There is insufficient evidence to support an evidence-based recommendation specific to penetrating brain injury for ED care strategies (e.g., correction of coagulopathy, cardiopulmonary resuscitation [CPR], airway maneuvers, oxygen administration, cervical spine immobilization, specific fluid administration including hypertonic saline, mannitol administration, pain management, hyperventilation, posture), including the prevention of secondary injury.

In the absence of direct scientific evidence, EXPERT CONSENSUS concluded that:

• Practitioners should adhere to the recommendations of the Prehospital Guidelines for the Management of Traumatic Brain Injury - 3rd Edition36 and the BTF 4th edition TBI guidelines28 concerning prehospital and emergency department resuscitation strategies. (100% consensus)
• Cervical collars are not required in isolated penetrating brain injury in patients without clinical or CT findingss of cervical spine injury. (100% consensus)
• In patients with signs of hemorrhagic shock or massive external hemorrhage, the primary focus should be on hemorrhage control and resuscitation using whole blood or equivalent blood products. (100% consensus)
• Massive bleeding into the oropharynx often requires a definitive airway prior to packing the oropharynx with a hemostatic dressing or gauze packing. (93.3% consensus)

No evidence or expert opinion supported distinct recommendations based on patient gender, age, wounding mechanism, or military vs. civilian context.

pTBI presents unique challenges for prehospital and ED healthcare providers, who are tasked with implementing a range of resuscitation strategies aimed at stabilizing the patient and minimizing secondary injury. These strategies include, but are not limited to, correction of coagulopathy, CPR, airway management, oxygen administration, cervical spine immobilization, specific fluid administration (e.g., hypertonic saline, mannitol), pain management, hyperventilation, and posture adjustment. The goal of these interventions is not only to address the immediate life-threatening conditions but also to prevent further brain damage, such as cerebral edema and neuronal loss.

Despite the critical importance of these resuscitation strategies in the management of pTBI, there is a notable lack of evidence to support the superiority or optimal combination of these treatments. The complexity of pTBI cases, coupled with the variability in injury mechanisms and patient conditions, makes it challenging to conduct large-scale, randomized controlled trials that could provide high-quality evidence. The available literature on pTBI resuscita-tion strategies reveals a mixed picture. Some studies suggest po-tential benefits of certain interventions, such as the use of mannitol and hypertonic saline for the management of cerebral edema, or aggressive resuscitation with blood products in patients with coagulopathy. However, these findings are often limited by small sample sizes, retrospective designs, and the inherent confounding factors associated with trauma care, where sicker patients are more likely to receive intensive interventions.

The previous version of these guidelines16 did not address the benefits or harms of prehospital and ED resuscitation strategies or the impact on the prevention of secondary injury in pTBI patients.

No studies were identified meeting inclusion criteria that addressed the benefits and harms of resuscitation strategies for patients with pTBI in prehospital or ED settings, comparing those who received interventions to those who did not. A single non-randomized study published by Mansour et al involving 89 U.S. civilians with GSW to the head compared ED patients presenting with coagulopathy to those without48 (Table 5). Coagulopathy was defined by an international normalized ratio (INR) greater than 1.3, platelet count below 100 000/µL, or partial throm-boplastin time over 37 seconds. This study analyzed patient characteristics and outcomes between those diagnosed with coagulopathy after initial resuscitation, without specifying the resuscitation strategies used. It reported significantly higher mortality rates among patients with coagulopathy (73% vs 25%, P < .001), but this association disappeared after adjusting for Glasgow Coma Scale-Motor score (GCS-M) in a multivariable logistic regression (odds ratio 1.34, 95% CI, 0.22 to 8.10, P = .75). Among patients with coagulopathy at presentation who survived at least 24 hours, a comparison between those who corrected their coagulopathy within 24 hours and those who did not showed no statistically significant difference (75% vs 38%, P = .29) in survivability. The study was underpowered, relevant to interpretation of the results.

