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

Blood pressure should be monitored and hypotension (systolic blood pressure < 90 mm Hg) avoided.

Oxygenation should be monitored and hypoxia (PaO2 < 60 mm Hg or O2 saturation < 90%) avoided.

For ethical reasons, a prospective, controlled study concerning the effects of hypotension or hypoxia on outcome from severe traumatic brain injury (TBI) has never been done. Nevertheless, there is a growing body of evidence that secondary insults occur frequently and exert a powerful, adverse influence on outcomes from severe TBI. These effects appear to be more profound than those that result when hypoxic or hypotensive episodes of similar magnitude occur in trauma patients without neurologic involvement. Therefore, it is important to determine if there is evidence for specific threshold values for oxygenation and blood pressure support.

For this update, Medline was searched from 1996 through April of 2006 (see Appendix B for search strategy), and results were supplemented with literature recommended by peers or identified from reference lists. Of 17 potentially relevant studies, 3 were added to the existing table and used as evidence for this question (Evidence Table I).

In TBI patients, secondary brain injury may result from systemic hypotension and hypoxemia. The effect of hypoxemia was demonstrated by the analysis of a large, prospectively collected data set from the Traumatic Coma Data Bank (TCDB).2,11 Hypoxemia occurred in 22.4% of severe TBI patients and was significantly associated with increased morbidity and mortality. In a helicopter transport study, which was not adjusted for confounding factors, 55% of TBI patients were hypoxemic prior to intubation.18 Of the hypoxemic patients, 46% did not have concomitant hypotension. In non-hypoxemic patients, mortality was 14.3% with a 4.8% rate of severe disability. However, in patients with documented O2 saturations of <60%, the mortality rate was 50% and all of the survivors were severely disabled. In an inhospital study of 124 patients with TBI of varying degrees of severity, Jones et al. performed a subgroup analysis of 71 patients for whom there was data collection for eight different types of secondary insults (including hypoxemia and hypotension).8 Duration of hypoxemia (defined as SaO₂ ≤ 90%; median duration ranging from 11.5 to 20 min) was found to be an independent predictor of mortality (p = 0.024) but not morbidity ("good" outcome [12-month GCS of good recovery and moderate disability] versus "bad" outcome [GCS of severe disability, vegetative survival, or death], p = 0.1217).

Both prehospital and inhospital hypotension have been shown to have a deleterious influence on outcome from severe TBI. In the TCDB studies referenced above, a single prehospital observation of hypotension (systolic blood pressure [SBP] < 90 mm Hg) was among the fivemost powerful predictors of outcome. This was statistically independent of the other major predictors such as age, admission Glasgow Coma Scale (GCS) score, admission GCS motor score, intracranial diagnosis, andpupillary status. A single episode of hypotension was associated with increased morbidity and a doubling of mortality as compared with a matched group of patients without hypotension. These data validate similar retrospectively analyzed Class III reports published previously. Several studies analyzed the association of inhospital hypotension with unfavorable outcomes. Manley et al. reported a non-significant trend toward increased mortality in patients with GCS < 13 experiencing a single inhospital event of hypotension (SBP = 90) (relative risk 2.05, 95% CI 0.67-6.23). The relative risk increased to 8.1 (95% CI 1.63-39.9) for those with two or more episodes. Thus repeated episodes of hypotension in the hospital may have a strong effect on mortality. Jones et al. found that in patients with episodes of in-hospital hypotension, increased total duration of hypotensive episodes was a significant predictor of both mortality (p= 0.0064) and morbidity ("Good" vs. "Bad" outcome, p=0.0118). The question of the influence of hypoxia and hypotension on outcome has not been subject to manipulativeinvestigation, as it is unethical to assign patients to experimental hypotension. Therefore the large, prospectively collected, observational data set from the TCDB is the best information on the subject that is available. This and other studies show a strong association between hypotension and poor outcomes. However, because of ethical considerations there is no Class I study of the effect of blood pressure resuscitation on outcome. In a series of studies by Vassar et al., designed to determine the optimal choice of resuscitation fluid, correcting hypotension was associated with improved outcomes. One of these studies was a randomized, doubleblind, multicenter trial comparing the efficacy of administering 250 mL of hypertonic saline versus normal saline as the initial resuscitation fluid in 194 hypotensive trauma patients; 144 of these patients (74%) had a severe TBI (defined as an abbreviated injury score [AIS] for the head of 4, 5, or 6). Hypertonic saline significantly increased blood pressure and decreased overall fluid requirements.

The value of 90 mm Hg as a systolic pressure threshold for hypotension has been defined by blood pressure distributions for normal adults. Thus, this is more a statistical than a physiological finding. Given the influence of cerebral perfusion pressure (CPP) on outcome, it is possible that systolic pressures higher than 90 mm Hg would be desirable during the prehospital and resuscitation phase, but no studies have been performed thus far to corroborate this. The importance of mean arterial pressure, as opposed to systolic pressure, should also be stressed, not only because of its role in calculating CPP, but because the lack of a consistent relationship between systolic and mean pressures makes calculations based on systolic values unreliable. It may be valuable to maintain mean arterial pressures considerably above those represented by systolic pressures of 90 mm Hg throughout the patient's course, but currently there are no data to support this. As such, 90 mm Hg should be considered a threshold to avoid; the actual values to target remain unclear.

A significant proportion of TBI patients have hypoxemia or hypotension in the prehospital setting as well as inhospital. Hypotension or hypoxia increase morbidity and mortality from severe TBI. At present, the defining level of hypotension is unclear. Hypotension, defined as a single observation of an SBP of less than 90 mm Hg, must be avoided if possible, or rapidly corrected in severe TBI patients.^{1,4 A similar situation applies to the definition of hypoxia as apnea cyanosis in the field, or a PaO2 < 60 mm Hg. Clinical intuition suggests that correcting hypotension and hypoxia improves outcomes; however, clinical studies have failed to provide the supporting data.}

The major questions for resuscitating the severe TBI patient are as follows:

• The level of hypoxia and hypotension that correlates with poor outcome
• Treatment thresholds
• Optimal resuscitation protocols for hypoxia and hypotension
• The impact of correcting hypoxia and hypotension on outcome
• Specification of target values