A model of diffuse traumatic brain injury in the immature rat

1996 ◽  
Vol 85 (5) ◽  
pp. 877-884 ◽  
Author(s):  
P. David Adelson ◽  
Paul Robichaud ◽  
Ronald L. Hamilton ◽  
Patrick M. Kochanek

✓ Diffuse cerebral swelling after severe traumatic brain injury (TBI) develops more commonly in children than adults; however, models of diffuse brain injury in immature animals are lacking. The authors developed a new model of diffuse severe TBI in immature rats by modifying a recently described closed head injury model for adult rats. A total of 105 Sprague—Dawley immature rats (17 days old; average weight 38.5 ± 5.46 g) were subjected to head impact using variable weights (0 g (sham), 75 g, 100 g, or 125 g) delivered from a height of 2 m onto a metal disk cemented to the intact cranium. Mortality, physiological and neurological parameters (from early reflex recovery to escape), and early histopathological changes were assessed. During the acute period after severe injury (SI) (100 g delivered from a height of 2 m; 50 rats), apnea was frequently observed and the mortality rate was 38%. Neurological recovery was complete in the sham-injured animals (11 rats) by 4.1 ± 0.23 minutes (mean ± standard error of the mean), but was delayed in both moderately injured (MI) (75 g/2 m; 11 rats) (14.97 ± 3.99 minutes) and SI (20.57 ± 1.31 minutes (p < 0.05)) rats. In the first 24 hours, the sham-injured animals were more active than the injured ones as reflected by a greater net weight gain: 2.9 ± 1.0 g, 1.2 ± 1.6 g, and −0.6 ± 2.1 g in sham-injured, MI, and SI animals, respectively. Immediately after injury, transient hypertension (lasting < 15 seconds) was followed by hypotension (lasting < 3 minutes) and loss of temperature regulation. Both injuries also induced apnea (0.75 ± 0.7 minutes and 1.27 ± 0.53 minutes in MI and SI groups, respectively), which either resolved or deteriorated to death. Intubation and assisted ventilation in animals with SI for 9.57 ± 3.27 minutes in the peritrauma period eliminated mortality (p < 0.05, intubated vs. nonintubated). Histologically, after SI, there was diffuse edema throughout the corpus callosum below the region of injury and in the thalami. Other injuries included neuronal death in the deep nuclei, bilateral disruption of CA3, diffuse subarachnoid hemorrhage, and, in some, ventriculomegaly. Following a diffuse TBI in immature rats, SI produced a mortality rate, neurological deficit, and histological changes similar to those previously reported for an injury resulting from a 450-g weight dropped from 2 m in adult rats. A graded insult was achieved by maintaining the height of the weight drop but varying the weights. Weight loss, acute physiological instability, and acute neurological deficits were also indicative of an SI. Mortality was eliminated when ventilatory support was used during the peritrauma period. This model should be useful in studying the response of the immature rat to diffuse severe TBI.

2021 ◽  
Vol 11 (12) ◽  
pp. 1339
Author(s):  
Chien-Hung Chen ◽  
Yu-Wei Hsieh ◽  
Jen-Fu Huang ◽  
Chih-Po Hsu ◽  
Chia-Ying Chung ◽  
...  

