistent cognitive and behavioral impairments that often occur after mTBI. Through the use of newer DTI analysis techniques such as automated region of interest analysis, tract-based voxel-wise analysis, and quantitative tractography, researchers have shown that frontal and temporal association white matter pathways are most frequently damaged in mTBI and that the microstructural integrity of these tracts correlates with behavioral and cognitive measures. Future longitudinal DTI studies are needed to elucidate how symptoms and the microstructural pathology evolve over time. Moving forward, large-scale investigations will ascertain whether DTI can serve as a predictive imaging biomarker for long-term neurocognitive deficits after mTBI that would be of value for triaging patients to clinical trials of experimental cognitive enhancement therapies and rehabilitation methods, as well as for monitoring their response to these interventions.

Diffusion tensor imaging of mild traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death in the young age group and leads to persisting neurological impairment in many of its victims. It may result in permanent functional deficits because of both primary and secondary damages. This review addresses the role of oxidative stress in TBI-mediated secondary damages by affecting the function of the vascular unit, changes in blood-brain barrier (BBB) permeability, posttraumatic edema formation, and modulation of various pathophysiological factors such as inflammatory factors and enzymes associated with trauma. Oxidative stress plays a major role in many pathophysiologic changes that occur after TBI. In fact, oxidative stress occurs when there is an impairment or inability to balance antioxidant production with reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels. ROS directly downregulate proteins of tight junctions and indirectly activate matrix metalloproteinases (MMPs) that contribute to open the BBB. Loosening of the vasculature and perivascular unit by oxidative stress-induced activation of MMPs and fluid channel aquaporins promotes vascular or cellular fluid edema, enhances leakiness of the BBB, and leads to progression of neuroinflammation. Likewise, oxidative stress activates directly the inflammatory cytokines and growth factors such as IL-1β, tumor necrosis factor-α (TNF-α), and transforming growth factor-beta (TGF-β) or indirectly by activating MMPs. In another pathway, oxidative stress-induced degradation of endothelial vascular endothelial growth factor receptor-2 (VEGFR-2) by MMPs leads to a subsequent elevation of cellular/serum VEGF level. The decrease in VEGFR-2 with a subsequent increase in VEGF-A level leads to apoptosis and neuroinflammation via the activation of caspase-1/3 and IL-1β release.

Interactions of Oxidative Stress and Neurovascular Inflammation in the Pathogenesis of Traumatic Brain Injury

Mild traumatic brain injury (mTBI), or concussion, is the most common type of traumatic brain injury. With mTBI comes symptoms that include headaches, fatigue, depression, anxiety and irritability, as well as impaired cognitive function. Symptom resolution is thought to occur within 3 months post-injury, with the exception of a small percentage of individuals who are said to experience persistent post-concussion syndrome. The number of individuals who experience persistent symptoms appears to be low despite clear evidence of longer-term pathophysiological changes resulting from mTBI. In light of the incongruency between these longer-term changes in brain pathology and the number of individuals with longer-term mTBI-related symptoms, particularly impaired cognitive function, we performed a scoping review of the literature that behaviourally assessed short- and long-term cognitive function in individuals with a single mTBI, with the goal of identifying the impact of a single concussion on cognitive function in the chronic stage post-injury. CINAHL, Embase, and Medline/Ovid were searched July 2015 for studies related to concussion and cognitive impairment. Data relating to the presence/absence of cognitive impairment were extracted from 45 studies meeting our inclusion criteria. Results indicate that, in contrast to the prevailing view that most symptoms of concussion are resolved within 3 months post-injury, approximately half of individuals with a single mTBI demonstrate long-term cognitive impairment. Study limitations notwithstanding, these findings highlight the need to carefully examine the long-term implications of a single mTBI.

/pdf/mild-traumatic-brain-injury-mtbi-and-chronic-cognitive-3wo1jk6m7c.pdf

Mild Traumatic Brain Injury (mTBI) and chronic cognitive impairment: A scoping review

Neuroimaging identified abnormalities associated with traumatic brain injury (TBI) are but gross indicators that reflect underlying trauma-induced neuropathology at the cellular level. This review examines how cellular pathology relates to neuroimaging findings with the objective of more closely relating how neuroimaging findings reveal underlying neuropathology. Throughout this review an attempt will be made to relate what is directly known from post-mortem microscopic and gross anatomical studies of TBI of all severity levels to the types of lesions and abnormalities observed in contemporary neuroimaging of TBI, with an emphasis on mild traumatic brain injury (mTBI). However, it is impossible to discuss the neuropathology of mTBI without discussing what occurs with more severe injury and viewing pathological changes on some continuum from the mildest to the most severe. Historical milestones in understanding the neuropathology of mTBI are reviewed along with implications for future directions in the examination of neuroimaging and neuropathological correlates of TBI.

