There are insufficient data to support a Level I recommendation for this topic.

There are insufficient data to support a Level II recommendation for this topic.

Jugular venous saturation (<50%) or brain tissue oxygen tension (<15 mm Hg) are treatment thresholds.

Jugular venous saturation or brain tissue oxygen monitoring measure cerebral oxygenation.

Intracranial pressure (ICP) monitoring is routinely used for patients with severe TBI. ICP is influenced by several factors that affect the pressure-volume relationship. However, monitoring ICP gives only limited information regarding other factors known to be important to the pathophysiology of TBI, such as cerebral blood flow and metabolism. The development of additional monitoring systems to provide information regarding cerebral blood flow and metabolism has been a long-standing aim in neurocritical care.

Therapy following severe TBI is directed towards preventing secondary brain injury. Achieving this objective relies on assuring the delivery of an adequate supply of oxygen and metabolic substrate to the brain. Delivery of oxygen to the brain is a function of the oxygen content of the blood and the cerebral blood flow (CBF). Delivery of glucose and other metabolic substrates to the brain also depends on CBF. Kety and Schmidt pioneered methods to measure CBF in experimental animals and humans. Their methods are still used today, and have served as the scientific basis for many of the technologies used to measure CBF, including Xe-CT, positron emission tomography (PET) studies of CBF, and others. While these technologies have made important contributions to our current understanding of pathophysiology in severe TBI, none are in common clinical use. In part, this is due to expense, expertise requirements, and patient transport necessary to perform these studies. In addition, the intermittent nature of the measurements has also limited their clinical utility. Also, any measurement of flow must be interpreted in the context of possible alterations of cerebral metabolism in the injured brain.

In recent years, methods to continuously monitor measures of adequate cerebral perfusion have been developed. Broadly, these monitoring systems seek either to measure CBF directly (thermal diffusion probes, trans-cranial Doppler), to measure adequate delivery of oxygen (jugular venous saturation monitors, brain tissue oxygen monitors, near-infrared spectroscopy), or to assess the metabolic state of the brain (cerebral microdialysis). A full discussion of all these technologies is beyond the scope of this topic. We have focused our analysis only on those monitoring systems which to date have yielded sufficient clinical experience to relate the data to outcomes in patients with TBI, namely jugular and brain tissue oxygen monitoring.

For this new topic, Medline was searched from 1966 through the April of 2006 (see Appendix B for search strategy), and results were supplemented with literature recommended by peers or identified from reference lists. Of 217 potentially relevant studies, 12 were included as evidence for this topic (Evidence Table I).

A number of studies have assessed the role of jugular venous saturation monitoring in patients with severe TBI. In 1993, Robertson reported a prospective case series of 116 patients with severe TBI. Seventy-six episodes of desaturation (SjO₂ < 50%) were confirmed in 46 patients. In patients without desaturation episodes, mortality was 18%. Patients with one or multiple desaturation episodes had mortality rates of 46% and 71%, respectively. A further study by Robertson et al., in 1995 included 177 patients with severe TBI (Glasgow Coma Scale Score [GCS] ≤ 8) and demonstrated that 39% of monitored patients had at least one episode of desaturation. The causes of desaturation were about equally divided between systemic (hypotension, hypoxia, hypocarbia, anemia) and cerebral (elevated ICP, vasospasm) etiologies. Good recovery or moderate disability occurred in 44% of patients with no episodes of desaturation, 30% of patients with one episode, and 15% of patients with multiple episodes of desaturation. Mortality was found to be higher in patients with one or multiple episodes (37% and 69%), as opposed to no episodes of desaturation (21%).

Episodes of desaturation may be more common early after injury. In 1995, Schneider et al. reported a prospective case series of 54 patients of whom 28 suffered severe TBI. Episodes of desaturation were frequent in the first 48 h after injury in non-survivors, while patients who survived typically had episodes of desaturation 3-5 days after injury.

High SjO₂ values have also been associated with poor outcome. In 1999, Cormio et al. reported a retrospective series of 450 patients who underwent jugular venous saturation monitoring. Patients with mean SjO₂ > 75% were found to have significantly higher cerebral blood flow measured intermittently by the Kety-Schmidt nitrous oxide method. High SjO₂ occurs with hyperemia or after infarction, as non-viable tissue does not extract oxygen. In addition, this group was found to have significantly worse outcome measured by Glasgow Outcome Scale Score (GOS) at 6 months post-injury, compared with patients whose mean SjO₂ was 56-74%.

SjO₂ values alone may not provide the best critical threshold indicator of prognosis. In a consecutive study of 229 comatose TBI patients, arterio-jugular difference of oxygen content (AJDO2) in addition to SjO₂ was obtained every 12 h, and the measurements correlated with 6-month outcome. SjO₂ measurements below 55% were recorded in 4.6% with the majority due to profound hyperventilation or CPP < 60. Higher mean AJDO2 (4.3 vol %) was found to be associated with a good outcome and it was an independent predictor of outcome. The authors postulate that a low SjO₂ may indicate low oxygen delivery but AJDO2 represents oxygen extraction by the brain. In either case, the missing variable is cerebral blood flow, which is needed to calculate the cerebral metabolic rate for brain oxygen consumption.