(1) Background: Road traffic accidents (RTAs) are the leading cause of pediatric traumatic brain injury (TBI) and are associated with high mortality. Few studies have focused on RTA-related pediatric TBI. We conducted this study to analyze the clinical characteristics of RTA-related TBI in children and to identify early predictors of in-hospital mortality in children with severe TBI. (2) Methods: In this 15-year observational cohort study, a total of 618 children with RTA-related TBI were enrolled. We collected the patients’ clinical characteristics at the initial presentations in the emergency department (ED), including gender, age, types of road user, the motor components of the Glasgow Coma Scale (mGCS) score, body temperature, blood pressure, blood glucose level, initial prothrombin time, and the intracranial computed tomography (CT) Rotterdam score, as potential mortality predictors. (3) Results: Compared with children exhibiting mild/moderate RTA-related TBI, those with severe RTA-related TBI were older and had a higher mortality rate (p < 0.001). The in-hospital mortality rate for severe RTA-related TBI children was 15.6%. Compared to children who survived, those who died in hospital had a higher incidence of presenting with hypothermia (p = 0.011), a lower mGCS score (p < 0.001), a longer initial prothrombin time (p < 0.013), hyperglycemia (p = 0.017), and a higher Rotterdam CT score (p < 0.001). Multivariate analyses showed that the mGCS score (adjusted odds ratio (OR): 2.00, 95% CI: 1.28–3.14, p = 0.002) and the Rotterdam CT score (adjusted OR: 2.58, 95% CI: 1.31–5.06, p = 0.006) were independent predictors of in-hospital mortality. (4) Conclusions: Children with RTA-related severe TBI had a high mortality rate. Patients who initially presented with hypothermia, a lower mGCS score, a prolonged prothrombin time, hyperglycemia, and a higher Rotterdam CT score in brain CT analyses were associated with in-hospital mortality. The mGCS and the Rotterdam CT scores were predictive of in-hospital mortality independently.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jelmer-Joost Lenstra ◽  
Lidija Kuznecova-Keppel Hesselink ◽  
Sacha la Bastide-van Gemert ◽  
Bram Jacobs ◽  
Maarten Willem Nicolaas Nijsten ◽  
...  

The aim of this study was to evaluate the frequency of electrocardiographic (ECG) abnormalities in the acute phase of severe traumatic brain injury (TBI) and the association with brain injury severity and outcome. In contrast to neurovascular diseases, sparse information is available on this issue. Data of adult patients with severe TBI admitted to the Intensive Care Unit (ICU) for intracranial pressure monitoring of a level-1 trauma center from 2002 till 2018 were analyzed. Patients with a cardiac history were excluded. An ECG recording was obtained within 24 h after ICU admission. Admission brain computerized tomography (CT)-scans were categorized by Marshall-criteria (diffuse vs. mass lesions) and for location of traumatic lesions. CT-characteristics and maximum Therapy Intensity Level (TILmax) were used as indicators for brain injury severity. We analyzed data of 198 patients, mean (SD) age of 40 ± 19 years, median GCS score 3 [interquartile range (IQR) 3–6], and 105 patients (53%) had thoracic injury. In-hospital mortality was 30%, with sudden death by cardiac arrest in four patients. The incidence of ECG abnormalities was 88% comprising ventricular repolarization disorders (57%) mostly with ST-segment abnormalities, conduction disorders (45%) mostly with QTc-prolongation, and arrhythmias (38%) mostly of supraventricular origin. More cardiac arrhythmias were observed with increased grading of diffuse brain injury (p = 0.042) or in patients treated with hyperosmolar therapy (TILmax) (65%, p = 0.022). No association was found between ECG abnormalities and location of brain lesions nor with thoracic injury. Multivariate analysis with baseline outcome predictors showed that cardiac arrhythmias were not independently associated with in-hospital mortality (p = 0.097). Only hypotension (p = 0.029) and diffuse brain injury (p = 0.017) were associated with in-hospital mortality. In conclusion, a high incidence of ECG abnormalities was observed in patients with severe TBI in the acute phase after injury. No association between ECG abnormalities and location of brain lesions or presence of thoracic injury was present. Cardiac arrhythmias were indicative for brain injury severity but not independently associated with in-hospital mortality. Therefore, our findings likely suggest that ECG abnormalities should be considered as cardiac mimicry representing the secondary effect of traumatic brain injury allowing for a more rationale use of neuroprotective measures.


