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Guidelines for Prehospital Management of Traumatic Brain Injury 3rd Edition: Executive Summary. Prehospital care markedly influences outcome from traumatic brain injury, yet it remains highly variable. The Brain Trauma Foundation's guidelines informing prehospital care, first published in 2002, have sought to identify and disseminate best practices. Many of its recommendations relate to the management of airway, breathing and circulation, and infrastructure for this care. Compliance with the second edition of these guidelines has been associated with significantly improved survival. A working group developed evidence-based recommendations informing assessment, treatment, and transport decision-making relevant to the prehospital care of brain injured patients. A literature search spanning May 2005 to January 2022 supplemented data contained in the 2nd edition. Identified studies were assessed for quality and used to inform evidence-based recommendations. A total of 122 published articles formed the evidentiary base for this guideline update including 5 providing Class I evidence, 35 providing Class II evidence, and 98 providing Class III evidence for the various topics. Forty evidence-based recommendations were generated, 30 of which were strong and 10 of which were weak. In many cases, new evidence allowed guidelines from the 2nd edition to be strengthened. Development of guidelines on some new topics was possible including the prehospital administration of tranexamic acid. A management algorithm is also presented. These guidelines help to identify best practices for prehospital traumatic brain injury care, and they also identify gaps in knowledge which we hope will be addressed before the next edition.

Twenty-three panelists were selected and screened for conflicts of interest. Using a Population, Intervention, Comparator, Outcomes, Timing framework, the workgroup specified key clinical questions pertaining to both adult and pediatric populations for (1) Assessment, 2) Treatment, and 3) Transport and Decision-Making. Study inclusion criteria were as follows: human subjects, traumatic brain injury, English language, ≥25 subjects, randomized controlled trials, cohort studies, case-control studies, case series, databases, and registries. Exclusion criteria included inappropriate independent or dependent variables, statistics inappropriate to the research design, variables and/or sample size, case studies, editorials, comments, and letters. The systematic review was registered (PROSPERO CRD42021269941) and conducted based on established methods and reporting standards.13-16 Ethics approval and patient consent were not required for this review of published studies. The literature search examined publications from May of 2005 through January 2022. Search strategies included Ovid MEDLINE and Cochrane databases for published literature and ClinicalTrials.gov for ongoing/completed trials. Electronic searches were supplemented by workgroup recommendations and cross-referencing.

udies. The literature search examined publications from May of 2005 through January 2022. Search strategies included Ovid MEDLINE and Cochrane databases for published literature and ClinicalTrials.gov for ongoing/completed trials. Electronic searches were supplemented by workgroup recommendations and cross-referencing. Predefined criteria based on those developed by the US Preventive Services Task Force, the National Health Service Centre for Reviews and Dissemination, and the Cochrane Collaboration were used to assess the quality of the included studies. The quality of evidence for each topic was assessed using the standards established by the Agency for Healthcare Research and Quality Evidence-Based Practice methods guidance, including study limitations, consistency, directness, and precision. The strength of the body evidence was classed as high, moderate, low, or insufficient. Recommendations were categorized for strength and quality of evidence. The strength of the recommendation was derived from the overall quality of the body of evidence used to assess the topic. Consistent with methods generated by the Grades of Recommendation, Assessment, Development, and Evaluation working group, recommendations were categorized as either strong or weak, reflecting the degree of confidence that the favorable effects of recommendation adherence outweigh the unfavorable effects.

Twenty-three panelists were selected and screened for conflicts of interest. Using a Population, Intervention, Comparator, Outcomes, Timing framework, the workgroup specified key clinical questions pertaining to both adult and pediatric populations for (1) Assessment, 2) Treatment, and 3) Transport and Decision-Making.

Study inclusion criteria were as follows: human subjects, traumatic brain injury, English language, ≥25 subjects, randomized controlled trials, cohort studies, case-control studies, case series, databases, and registries. Exclusion criteria included inappropriate independent or dependent variables, statistics inappropriate to the research design, variables and/or sample size, case studies, editorials, comments, and letters.

