There is insufficient evidence to support an evidence-based recommendation related to delaying surgery for better operative conditions.

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

• Patients with penetrating brain injury who are neurologically stable should be transferred to a facility with neurosurgical expertise as soon as feasible. (100% Consensus)

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

In high-income countries, especially in urban settings, patients with pTBI can be transferred to neurosurgical centers where surgery can be performed promptly after resuscitation and cross-sectional imaging. In contrast, when pTBI occurs in remote or austere locations, clinicians are faced with a dilemma. Surgery can be performed early in the evacuation chain, but often in more difficult conditions. Alternatively, transfer to a fully equipped neurosurgical center may result in significant delays before reaching surgical care.

The 2001 pTBI clinical practice guidelines recommended that surgery be performed promptly when a surgical indication is present.1 The authors did not investigate the benefits and harms of delaying care to obtain better operative conditions for neurologically stable patients.

The systematic review did not identify any studies that specifically documented the benefits and harms of delaying surgery to obtain better operative conditions in neurologically stable patients. However, some observational studies that did not meet the inclusion criteria provide indirect evidence to inform our recommendation.

A study conducted in South Africa by Leibenberg et al. highlights that delays in care may result in fatal outcomes for patients with pTBI.2 The retrospective study describes an approach in which care was deliberately delayed in an attempt to preserve resources.2 One hundred and twenty-five patients were included in the study. Emergency surgery was only performed for obstructive hydrocephalus or significant hematomas. Patients without these indications had superficial wound debridement and closure in the emergency department and were transferred to a critical care unit with limited resources. Delayed surgery was offered to patients who survived the initial phase of supportive care. Twenty-seven patients (21.6% of the entire cohort) underwent surgical treatment at a mean of 11 days post-injury. Emergency surgery was performed in only three patients. Delayed surgical debridement was performed in the remaining 24 patients, six of which required multiple debridements for infection. The mortality rate was 69.6% for the entire cohort (87/125) and 7.4% (2/27) in patients who underwent surgery. Fifty-six patients died within 8 hours of admission. The infection rate was 26% in the 38 patients who survived. The most notable finding was a mortality rate of 25% (7/28) in patients with an admission GCS of 13-15, including three who died from uncontrolled intracranial pressure. The authors concluded that their management strategy led to a high mortality rate, even in patients with an admission GCS ≥ 13.

A study of combat-related pTBI published by Aarabi et al. found that surgery performed at higher echelons of care was associated with a reduced rate of infection. This retrospective study reported the outcomes of 964 patients with pTBI sustained in the Iran-Iraq war.3 Five hundred patients underwent an initial neurosurgical procedure at a base hospital, located near the Iran-Iraq geographical border, and were subsequently transferred to a major provincial hospital (i.e., a tertiary neurosurgical center) close to 200 miles inside main land Iran. In the remaining 414 patients the initial neurosurgical procedure - with a radical approach to debridement - was performed at the same major provincial hospital. The mean time between wounding and surgery at the provincial center was 55.9 hours. The time between wounding and surgery at the base hospital was not reported, but, for perspective, the senior author reported on a smaller pTBI cohort earlier in the war in which the time to surgery at the base hospital was 19.1 hours compared to 66.5 hours at the provincial center.4 Fifty-five percent of the 500 patients who had surgery at a base hospital required revision surgery at provincial hospital because the initial procedure was deemed inadequate. The indications for re-operation included (1) retained bone fragments, (2) inadequate debridement of the scalp or brain (3) intracranial hematoma, and (4) cerebrospinal fluid leakage. Fifty patients did not undergo debridement at either the base hospital or provincial center. The major finding of this study is that patients who had their index procedure at the provincial (tertiary) hospital had a lesser incidence of infection than patients who were first operated at the base hospital, despite a greater delay before surgery (table 1). A multivariate regression analysis that incorporated, inter alia, the mechanism and the anatomic extent of injury found a statistically significant odds ratio for infection of 2.5 in patients who underwent primary surgery at a base hospital and did not require reoperation. Patients who underwent primary surgery at a base hospital and required a subsequent operation had an odds ratio for infection of 1.9, which did not reach statistical significance.

