Aiolfi A, Benjamin E, Recinos G, De Leon Castro A, Inaba K, Demetriades D
J Emerg Med. 2017 Dec 16. pii: S0736-4679(17)31094-6.
BACKGROUND: The effect of prehospital helicopter emergency medical services (HEMS) on mortality has been analyzed previously in polytrauma patients with discordant results.
OBJECTIVE: Our aim was to compare outcomes in patients with isolated severe blunt traumatic brain injuries (TBIs) transported by HEMS or ground emergency medical services (GEMS).
METHODS: We conducted a National Trauma Data Bank study (2007-2014). All adult patients (≥16 years old) who sustained an isolated severe blunt TBI and were transported by HEMS or GEMS were included in the study.
RESULTS: There were 145,559 patients who met the inclusion criteria. Overall, 116,391 (80%) patients were transported via GEMS and 29,168 (20%) via HEMS. Median transportation time was longer for HEMS patients (41 vs. 25 min; p < 0.001). HEMS patients were more likely to have hypotension (2.7% vs. 1.5%; p < 0.001), Glasgow Coma Scale (GCS) score < 9 (38.2% vs. 10.9%; p < 0.001), and head Abbreviation Injury Scale (AIS) score of 5 (20.1% vs. 9.7%; p < 0.001). Stepwise logistic regression analysis identified age ≥ 65 years old, male sex, hypotension, GCS score < 9, prehospital intubation, and head AIS scores 4 and 5 as independent predictors of mortality. Helicopter transportation was independently associated with improved survival (odds ratio [OR] 0.55; 95% confidence interval [CI] 0.47-0.67; p < 0.001). Admission to a Level I trauma center was an independent predictor of survival (OR 0.64; 95% CI 0.53-0.82; p = 0.001). Regardless of head AIS, helicopter transport was an independent predictor of survival (AIS 3: OR 0.35; p < 0.001; AIS 4: OR 0.44; p < 0.001; AIS 5: OR 0.76; p < 0.001). A prolonged transport time was not an independent predictor of mortality.
CONCLUSIONS: Helicopter transport, in adult patients with isolated severe TBI, is associated with improved survival.
Holzmacher JL, Reynolds C, Patel M, Maluso P, Holland S, Gamsky N, Moore H, Acquista E, Carrick M, Amdur R, Hancock H, Metzler M, Dunn J, Sarani B
Brain Inj. 2018;32(3):325-330
INTRODUCTION: Platelet dysfunction following traumatic brain injury (TBI) is associated with worse outcomes. The efficacy of platelet transfusion to reverse antiplatelet medication (APM) remains unknown. Thrombelastography platelet mapping (TEG-PM) assesses platelet function. We hypothesize that platelet transfusion can reverse the effects of APM but does not improve outcomes following TBI.
METHODS: An observational study at six US trauma centres was performed. Adult patients on APM with CT evident TBI after blunt injury were enrolled. Demographics, brain CT and TEG-PM results before/after platelet transfusion, length of stay (LOS), and injury severity score (ISS) were abstracted.
RESULTS: Sixty six patients were enrolled (89% aspirin, 50% clopidogrel, 23% dual APM) with 23 patients undergoing platelet transfusion. Transfused patients had significantly higher ISS and admission CT scores. Platelet transfusion significantly reduced platelet inhibition due to aspirin (76.0 ± 30.2% to 52.7 ± 31.5%, p < 0.01), but had a non-significant impact on clopidogrel-associated inhibition (p = 0.07). Platelet transfusion was associated with longer length of stay (7.8 vs. 3.5 days, p < 0.01), but there were no differences in mortality.
CONCLUSION: Platelet transfusion significantly decreases platelet inhibition due to aspirin but is not associated with change in outcomes in patients on APM following TBI.
Ley EJ, Leonard SD, Barmparas G, Dhillon NK, Inaba K, Salim A, OʼBosky KR, Tatum D, Azmi H, Ball CG, Engels PT, Dunn JA, Carrick MM, Meizoso JP, Lombardo S, Cotton BA, Schroeppel TJ, Rizoli S, Chang DSJ, de León LA, Rezende-Neto J, Jacome T, Xiao J, Mallory G, Rao K, Widdel L, Godin S, Coates A, Benedict LA, Nirula R, Kaul S, Li T; Beta Blockers TBI Study Group Collaborators.
