Head Trauma / Traumatic Brain Injury (TBI)

#### HEAD TRAUMA / TRAUMATIC BRAIN INJURY (TBI)

J Emerg Trauma Shock. 2018 Jul-Sep;11(3):205-210

# Clinical Profile and Autopsy Findings in Fatal Head Injuries.

Alexis R, Jagdish S, Sukumar S, Pandit V, Palnivel C, Antony M

Aims: This study aims to correlate the autopsy findings with the clinical picture and imaging report in fatal head injury patients.

Settings and Design: A descriptive study conducted at tertiary care hospital in South India from July 2015 to December 2016.

Patients and Methods: All patients with head injuries who were admitted to our Emergency and Trauma Centre and underwent autopsy were included in the study. A structured pro forma was used for collecting information. Autopsy findings were considered as a gold standard to correlate with antemortem findings in fatal head injury. The data were analyzed with EpiData and OpenEpi statistical analyzing software.

Results: Of the 303 fatal head injury patients, a majority were males and age group between 21 and 40 years. Eighty-eight percent (267/303) of fatal head injuries were due to road traffic accidents. Twenty-five of the 303 patients reached our center within 1 h (golden hour) of trauma. Of the 303 fatal head injuries, 153 (50.5%) died within 24 h of reaching our center. The most common autopsy finding in this study was subarachnoid hemorrhage (SAH) (247/303, 81.3%). Diagnostic accuracy of Epi dural hemorrhage (EDH) antemortem had the highest value (98.35%). SAH had least diagnostic accuracy value (45.72). subdural hemorrhage (SDH) had highest sensitivity (57.02%). EDH had higher specificity (100%). Significant SDH, SAH, and brain contusions were not detected during antemortem evaluation.

Conclusions: Our study revealed that among fatal head injury patients, half of them died within first 24 h after reaching to tertiary care center. Diagnostic accuracy to detect extradural hemorrhage antemortem had the highest value and SAH had least diagnostic accuracy value. Significant subdural hemorrhage, subarachniod hemorrhage, and brain contusion were not detected during antemortem evaluation. Expertise in interpretation of imaging, adequate clinical examination, proper documentation, and early resuscitation may reduce the chances of missed injuries in head injury patients.

BMC Emerg Med. 2019 Jan 23;19(1):13

# Enhanced prehospital volume therapy does not lead to improved outcomes in severely injured patients with severe traumatic brain injury.

Hussmann B, Schoeneberg C, Jungbluth P, Heuer M Lefering R, Maek T, Hildebrand F, Lendemans S, Pape H

BACKGROUND: Whether enhanced prehospital volume therapy leads to outcome improvements in severely injured patients with severe traumatic brain injury (TBI) remains controversial. The aim of this study was to investigate the influence of prehospital volume therapy on the clinical course of severely injured patients with severe TBI.

METHODS: Data for 122,672 patients from TraumaRegister DGU® (TR-DGU) was analyzed. Inclusion criteria were defined as follows: Injury Severety Score (ISS) ≥ 16, primary admission, age ≥ 16 years, Abbreviated Injury Scale (AIS) head ≥3, administration of at least one unit of packed red blood cells (pRBCs), and available volume and blood pressure data. Stratification based on the following matched-pair criteria was performed: group 1: prehospital volumes of 0-1000 ml; group 2: prehospital volumes of ≥1501 ml; AIS head (3, 4, 5 + 6 and higher than for other body regions); age (16-54, 55-69, ≥ 70 years); gender; prehospital intubation (yes/no); emergency treatment time +/- 30 min.; rescue resources (rescue helicopter, emergency ambulance); blood pressure (20-60, 61-90, ≥ 91 mmHg); year of accident (2002-2005, 2006-2009, 2010-2012); AIS thorax, abdomen, and extremities plus pelvis.

RESULTS: A total of 169 patients per group fulfilled the inclusion criteria. Increasing volume administration was associated with reduced coagulation capability and reduced hemoglobin (Hb) levels (prothrombin ratio: group 1: 68%, group 2: 63.7%; p ≤ 0.04; Hb: group 1: 11.2 mg/dl, group 2: 10.2 mg/dl; p ≤ 0.001). It was not possible to show a significant reduction in the mortality rate with increasing volumes (group 1: 45.6, group 2: 45.6; p = 1).

CONCLUSIONS: The data presented in this study demonstrates that prehospital volume administration of more than 1500 ml does not improve severely injured patients with severe traumatic brain injury (TBI).

Scand J Trauma Resusc Emerg Med. 2018 Aug 22;26(1):68

# Prehospital treatment of patients with acute intracranial pathology: adherence to guidelines and blood pressure recommendations by the Danish Air Ambulance.

Juelsgaard J, Rognås L, Knudsen L, Hansen T, Rasmussen M

BACKGROUND: Hypoxia and hypotension may be associated with secondary brain injury and negative outcomes in patients with traumatic and non-traumatic intracranial pathology. Guidelines exist only for the prehospital management of patients with severe traumatic brain injury (TBI). In patients with non-traumatic intracranial pathology, TBI guideline recommendations may be applied to assess whether hypoxia and hypotension should be avoided during prehospital treatment. The main study objective was to assess the extent to which Danish Helicopter Emergency Medical Service (HEMS) critical care teams adhere to the prehospital TBI guideline recommendations for the management of patients with a clinical diagnosis of non-traumatic intracranial pathology or isolated TBI. Furthermore, in the same two groups of patients, we evaluated the adherence of the Danish HEMS critical care teams to recommendations aiming to maintain systolic blood pressure (SBP) > 110 mmHg and > 120 mmHg.

METHODS: In total, 211 prehospital patient records were studied. All patients were treated for non-traumatic intracranial pathology or isolated TBI by the Danish HEMS critical care teams from October 1, 2014, to January 1, 2017. Adherence to the prehospital TBI guideline recommendations and the SBP recommendations above was assessed in non-TBI and TBI populations.

RESULTS: The adherence rates to TBI guideline recommendations among Danish HEMS critical care teams were 69% (n = 106 [95% CI: 61-77%]) in the non-TBI population and 74% (n = 43 [95% CI: 61-85%]) in the TBI population. SBP > 110 mmHg was observed in 74% (n = 113 [95% CI: 66-81%]) and 69% (n = 40 [95% CI: 56-81%]) of cases in the non-TBI and TBI population, respectively. SBP > 120 mmHg was observed in 55% (n = 84, [95% CI: 47-63%]) of patients in the non-TBI population and 55% (n = 32 [95% CI: 42-68%]) of the patients in the TBI population.

