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Anesthetics Influence Mortality in a Drosophila Model of Blunt Trauma With Traumatic Brain Injury.

ABSTRACT: BACKGROUND:Exposure to anesthetics is common in the majority of early survivors of life-threatening injuries. Whether and to what degree general anesthetics influence outcomes from major trauma is unknown. Potential confounding effects of general anesthetics on outcome measures are usually disregarded. We hypothesized that exposure to isoflurane or sevoflurane modulates the outcome from blunt trauma with traumatic brain injury (bTBI). METHODS:We tested the hypothesis in a novel model of bTBI implemented in Drosophila melanogaster. Fruit flies of the standard laboratory strain w were cultured under standard conditions. We titrated the severity of bTBI to a mortality index at 24 hours (MI24) of approximately 20% under control conditions. We administered standard doses of isoflurane and sevoflurane before, before and during, or after bTBI and measured the resulting MI24. We report the MI24 as mean ± standard deviation. RESULTS:Isoflurane or sevoflurane administered for 2 hours before bTBI reduced the MI24 from 22.3 ± 2.6 to 10.4 ± 1.8 (P < 10, n = 12) and from 19.3 ± 0.9 to 8.9 ± 1.1 (P < .0001, n = 8), respectively. In contrast, administration of isoflurane after bTBI increased the MI24 from 18.5% ± 4.3% to 25.3% ± 9.1% (P = .0026, n = 22), while sevoflurane had no effect (22.4 ± 7.1 and 21.5 ± 5.8, n = 22). CONCLUSIONS:In a whole animal model of bTBI, general anesthetics were not indifferent with respect to early mortality. Therefore, collateral effects of general anesthetics should be considered in the interpretation of results obtained in vertebrate trauma models. Invertebrate model organisms can serve as a productive platform to interrogate anesthetic targets that mediate collateral effects and to inform trauma research in higher organisms about the potential impact of anesthetics on outcomes.

SUBMITTER: Fischer JA

PROVIDER: S-EPMC6260981 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Anesthetics Influence Mortality in a Drosophila Model of Blunt Trauma With Traumatic Brain Injury.

Fischer Julie A JA Olufs Zachariah P G ZPG Katzenberger Rebeccah J RJ Wassarman David A DA Perouansky Misha M

Anesthesia and analgesia 20180601 6

<h4>Background</h4>Exposure to anesthetics is common in the majority of early survivors of life-threatening injuries. Whether and to what degree general anesthetics influence outcomes from major trauma is unknown. Potential confounding effects of general anesthetics on outcome measures are usually disregarded. We hypothesized that exposure to isoflurane or sevoflurane modulates the outcome from blunt trauma with traumatic brain injury (bTBI).<h4>Methods</h4>We tested the hypothesis in a novel mo ...[more]

PMID: 29596093

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Project description:Disruption of the blood-brain barrier (BBB) results in cerebral edema formation, which is a major cause for high mortality after traumatic brain injury (TBI). As anesthetic care is mandatory in patients suffering from severe TBI it may be important to elucidate the effect of different anesthetics on cerebral edema formation. Tight junction proteins (TJ) such as zonula occludens-1 (ZO-1) and claudin-5 (cl5) play a central role for BBB stability. First, the influence of the volatile anesthetics sevoflurane and isoflurane on in-vitro BBB integrity was investigated by quantification of the electrical resistance (TEER) in murine brain endothelial monolayers and neurovascular co-cultures of the BBB. Secondly brain edema and TJ expression of ZO-1 and cl5 were measured in-vivo after exposure towards volatile anesthetics in native mice and after controlled cortical impact (CCI). In in-vitro endothelial monocultures, both anesthetics significantly reduced TEER within 24 hours after exposure. In BBB co-cultures mimicking the neurovascular unit (NVU) volatile anesthetics had no impact on TEER. In healthy mice, anesthesia did not influence brain water content and TJ expression, while 24 hours after CCI brain water content increased significantly stronger with isoflurane compared to sevoflurane. In line with the brain edema data, ZO-1 expression was significantly higher in sevoflurane compared to isoflurane exposed CCI animals. Immunohistochemical analyses revealed disruption of ZO-1 at the cerebrovascular level, while cl5 was less affected in the pericontusional area. The study demonstrates that anesthetics influence brain edema formation after experimental TBI. This effect may be attributed to modulation of BBB permeability by differential TJ protein expression. Therefore, selection of anesthetics may influence the barrier function and introduce a strong bias in experimental research on pathophysiology of BBB dysfunction. Future research is required to investigate adverse or beneficial effects of volatile anesthetics on patients at risk for cerebral edema.