J Trauma Acute Care Surg. 2018 Feb;84(2):234-244
BACKGROUND: Beta blockers, a class of medications that inhibit endogenous catecholamines interaction with beta adrenergic receptors, are often administered to patients hospitalized after traumatic brain injury (TBI). We tested the hypothesis that beta blocker use after TBI is associated with lower mortality, and secondarily compared propranolol to other beta blockers.
METHODS: The American Association for the Surgery of Trauma Clinical Trial Group conducted a multi-institutional, prospective, observational trial in which adult TBI patients who required intensive care unit admission were compared based on beta blocker administration.
RESULTS: From January 2015 to January 2017, 2,252 patients were analyzed from 15 trauma centers in the United States and Canada with 49.7% receiving beta blockers. Most patients (56.3%) received the first beta blocker dose by hospital day 1. Those patients who received beta blockers were older (56.7 years vs. 48.6 years, p < 0.001) and had higher head Abbreviated Injury Scale scores (3.6 vs. 3.4, p < 0.001). Similarities were noted when comparing sex, admission hypotension, mean Injury Severity Score, and mean Glasgow Coma Scale. Unadjusted mortality was lower for patients receiving beta blockers (13.8% vs. 17.7%, p = 0.013). Multivariable regression determined that beta blockers were associated with lower mortality (adjusted odds ratio, 0.35; p < 0.001), and propranolol was superior to other beta blockers (adjusted odds ratio, 0.51, p = 0.010). A Cox-regression model using a time-dependent variable demonstrated a survival benefit for patients receiving beta blockers (adjusted hazard ratio, 0.42, p < 0.001) and propranolol was superior to other beta blockers (adjusted hazard ratio, 0.50, p = 0.003).
CONCLUSION: Administration of beta blockers after TBI was associated with improved survival, before and after adjusting for the more severe injuries observed in the treatment cohort. This study provides a robust evaluation of the effects of beta blockers on TBI outcomes that supports the initiation of a multi-institutional randomized control trial.
Melville LD, Shah K
Ann Emerg Med. 2017 Dec;70(6):910-911
Antiplatelet therapy appears to increase the risk for intracranial bleeding in patients with traumatic brain injury compared with those receiving warfarin or no antiplatelet therapy; however, this may not apply to aspirin monotherapy.
Nikolian VC, Dekker SE, Bambakidis T, Higgins GA, Dennahy IS, Georgoff PE, Williams AM, Andjelkovic AV, Alam HB
Crit Care Med. 2018 Jan;46(1):e59-e66
OBJECTIVE: Combined traumatic brain injury and hemorrhagic shock are highly lethal. Following injuries, the integrity of the blood-brain barrier can be impaired, contributing to secondary brain insults. The status of the blood-brain barrier represents a potential factor impacting long-term neurologic outcomes in combined injuries. Treatment strategies involving plasma-based resuscitation and valproic acid therapy have shown efficacy in this setting. We hypothesize that a component of this beneficial effect is related to blood-brain barrier preservation.
DESIGN: Following controlled traumatic brain injury, hemorrhagic shock, various resuscitation and treatment strategies were evaluated for their association with blood-brain barrier integrity. Analysis of gene expression profiles was performed using Porcine Gene ST 1.1 microarray. Pathway analysis was completed using network analysis tools (Gene Ontology, Ingenuity Pathway Analysis, and Parametric Gene Set Enrichment Analysis).
SUBJECTS: Female Yorkshire swine were subjected to controlled traumatic brain injury and 2 hours of hemorrhagic shock (40% blood volume, mean arterial pressure 30-35 mmHg).
INTERVENTIONS: Subjects were resuscitated with 1) normal saline, 2) fresh frozen plasma, 3) hetastarch, 4) fresh frozen plasma + valproic acid, or 5) hetastarch + valproic acid (n = 5 per group). After 6 hours of observation, brains were harvested for evaluation.
MEASUREMENTS AND MAIN RESULTS: Immunofluoroscopic evaluation of the traumatic brain injury site revealed significantly increased expression of tight-junction associated proteins (zona occludin-1, claudin-5) following combination therapy (fresh frozen plasma + valproic acid and hetastarch + valproic acid). The extracellular matrix protein laminin was found to have significantly improved expression with combination therapies. Pathway analysis indicated that valproic acid significantly modulated pathways involved in endothelial barrier function and cell signaling.