The systematic review was registered (PROSPERO CRD42021269941) and conducted based on established methods and reporting standards.13-16 Ethics approval and patient consent were not required for this review of published studies. The literature search examined publications from May of 2005 through January 2022. Search strategies included Ovid MEDLINE and Cochrane databases for published literature and ClinicalTrials.gov for ongoing/completed trials. Electronic searches were supplemented by workgroup recommendations and cross-referencing.

Predefined criteria based on those developed by the US Preventive Services Task Force, the National Health Service Centre for Reviews and Dissemination, and the Cochrane Collaboration were used to assess the quality of the included studies. The quality of evidence for each topic was assessed using the standards established by the Agency for Healthcare Research and Quality Evidence-Based Practice methods guidance, including study limitations, consistency, directness, and precision. The strength of the body evidence was classed as high, moderate, low, or insufficient.

Recommendations were categorized for strength and quality of evidence. The strength of the recommendation was derived from the overall quality of the body of evidence used to assess the topic. Consistent with methods generated by the Grades of Recommendation, Assessment, Development, and Evaluation working group, recommendations were categorized as either strong or weak, reflecting the degree of confidence that the favorable effects of recommendation adherence outweigh the unfavorable effects.

A total of 122 published articles formed the evidentiary base for this guideline update.12 For the included topics, 5 studies provided Class I evidence, 35 provided Class II evidence, and 98 provided Class III evidence. Sixteen manuscripts provided evidence for more than 1 topic. From this evidence, 40 evidence-based recommendations were generated, 30 of which were strong and 10 of which were weak. This contrasts with the second edition in which all recommendations were graded weak. Consistent with the structure of the preceding 2nd edition, recommendations were grouped into topics including Assessment, Treatment, and Transport Decision-Making. Key evidence supporting a higher SBP threshold for hypotension. Unadjusted analysis of probability of death by SBP. Unadjusted analysis of the probability of dying in the hospital plotted against lowest out-of-hospital SBP. The dotted lines represent 95% confidence bands. Reprinted from “Annals of Emergency Medicine,” 80 (1). Spaite DW, et al. “Optimal Out-of-Hospital Blood Pressure in Major Traumatic Brain Injury: A Challenge to the Current Understanding of Hypotension,” pages 46–59, 2022, with permission from Elsevier. SBP, systolic blood pressure.

ines represent 95% confidence bands. Reprinted from “Annals of Emergency Medicine,” 80 (1). Spaite DW, et al. “Optimal Out-of-Hospital Blood Pressure in Major Traumatic Brain Injury: A Challenge to the Current Understanding of Hypotension,” pages 46–59, 2022, with permission from Elsevier. SBP, systolic blood pressure. Key evidence supporting maintenance of euthermia. Lowest smoothing function for unadjusted mortality vs initial trauma center temperature. Reprinted from “Body Temperature after EMS Transport: Association with Traumatic Brain Injury Outcomes,” Gaither JB, et al, Prehospital Emergency Care, copyright © 2017 National Association of EMS Physicians, reprinted by permission of Informa UK Limited, trading as Taylor & Francis Group, www.tandfonline.com on behalf of 2017 National Association of EMS Physicians.

port: Association with Traumatic Brain Injury Outcomes,” Gaither JB, et al, Prehospital Emergency Care, copyright © 2017 National Association of EMS Physicians, reprinted by permission of Informa UK Limited, trading as Taylor & Francis Group, www.tandfonline.com on behalf of 2017 National Association of EMS Physicians. The Assessment section was subdivided into 3 subtopics including Oxygenation, Blood Pressure, and Temperature; Glasgow Coma Scale; and Pupil Examination (Table 1). The new Oxygenation, Blood Pressure, and Temperature section contains 13 recommendations and subrecommendations. In general, these recommendations suggest frequent or continuous monitoring of these physiologic variables. They recommend using appropriately sized equipment and target values with pediatric patients. Nine of the new recommendations are strong while 4 are weak. A new weak recommendation now suggests that temperature be measured in the prehospital environment and that euthermia be maintained (98-99°F or 36-37°C). Although the oxygen saturation threshold of 90% remains unchanged in the third edition, all adult and pediatric blood pressure targets have been increased to higher threshold values. For adults, the new recommendation is to maintain systolic blood pressure (SBP) >110 mm Hg. There are new recommendations to avoid hyperventilation by maintaining end tidal CO2 values between 35 and 45 mm Hg (4.6-6.0 kPa). Recommended pediatric blood pressure cuff sizes are now presented. Recommendations Related to the Prehospital Assessment of Brain Injured Patients

