There is insufficient evidence to support a strong or moderate strength recommendation related to intracranial pressure (ICP) or cerebral perfusion pressure.

Pediatric and adult severe pTBI patients should be managed using ICP monitoring to reduce mortality, though it is associated with longer duration of intensive care.

ICP should be maintained below 22 mmHg in pediatric and adult severe pTBI patients to reduce mortality and improve 6-month neurological outcomes.

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

• Cerebral perfusion pressure (CPP) should be managed as per recommendations provided in the 4th edition adult coma guidelines28 and the 3rd edition pediatric guidelines for non-penetrating TBI298 (92% consensus):

  Adult: "The recommended target cerebral perfusion pressure (CPP) value for survival and favorable outcomes is between 60 and 70 mmHg. Whether 60 or 70 mmHg is the minimum optimal CPP threshold is unclear and may depend upon the patient's autoregulatory status.28"

  Pediatric: "Age dependent thresholds should be used for pediatric patients with a minimum CPP of 40-50 mm Hg, with infants at the lower end and adolescents at the higher end.28"

• ICP monitoring can facilitate the detection of an expanding intracranial mass lesion following pTBI. (100% consensus)

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

Intracranial pressure can be a source of secondary insult following TBI. As ICP elevation can reduce cerebral perfusion (CPP=MAP-ICP), concomitant measurement of CPP can help to ensure adequate perfusion of the injured brain. Treatment thresholds for ICP and CPP have been identified and an effort is made to optimize these values during the critical care management of severe TBI patients. It is uncertain if the critical values for ICP and CPP are the same in pTBI as they are in blunt TBI1,2. Given the higher preponderane of vascular injuries in pTBI it is possible that distinct values could be indicated.

Over the 4 iterations of the Brain Trauma Foundation's adult coma guidelines for severe TBI, the ICP threshold has evolved from 25 to 20 to 22mmHg (4^th edition). A randomized controlled trial demonstrated harm when CPP values >70mmHg are targeted in severe TBI3. This has also led to a recommended CPP range of 60-70mmHg.1 The importance of cerebral autoregulation has been demonstrated in recent years and it is important for clinicians to be able to diagnose when pressure autoregulation is intact and when it is dysfunctional. Patients who have preserved autoregulation can tolerate a wider range of CPP compared to those with impaired autoregulation. Such patients may benefit from higher CPP values as these are associated with a reduction in intracranial pressure.4-6 Conversely, pressure passive patients with dysfunctional pressure autoregulation benefit from lower CPP values as these lower values reduce ICP in such patients. Different techniques for assessing autoregulation have been established including transcranial doppler, ICP waveform, cerebral oximetry and others6,7. "Optimal CPP" - or CPP_opt - has been defined as the CPP achieved within autoregulation range using pressure reactivity index, and is being further investigated by the CoGiTATE trial.8,9 Management targetting CPP_opt is currently supported by limited evidence, however.

The prior penetrating head injury guidelines (2001) make an "optional" recommendation (Level III/IV) that "early ICP monitoring is recommended when the clinician is unable to assess the neurological exam accurately; the need to evacuate a mass lesion is unclear; or imaging studies suggest elevated intracranial pressure".10 Furthermore, they stated that in the absence of studies specific to penetrating TBI, recommendations from contemporary guidelines for the overall management of severe TBI be used. Of the 6 studies included in the first edition of the guidelines, none met inclusion criteria for informing these new recommendations.

A. Intracranial Pressure Monitoring

The data on benefits and harms of intracranial pressure (ICP) monitoring in penetrating traumatic brain injury (pTBI) is sparse. We identified one non-randomized study from the National Trauma Data Bank (NTDB; 2017 to 2019) in adults (N=466, mean age 32 years) with primarily gunshot wounds to the head.12 This study used propensity-score matching to compare outcomes in patients who underwent ICP monitoring with patients who did not receive ICP monitoring, and found a lower mortality rate with ICP monitoring (30.9% vs. 40.8%, odds ratio [OR] 0.65; 95% confidence interval [CI], 0.44 to 0.95), but twice the length of intensive care unit (ICU) stay with ICP monitoring (median 15 days vs. 7 days, p<0.001).