CONCLUSIONS: Resuscitation with fresh frozen plasma results in improved expression of proteins essential for blood-brain barrier integrity. The addition of valproic acid provides significant improvement to these protein expression profiles. This is likely secondary to activation of key pathways related to endothelial functions.
Nikolian VC, Georgoff PE, Pai MP, Dennahy IS, Chtraklin K, Eidy H, Ghandour MH, Han Y, Srinivasan A, Li Y, Alam HB.
J Trauma Acute Care Surg. 2017 Dec;83(6):1066-1073
BACKGROUND: We have previously shown that treatment with valproic acid (VPA) decreases brain lesion size in swine models of traumatic brain injury (TBI) and controlled hemorrhage. To translate this treatment into clinical practice, validation of drug efficacy and evaluation of pharmacologic properties in clinically realistic models of injury are necessary. In this study, we evaluate neurologic outcomes and perform pharmacokinetic analysis of a single dose of VPA in swine subjected to TBI, hemorrhagic shock, and visceral hemorrhage.
METHODS: Yorkshire swine (n = 5/cohort) were subjected to TBI, hemorrhagic shock, and polytrauma (liver and spleen injury, rib fracture, and rectus abdominis crush). Animals remained in hypovolemic shock for 2 hours before resuscitation with isotonic sodium chloride solution (ISCS; volume = 3× hemorrhage) or ISCS + VPA (150 mg/kg). Neurologic severity scores were assessed daily for 30 days, and brain lesion size was measured via magnetic resonance imaging on postinjury days (PID) 3 and 10. Serum samples were collected for pharmacokinetic analysis.
RESULTS: Shock severity and response to resuscitation were similar in both groups. Valproic acid-treated animals demonstrated significantly less neurologic impairment between PID 1 to 5 and smaller brain lesions on PID 3 (mean lesion size ± SEM, mm: ISCS = 4,956 ± 1,511 versus ISCS + VPA = 828 ± 279; p = 0.047). No significant difference in lesion size was identified between groups at PID 10 and all animals recovered to baseline neurologic function during the 30-day observation period. Animals treated with VPA had faster neurocognitive recovery (days to initiation of testing, mean ± SD: ISCS = 6.2 ± 1.6 vs ISCS + VPA = 3.6 ± 1.5; p = 0.002; days to task mastery: ISCS = 7.0 ± 1.0 vs ISCS + VPA = 4.8 ± 0.5; p = 0.03). The mean ± SD maximum VPA concentrations, area under the curve, and half-life were 145 ± 38.2 mg/L, 616 ± 150 hour·mg/L, and 1.70 ± 0.12 hours.
CONCLUSIONS: In swine subjected to TBI, hemorrhagic shock, and polytrauma, VPA treatment is safe, decreases brain lesion size, and reduces neurologic injury compared to resuscitation with ISCS alone. These benefits are achieved at clinically translatable serum concentrations of VPA.
LEVEL OF EVIDENCE: Therapeutic (preclinical study).
Ruiz IA, Squair JW, Phillips AA, Lukac CD, Huang D, Oxciano P, Yan D, Krassioukov AV
J Neurotrauma. 2018 Feb 1;35(3):461-466
Neurogenic shock, a distributive type of circulatory shock after spinal cord injury (SCI), results in profound hypotension. The consequent hemodynamic instability complicates clinical management, delays surgical intervention, and impacts neurological outcome. Moreover, the reported incidence of this condition varies significantly. We establish the true incidence of neurogenic shock by comparing the most common clinical definitions used to diagnose the condition. Further, we characterize the acute progression and recovery of neurogenic shock. Daily blood pressure, heart rate, and fluid management as well as vasopressor therapy and neurologic status were collected over 30 days from 84 adults admitted to our tertiary trauma center after cervical (n = 56) and thoracic (n = 28) SCI. We found that the reported incidence of neurogenic shock varied greatly depending on which clinical definition was applied. By using a novel combination of hemodynamic and laboratory criteria to define neurogenic shock, the calculated incidence (29% cervical SCI) in our sample most appropriately reflects the true incidence, finding that hypovolemia was the primary factor responsible for the inconsistency in incidence reports between studies. In addition, we found a characteristic decline in blood pressure after the first week post-injury and that fluid management is not currently an integral aspect of clinical management (all persons were treated at a net fluid intake ≤ zero). The results demonstrate the need for accurate identification of neurogenic shock through consistent and appropriate criteria, which is not only important from a clinical point of view, but also in establishing accurate epidemiology to responsibly allocate resources to its management.