The Assessment section was subdivided into 3 subtopics including Oxygenation, Blood Pressure, and Temperature; Glasgow Coma Scale; and Pupil Examination (Table 1). The new Oxygenation, Blood Pressure, and Temperature section contains 13 recommendations and subrecommendations. In general, these recommendations suggest frequent or continuous monitoring of these physiologic variables. They recommend using appropriately sized equipment and target values with pediatric patients. Nine of the new recommendations are strong while 4 are weak. A new weak recommendation now suggests that temperature be measured in the prehospital environment and that euthermia be maintained (98-99°F or 36-37°C). Although the oxygen saturation threshold of 90% remains unchanged in the third edition, all adult and pediatric blood pressure targets have been increased to higher threshold values. For adults, the new recommendation is to maintain systolic blood pressure (SBP) >110 mm Hg. There are new recommendations to avoid hyperventilation by maintaining end tidal CO2 values between 35 and 45 mm Hg (4.6-6.0 kPa). Recommended pediatric blood pressure cuff sizes are now presented. Recommendations Related to the Prehospital Assessment of Brain Injured Patients GCS, Glasgow Coma Scale; SBP, systolic blood pressure; SMS, Simplified Motor Score; TBI, traumatic brain injury. Strong recommendations are presented in bold. Weak recommendations are presented in unbolded font. Reproduced from Lulla et al 202312 with permission from the authors.

Recommendations Related to the Prehospital Assessment of Brain Injured Patients GCS, Glasgow Coma Scale; SBP, systolic blood pressure; SMS, Simplified Motor Score; TBI, traumatic brain injury. Strong recommendations are presented in bold. Weak recommendations are presented in unbolded font. Reproduced from Lulla et al 202312 with permission from the authors. In this edition, 8 recommendations are provided related to application of the Glasgow Coma Scale (GCS),17 6 of which were rated strong. There is a new recommendation to reassess the GCS at least every 30 minutes. Also new is the recommendation to communicate the GCS and changes in GCS during every communication with the receiving hospital's care team. A new recommendation also acknowledges the important prognostic information inherent to the motor component of the GCS which can also be assessed using the Simplified Motor Score.18,19 In the third edition, 2 recommendations are provided related to pupil examination, both of which were rated as strong. The new recommendations are only subtly changed, recommending communication of the pupil findings to the hospital care team as well as the identification and recording of potential confounds to the pupil examination. The second edition guidelines subdivided Treatment into 3 parts including Airway, Ventilation, and Oxygenation; Fluid Resuscitation; and Cerebral Herniation. In the new third edition, the subtopic Cerebral Herniation is renamed Hyperventilation and Hyperosmolar Therapy for Suspected Increased Intracranial Pressure (Table 2).

cond edition guidelines subdivided Treatment into 3 parts including Airway, Ventilation, and Oxygenation; Fluid Resuscitation; and Cerebral Herniation. In the new third edition, the subtopic Cerebral Herniation is renamed Hyperventilation and Hyperosmolar Therapy for Suspected Increased Intracranial Pressure (Table 2). Recommendations Related to the Prehospital Treatment of Brain-Injured Patients EMS, Emergency Medical Service; GCS, Glasgow Coma Scale; ICH, intracranial hemorrhage; ICP, intracranial pressure; RSI, rapid sequence intubation; SpO2, oxygen saturation; TBI, traumatic brain injury; TXA, tranexamic acid. Strong recommendations are presented in bold. Weak recommendations are presented in unbolded font. Reproduced from Lulla et al 202312 with permission from the authors.