2016 ◽  
Vol 125 (5) ◽  
pp. 1229-1234 ◽  
Author(s):  
Aditya Vedantam ◽  
Jose-Miguel Yamal ◽  
Maria Laura Rubin ◽  
Claudia S. Robertson ◽  
Shankar P. Gopinath

OBJECT There is limited literature available to guide transfusion practices for patients with severe traumatic brain injury (TBI). Recent studies have shown that maintaining a higher hemoglobin threshold after severe TBI offers no clinical benefit. The present study aimed to determine if a higher transfusion threshold was independently associated with an increased risk of progressive hemorrhagic injury (PHI), thereby contributing to higher rates of morbidity and mortality. METHODS The authors performed a secondary analysis of data obtained from a recently performed randomized clinical trial studying the effects of erythropoietin and blood transfusions on neurological recovery after severe TBI. Assigned hemoglobin thresholds (10 g/dl vs 7 g/dl) were maintained with packed red blood cell transfusions during the acute phase after injury. PHI was defined as the presence of new or enlarging intracranial hematomas on CT as long as 10 days after injury. A severe PHI was defined as an event that required an escalation of medical management or surgical intervention. Clinical and imaging parameters and transfusion thresholds were used in a multivariate Cox regression analysis to identify independent risk factors for PHI. RESULTS Among 200 patients enrolled in the trial, PHI was detected in 61 patients (30.5%). The majority of patients with PHI had a new, delayed contusion (n = 29) or an increase in contusion size (n = 15). The mean time interval between injury and identification of PHI was 17.2 ± 15.8 hours. The adjusted risk of severe PHI was 2.3 times higher for patients with a transfusion threshold of 10 g/dl (95% confidence interval 1.1–4.7; p = 0.02). Diffuse brain injury was associated with a lower risk of PHI events, whereas higher initial intracranial pressure increased the risk of PHI (p < 0.001). PHI was associated with a longer median length of stay in the intensive care unit (18.3 vs 14.4 days, respectively; p = 0.04) and poorer Glasgow Outcome Scale scores (42.9% vs 25.5%, respectively; p = 0.02) at 6 months. CONCLUSIONS A higher transfusion threshold of 10 g/dl after severe TBI increased the risk of severe PHI events. These results indicate the potential adverse effect of using a higher hemoglobin transfusion threshold after severe TBI.


2015 ◽  
Vol 122 (1) ◽  
pp. 202-210 ◽  
Author(s):  
Halinder S. Mangat ◽  
Ya-Lin Chiu ◽  
Linda M. Gerber ◽  
Marjan Alimi ◽  
Jamshid Ghajar ◽  
...  

OBJECT Increased intracranial pressure (ICP) in patients with traumatic brain injury (TBI) is associated with a higher mortality rate and poor outcome. Mannitol and hypertonic saline (HTS) have both been used to treat high ICP, but it is unclear which one is more effective. Here, the authors compare the effect of mannitol versus HTS on lowering the cumulative and daily ICP burdens after severe TBI. METHODS The Brain Trauma Foundation TBI-trac New York State database was used for this retrospective study. Patients with severe TBI and intracranial hypertension who received only 1 type of hyperosmotic agent, mannitol or HTS, were included. Patients in the 2 groups were individually matched for Glasgow Coma Scale score (GCS), pupillary reactivity, craniotomy, occurrence of hypotension on Day 1, and the day of ICP monitor insertion. Patients with missing or erroneous data were excluded. Cumulative and daily ICP burdens were used as primary outcome measures. The cumulative ICP burden was defined as the total number of days with an ICP of > 25 mm Hg, expressed as a percentage of the total number of days of ICP monitoring. The daily ICP burden was calculated as the mean daily duration of an ICP of > 25 mm Hg, expressed as the number of hours per day. The numbers of intensive care unit (ICU) days, numbers of days with ICP monitoring, and 2-week mortality rates were also compared between the groups. A 2-sample t-test or chi-square test was used to compare independent samples. The Wilcoxon signed-rank or Cochran-Mantel-Haenszel test was used for comparing matched samples. RESULTS A total of 35 patients who received only HTS and 477 who received only mannitol after severe TBI were identified. Eight patients in the HTS group were excluded because of erroneous or missing data, and 2 other patients did not have matches in the mannitol group. The remaining 25 patients were matched 1:1. Twenty-four patients received 3% HTS, and 1 received 23.4% HTS as bolus therapy. All 25 patients in the mannitol group received 20% mannitol. The mean cumulative ICP burden (15.52% [HTS] vs 36.5% [mannitol]; p = 0.003) and the mean (± SD) daily ICP burden (0.3 ± 0.6 hours/day [HTS] vs 1.3 ± 1.3 hours/day [mannitol]; p = 0.001) were significantly lower in the HTS group. The mean (± SD) number of ICU days was significantly lower in the HTS group than in the mannitol group (8.5 ± 2.1 vs 9.8 ± 0.6, respectively; p = 0.004), whereas there was no difference in the numbers of days of ICP monitoring (p = 0.09). There were no significant differences between the cumulative median doses of HTS and mannitol (p = 0.19). The 2-week mortality rate was lower in the HTS group, but the difference was not statistically significant (p = 0.56). CONCLUSIONS HTS given as bolus therapy was more effective than mannitol in lowering the cumulative and daily ICP burdens after severe TBI. Patients in the HTS group had significantly lower number of ICU days. The 2-week mortality rates were not statistically different between the 2 groups.