We also identified one non-randomized study of pediatric patients (aged 0 to 18 years) from the NTDB (2014 to 2017) that examined the association of clinical and treatment variables on outcomes in a population of pediatric patients with cranial gunshot wounds (N=209).13 ICP monitor placement occurred in 25.8% of the study population (N=54). Regression analyses were performed with covariates: age, presence of shock, ICP monitor placement, craniotomy, sex, ethnicity, and insurance status to determine impact on mortality. The authors report a lower risk of mortality with ICP monitor placement (OR 0.267; 95% CI, 0.082 to 0.864). This association was not present on subgroup analysis in patients presenting with Glasgow Coma Scale (GCS) scores of 9 to 15 (OR 0.65; 95% CI, 0.038 to 11.054). Discharge disposition was also examined, and the authors reported that no association was present between ICP monitor placement and discharge disposition for the entire group (OR 0.707; 95% CI, 0.196 to 2.551) or on subgroup analysis for patients with a GCS of 9 to 15 (OR 0.596; 95% CI, 0.089 to 3.998).13

Additionally, one non-randomized study in an adult population (aged 18 to 90 years) that aimed to determine the rate and risk factors for central nervous system (CNS) infection after pTBI and to examine the impact of antibiotic prophylaxis on those outcomes.14,15 The authors reported an association of ICP monitor placement with development of CNS infection. Twenty nine percent of patients (N=223/763) in the study underwent ICP monitor placement after pTBI. The authors reported an increased proportion of infections in the ICP monitor group compared with those without a monitor placed (N=540, 12% vs. 4%, p<0.0001). On multivariable analysis ICP monitor placement was associated with an infection OR of 2.27 (95% CI, 1.18 to 4.4, p=0.01). However, infections were determined clinically and supported by CSF cultures, only available with ventricular CSF ICP monitors, and wound swabs when available, which occurred in 74% of reported cases.

These studies provide low-strength evidence that ICP monitoring is associated with lower mortality in adults and pediatric populations, increased length of stay; and no difference in discharge disposition compared with no ICP monitoring in patients suffering penetrating TBI. Further ICP monitoring with external ventricular drains may be associated with increase in risk of ventriculitis though the recent advent of antibiotic impregnated external ventricular drains has significantly reduced this risk.

B. Intracranial Pressure Thresholds

In blunt TBI blood pressure, intracranial pressure (ICP) and cerebral perfusion pressure (CPP) thresholds are established and central to patient care. Indeed, compliance with these thresholds has been associated with improved outcomes. It is unclear if those same thresholds should be applied in penetrating traumatic brain injury (pTBI) or if different values are appropriate. No studies were identified that examined systolic, diastolic, or mean blood pressure thresholds for either ICP or CPP directed treatment strategies in pTBI.

For ICP/CPP management thresholds, one small non-randomized study in pediatric patients (aged 8 months to 15 years) with gunshot wounds to the head (N=33) reported that ICP monitoring was performed in 18 patients with a threshold of 20 mmHg used in treatment.1 Of the 18 children who received ICP monitoring, eight died with ICP greater than 40 mmHg and one patient died of pneumonia with ICP less than 30 mmHg. Of the nine survivors, ICP was less than 20 mmHg for all readings in three patients, two patients had an ICP less than 30 mmHg with treatment and four patients had ICP measurements greater than 40 mmHg despite treatment. At 6 months, two of the four patients with ICP measures greater than 40 mmHg had severe disability and two had moderate disability.

Kelly et al report a non-randomized study in adult patients (N=26 had ICP monitoring, mean age 38 years) with gunshot wounds to the head reported that ICP less than 20 mmHg was maintained with hyperosmolar therapy.2 Median maximum ICP in those who survived to discharge was 22 mmHg and was 33 mmHg in those who did not survive to discharge. Median maximum ICP in those with a good functional outcome was 22 mmHg and was 26 mmHg in those with a poor functional outcome.

Other studies not included

One non-randomized study in mostly adults (N=119, aged 12 to 73 years) reported patients with gunshot wounds to the head received vasopressors and fluids to keep CPP greater than 60 mmHg, with an ICP target less than 20mm Hg, managed with CSF drainage, sedation, mannitol, and hyperventilation.3 Individuals who presented with an initial ICP of 21 mmHg or more were more likely to die than those who did not (50% [11/22] vs. 24% [10/41]), although the results were not statistically significant (OR 2.56; 95% CI, 0.85 to 7.68). However, ICP and CPP pressure readings during the course of treatment.