EMS, Emergency Medical Service; GCS, Glasgow Coma Scale; ICH, intracranial hemorrhage; ICP, intracranial pressure; RSI, rapid sequence intubation; SpO2, oxygen saturation; TBI, traumatic brain injury; TXA, tranexamic acid. Strong recommendations are presented in bold. Weak recommendations are presented in unbolded font. Reproduced from Lulla et al 202312 with permission from the authors. In the Airway, Ventilation, and Oxygenation section, there are 6 strong recommendations. A new recommendation suggests placing all brain-injured patients on supplemental oxygen in the prehospital environment irrespective of their baseline oxygen saturation to reduce secondary insults related to hypoxia. Also new is the recommendation to ensure appropriate airway positioning as a means of correcting hypoxia. The recommendation to avoid routine use of paralytics to assist the intubation of spontaneously breathing patients which appeared in the second edition no longer appears in the 3rd edition. Different options for airway management are now explicitly articulated. Capnography is now recommended as an additional strategy to confirm successful placement of an endotracheal tube. Approximately 10 breaths per minute is now recommended to maintain a normal breathing rate, and ventilatory adjuncts such as pressure-controlled bags, ventilation rate timers, ETCO2 monitoring, and ventilators are now recommended to minimize hypoventilation and hyperventilation.

ssful placement of an endotracheal tube. Approximately 10 breaths per minute is now recommended to maintain a normal breathing rate, and ventilatory adjuncts such as pressure-controlled bags, ventilation rate timers, ETCO2 monitoring, and ventilators are now recommended to minimize hypoventilation and hyperventilation. In the Hyperventilation and Hyperosmolar Therapy for Suspected Increased Intracranial Pressure subsection, there are now 4 strong recommendations and 1 weak recommendation. A 2-point GCS change is no longer recommended as a threshold for declaring neurological deterioration. Prophylactic hyperventilation remains discouraged and capnography is now recommended to help maintain eucapnia. While the previous edition recommended breathing rates to achieve hyperventilation, the third edition has removed these and instead recommends targeting capnography values. This section contains 2 new recommendations related to the prehospital administration of hyperosmolar therapy and tranexamic acid (TXA): prophylactic administration of hyperosmolar therapy in the absence of signs of herniation is discouraged as is prehospital administration of TXA for suspected intracerebral hemorrhage or intracranial pressure elevation. In the Fluid Resuscitation section, 3 recommendations are largely unchanged from the previous edition. Those related to the administration of isotonic intravenous fluids have been upgraded to strong recommendations while the third recommendation permitting hypertonic resuscitation remains weak.

In the Hyperventilation and Hyperosmolar Therapy for Suspected Increased Intracranial Pressure subsection, there are now 4 strong recommendations and 1 weak recommendation. A 2-point GCS change is no longer recommended as a threshold for declaring neurological deterioration. Prophylactic hyperventilation remains discouraged and capnography is now recommended to help maintain eucapnia. While the previous edition recommended breathing rates to achieve hyperventilation, the third edition has removed these and instead recommends targeting capnography values. This section contains 2 new recommendations related to the prehospital administration of hyperosmolar therapy and tranexamic acid (TXA): prophylactic administration of hyperosmolar therapy in the absence of signs of herniation is discouraged as is prehospital administration of TXA for suspected intracerebral hemorrhage or intracranial pressure elevation. In the Fluid Resuscitation section, 3 recommendations are largely unchanged from the previous edition. Those related to the administration of isotonic intravenous fluids have been upgraded to strong recommendations while the third recommendation permitting hypertonic resuscitation remains weak. In the section Decision-Making Within the EMS System: Dispatch, Scene, Transportation, and Destination, 6 strong and 1 weak recommendation are now provided (Table 3). Although the strength of these recommendations has increased, the content has only changed minimally. The new guidelines do provide new emphasis on the importance of comprehensive documentation of the time, assessment, and treatment provided by first responders.

ong and 1 weak recommendation are now provided (Table 3). Although the strength of these recommendations has increased, the content has only changed minimally. The new guidelines do provide new emphasis on the importance of comprehensive documentation of the time, assessment, and treatment provided by first responders. Recommendations Related to Transport and Decision-Making Within the EMS System for Brain-Injured Patients CT, computed tomography; EMS, Emergency Medical Service; TBI, traumatic brain injury. Strong recommendations are presented in bold. Weak recommendations are presented in unbolded font. Reproduced from Lulla et al 202312 with permission from the authors.