Another study of combat-related pTBI published by Singh et al. also found a high rate of reoperations for patient operated in austere conditions.5 The series included 60 patients injured by explosive fragments (n=48) and missiles (n=12). Thirty patients were initially treated at forward hospitals while thirty were transferred directly to a command hospital in the rear. The average time between wounding and surgery was 36 hours. Six of eight patients (75%) who had surgery in forward locations required a second surgery at the command hospital due to an "inadequate" initial procedure. The authors do not provide enough information to determine whether these patients had planned reoperations as part of a damage control approach or required a secondary surgery due to complications. The neurologic status of patients operated at each location is also not reported separately, making it difficult to extrapolate to the specific subset of neurologically stable patients.

In contrast, Arendall et al. published a study of pTBI associated with air sinus injury that suggests that early surgery in relatively austere conditions is not always detrimental.6 The study included 120 patients with pTBI sustained during the Korean War. During the initial phase of the war, patients were transferred to an American military hospital in Japan for neurosurgical care. As the conflict progressed, neurosurgeons were deployed to field hospitals and mobile army field hospitals in Korea to provide quicker access to surgery. The infection rate was 5% when surgery was performed less than 12 hours after injury, 43% for surgery between 12-24 hours, and 33% for surgery performed later than 24 hours despite the presumably harsher operative conditions in the field.

The scientific literature provides limited evidence about the benefits and harms of delaying surgery to obtain better operative conditions for pTBI patients who are neurologically stable. The studies summarized above do not meet inclusion criteria for formal inclusion as evidence as they do not describe the operative conditions with enough detail to inform our recommendations. In addition, the evidence base for our recommendations spans over 70 years, a period of significant change in neurosurgery, critical care, microbiology, and combat casualty care.

The theoretical risks of delayed surgery include infection and neurologic deterioration secondary to hemorrhage or oedema. However, there is little evidence that performing surgery in poor conditions will prevent these adverse outcomes. In military operations, medical treatment facilities located close to the point of injury may be limited to surgical theatres with poor lighting, contaminated surfaces, and rudimentary equipment. In addition, neurosurgical expertise and advanced imaging are rarely present in these facilities.

Due to the complex and multidisciplinary nature of surgery for pTBI, we believe that the quality of the initial neurosurgical procedure is more important than its timing for neurologically stable patients. We therefore recommend that these patients be urgently evacuated to a neurosurgical center, and that surgery, if indicated, be performed promptly. The evidence does not allow us to establish precise recommendations for an acceptable delay before surgery for neurologically stable patients. Delays in transfer should be minimized as even patients with a high Glasgow Coma Score who appear neurologically stable can deteriorate, with catastrophic results.

This research question is unlikely to be amenable to clinical trials. Therefore, our main recommendation for future investigators is to capture as much data as possible to allow comparison between studies and secondary analyses. We acknowledge that data collection is challenging during armed conflict and express our gratitude to present and future clinicians who document their experience.

Specifically, to further advance our understanding of the implications of delaying surgery for stable patients with pTBI, future investigations should aim to:

1. Document the delay between wounding and surgery.
2. Document the initial GCS.
3. Document specific outcomes such as mortality, infection, and unplanned reoperations for neurosurgical procedures performed in austere or remote locations.
4. Document the outcome of neurosurgical procedures performed by non-neurosurgeons.
5. Establish a pTBI registry with data collection methods compatible with low-resource environments.
6. Review prospectively collected data of war-related pTBI to provide comparative analyses between patients receiving surgery in forward (military) surgical facilities and those treated initially at higher echelons of care.6
7. Make accessible complete datasets to allow for secondary analyses at a future pTBI consensus conference.
8. Describe the operative conditions. This should include, when possible, details about the facility (e.g., field hospital, mobile surgical team), operating room equipment, operating room lighting, pre-operative imaging, tactical conditions, and the specialty of the operating surgeon.