CONCLUSIONS: Due to a lack of comparative data, it is difficult to determine the performance quality of the Danish HEMS critical care teams. Our findings may suggest that adherence to TBI guidelines and SBP recommendations needs to be a continuous focal point for the Danish HEMS to avoid secondary brain damage.

Continuum (Minneap Minn). 2018 Dec;24(6):1588-1602

# Cerebral Edema and Elevated Intracranial Pressure.

Koenig M

PURPOSE OF REVIEW: This article reviews the management of cerebral edema, elevated intracranial pressure (ICP), and cerebral herniation syndromes in neurocritical care.

RECENT FINDINGS: While corticosteroids may be effective in reducing vasogenic edema around brain tumors, they are contraindicated in traumatic cerebral edema. Mannitol and hypertonic saline use should be tailored to patient characteristics including intravascular volume status. In patients with traumatic brain injury who are comatose, elevated ICP should be managed with an algorithmic, multitiered treatment protocol to maintain an ICP of 22 mm Hg or less. Third-line ICP treatments include anesthetic agents, induced hypothermia, and decompressive craniectomy. Recent clinical trials have demonstrated that induced hypothermia and decompressive craniectomy are ineffective as early neuroprotective strategies and should be reserved for third-line management of refractory ICP elevation in severe traumatic brain injury. Monitoring for cerebral herniation should include bedside pupillometry in supratentorial space-occupying lesions and recognition of upward herniation in patients with posterior fossa lesions.

SUMMARY: Although elevated ICP, cerebral edema, and cerebral herniation are interrelated, treatments should be based on the distinct pathophysiologic process. Focal lesions resulting in brain compression are primarily managed with surgical decompression, whereas global or multifocal brain injury requires a treatment protocol that includes medical and surgical interventions.

Crit Care Med. 2019 Feb 5; Epub ahead of print

# The Effect of Goal-Directed Therapy on Patient Morbidity and Mortality After Traumatic Brain Injury, Results From the Progesterone for the Treatment of Traumatic Brain Injury III Clinical Trial.

Merck L, Yeatts S, Silbergleit R, Manley G, Pauls Q, Palesch Y, Conwit R, Le Roux P, Miller J, Frankel M, Wright D

OBJECTIVES: To estimate the impact of goal-directed therapy on outcome after traumatic brain injury, our team applied goal-directed therapy to standardize care in patients with moderate to severe traumatic brain injury, who were enrolled in a large multicenter clinical trial.

DESIGN: Planned secondary analysis of data from Progesterone for the Treatment of Traumatic Brain Injury III, a large, prospective, multicenter clinical trial.

SETTING: Forty-two trauma centers within the Neurologic Emergencies Treatment Trials network.

PATIENTS: Eight-hundred eighty-two patients were enrolled within 4 hours of injury after nonpenetrating traumatic brain injury characterized by Glasgow Coma Scale score of 4-12.

MEASUREMENTS AND MAIN RESULTS: Physiologic goals were defined a priori in order to standardize care across 42 sites participating in Progesterone for the Treatment of Traumatic Brain Injury III. Physiologic data collection occurred hourly; laboratory data were collected according to local ICU protocols and at a minimum of once per day. Physiologic transgressions were predefined as substantial deviations from the normal range of goal-directed therapy. Each hour where goal-directed therapy was not achieved was classified as a "transgression." Data were adjudicated electronically and via expert review. Six-month outcomes included mortality and the stratified dichotomy of the Glasgow Outcome Scale-Extended. For each variable, the association between outcome and either 1) the occurrence of a transgression or 2) the proportion of time spent in transgression was estimated via logistic regression model.

RESULTS: For the 882 patients enrolled in Progesterone for the Treatment of Traumatic Brain Injury III, mortality was 12.5%. Prolonged time spent in transgression was associated with increased mortality in the full cohort for hemoglobin less than 8 gm/dL (p = 0.0006), international normalized ratio greater than 1.4 (p < 0.0001), glucose greater than 180 mg/dL (p = 0.0003), and systolic blood pressure less than 90 mm Hg (p < 0.0001). In the patient subgroup with intracranial pressure monitoring, prolonged time spent in transgression was associated with increased mortality for intracranial pressure greater than or equal to 20 mm Hg (p < 0.0001), glucose greater than 180 mg/dL (p = 0.0293), hemoglobin less than 8 gm/dL (p = 0.0220), or systolic blood pressure less than 90 mm Hg (p = 0.0114). Covariates inversely related to mortality included: a single occurrence of mean arterial pressure less than 65 mm Hg (p = 0.0051) or systolic blood pressure greater than 180 mm Hg (p = 0.0002).

CONCLUSIONS: The Progesterone for the Treatment of Traumatic Brain Injury III clinical trial rigorously monitored compliance with goal-directed therapy after traumatic brain injury. Multiple significant associations between physiologic transgressions, morbidity, and mortality were observed. These data suggest that effective goal-directed therapy in traumatic brain injury may provide an opportunity to improve patient outcomes.

Scand J Trauma Resusc Emerg Med. 2019 Jan 28;27(1):9.

# Prehospital on-scene anaesthetist treating severe traumatic brain injury patients is associated with lower mortality and better neurological outcome.

Pakkanen T, Nurmi J, Huhtala H, Silfvast T

BACKGROUND: Patients with isolated traumatic brain injury (TBI) are likely to benefit from effective prehospital care to prevent secondary brain injury. Only a few studies have focused on the impact of advanced interventions in TBI patients by prehospital physicians. The primary end-point of this study was to assess the possible effect of an on-scene anaesthetist on mortality of TBI patients. A secondary end-point was the neurological outcome of these patients.

METHODS: Patients with severe TBI (defined as a head injury resulting in a Glasgow Coma Score of ≤8) from 2005 to 2010 and 2012-2015 in two study locations were determined. Isolated TBI patients transported directly from the accident scene to the university hospital were included. A modified six-month Glasgow Outcome Score (GOS) was defined as death, unfavourable outcome (GOS 2-3) and favourable outcome (GOS 4-5) and used to assess the neurological outcomes. Binary logistic regression analysis was used to predict mortality and good neurological outcome. The following prognostic variables for TBI were available in the prehospital setting: age, on-scene GCS, hypoxia and hypotension. As per the hypothesis that treatment provided by an on-scene anaesthetist would be beneficial to TBI outcomes, physician was added as a potential predictive factor with regard to the prognosis.