Recommendations Related to the Prehospital Assessment of Brain Injured Patients GCS, Glasgow Coma Scale; SBP, systolic blood pressure; SMS, Simplified Motor Score; TBI, traumatic brain injury. Strong recommendations are presented in bold. Weak recommendations are presented in unbolded font. Reproduced from Lulla et al 202312 with permission from the authors. In this edition, 8 recommendations are provided related to application of the Glasgow Coma Scale (GCS),17 6 of which were rated strong. There is a new recommendation to reassess the GCS at least every 30 minutes. Also new is the recommendation to communicate the GCS and changes in GCS during every communication with the receiving hospital's care team. A new recommendation also acknowledges the important prognostic information inherent to the motor component of the GCS which can also be assessed using the Simplified Motor Score.18,19 In the third edition, 2 recommendations are provided related to pupil examination, both of which were rated as strong. The new recommendations are only subtly changed, recommending communication of the pupil findings to the hospital care team as well as the identification and recording of potential confounds to the pupil examination.

The second edition guidelines subdivided Treatment into 3 parts including Airway, Ventilation, and Oxygenation; Fluid Resuscitation; and Cerebral Herniation. In the new third edition, the subtopic Cerebral Herniation is renamed Hyperventilation and Hyperosmolar Therapy for Suspected Increased Intracranial Pressure (Table 2). Recommendations Related to the Prehospital Treatment of Brain-Injured Patients EMS, Emergency Medical Service; GCS, Glasgow Coma Scale; ICH, intracranial hemorrhage; ICP, intracranial pressure; RSI, rapid sequence intubation; SpO2, oxygen saturation; TBI, traumatic brain injury; TXA, tranexamic acid. Strong recommendations are presented in bold. Weak recommendations are presented in unbolded font. Reproduced from Lulla et al 202312 with permission from the authors.

In the section Decision-Making Within the EMS System: Dispatch, Scene, Transportation, and Destination, 6 strong and 1 weak recommendation are now provided (Table 3). Although the strength of these recommendations has increased, the content has only changed minimally. The new guidelines do provide new emphasis on the importance of comprehensive documentation of the time, assessment, and treatment provided by first responders. Recommendations Related to Transport and Decision-Making Within the EMS System for Brain-Injured Patients CT, computed tomography; EMS, Emergency Medical Service; TBI, traumatic brain injury. Strong recommendations are presented in bold. Weak recommendations are presented in unbolded font. Reproduced from Lulla et al 202312 with permission from the authors.

The third edition of the BTF's Guidelines for Prehospital Management of Traumatic Brain Injury12 updates the recommendations provided in 2008.6 This edition includes additional evidence published over a subsequent 17-year period. Without question, the most important difference in this update is that 75% of the recommendations are now strong—in the second edition, all of the recommendations were graded as weak. There are additional noteworthy changes in these updated guidelines. The blood pressure targets have been increased across the age spectrum. This parallels the change in the BTF's 4th edition adult severe TBI guidelines.20 Immediate application of supplemental oxygen is now recommended for all patients with suspicion of moderate or severe TBI irrespective of their baseline oxygen saturation. Capnography is now more strongly and frequently recommended to guide care, especially the avoidance of hyperventilation in the absence of herniation. Recommendations related to temperature management now appear for the first time. The 3rd edition guidelines place a greater emphasis on the motor component of the GCS and no longer refer to a global 2-point change as a threshold for intervention similar to the SIBICC algorithms.21,22 These guidelines put greater emphasis on documentation and communication and provide more explicit, helpful recommendations related to airway management options and patient monitoring. The new edition includes a management algorithm (Figure 3); one had accompanied the first5 but not the second edition6 of these guidelines.

e guidelines put greater emphasis on documentation and communication and provide more explicit, helpful recommendations related to airway management options and patient monitoring. The new edition includes a management algorithm (Figure 3); one had accompanied the first5 but not the second edition6 of these guidelines. Prehospital algorithm for evaluation and management of patients with suspicion for moderate-to-severe TBI. This figure details pathways for managing the airway, breathing, and circulation in patients with suspected moderate or severe traumatic brain injury as well as a process for managing impaired level of consciousness. Key values for pediatric patients are presented. © 2023, Al Lulla. Used with permission. BGL, blood glucose; etCO2, end-tidal carbon dioxide; GCS, Glasgow Coma Scale; SBP, systolic blood pressure; TBI, traumatic brain injury.