Other studies reported that ICP was associated with favorable or unfavorable outcomes or not associated with outcomes, but did not report ICP or CPP management thresholds,4-9 while other studies reported thresholds used, but did not report outcomes by ICP or CPP,10-18 and 1 study reporting both had only 4 survivors in a case series of 11 comatose children suffering gunshot wounds to the head.19

These studies provide very low strength of evidence that successful management of ICP to maintain a threshold of 20-22 mmHg or lower is associated with better outcomes (mortality, function) than if ICP thresholds are not targeted. However, as detailed in the discussion below, for pragmatic reasons and to avoid confusion amongst practitioners, the ICP threshold has been chosen to be consistent with the 4^th edition severe TBI threshold of <22mmHg.20

While ICP monitoring as well as ICP-directed management is supported and practiced extensively in blunt severe TBI, the data specific to pTBI remains sparse. In fact, the included 2 studies were published in the past 5 years.

The enduring discussion and study of intracranial pressure following all forms of TBI reflects the presumed importance of ICP despite the fact that there remains paucity of high-quality evidence that conclusively show a relationship between ICP-directed treatment and improved outcomes. Ultimately, in spite of only Level III recommendations supporting ICP monitoring in the management of adult and pediatric severe TBI20,21, there has been widespread adoption of ICP directed treatment with up to 90% of neurotraumatologists in European Level I trauma centers using ICP monitoring in severe TBI patients.22

When ICP exceeds the focal and regional arteriolar critical closing pressure, nutrients cannot flow to the brain and there is therefore no question that ICP elevation can be harmful and is more than a mere marker of disease severity. However, the benefits of treating raised ICP remain insufficiently informed. The precise ICP threshold which should be employed also remains uncertain. The adult severe TBI guidelines have recommended 25 mmHg, 20-25 mmHg, 20 mmHg and now 22 mmHg over the course of its four editions, depending on newer studies. It is also unclear if there may be a basis for individualizing the treatment threshold.23 Recent studies raise the possibility that this harm may begin below 20 mmHg and cumulative ICP dose may be a more critical determinant of outcomes.24

It must be remembered that ICP is a very information-dense measurement. It can be used to derive CPP and to determine autoregulatory status which is increasingly viewed as playing an important role in neurocritical care. Analysis of the ICP waveform is also believed to inform compliance/compensatory reserve. Evidence suggests that ICP be monitored and treated through the course of pTBI management, even if a decompressive craniectomy is performed as ICP can be elevated despite a DC having been performed. And of course ICP monitoring can detect an expanding intracranial mass lesion requiring surgical evacuation.

However, a key question at hand is whether there is sufficient evidence to recommend a distinct ICP treatment threshold for pTBI as compared with the over-arching recommendation provided by the 4^th edition guidelines. The value of 20-22 mmHg identified in the two pTBI studies taken as evidence here does not provide clear evidence that that either specific value is more meaningful in pTBI. Kelly et al2 demonstrated that in a large sample (n=297) of GSW victims treated for ICP lowering, the median maximum ICP amongst survivors was 22 mmHg. Therefore, in view of the authors, selecting a more uniform ICP threshold of 22 mmHg is useful and consistent with the recommendations in the 4^th edition of severe TBI management guidelines, which provides pragmatic consistency in treatment of all TBI patients, and equally importantly minimizes confusion for practitioners.

With no available data on CPP management in pTBI, the expert panel opined to seek consensus on whether 4^th edition guidelines may be used for thresholds that would encompass pTBI in addition to blunt severe TBI. High-level consensus was reached on adopting such a measure, viz. CPP thresholds be 60-70mmHg for adults, and 40-50mmHg for children, with infants being closer to the lower limit and adolescents to the upper limit.

The role of ICP monitoring and the treatment threshold that should be used remains a matter of ongoing investigation across the breadth of TBI. As studies aim to refine the role of ICP monitoring and the specific treatment threshold that should be utilized - as well as whether there is a basis for individualizing the threshold - there should be an effort to determine whether patients with pTBI should be subject to distinct treatment. Randomized controlled trials have proven feasible for examining ICP monitoring, providing hope that future high-quality studies will improve upon what we have learned to date. Indeed, as in closed TBI, data for treatment of pTBI patients comes largely from retrospective cohort studies so far, which limits the quality of evidence currently available. Compliance with ICP monitoring remains heterogenous across the United States. Comparative effectiveness research which associates variations in practice with outcome thus also holds promise for improving our understanding of ICP monitoring, ICP-CPP thresholds, and the role of cerebral autoregulation in pTBI compared to closed TBI, and whether autoregulation determined CPP (CPP_opt) achieves improved outcomes in pTBI.