RESULTS: The mortality data for 651 patients and neurological outcome data for 634 patients were available for primary and secondary analysis. In the primary analysis higher age (OR 1.06 CI 1.05-1.07), lower on-scene GCS (OR 0.85 CI 0.79-0.92) and the unavailability of an on-scene anaesthetist (OR 1.89 CI 1.20-2.94) were associated with higher mortality together with hypotension (OR 3.92 CI 1.08-14.23). In the secondary analysis lower age (OR 0.95 CI 0.94-0.96), a higher on-scene GCS (OR 1.21 CI 1.20-1.30) and the presence of an on-scene anaesthetist (OR 1.75 CI 1.09-2.80) were demonstrated to be associated with good patient outcomes while hypotension (OR 0.19 CI 0.04-0.82) was associated with poor outcome.

CONCLUSION: Prehospital on-scene anaesthetist treating severe TBI patients is associated with lower mortality and better neurological outcome.

Med Sci (Basel). 2019 Jan 21;7(1)

# Prehospital and Emergency Care in Adult Patients with Acute Traumatic Brain Injury.

Pélieu I, Kull C, Walder B

Traumatic brain injury (TBI) is a major healthcare problem and a major burden to society. The identification of a TBI can be challenging in the prehospital setting, particularly in elderly patients with unobserved falls. Errors in triage on scene cannot be ruled out based on limited clinical diagnostics. Potential new mobile diagnostics may decrease these errors. Prehospital care includes decision-making in clinical pathways, means of transport, and the degree of prehospital treatment. Emergency care at hospital admission includes the definitive diagnosis of TBI with, or without extracranial lesions, and triage to the appropriate receiving structure for definitive care. Early risk factors for an unfavorable outcome includes the severity of TBI, pupil reaction and age. These three variables are core variables, included in most predictive models for TBI, to predict short-term mortality. Additional early risk factors of mortality after severe TBI are hypotension and hypothermia. The extent and duration of these two risk factors may be decreased with optimal prehospital and emergency care. Potential new avenues of treatment are the early use of drugs with the capacity to decrease bleeding, and brain edema after TBI. There are still many uncertainties in prehospital and emergency care for TBI patients related to the complexity of TBI patterns.

J Intensive Care Med. 2018 Dec 4: Epub ahead of print

# Management Strategies for Intracranial Pressure Crises in Subarachnoid Hemorrhage.

Ravishankar N, Nuoman R, Amuluru K, El-Ghanem M, Thulasi V, Dangayach N, Lee K, Al-Mufti F

OBJECTIVES: Standard management strategies for lowering intracranial pressure (ICP) in traumatic brain injury has been well-studied, but the use of lesser known interventions for ICP in subarachnoid hemorrhage (SAH) remains elusive. Searches were performed in PubMed and EBSCO Host to identify best available evidence for evaluation and management of medically refractory ICP in SAH. The role of standard management strategies such as head elevation, hyperventilation, mannitol and hypertonic saline as well as lesser known management such as sodium bicarbonate, indomethacin, tromethamine, decompressive craniectomy, decompressive laparotomy, hypothermia, and barbiturate coma are reviewed. We also included dose concentrations, dose frequency, infusion volume, and infusion rate for these lesser known strategies. Nonetheless, there is still a gap in the evidence to recommend optimal dosing, timing and its role in the improvement of outcomes but early diagnosis and appropriate management reduce adverse outcomes.

Am J Emerg Med. 2018 Dec 20;Epub ahead of print

# Effect of hypoxia on mortality and disability in traumatic brain injury according to shock status: A cross-sectional analysis.

Seo D, Shin S, Song K, Ro Y, Hong K, Park J

OBJECTIVES: This study aimed to test the association between hypoxia level and outcomes according to shock status in traumatic brain injury (TBI) patients.

METHODS: Adult TBI patients transported by emergency medical services in 10 provinces were enrolled. Hypoxia was a main exposure; three groups by oxygen saturation (SaO2, non-hypoxia (≥94%), mild hypoxia (90 ≤ SaO2 < 94%)), and severe hypoxia (<90%). Shock status (<systolic blood pressure 90 mmHg) was an interactive exposure. The outcomes were hospital mortality and worsened disability (a 2-point increase of Glasgow Outcome Scale). Multivariable logistic regression was used to calculate the adjusted odds (AORs) with 95% Confidence intervals (CIs).

RESULTS: Of the 6125 patients, the mortality/disability rates were 49.4%/69.0% in severe hypoxia, 30.7%/46.9% in mild hypoxia, and 18.5%/27.5% in normoxia (p < 0.0001). Mortality/disability rates were 47.1%/57.1% in shock status and 20.5%/31.4% in non-shock status (p < 0.0001). AORs (95% CIs) for worsened disability/mortality compared with normoxia (reference) were 3.23 (2.47-4.21)/2.24 (1.70-2.96) in patients with severe hypoxia and 2.11 (1.63-2.74)/1.84 (1.39-2.45) in those with mild hypoxia. AORs (95% CIs) for worsened disability/mortality was 1.58 (1.20-2.09)/1.33 (1.01-1.76) by severe hypoxia than normoxia in patient with only non-shock status in the interaction analysis.

CONCLUSIONS: There was a trend toward worsened outcomes with mild and severe hypoxia in patient with and without shock, however, the only met statistical significance for patients with both severe hypoxia and non-shock status.

Neurocrit Care. 2019 Apr;30(2):364-371

# Intraosseous Administration of 23.4% NaCl for Treatment of Intracranial Hypertension.

Wang J, Fang Y, Ramesh S, Zakaria A, Putman M, Dinescu D, Paik J, Geocadin R, Tahsili-Fahadan P, Altaweel LR

BACKGROUND/OBJECTIVE: Prompt treatment of acute intracranial hypertension is vital to preserving neurological function and frequently includes administration of 23.4% NaCl. However, 23.4% NaCl administration requires central venous catheterization that can delay treatment. Intraosseous catheterization is an alternative route of venous access that may result in more rapid administration of 23.4% NaCl.

METHODS: Single-center retrospective analysis of 76 consecutive patients, between January 2015 and January 2018, with clinical signs of intracranial hypertension received 23.4% NaCl through either central venous catheter or intraosseous access.