The association of low and high SjO₂ with poor outcome still leaves open the question of whether treatment directed at restoring normal jugular venous saturation improves outcome. In 1998, Cruz reported a prospective controlled, but non-randomized and non-blinded study of 353 patients with severe TBI and diffuse brain swelling on CT. The control group (n = 175) underwent monitoring and management of cerebral perfusion pressure alone, while the experimental group (n = 178) underwent monitoring and management of arteriovenous oxygen difference (AVDO2) as well as cerebral perfusion pressure. At 6 months post-injury, the authors found improved GOS in the experimental group. However, the lack of randomization and the non-blinded nature of the study raise concern regarding possible selection and treatment bias. In 1997, Le Roux et al. reported a prospective case series of 32 patients with severe TBI treated for worsening AVDO2 with either mannitol or craniotomy, and found that patients with limited improvement in AVDO2 following treatment had increased incidence of delayed cerebral infarction and worse outcome at 6 months postinjury.

Several studies investigated the relationship between outcome and brain tissue oxygen tension (PbrO₂). In 1998, Valadka et al. reported a prospective case series of 34 patients with severe TBI and found that the likelihood of death increased with increasing duration of time of PbrO₂ less that 15 mm Hg. Additionally, their data suggest that the occurrence of any PbrO₂ less than or equal to 6 mm Hg, regardless of its duration, is associated with an increased chance of death. Bardt et al. also reported in 1998 a prospective case series of 35 patients with severe TBI and found that PbrO₂ values less than 10 mm Hg for more than 30 min had considerably higher rates of mortality (56% vs. 9%). Likewise, rates of favorable outcome (GOS 4-5) were lower (22% vs. 73%) in this group. In 2000, van den Brink et al. reported a prospective case series of 101 patients and found that initial PbrO₂ values less than 10 mm Hg lasting for more than 30 min were associated with increased mortality and worse outcomes. In this study both depth and duration of low PbrO₂ correlated with mortality. A 50% risk of death was associated with PbrO₂ values less than 15 mm Hg lasting 4 h or longer.

The association of low PbrO₂ values with poor outcome raises the question of whether treatment directed at improving PbrO₂ improves outcome. Studies have explored the relationship of oxygen-directed therapy on both metabolic and clinical outcome parameters. In 2004, Tolias et al. studied 52 patients with severe TBI treated with an FiO2 of 1.0 beginning within 6 h of admission and compared these to a cohort of 112 matched historical controls. They measured ICP and used microdialysis to study brain metabolites. They found an increase in brain glucose, and a decrease in brain glutamate, lactate, lactate/glucose, and lactate/pyruvate ratio in the group treated with an FiO2 of 1.0. They also noted a decrease in ICP without change in CPP in the patient group treated with oxygen-directed therapy. While suggesting improved metabolic patterns in patients placed on an FiO2 of 1.0 soon after injury, definitive conclusions regarding treatment cannot be drawn from this study which used historical controls and found a nonsignificant improvement in outcome in the treatment group. In 2005, Stieffel et al. reported a series of 53 patients with severe TBI treated with both standard ICP and CPP treatment goals (ICP < 20 mm Hg, CPP > 60 mm Hg) and the addition of an oxygen-directed therapy protocol aimed at maintaining PbrO₂ greater than 25 mm Hg. They compared mortality and outcome at discharge with historical controls, finding a significant decrease in mortality (44% to 25%) in those treated with an oxygen-directed therapy protocol. Limitations of this study, including the reliance on historical controls which had significant mortality by today's standards and the lack of any medium or longterm outcome measures, limits the possibility of drawing definitive recommendations regarding therapy in severe TBI patients.

Evidence supports a Level III recommendation for use of jugular venous saturation and brain tissue oxygen monitoring, in addition to standard intracranial pressure monitors, in the management of patients with severe TBI. However, the accuracy of jugular venous saturation and brain tissue oxygen monitoring was not evaluated in this guideline. Current evidence suggests that episodes of desaturation (SjO₂ < 50-55%) are associated with worse outcomes, and high extraction (AJVO2) are associated with good outcome. Low values of PbrO₂ (<10-15 mm Hg) and the extent of their duration (greater than 30 min) are associated with high rates of mortality.

Though many technologies including cerebral microdialysis, thermal diffusion probes, transcranial Doppler, near-infrared spectroscopy, and others hold promise in advancing the care of severe TBI patients, there is currently insufficient evidence to determine whether the information they provide is useful for patient management or prognosis.

While the establishment of critical thresholds for SjO₂, AJDO2, and PbrO₂ are important milestones, future investigations need to explore what specific therapeutic strategies can prevent these thresholds from being crossed and whether this intervention improves outcome. If treatment preventing desaturation events or low PbrO₂ is shown to improve outcome in patients with severe TBI, the use of these monitoring systems will mark an important advance in the care of TBI patients.

For SjO₂ monitors, issues of reliability need to be addressed and may require technological improvements. For brain tissue oxygen monitors, studies are needed to address issues of probe placement with respect to the location of the injury (most injured vs. least injured hemisphere; pericontusional vs. relatively uninjured brain).