Nine studies were identified that reported on the use of one or more resuscitation strategies (e.g., intubation, blood transfusion, hyperosmolar therapy) and their outcomes in terms of mortality or Glasgow Outcome Scale (GOS) scores. Three of these studies specifically examined the administration of mannitol, with mixed findings related to mortality and unfavorable outcomes among patients with GSWs to the head from various contexts, including the Syrian civil war and incidents in the United States and India. One study by Kaufman et al (N = 143) of U.S. civilians with GSWs, seven of which were not penetrating, reported 38% of those who survived were administered mannitol compared with 56% of those who died.37 They noted in most cases the patients had been previously hypotensive. No other information on re-suscitation strategies was reported. The second study by Can et al (N = 104), of patients in the Syrian civil war with sniper GSWs to the head, reported giving all patients hyperosmolar therapy, in-cluding mannitol and 3% hypertonic saline, in the ED for cerebral edema and reported a mortality rate of 36%.49 They also reported 26% of the patients required endotracheal intubation and of those 63% (17/27, P < .01) died. The third study by Wani et al (N = 26), of patients (unclear if civilian, military, or a mix) in India with GSWs or blast injuries to the head, followed a standard protocol for resuscitation in the ED of airway, breathing, and circulation (ABC), reported all patients received mannitol 1 g/kg, and re-ported 92% (24/26) had an unfavorable outcome (GOS <e;3).50

Two studies of civilians in South Africa with isolated GSWs to the head reported following the Advanced Trauma Life Support (ATLS ) principles. One by Glapa et al (N = 72) intubated 75% (48/64) of patients with pTBIs (89%, 64/72) and reported 79% died compared with 25% who died of those who were not in-tubated when they arrived at the hospital (P = .0002).51 The other study by Kong et al (N = 102) placed a cervical collar on all patients, 26% by emergency medical service (EMS) personnel and the remaining 74% in the ED. The study reported no cervical spinal injuries in any of the patients and all were cleared to remove the cervical collars. The mortality rate was 22% in the study.52

Two studies compared the administration of aggressive re-suscitation products. One study by Joseph et al (N = 132) of civilians in the United States with pTBIs due to GSWs compared those who survived with those who did not and reported survivors used more blood products (57% vs 34%, P = .05), hyperosmolar therapy (53% vs 31%, P = .03), and prothrombin complex concentrate (PCC) (P = .06) but there was no difference in use of vasopressors (41% vs 35%, P = .6) in survival.53 The study also reported the use of aggressive management in their institution increased from 30% in 2008 to 70% in 2011. The other study by Singh et al (N = 96) was of patients with missile injuries to the head from terrorist attacks, assaults, accidents, or self-injuries in India and reported following a protocol at the clinician's discretion, in hemodynamically unstable patients and patients with coagulopathy. Authors reported more patients survived than died when given blood products (55% vs 30%, P < .05), hypertonic saline (51% vs 26%, P < .05), and ionotropes (39% vs 29%, P < .5).54

A study by McNickle et al (N = 241) of civilians in the United States with GSWs to the head and face reported EMS placed spinal motion restriction on 50% of the patients before arriving at the ED and an additional 2% had collars placed in the hospital.55 Cardio-pulmonary resuscitation by EMS was done in 19% of patients and they intubated 46% prior to arriving at the hospital. The mortality rate in the overall study was 57%, mortality was not reported based on resuscitation strategies. The study did report six patients with collars placed by EMS were identified with cervical spine fractures, two died, and one underwent spine surgery and survived but was admitted to a long-term acute care facility after discharge.

A study by Ospina-Delgado (N = 95) of civilians in Colombia with GSWs to the head reported more patients who were in-tubated in the ED (36%, 34/95) compared with those who did not require or need reintubation (64%, 61/95) died (53.5% vs 46.5%).56 However, there are discrepancies between the text and the table. Seven studies reported using a protocol but did not elaborate on details or provide outcome comparisons.57-63

Despite these findings, the studies discussed are confounded by the fact that patients with more severe pTBI are more likely to require multiple resuscitation strategies and have worse outcomes, making it difficult to assess the benefits and harms of any specific strategy. Furthermore, the study comparing successfully corrected coagulopathy to unsuccessfully corrected coagulopathy provided insufficient evidence to determine the benefits and harms of coa-gulopathy correction in pTBI, suggesting that larger studies are needed to potentially demonstrate increased survivability.