RESULTS: Intraosseous cannulation was successful on the first attempt in 97% of patients. No immediate untoward effects were seen with intraosseous cannulation. Time to treatment with 23.4% NaCl was significantly shorter in patients with intraosseous access compared to central venous catheter (p < 0.0001).

CONCLUSIONS: Intraosseous cannulation resulted in more rapid administration of 23.4% NaCl with no immediate serious complications. Further investigations to identify the clinical benefits and safety of hypertonic medication administration via intraosseous cannulation are warranted.

World Neurosurg. 2019 Mar;123:128-135

# Effect of Tranexamic Acid in Patients with Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Weng S, Wang W, Wei Q, Lan H, Su J, Xu Y

OBJECTIVE: Tranexamic acid (TXA) reduces hemorrhage volume and consequently the need for operative intervention. However, its effectiveness and safety in patients with traumatic brain injury (TBI) is unclear. We conducted this systematic review and meta-analysis to evaluate the safety and efficacy of TXA in patients with TBI.

METHODS: In July 2018, a systematic search for studies including patients with TBI treated with TXA was conducted using PubMed, Embase, and the Cochrane Library databases. Only related randomized controlled trials were included. Main outcomes included hematoma expansion, surgery rate, death rate, neurologic outcome, and any thrombosis events.

RESULTS: Of the identified 426 studies, 5 randomized controlled trials involving 917 patients met our inclusion criteria. For hematoma expansion, pooled results showed that TXA significantly decreased hemorrhage growth rate and total hemorrhage growth in patients with TBI. Regarding clinical outcomes, pooled results of surgery, mortality, and neurologic outcome showed no significant difference between the groups, and rate of thrombosis events was similar. Following sensitivity analysis, one study was excluded due to low quality. Then, results of TXA effect on mortality and neurologic outcomes became significant. We confirm that the earlier the TXA treatment is performed, the smaller the size of hematoma will be.

CONCLUSIONS: TXA demonstrates significant effect in reducing the risk of hematoma expansion by lowering the mortality rate and improving favorable neurologic outcomes in patients with TBI while not affecting thrombosis event rates. In addition, early TXA treatment is more effective in decreasing hematomas.

J Trauma Acute Care Surg. 2019 Mar;86(3):415-423

# Traumatic brain injury may worsen clinical outcomes after prolonged partial resuscitative endovascular balloon occlusion of the aorta in severe hemorrhagic shock model.

Williams A, Bhatti U, Dennahy S, Graham N, Nikolian V, Chtraklin K, Chang P, Zhou J, Biesterveld B, Eliason J, Alam H

BACKGROUND: The use of partial resuscitative endovascular balloon occlusion of the aorta (pREBOA) in combined hemorrhagic shock (HS) and traumatic brain injury (TBI) has not been well studied. We hypothesized that the use of pREBOA in the setting of TBI would be associated with worse clinical outcomes.

METHODS: Female Yorkshire swine were randomized to the following groups: HS-TBI, HS-TBI-pREBOA, and HS-pREBOA (n = 5/cohort). Animals in the HS-TBI group were left in shock for a total of 2 hours, whereas animals assigned to pREBOA groups were treated with supraceliac pREBOA deployment (60 minutes) 1 hour into the shock period. All animals were then resuscitated, and physiologic parameters were monitored for 6 hours. Further fluid resuscitation and vasopressors were administered as needed. At the end of the observation period, brain hemispheric swelling (%) and lesion size (mm) were assessed.

RESULTS: Mortality was highest in the HS-TBI-pREBOA group (40% [2/5] vs. 0% [0/5] in the other groups, p = 0.1). Severity of shock was greatest in the HS-TBI-pREBOA group, as defined by peak lactate levels and pH nadir (p < 0.05). Fluid resuscitation and norepinephrine requirements were significantly higher in the HS-TBI-pREBOA group (p < 0.05). No significant differences were noted in brain hemispheric swelling and lesion size between the groups.

CONCLUSION: Prolonged application of pREBOA in the setting of TBI does not contribute to early worsening of brain lesion size and edema. However, the addition of TBI to HS-pREBOA may worsen the severity of shock. Providers should be aware of the potential physiologic sequelae induced by TBI.

Crit Care Med. 2019 May;47(5):623-631

# The Effect of Goal-Directed Therapy on Patient Morbidity and Mortality After Traumatic Brain Injury: Results From the Progesterone for the Treatment of Traumatic Brain Injury III Clinical Trial.

Merck L, Yeatts S, Silbergleit R, Manley G, Pauls Q, Palesch Y, Conwit R, Le Roux P, Miller J, Frankel M, Wright D

OBJECTIVES: To estimate the impact of goal-directed therapy on outcome after traumatic brain injury, our team applied goal-directed therapy to standardize care in patients with moderate to severe traumatic brain injury, who were enrolled in a large multicenter clinical trial.

DESIGN: Planned secondary analysis of data from Progesterone for the Treatment of Traumatic Brain Injury III, a large, prospective, multicenter clinical trial.

SETTING: Forty-two trauma centers within the Neurologic Emergencies Treatment Trials network.

PATIENTS: Eight-hundred eighty-two patients were enrolled within 4 hours of injury after nonpenetrating traumatic brain injury characterized by Glasgow Coma Scale score of 4-12.

MEASUREMENTS AND MAIN RESULTS: Physiologic goals were defined a priori in order to standardize care across 42 sites participating in Progesterone for the Treatment of Traumatic Brain Injury III. Physiologic data collection occurred hourly; laboratory data were collected according to local ICU protocols and at a minimum of once per day. Physiologic transgressions were predefined as substantial deviations from the normal range of goal-directed therapy. Each hour where goal-directed therapy was not achieved was classified as a "transgression." Data were adjudicated electronically and via expert review. Six-month outcomes included mortality and the stratified dichotomy of the Glasgow Outcome Scale-Extended. For each variable, the association between outcome and either: 1) the occurrence of a transgression or 2) the proportion of time spent in transgression was estimated via logistic regression model.