Project description:ImportanceIncreased use of computed tomography (CT) in children is concerning owing to the cancer risk from ionizing radiation, particularly in children younger than 2 years. A guardian report that a child is acting abnormally is a risk factor for clinically important traumatic brain injury (ciTBI) and may be a driving factor for CT use in the emergency department.ObjectiveTo determine the prevalence of ciTBIs and TBIs in children younger than 2 years with minor blunt head trauma and a guardian report of acting abnormally with (1) no other findings or (2) other concerning findings for TBI.Design, setting, and participantsSecondary analysis of a large, prospective, multicenter cohort study that included 43 399 children younger than 18 years with minor blunt head trauma evaluated in 25 emergency departments. The study was conducted on data obtained between June 2004 and September 2006. Data analysis was performed between August 21, 2014, and March 9, 2015.ExposuresA guardian report that the child was acting abnormally after minor blunt head trauma.Main outcomes and measuresThe prevalence of ciTBI (defined as death, neurosurgery, intubation for >24 hours, or hospitalization for ≥2 nights in association with TBI on CT imaging) and TBI on CT imaging in children with a guardian report of acting abnormally with (1) no other findings and (2) other concerning findings for TBI.ResultsOf 43 399 children in the cohort study, a total of 1297 children had reports of acting abnormally, of whom 411 (31.7%) had this report as their only finding. Reported as percentage (95% CI), 1 of 411 (0.2% [0-1.3%]) had a ciTBI, and 4 TBIs were noted on the CT scans in 185 children who underwent imaging (2.2% [0.6%-5.4%]). In children with reports of acting abnormally and other concerning findings for TBI, 29 of 886 (3.3% [2.2%-4.7%]) had ciTBIs and 66 of 674 (9.8% [7.7%-12.3%]) had TBIs on CT.Conclusions and relevanceClinically important TBIs are very uncommon, and TBIs noted on CT are uncommon in children younger than 2 years with minor blunt head trauma and guardian reports of the child acting abnormally with no other clinical findings suspicious for TBI. Computed tomographic scans are generally not indicated in these children although observation in the emergency department may be warranted.

Project description:PurposeEarly diagnosis of traumatic brain injury (TBI) is important for improving survival and neurologic outcome in trauma victims. The purpose of this study was to assess whether Glasgow Coma Scale (GCS) of 12 or less can predict the presence of TBI and the severity of associated injuries in blunt trauma patients.MethodsA retrospective cohort study including 303,435 blunt trauma patients who were transferred from the scene to hospital from 1998 to 2013. The data was obtained from the records of the National Trauma Registry maintained by Israel's National Center for Trauma and Emergency Medicine Research, in the Gertner Institute for Epidemiology and Health Policy Research. All blunt trauma patients with GCS 12 or less were included in this study. Data collected in the registry include age, gender, mechanism of injury, GCS, initial blood pressure, presence of TBI and incidence of associated injuries. Patients younger than 14 years old and trauma victims with GCS 13-15 were excluded from the study. Statistical analysis was performed by using Statistical Analysis Software Version 9.2. Statistical tests performed included Chi-square tests. A p-value less than 0.05 was considered statistically significant.ResultsThere were 303,435 blunt trauma patients, 8731 (2.9%) of them with GCS of 3-12 that including 6351 (72%) patients with GCS of 3-8 and 2380 (28%) patient with GCS of 9-12. In these 8731 patients with GCS of 3-12, 5372 (61.5%) patients had TBI. There were total 1404 unstable patients in all the blunt trauma patients with GCS of 3-12, 1256 (89%) patients with GCS 3-8, 148 (11%) patients with GCS 9-12. In the 5095 stable blunt trauma patients with GCS 3-8, 32.4% of them had no TBI. The rate in the 2232 stable blunt trauma patients with GCS 9-12 was 50.1%. In the unstable patients with GCS 3-8, 60.5% of them had TBI, and in subgroup of patients with GCS 9-12, only 37.2% suffered from TBI.ConclusionThe utility of a GCS 12 and less is limited in prediction of brain injury in multiple trauma patients. Significant proportion of trauma victims with low GCS had no TBI and their impaired neurological status is related to severe extra-cranial injuries. The findings of this study showed that using of GCS in initial triage and decision making processes in blunt trauma patients needs to be re-evaluated.

Dataset Information

Anesthetics Influence Mortality in a Drosophila Model of Blunt Trauma With Traumatic Brain Injury.

Publications

Anesthetics Influence Mortality in a Drosophila Model of Blunt Trauma With Traumatic Brain Injury.

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