vere traumatic brain injury as well as a process for managing impaired level of consciousness. Key values for pediatric patients are presented. © 2023, Al Lulla. Used with permission. BGL, blood glucose; etCO2, end-tidal carbon dioxide; GCS, Glasgow Coma Scale; SBP, systolic blood pressure; TBI, traumatic brain injury. Recent literature has led to important changes in our understanding of hypotension in the prehospital environment. In the past, studies investigated arbitrary cut-points leading to thresholds that were merely statistical artifacts. As well, in older literature, prehospital measures were not associated with outcome data subsequent to hospital admission. Perhaps the most important new study on this topic comes from Spaite et al23 who overcame these limitations in conjunction with the previously described EPIC study. In their analysis of 12 169 patients, the investigators were able to associate prehospital blood pressure measurements with outcome in a continuous fashion (Figure 1). The results strongly suggested that the traditional SBP threshold for defining hypotension—90 mm Hg—is too low. The lowest risk of mortality associated was seen when SBP was maintained above 125 mm Hg. Ultimately, the 3rd edition panelists chose to recommend maintaining SBP >110 mm Hg while acknowledging that the optimal threshold may be higher.12 Overall, the literature more strongly supports the avoidance of hypotension than inducing hypertension. Spaite et al12 and others24,25 have associated high blood pressures early after TBI with poor outcomes. Careful interpretation is necessary here as dropping the blood pressure in a patient with an adaptive Cushing response risks harm from cerebral hypoperfusion.

the avoidance of hypotension than inducing hypertension. Spaite et al12 and others24,25 have associated high blood pressures early after TBI with poor outcomes. Careful interpretation is necessary here as dropping the blood pressure in a patient with an adaptive Cushing response risks harm from cerebral hypoperfusion. The new recommendation to provide supplemental oxygen to all patients with TBI in the prehospital environment—even those who are normoxic—aligns with growing interest in monitoring, treating, and preventing brain hypoxia after head injury. This practice was used in Arizona in conjunction with the state-wide EPIC study.9 It was associated with a greater likelihood of having an oxygen saturation of 100%, greater rates of reversal of hypoxemia, a lower rate of intubation and higher rate of bag valve mask-only airway management despite increased severity of both brain and overall injury in the post-intervention group. Brain hypoxia has long been understood a key secondary insult worsening outcome from TBI.26 It is underappreciated that brain hypoxia can induce cerebral vasodilation through autoregulatory mechanisms, contributing to intracranial hypertension.27,28

erity of both brain and overall injury in the post-intervention group. Brain hypoxia has long been understood a key secondary insult worsening outcome from TBI.26 It is underappreciated that brain hypoxia can induce cerebral vasodilation through autoregulatory mechanisms, contributing to intracranial hypertension.27,28 This update of the Prehospital Guidelines contains a weak recommendation to maintain euthermia—the first such recommendation in the Prehospital Guidelines. This recommendation is based on a single study published by Gaither et al29 (Figure 2) which was also published in conjunction with the EPIC study. Their analysis of 11 877 patients associated both low and high temperatures with worse outcome. Although this is an association that does not provide evidence of causation, it was judged sufficient to generate a recommendation. A preference for euthermia may relate to coagulopathy and predisposition to infection with hypothermia as well as increased metabolic demand and energy failure with hyperthermia.30

utcome. Although this is an association that does not provide evidence of causation, it was judged sufficient to generate a recommendation. A preference for euthermia may relate to coagulopathy and predisposition to infection with hypothermia as well as increased metabolic demand and energy failure with hyperthermia.30 TXA administration in the prehospital environment has been extensively investigated in recent years.31,32 Several large, high-quality studies have failed to support benefit for most brain-injured patients, leading to a strong recommendation against routine use in these guidelines. The Brain Injury: Prehospital Registry of Outcome, Treatments and Epidemiology of Cerebral Trauma study was a large prospective observational study of 1827 patients which reported increased mortality in patients treated with TXA (odds ratio 1.34, P < .001).31 The CRASH-3 study33 demonstrated beneficial effects of TXA only in mild and moderate TBI.34 The prehospital TXA for TBI trial was a randomized double-blind multicenter phase II trial performed in 20 trauma centers which demonstrated no statistical benefit with the administration of TXA.35 Given this, our panelists recommended that prehospital TXA not be routinely administered to TBI victims, although they allow for its use in special circumstances and care environments.