RESULTS: For the 882 patients enrolled in Progesterone for the Treatment of Traumatic Brain Injury III, mortality was 12.5%. Prolonged time spent in transgression was associated with increased mortality in the full cohort for hemoglobin less than 8 gm/dL (p = 0.0006), international normalized ratio greater than 1.4 (p < 0.0001), glucose greater than 180 mg/dL (p = 0.0003), and systolic blood pressure less than 90 mm Hg (p < 0.0001). In the patient subgroup with intracranial pressure monitoring, prolonged time spent in transgression was associated with increased mortality for intracranial pressure greater than or equal to 20 mm Hg (p < 0.0001), glucose greater than 180 mg/dL (p = 0.0293), hemoglobin less than 8 gm/dL (p = 0.0220), or systolic blood pressure less than 90 mm Hg (p = 0.0114). Covariates inversely related to mortality included: a single occurrence of mean arterial pressure less than 65 mm Hg (p = 0.0051) or systolic blood pressure greater than 180 mm Hg (p = 0.0002).

CONCLUSIONS: The Progesterone for the Treatment of Traumatic Brain Injury III clinical trial rigorously monitored compliance with goal-directed therapy after traumatic brain injury. Multiple significant associations between physiologic transgressions, morbidity, and mortality were observed. These data suggest that effective goal-directed therapy in traumatic brain injury may provide an opportunity to improve patient outcomes.

Am J Surg. 2018 Nov 27;Epub ahead of print

# Trends in civilian penetrating brain injury: A review of 26,871 patients.

Skarupa D, Khan M, Hsu A, Madbak F, Ebler D, Yorkgitis B, Rahmathulla G, Alcindor D, Joseph B

INTRODUCTION: The aim of our study is to analyze the 5 years' trends, mortality rate, and factors that influence mortality after civilian penetrating traumatic brain injury (pTBI).

METHODS: We performed a 5-year-analysis of all trauma patients diagnosed with pTBI in the TQIP. Our outcome measures were trends of pTBI.

RESULTS: A total of 26,871 had penetrating brain injury over the 5-year period. Mean age was 36.2 ± 18 years. Overall 55% of the patients had severe TBI and mortality rate was 43.8%. There was an increase in the rate of pTBI from 3042/100,000 (2010) to 7578/100,000 trauma admissions (2014) (p < 0.001). The mortality rate has increased from 35% (2010) to 48% (2011) (p < 0.001) followed by a linear decrease in mortality to 40% (2014). Independent predictors of mortality were age, pre-hospital intubation, suicide attempt, and craniotomy/craniectomy.

CONCLUSIONS: Incidence and mortality for patients who are brought to hospitals following pTBI have gradually increased over the five-year period. Self-inflicted injury and prehospital intubation were the two most significant predictors of mortality.

JAMA Surg. 2019 May 8:Epub ahead of print

# Association of Statewide Implementation of the Prehospital Traumatic Brain Injury Treatment Guidelines With Patient Survival Following Traumatic Brain Injury: The Excellence in Prehospital Injury Care (EPIC) Study.

Spaite D, Bobrow B, Keim S, Barnhart B, Chikani V, Gaither J, Sherrill D, Denninghoff K, Mullins T, Adelson P, Rice A, Viscusi C, Hu C

Importance: Traumatic brain injury (TBI) is a massive public health problem. While evidence-based guidelines directing the prehospital treatment of TBI have been promulgated, to our knowledge, no studies have assessed their association with survival.

Objective: To evaluate the association of implementing the nationally vetted, evidence-based, prehospital treatment guidelines with outcomes in moderate, severe, and critical TBI.

Design, Setting, and Participants: The Excellence in Prehospital Injury Care (EPIC) Study included more than 130 emergency medical services systems/agencies throughout Arizona. This was a statewide, multisystem, intention-to-treat study using a before/after controlled design with patients with moderate to critically severe TBI (US Centers for Disease Control and Prevention Barell Matrix-Type 1 and/or Abbreviated Injury Scale Head region severity ≥3) transported to trauma centers between January 1, 2007, and June 30, 2015. Data were analyzed between October 25, 2017, and February 22, 2019.

Interventions: Implementation of the prehospital TBI guidelines emphasizing avoidance/treatment of hypoxia, prevention/correction of hyperventilation, and avoidance/treatment of hypotension.

Main Outcomes and Measures: Primary: survival to hospital discharge; secondary: survival to hospital admission.

Results: Of the included patients, the median age was 45 years, 14 666 (67.1%) were men, 7181 (32.9%) were women; 16 408 (75.1% ) were white, 1400 (6.4%) were Native American, 743 (3.4% ) were Black, 237 (1.1%) were Asian, and 2791 (12.8%) were other race/ethnicity. Of the included patients, 21 852 met inclusion criteria for analysis (preimplementation phase [P1]: 15 228; postimplementation [P3]: 6624). The primary analysis (P3 vs P1) revealed an adjusted odds ratio (aOR) of 1.06 (95% CI, 0.93-1.21; P = .40) for survival to hospital discharge. The aOR was 1.70 (95% CI, 1.38-2.09; P < .001) for survival to hospital admission. Among the severe injury cohorts (but not moderate or critical), guideline implementation was significantly associated with survival to discharge (Regional Severity Score-Head 3-4: aOR, 2.03; 95% CI, 1.52-2.72; P < .001; Injury Severity Score 16-24: aOR, 1.61; 95% CI, 1.07-2.48; P = .02). This was also true for survival to discharge among the severe, intubated subgroups (Regional Severity Score-Head 3-4: aOR, 3.14; 95% CI, 1.65-5.98; P < .001; Injury Severity Score 16-24: aOR, 3.28; 95% CI, 1.19-11.34; P = .02).

Conclusions and Relevance: Statewide implementation of the prehospital TBI guidelines was not associated with significant improvement in overall survival to hospital discharge (across the entire, combined moderate to critical injury spectrum). However, adjusted survival doubled among patients with severe TBI and tripled in the severe, intubated cohort. Furthermore, guideline implementation was significantly associated with survival to hospital admission. These findings support the widespread implementation of the prehospital TBI treatment guidelines.

Scand J Trauma Resusc Emerg Med. 2016 Dec 9;24(1):147.

# Impact of Cushing's sign in the prehospital setting on predicting the need for immediate neurosurgical intervention in trauma patients: a nationwide retrospective observational study.

Yumoto T, Mitsuhashi T, Yamakawa Y, Iida A, Nosaka N, Tsukahara K, Naito H, Nakao A

BACKGROUND: Cushing's reflex usually results from intracranial hypertension. Although Cushing's sign can implicate severe traumatic brain injury (TBI) in injured patients, no major investigations have been made. The purpose of this study was to assess the predictability of life-threatening brain injury requiring immediate neurosurgical intervention (LT-BI) among trauma patients with Cushing's sign in the prehospital setting.