2009 ◽  
Vol 111 (4) ◽  
pp. 695-700 ◽  
Author(s):  
Gill E. Sviri ◽  
Rune Aaslid ◽  
Colleen M. Douville ◽  
Anne Moore ◽  
David W. Newell

Object The aim of the present study was to evaluate the time course for cerebral autoregulation (AR) recovery following severe traumatic brain injury (TBI) Methods Thirty-six patients (27 males and 9 females, mean ± SEM age 33 ± 15.1 years) with severe TBI underwent serial dynamic AR studies with leg cuff deflation as a stimulus, until recovery of the AR responses was measured. Results The AR was impaired (AR index < 2.8) in 30 (83%) of 36 patients on Days 3–5 after injury, and in 19 individuals (53%) impairments were found on Days 9–11 after the injury. Nine (25%) of 36 patients exhibited a poor AR response (AR index < 1) on postinjury Days 12–14, which eventually recovered on Days 15–23. Fifty-eight percent of the patients with a Glasgow Coma Scale score of 3–5, 50% of those with diffuse brain injury, 54% of those with elevated intracranial pressure, and 40% of those with poor outcome had no AR recovery in the first 11 days after injury. Conclusions Autoregulation recovery after severe TBI can be delayed, and failure to recover during the 2nd week after injury occurs mainly in patients with a lower Glasgow Coma Scale score, diffuse brain injury, elevated ICP, or unfavorable outcome. The finding suggests that perfusion pressure management should be considered in some of the patients for a period of at least 2 weeks.


2014 ◽  
Vol 42 (1) ◽  
pp. 129-141 ◽  
Author(s):  
Serge C. Thal ◽  
Ralph Timaru-Kast ◽  
Florian Wilde ◽  
Philipp Merk ◽  
Frederik Johnson ◽  
...  

2017 ◽  
Vol 126 (3) ◽  
pp. 760-767 ◽  
Author(s):  
Pedram Emami ◽  
Patrick Czorlich ◽  
Friederike S. Fritzsche ◽  
Manfred Westphal ◽  
Johannes M. Rueger ◽  
...  