It is almost certain that management and resuscitation strategies employed in prehospital and ED setting impact the screening, di-agnosis, and outcome of patients with pTBI, however the degree of impact and the interaction between the different strategies remains unknown. These strategies are also crucial for patient stabilization and minimizing secondary injuries such as cerebral edema and diffuse axonal injury and encompass a wide range of interventions, including but not limited to the correction of coagulopathy, CPR, airway management, oxygen administration, cervical spine immo-bilization, specific fluid administration (notably hypertonic saline and mannitol), pain management, hyperventilation, and posture adjustments. Despite the critical importance of these interventions, the existing literature provides insufficient evidence to strongly recommend specific ED strategies tailored for pTBI, reflecting the complexity and variability inherent in pTBI cases.

The unanimous recommendation for practitioners to adhere to the Prehospital Guidelines for the Management of Traumatic Brain Injury36 as well as the BTF's 4th edition adult coma guidelines28 underscores the importance of established protocols and guidelines in ensuring consistent and informed care for pTBI patients. The guidelines presented here, developed through comprehensive reviews of the literature and expert interpretation of available data, provide a foundation for decision-making in the absence of high-level evidence specific to penetrating brain injuries. They cover a wide range of resuscitation strategies, including airway management, ventilation, circulation support, and the management of coagulopathy, among others, tailored to the unique challenges presented by traumatic brain injuries.

The consensus statement regarding the non-requirement of cervical collars in cases of isolated penetrating brain injury without clinical or CT evidence of cervical spine injury addresses a specific and common practice in the management of pTBI and reflects a balance between potential benefits and harms of cervical spine immobilization in this patient population. Given the low likelihood of cervical spine injury in isolated penetrating brain injuries and the potential for complications associated with unnecessary immobilization, this consensus provides clear guidance that can streamline patient care and avoid unnecessary interventions.

Since the initial evidence table search, new data has emerged supporting the use of whole blood for resuscitative hemorrhagic shock in the prehospital setting. Although not specific to penetrating TBI, this evidence has been included as a "consensus" to ensure the guidelines remain relevant and the document stays up to date.

There is a pressing need for well-designed RCTs that compare different resuscitation strategies in pTBI patients. These studies should aim to include diverse patient populations and injury mechanisms to ensure broad applicability of the findings. Priority areas might include the effectiveness of mannitol vs hypertonic saline in managing cerebral edema, the benefits of early coagulopathy correction, and the impact of advanced airway management techniques on patient outcomes. Many resuscitation strategies are considered standard of care and will not be amenable to standard RCTs in trauma settings, however robust prospective observational studies can provide valuable insights into the real-world effectiveness of various resuscitation interventions. These studies should focus on systematically collecting data on patient characteristics, treatment protocols, and outcomes to identify best practices and areas needing improvement. This could involve studying the genetic, physiological, and clinical factors that influence patient responses to different resuscitation strategies, with the goal of tailoring treatments to individual patient needs and improving outcomes. Future studies should compare the effectiveness of different combinations of resuscitation strategies to identify the most effective protocols for specific patient subgroups or injury types. This research could inform the development of more nuanced and effective clinical guidelines. Understanding the long-term outcomes of pTBI patients who receive various resuscitation strategies is crucial for assessing the enduring impacts of these interventions. Future research should include follow-up studies that evaluate functional outcomes, quality of life, and long-term mortality rates. Investigating the organizational, financial, and logistical aspects of delivering resuscitation care to pTBI patients can provide insights into how healthcare systems can better support the delivery of effective and efficient trauma care.