METHODS: This was a retrospective study using data from the Japan Trauma Data Bank from the period of 2010 to 2014. Patients 16 years old or older with blunt mechanisms of injury who were transported directly from the scene and Glasgow Coma Scale for eye opening of one in the prehospital setting were included. LT-BI was defined as patients requiring burr hole evacuation or craniotomy within 24 h of hospital arrival and patients who were non-survivors due to isolated severe

TBI. Prehospital systolic blood pressure (pSBP) and heart rate (pHR) were assessed using area under the receiver operating characteristic curve (AUROC) and multiple logistic regression analysis to predict LT-BI.

RESULTS: Of 6332 eligible patients, 1859 (29%) exhibited LT-BI. AUROC of LT-BI using pSBP and pHR was 0.666 (95% confidence interval (CI); 0.652-0.681, P < 0.001), and 0.578 (95% CI; 0.563-0.594, P < 0.001), respectively. AUROC of pSBP was the highest among the 60 ≤ pHR ≤ 99 subgroup, of which AUROC was 0.680 (95% CI; 0.662-0.699, P < 0.001). Multiple logistic regression analysis showed that the higher the pSBP and the lower the pHR, the more likely that the patients had LT-BI. In a group with pSBP ≥ 180 mmHg and pHR ≤ 59 beats/min, the odds ratio and 95% CI of LT-BI after adjusting for age, sex, and severity of injuries to other body regions was 4.77 (2.85-7.97), P < 0.001 was compared with the reference group, which was defined as patients with normal vital signs.

DISCUSSION: Our study has found that the combination of hypertension and bradycardia, which are the components of Cushing's sign without eye opening in the prehospital setting was a weak but a significant predictor of LT-BI, or death due to possible isolated severe TBI.

CONCLUSIONS: Prehospital Cushing's sign with disturbed level of consciousness in trauma patients was a weak but significant predictor of the need for immediate neurosurgical intervention.

World Neurosurg. 2019 Feb;122:e1312-e1320

# The Relationship Between Colloid Transfusion During Surgical Decompression Hemicraniectomy Period and Postoperative Pneumonia or Long-Term Outcome After Space-Occupying Cerebral Infarction: A Retrospective Study.

Zhang L, Li R, Zhao X, Wang M, Fu Y

BACKGROUND: Colloid transfusion during surgical decompressive hemicraniectomy (DHC) to treat space-occupying cerebral infarction induced by middle cerebral artery (MCA) is controversial. A multicenter retrospective study was conducted to determine whether an increased colloid transfusion during surgery is associated with a lower incidence of postoperative pneumonia and better long-term outcomes after space-occupying cerebral infarction.

METHODS: Data from surgical DHC within 48 hours to treat space-occupying cerebral infarction that took place between November 30, 2013, and March 30, 2016, were collected in a multicenter chart. Univariate analysis, Spearman correlation, χ2 test, and bivariate and multivariate logistic regression were performed to account for the associations between colloid transfusion and postoperative pneumonia or long-term outcomes (indicated by modified Rankin Scale [mRS] scores).

RESULTS: Univariate analysis showed that surgical duration and mRS were significantly different between the subjects older and younger than 60 years who underwent surgical DHC (P < 0.05). In the entire population studied, increased National Institutes of Health Stroke Scale was associated with a greater incidence of postoperative pneumonia (odds ratio [OR] 1.255, P = 0.003) and increased mRS (OR 1.229, P = 0.014). In the population older than 60 years, it was revealed that increased colloid transfusion was associated with a lower incidence of postoperative pneumonia (OR 0.761, P = 0.030) or better outcomes, as indicated with lower mRS (OR 0.837, P = 0.045).

CONCLUSIONS: Our retrospective study demonstrated that there is a robust association between increased perioperative colloid transfusion and lower incidence of postoperative pneumonia and better outcomes among the patients older than 60 years after space-occupying cerebral infarction.

World Neurosurg X. 2019 Feb 13;2:100020. doi: 10.1016/j.wnsx.2019.100020. eCollection 2019 Apr.

# Prehospital Factors Associated with Discharge Outcomes: Baseline Data from the Andhra Pradesh Traumatic Brain Injury Project.

Ram K, VaraPrasad K, Krishna M, Kannan N, Sundar V, Joseph M, Sinha V, Shukla D, Gururaj G, Narayan R, Pattisapu J, Vavilala M

Objective: Strategies to improve traumatic brain injury (TBI) outcomes in India are ill defined. The objective of this study was to examine baseline prehospital (PH) factors associated with outcomes from the Andhra Pradesh Traumatic Brain Injury Project.

Methods: We conducted a prospective observational cohort study of adult patients with TBI admitted to the primary referral hospital. Modes of injury, prehospital care and transport, and factors associated with increased in-hospital mortality were evaluated. Poisson regression with robust error variance and adjusted attributable risk percent estimates determined factors associated with outcomes.

Results: A total of 447 adults (38% with mild TBI, 30% with moderate TBI, and 32% with severe TBI; 81% men) with isolated TBI (89%) from road traffic accidents (48.1%) or falls (46.5%) were enrolled. Of the patients, 45.7% were transported by ambulance, 61% had scalp/facial bleeding, 11% had respiratory distress, and 7% had cervical spine stabilization. Of these, 25.3% died and 34% had unfavorable outcomes. Among 335 direct admits, 45% traveled more than 50 km and nearly 20% traveled more than 100 km. Bleeding was associated with higher mortality (adjusted relative risk [aRR], 1.56; 95% confidence interval [CI], 1.05-2.31) and unfavorable outcome (aRR, 1.60; 95% CI, 1.18-2.17). Of the patients, 45 (31%) with severe TBI received PH airway management prior to definitive treatment, and respiratory distress was associated with unfavorable discharge outcomes (aRR, 1.23; 95% CI, 1.00-1.51).

Conclusions: Patients with TBI often received treatment far away from injury, bypassing closer hospitals. Scalp/facial bleeding was common and associated with unfavorable outcomes. Ambulance use was infrequent, and few patients received PH airway management, hemorrhage control, or cervical spine stabilization when needed.