Neuropathology of mild traumatic brain injury: relationship to neuroimaging findings

Objectives: The aim of this study was to determine the general characteristics of childhood falls, factors affecting on mortality, and to compare the Injury Severity Score (ISS) and the New Injury Severity Score (NISS) as predictors of mortality and length of hospital stay in childhood falls Methods: We retrospectively analysed over a period of 8 years children aged younger than14 years who had sustained falls and who were admitted to our emergency department Data on the patients’ age, sex, type of fall, height fallen, arrival type, type of injuries, scoring systems, and outcome were investigated retrospectively The ISS and NISS were calculated for each patient Comparisons between ISS and NISS for prediction of mortality were made by receiver operating characteristic (ROC) curve and Hosmer-Lemeshow (HL) goodness of fit statistics Results: In total, there were 2061 paediatric trauma patients Falls comprised 36 (n = 749) of these admissions There were 479 male and 270 female patients The mean (SD) age was 501 (348) years, and height fallen was 38 (3) metres Over half (566%) of patients were referred by other centres The most common type of fall was from balconies (385%), and head trauma was the most common injury (50%) The overall mortality rate was 36% The cut off value for both the ISS and NISS in predicting mortality was 22 (sensitivity 905%, specificity 954% for ISS; sensitivity 100%, specificity 887% for NISS) (p>005) Significant factors affecting mortality in logistic regression analysis were Glasgow Coma Scale (GCS) 22, and NISS >22 There were no significant differences in ROC between three scoring systems The HL statistic showed poorer calibration (p = 002 v p = 037, respectively) of the NISS compared with the ISS Conclusions: In our series, the head was the most frequent site of injury, and the most common type of fall was from balconies Scores on the GCS, NISS, and ISS are significantly associated with mortality The performance of the NISS and ISS in predicting mortality in childhood falls was similar

/pdf/childhood-falls-characteristics-outcome-and-comparison-of-2vge3lul9v.pdf

Childhood falls: characteristics, outcome, and comparison of the Injury Severity Score and New Injury Severity Score

The objective of this study was to investigate the diagnostic value of serum tau protein in determining the severity of traumatic brain injury in patients with mild traumatic brain injury (mTBI) and high-risk patients. Adult patients who presented to our emergency department (ED) with mTBI over 1 year were prospectively enrolled. Patients underwent cranial computed tomography (CT) and were subdivided into high and low-risk groups, according to the probability of resultant intracranial injury. Serum tau levels of 60 patients and 20 healthy volunteers, who served as a control group, were measured. The mean age of the 60 patients (45 males, 15 females) was 32.5 years (range, 15–66 y). Mean Glasgow Coma Scale (GCS) score was 14±0.6. CT scans demonstrated intracranial injury in 11 patients (18.3%) and depressed fracture in 4 patients (6.7%). Serum tau levels of patients (188±210 pg/mL), compared with those of controls (86±48 pg/mL), were relatively higher; however, differences were not statistically significant (P=.445). Also, serum tau levels of high-risk patients (307±246 pg/mL) were significantly higher than those of low-risk patients (77±61 pg/mL) (P=.001). A total of 48 patients (80%) were accessible for follow-up after 6 months. Postconcussive syndrome was observed in 8 patients, 5 of whom had serum tau protein levels that were higher than those of the other 3 patients. However, no statistically significant difference was observed (P > .05). Investigators of the present study noted that serum tau levels in patients with mTBI were increased. Therefore, it is believed that this biomarker may prove helpful in identifying high-risk patients with mTBI. However, additional studies are needed to establish the diagnostic value of serum tau in detecting traumatic brain injury in patients with mTBI.

Tau protein as a serum marker of brain damage in mild traumatic brain injury: preliminary results.