Recent literature has led to important changes in our understanding of hypotension in the prehospital environment. In the past, studies investigated arbitrary cut-points leading to thresholds that were merely statistical artifacts. As well, in older literature, prehospital measures were not associated with outcome data subsequent to hospital admission. Perhaps the most important new study on this topic comes from Spaite et al23 who overcame these limitations in conjunction with the previously described EPIC study. In their analysis of 12 169 patients, the investigators were able to associate prehospital blood pressure measurements with outcome in a continuous fashion (Figure 1). The results strongly suggested that the traditional SBP threshold for defining hypotension—90 mm Hg—is too low. The lowest risk of mortality associated was seen when SBP was maintained above 125 mm Hg. Ultimately, the 3rd edition panelists chose to recommend maintaining SBP >110 mm Hg while acknowledging that the optimal threshold may be higher.12 Overall, the literature more strongly supports the avoidance of hypotension than inducing hypertension. Spaite et al12 and others24,25 have associated high blood pressures early after TBI with poor outcomes. Careful interpretation is necessary here as dropping the blood pressure in a patient with an adaptive Cushing response risks harm from cerebral hypoperfusion.

The new recommendation to provide supplemental oxygen to all patients with TBI in the prehospital environment—even those who are normoxic—aligns with growing interest in monitoring, treating, and preventing brain hypoxia after head injury. This practice was used in Arizona in conjunction with the state-wide EPIC study.9 It was associated with a greater likelihood of having an oxygen saturation of 100%, greater rates of reversal of hypoxemia, a lower rate of intubation and higher rate of bag valve mask-only airway management despite increased severity of both brain and overall injury in the post-intervention group. Brain hypoxia has long been understood a key secondary insult worsening outcome from TBI.26 It is underappreciated that brain hypoxia can induce cerebral vasodilation through autoregulatory mechanisms, contributing to intracranial hypertension.27,28

This update of the Prehospital Guidelines contains a weak recommendation to maintain euthermia—the first such recommendation in the Prehospital Guidelines. This recommendation is based on a single study published by Gaither et al29 (Figure 2) which was also published in conjunction with the EPIC study. Their analysis of 11 877 patients associated both low and high temperatures with worse outcome. Although this is an association that does not provide evidence of causation, it was judged sufficient to generate a recommendation. A preference for euthermia may relate to coagulopathy and predisposition to infection with hypothermia as well as increased metabolic demand and energy failure with hyperthermia.30

TXA administration in the prehospital environment has been extensively investigated in recent years.31,32 Several large, high-quality studies have failed to support benefit for most brain-injured patients, leading to a strong recommendation against routine use in these guidelines. The Brain Injury: Prehospital Registry of Outcome, Treatments and Epidemiology of Cerebral Trauma study was a large prospective observational study of 1827 patients which reported increased mortality in patients treated with TXA (odds ratio 1.34, P < .001).31 The CRASH-3 study33 demonstrated beneficial effects of TXA only in mild and moderate TBI.34 The prehospital TXA for TBI trial was a randomized double-blind multicenter phase II trial performed in 20 trauma centers which demonstrated no statistical benefit with the administration of TXA.35 Given this, our panelists recommended that prehospital TXA not be routinely administered to TBI victims, although they allow for its use in special circumstances and care environments.

It is generally believed that care provided early after TBI—largely aimed at resuscitating the patient and optimizing their vital signs—is more consequential for the ultimate outcome of a patient than care provided after admission to the hospital. The third edition of the BTF's Prehospital Guidelines for the Management of TBI12 aims to identify and disseminate best practices in prehospital care, updating the recommendations provided by the second edition 15 years ago. The updated recommendations guide patient assessment, treatment, and transport decision-making. It is hoped that implementation of these guidelines will further improve on the marked outcome benefits seen with the second edition.9,10 Moreover, we hope that these guidelines will draw attention to gaps in knowledge and inspire new research. Although many clinicians provide important contributions, neurosurgeons are the only physicians who can provide comprehensive care to TBI victims. It is thus important that neurosurgeons are familiar with recommendations for best practices across the continuum of care.