Air Med J. 2019 Sep - Oct;38(5):366-373

# Prehospital Airway Management in Severe Traumatic Brain Injury.

Gamberini L, Baldazzi M, Coniglio C, Gordini G, Bardi T

OBJECTIVE: Traumatic brain injury (TBI) is a leading cause of death and disability among trauma patients. The final outcome of TBI results from a complex interaction between primary and secondary mechanisms of injury that begin immediately after the traumatic event. The aim of this review was to evaluate the latest evidence regarding the impact of prehospital airway management and the outcome after traumatic brain injury.

METHODS: PubMed, Embase, and Cochrane searches were conducted using the MeSH database. Airway management, traumatic brain injury, pneumonia, and the subheadings of these Medical Subject Headings were combined.

RESULTS: The review is structured into 4 major topics: airway management devices, prehospital pharmacologic management, mortality and neurologic outcomes, and early respiratory infections. The available literature shows a shift toward a more comprehensive view of prehospital airway management, taking into account not only the location where airway management is attempted but also the drugs administered, the airway management devices used, and the skills of the main professional figures attending the scene.

CONCLUSIONS: Literature about this topic is still inconclusive; however, new evidence taking into consideration more complex aspects of airway management rather than orotracheal intubation per se shows improved outcomes with aggressive prehospital airway management.

Ann Intensive Care. 2019 Sep 5;9(1):99

# Serum sodium and intracranial pressure changes after desmopressin therapy in severe traumatic brain injury patients: a multi-centre cohort study.

Harrois A, Anstey J, Taccone F, Udy A, Citerio G, Duranteau J, Ichai C, Badenes R, Prowle J, Ercole A, Oddo M, Schneider A, van der Jagt M, Wolf S, Helbok R, Nelson D, Skrifvars M, Cooper D, Bellomo R; TBI Collaborative

BACKGROUND: In traumatic brain injury (TBI) patients desmopressin administration may induce rapid decreases in serum sodium and increase intracranial pressure (ICP).

AIM: In an international multi-centre study, we aimed to report changes in serum sodium and ICP after desmopressin administration in TBI patients.

METHODS: We obtained data from 14 neurotrauma ICUs in Europe, Australia and UK for severe TBI patients (GCS ≤ 8) requiring ICP monitoring. We identified patients who received any desmopressin and recorded daily dose, 6-hourly serum sodium, and 6-hourly ICP.

RESULTS: We studied 262 severe TBI patients. Of these, 39 patients (14.9%) received desmopressin. Median length of treatment with desmopressin was 1 [1-3] day and daily intravenous dose varied between centres from 0.125 to 10 mcg. The median hourly rate of decrease in serum sodium was low (- 0.1 [- 0.2 to 0.0] mmol/L/h) with a median period of decrease of 36 h. The proportion of 6-h periods in which the rate of natremia correction exceeded 0.5 mmol/L/h or 1 mmol/L/h was low, at 8% and 3%, respectively, and ICPs remained stable. After adjusting for IMPACT score and injury severity score, desmopressin administration was independently associated with increased 60-day mortality [HR of 1.83 (1.05-3.24) (p = 0.03)].

CONCLUSIONS: In severe TBI, desmopressin administration, potentially representing instances of diabetes insipidus is common and is independently associated with increased mortality. Desmopressin doses vary markedly among ICUs; however, the associated decrease in natremia rarely exceeds recommended rates and median ICP values remain unchanged. These findings support the notion that desmopressin therapy is safe.

J Surg Res. 2019 Aug 16;245:367-372

# Preinjury Statins Are Associated With Improved Survival in Patients With Traumatic Brain Injury.

Lokhandwala A, Hanna K, Gries L, Zeeshan M, Ditillo M, Tang A, Hamidi M, Joseph B

BACKGROUND: Statins have been shown to improve outcomes in traumatic brain injury (TBI) in animal models. The aim of our study was to determine the effect of preinjury statins on outcomes in TBI patients.

METHODS: We performed a 4-y (2014-2017) review of our TBI database and included all patients aged ≥18 y with severe isolated TBI. Patients were stratified into those who were on statins and those who were not and were matched (1:2 ratio) using propensity score matching. The primary outcome was in-hospital mortality. The secondary outcomes were skilled nursing facility disposition, Glasgow Outcome Scale-extended score, and hospital and intensive care unit length of stay (LOS).

RESULTS: We identified 1359 patients, of which 270 were matched (statin: 90, no-statin: 180). Mean age was 55 ± 8y, median Glasgow Coma Scale was 10 (8-12), and median head-abbreviated injury scale was 3 (3-5). Matched groups were similar in age, mechanism of injury, Glasgow Coma Scale, Injury Severity Score, neurosurgical intervention, type and size of intracranial hemorrhage, and preinjury anticoagulant or antiplatelet use. The overall in-hospital mortality rate was 18%. Patients who received statins had lower rates of in-hospital mortality (11% versus 21%, P = 0.01), skilled nursing facility disposition (19% versus 28%; P = 0.04), and a higher median Glasgow Outcome Scale-extended (11 [9-13] versus 9 [8-10]; P = 0.04). No differences were found between the two groups in terms of hospital LOS (6 [4-9] versus 5 [3-8]; P = 0.34) and intensive care unit LOS (3 [3-6] versus 4 [3-5]; P = 0.09).

CONCLUSIONS: Preinjury statin use in isolated traumatic brain injury patients is associated with improved outcomes. This finding warrants further investigations to evaluate the potential beneficial role of statins as a therapeutic drug in a TBI.

LEVEL OF EVIDENCE: Level III Therapeutic.

Acta Neurochir (Wien). 2019 Sep;161(9):1943-1953

# A retrospective study of the effect of fibrinogen levels during fresh frozen plasma transfusion in patients with traumatic brain injury.

Nakae R, Yokobori S, Takayama Y, Kanaya T, Fujiki Y, Igarashi Y, Suzuki G, Naoe Y, Fuse A, Yokota H

BACKGROUND: The association between traumatic brain injury (TBI) and coagulopathy is well established. While coagulopathy prophylaxis in TBI involves replenishing coagulation factors with fresh frozen plasma (FFP), its effectiveness is controversial. We investigated the relationship between plasma fibrinogen concentration 3 h after initiating FFP transfusion and outcomes and evaluated the correlation with D-dimer levels at admission.