Purpose: To evaluate the occurrence and distribution of mild traumatic brain injury (MTBI) caused by diffuse axonal injury (DAI) using magnetic resonance (MR) imaging and to attempt to correlate MR findings with post-concussion symptoms (PCS). Patients and methods: Forty MTBI patients (mean age: 32.5 years) with normal cranial computed tomography (CT) findings were examined with standard MR protocol including T1-weighted, T2-weighted, fluid attenuated inversion recovery (FLAIR), gradient echo (GRE) and diffusion-weighted (DW) sequences. MR imaging was performed within 24 hours of injury. The lesions were classified as DAI based on their location and morphologic appearance. Results: In MR imaging of five (12.5%) of the patients, the lesions compatible with DAI were observed. Four patients (10%) had the foci of low signal intensity compatible with hemorrhagic shear injury on the GRE sequence, and five (12.5%) patients had high signal intensity on FLAIR and DW sequence. Conclusion: MR imaging can be...

MR imaging in the detection of diffuse axonal injury with mild traumatic brain injury

BACKGROUND: The purpose of this study is to detect the mortality predictive power of new Glasgow coma scale, age, and arterial pressure (GAP) scoring system in major trauma patients admitted to the emergency department (ED). METHODS: A total of 100 major trauma patients admitted to Uludag University Faculty of Medicine ED who were 18 years of age or more were included in the study. In this prospective study, revised trauma score (RTS), injury severity score (ISS), trauma-related ISS (TRISS), Mechanism, GAP (MGAP) and GAP scores of the patients were calculated. RESULTS: A significant positive correlation was established between ISS, TRISS, MGAP, and GAP in predicting in-hospital mortality (p<0.0001). Short-term (24 hours) and long-term (4-week) mortality prediction rates and area under the curve in receiver operating characteristics analysis were 0.727-0.680 for RTS, 0.863-0.816 for ISS, 0.945-0,911 for TRISS, 0.970-0.938 for MGAP, and 0.910-0.904 for GAP. All calculated trauma scoring systems revealed a significant mortality prediction power (p<0.001). GAP score was found statistically and significantly selective and sensitive in predicting both in-ED and in-hospital mortality (p=0.0001). CONCLUSION: In major trauma patients, GAP score is an easily calculable system both in the field and at the time of admission in the EDs by providing emergency physicians with future decision-making schemes by means of mortality prediction of the patients.

/pdf/value-of-the-glasgow-coma-scale-age-and-arterial-blood-3imqo6b7bj.pdf

Value of the Glasgow coma scale, age, and arterial blood pressure score for predicting the mortality of major trauma patients presenting to the emergency department.

BACKGROUND The purpose of this study was to define the epidemiologic properties and correlation of physiological and anatomical risk factors with the mortality rate among patients with thorax trauma and to ensure early prediction of severe trauma. METHODS Files of 371 cases were retrospectively examined. Their initial state in the emergency department was analyzed in terms of mortality development. Age, gender, trauma mechanism, systolic blood pressure and respiration type on admission, accompanying injuries, thorax pathology, trauma scores, and treatment approaches in exitus and surviving cases were compared. Survival probabilities and unexpected mortality rates were computed using the Trauma Revised Score-Injury Severity Score (TRISS). RESULTS Age, hypotension, pathologic respiration, blunt injury, accompanying injury, abdominal trauma, high Injury Severity Score (ISS), and low Glasgow Coma Scale (GCS), Revised Trauma Score (RTS), and TRISS were the factors affecting mortality, and presence of blunt injuries, TRISS 22 and GCS <13 were found to be independent prognostic factors. The strongest factor indicating mortality was TRISS. Thirty-four of 307 cases with survival probability of over 50% died. CONCLUSION In the presence of factors affecting mortality, patients with thorax trauma should be evaluated as being in a high-risk group and treatment strategies must be aggressive. Case analysis based on the TRISS model would further reveal the mistakes and may improve patient care.

/pdf/factors-affecting-mortality-in-patients-with-thorax-trauma-50exy450mq.pdf

Özlem Köksal

Papers

Childhood falls: characteristics, outcome, and comparison of the Injury Severity Score and New Injury Severity Score

Tau protein as a serum marker of brain damage in mild traumatic brain injury: preliminary results.

MR imaging in the detection of diffuse axonal injury with mild traumatic brain injury

Value of the Glasgow coma scale, age, and arterial blood pressure score for predicting the mortality of major trauma patients presenting to the emergency department.

Factors affecting mortality in patients with thorax trauma.