OBJECTIVE Prediction of death and functional outcome is essential for determining treatment strategies and allocation of resources for patients with severe traumatic brain injury (TBI). The aim of this study was to evaluate, by using pupillary status and Glasgow Coma Scale (GCS) score, if patients with severe TBI who are ≤ 15 years old have a lower mortality rate and better outcome than adults with severe TBI. METHODS A retrospective cohort analysis of patients suffering from severe TBI registered in the Trauma Registry of the German Society for Trauma Surgery between 2002 and 2013 was undertaken. Severe TBI was defined as an Abbreviated Injury Scale of the head (AIShead) score of ≥ 3 and an AIS score for any other part of the body that does not exceed the AIShead score. Only patients with complete data (GCS score, age, and pupil parameters) were included. To assess the impact of GCS score and pupil parameters, the authors also used the recently introduced Eppendorf-Cologne Scale and divided the study population into 2 groups: children (0–15 years old) and adults (16–55 years old). Each patient's outcome was measured at discharge from the trauma center by using the Glasgow Outcome Scale. RESULTS A total of 9959 patients fulfilled the study inclusion criteria; 888 (8.9%) patients were ≤ 15 years old (median 10 years). The overall mortality rate and the mortality rate for patients with a GCS of 3 and bilaterally fixed and dilated pupils (19.9% and 16.3%, respectively) were higher for the adults than for the pediatric patients (85% vs 80.9%, respectively), although cardiopulmonary resuscitation rates were significantly higher in the pediatric patients (5.6% vs 8.8%, respectively). In the multivariate logistic regression analysis, no motor response (OR 3.490, 95% CI 2.240–5.435) and fixed pupils (OR 4.197, 95% CI 3.271–5.386) and bilateral dilated pupils (OR 2.848, 95% CI 2.282–3.556) were associated with a higher mortality rate. Patients ≤ 15 years old had a statistically lower mortality rate (OR 0.536, 95% CI 0.421–0.814; p = 0.001). The rate of good functional outcomes (Glasgow Outcome Scale Score 4 or 5) was higher in pediatric patients than in the adults (72.2% vs 63.1%, respectively). CONCLUSIONS This study found that severe TBI in children aged ≤ 15 years is associated with a lower mortality rate and superior functional outcome than in adults. Also, children admitted with a missing motor response or fixed and bilaterally dilated pupils also have a lower mortality rate and higher functional outcome than adults with the same initial presentation. Therefore, patients suffering from severe TBI, especially pediatric patients, could benefit from early and aggressive treatment.


2021 ◽  
Vol 11 (2) ◽  
pp. 136
Author(s):  
Chih-Chi Chen ◽  
Carl P. C. Chen ◽  
Chien-Hung Chen ◽  
Yu-Wei Hsieh ◽  
Chia-Ying Chung ◽  
...  

Traumatic brain injury (TBI) is the leading cause of mortality in children. There are few studies focused on school-aged children with TBI. We conducted this study to identify the early predictors of in-hospital mortality in school-aged children with severe TBI. In this 10 year observational cohort study, a total of 550 children aged 7–18 years with TBI were enrolled. Compared with mild/moderate TBI, children with severe TBI were older; more commonly had injury mechanisms of traffic accidents; and more neuroimage findings of subarachnoid hemorrhage (SAH), subdural hemorrhage (SDH), parenchymal hemorrhage, cerebral edema, and less epidural hemorrhage (EDH). The in-hospital mortality rate of children with severe TBI in our study was 23%. Multivariate analysis showed that falls, being struck by objects, motor component of Glasgow coma scale (mGCS), early coagulopathy, and SAH were independent predictors of in-hospital mortality. We concluded that school-aged children with severe TBI had a high mortality rate. Clinical characteristics including injury mechanisms of falls and being struck, a lower initial mGCS, early coagulopathy, and SAH are predictive of in-hospital mortality.


2019 ◽  
Author(s):  
Emily L. Dennis ◽  
Karen Caeyenberghs ◽  
Robert F. Asarnow ◽  
Talin Babikian ◽  
Brenda Bartnik-Olson ◽  
...  

Traumatic brain injury (TBI) is a major cause of death and disability in children in both developed and developing nations. Children and adolescents suffer from TBI at a higher rate than the general population; however, research in this population lags behind research in adults. This may be due, in part, to the smaller number of investigators engaged in research with this population and may also be related to changes in safety laws and clinical practice that have altered length of hospital stays, treatment, and access to this population. Specific developmental issues also warrant attention in studies of children, and the ever-changing context of childhood and adolescence may require larger sample sizes than are commonly available to adequately address remaining questions related to TBI. The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Pediatric Moderate-Severe TBI (msTBI) group aims to advance research in this area through global collaborative meta-analysis. In this paper we discuss important challenges in pediatric TBI research and opportunities that we believe the ENIGMA Pediatric msTBI group can provide to address them. We conclude with recommendations for future research in this field of study.


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