METHODS: We retrospectively examined data from 380 patients with severe isolated TBI with blood samples collected a maximum of 1 h following injury. Plasma fibrinogen and D-dimer concentrations were obtained at admission, and plasma fibrinogen concentration was again assessed 3-4 h following injury. The patients were divided into two groups based on whether or not they received FFP transfusion. Patients were also divided into subgroups according their fibrinogen level: ≥ 150 mg/dL (high-fibrinogen subgroup) or < 150 mg/dL (low-fibrinogen subgroup) 3 h after injury. Demographic, clinical, radiological and laboratory data were compared between these subgroups.

RESULTS: Glasgow Outcome Scale (GOS) scores at discharge and 3 months after injury were significantly lower in the FFP transfusion group than in the FFP non-transfusion group. Among patients who received FFP, GOS scores at discharge and 3 months after injury were significantly higher in the high-fibrinogen subgroup than in the low-fibrinogen subgroup. Elevated admission D-dimer predicted subsequent fibrinogen decrease.

CONCLUSIONS: In FFP transfusion, fibrinogen level ≥ 150 mg/dL 3 h after injury was associated with better outcomes in TBI patients. Assessing the admission D-dimer and tracking the fibrinogen are crucial for optimal coagulopathy prophylaxis in TBI patients.

Anesth Pain Med. 2019 Apr 28;9(2):e90858

# Significance of Cardiac Troponin I Elevation in Traumatic Brain Injury Patients.

Rimaz S, Ashraf A, Marzban S, Haghighi M, Zia Ziabari S, Biazar G, Rimaz S, Omidi S

Background: Myocardial dysfunction is frequently described as an underlying cause of mortality in traumatic brain injury (TBI) known as brain-cardiac link. However the impact on prognosis of a disease remains uncertain.

Objectives: The current study aimed at investigating the correlation between TBI and cardiac troponin I (cTnI) rise and in-hospital mortality rate among patients with TBI.

Methods: In the current prospective study TBI patients with abbreviated injury scale score (AIS) > 3 and Glasgow coma scale (GCS) score ≤ 8 with cTnI measurement within the first 24 hours of admission were evaluated. Chi-square, Kruskal-Wallis, Mann-Whitney U and Logistic Regression tests were used for data analysis.

Results: A total of 166 eligible patients were studied .The mean age of the cases was 37.64 ± 17.21 years, largely under 65 (93.4%) and male (86.7%).The most common injuries were cerebral contusion (35.1%), while motor vehicle crash (MVC) was the most common cause of injuries (83.73%); 59 % of the patients showed detectable cTnI concentrations within 24 hours of admission; 65.7% of the patients expired; they showed higher levels of cTnI compared to survivors that showed lower levels, 0.148 ± 0.074 vs 0.057 ± 0.055, respectively (P < 0.001). Moreover, a significant association was observed between mortality rate and lower admission GCS 3.49 ± 1.08 vs 6.79 ± 1.66, respectively (P < 0.001).

Conclusions: Increased cTnI levels could be a predictor of mortality among patients with TBI. Its measurement and investigation for therapeutic strategies could lead to better management of these cases.

JAMA Surg. 2019 Jul 1;154(7):e191152

# Association of Statewide Implementation of the Prehospital Traumatic Brain Injury Treatment Guidelines With Patient Survival Following Traumatic Brain Injury: The Excellence in Prehospital Injury Care (EPIC) Study.

Spaite D, Bobrow B, Keim S, Barnhart B, Chikani V, Gaither J, Sherrill D, Denninghoff K, Mullins T, Adelson P, Rice A, Viscusi C, Hu C

Importance: Traumatic brain injury (TBI) is a massive public health problem. While evidence-based guidelines directing the prehospital treatment of TBI have been promulgated, to our knowledge, no studies have assessed their association with survival.

Objective: To evaluate the association of implementing the nationally vetted, evidence-based, prehospital treatment guidelines with outcomes in moderate, severe, and critical TBI.

Design, Setting, and Participants: The Excellence in Prehospital Injury Care (EPIC) Study included more than 130 emergency medical services systems/agencies throughout Arizona. This was a statewide, multisystem, intention-to-treat study using a before/after controlled design with patients with moderate to critically severe TBI (US Centers for Disease Control and Prevention Barell Matrix-Type 1 and/or Abbreviated Injury Scale Head region severity ≥3) transported to trauma centers between January 1, 2007, and June 30, 2015. Data were analyzed between October 25, 2017, and February 22, 2019.

Interventions: Implementation of the prehospital TBI guidelines emphasizing avoidance/treatment of hypoxia, prevention/correction of hyperventilation, and avoidance/treatment of hypotension.

Main Outcomes and Measures: Primary: survival to hospital discharge; secondary: survival to hospital admission.

Results: Of the included patients, the median age was 45 years, 14 666 (67.1%) were men, 7181 (32.9%) were women; 16 408 (75.1% ) were white, 1400 (6.4%) were Native American, 743 (3.4% ) were Black, 237 (1.1%) were Asian, and 2791 (12.8%) were other race/ethnicity. Of the included patients, 21 852 met inclusion criteria for analysis (preimplementation phase [P1]: 15 228; postimplementation [P3]: 6624). The primary analysis (P3 vs P1) revealed an adjusted odds ratio (aOR) of 1.06 (95% CI, 0.93-1.21; P = .40) for survival to hospital discharge. The aOR was 1.70 (95% CI, 1.38-2.09; P < .001) for survival to hospital admission. Among the severe injury cohorts (but not moderate or critical), guideline implementation was significantly associated with survival to discharge (Regional Severity Score-Head 3-4: aOR, 2.03; 95% CI, 1.52-2.72; P < .001; Injury Severity Score 16-24: aOR, 1.61; 95% CI, 1.07-2.48; P = .02). This was also true for survival to discharge among the severe, intubated subgroups (Regional Severity Score-Head 3-4: aOR, 3.14; 95% CI, 1.65-5.98; P < .001; Injury Severity Score 16-24: aOR, 3.28; 95% CI, 1.19-11.34; P = .02).

Conclusions and Relevance: Statewide implementation of the prehospital TBI guidelines was not associated with significant improvement in overall survival to hospital discharge (across the entire, combined moderate to critical injury spectrum). However, adjusted survival doubled among patients with severe TBI and tripled in the severe, intubated cohort. Furthermore, guideline implementation was significantly associated with survival to hospital admission. These findings support the widespread implementation of the prehospital TBI treatment guidelines.