Impact of duration and magnitude of raised intracranial pressure on outcome after severe traumatic brain injury: A CENTER-TBI high-resolution group study

Abstract

Magnitude of intracranial pressure (ICP) elevations and their duration have been associated with worse outcomes in patients with traumatic brain injuries (TBI), however published thresholds for injury vary and uncertainty about these levels has received relatively little attention. In this study, we have analyzed high-resolution ICP monitoring data in 227 adult patients in the CENTER-TBI dataset. Our aim was to identify thresholds of ICP intensity and duration associated with worse outcome, and to evaluate the uncertainty in any such thresholds. We present ICP intensity and duration plots to visualize the relationship between ICP events and outcome. We also introduced a novel bootstrap technique to evaluate uncertainty of the equipoise line. We found that an intensity threshold of 18 ± 4 mmHg (2 standard deviations) was associated with worse outcomes in this cohort. In contrast, the uncertainty in what duration is associated with harm was larger, and safe durations were found to be population dependent. The pressure and time dose (PTD) was also calculated as area under the curve above thresholds of ICP. A relationship between PTD and mortality could be established, as well as for unfavourable outcome. This relationship remained valid for mortality but not unfavourable outcome after adjusting for IMPACT core variables and maximum therapy intensity level. Importantly, during periods of impaired autoregulation (defined as pressure reactivity index (PRx)>0.3) ICP events were associated with worse outcomes for nearly all durations and ICP levels in this cohort and there was a stronger relationship between outcome and PTD. Whilst caution should be exercised in ascribing causation in observational analyses, these results suggest intracranial hypertension is poorly tolerated in the presence of impaired autoregulation. ICP level guidelines may need to be revised in the future taking into account cerebrovascular autoregulation status considered jointly with ICP levels.

Fig 1. Calculation of AUC of ICP over time.

An example of how ICP dose as pressure times time dose is represented from a representative patient. The blue-coloured area is the AUC (i.e. the ICP dose) above threshold ICP = 10 mmHg and represents the PTD10.

Fig 2. Distribution of GOS-E score at 6 months.

Fig 3. Correlation between number of events above thresholds of intracranial pressure and durations, and outcome (GOS-E score).

Red indicates that ICP events are correlated to worse outcome at that specific ICP level and event duration on the map. A. The black line represents the transition line, where there is no correlation between number of events above threshold and outcome. B. The black line represents the mean transition line of 1000 bootstraps. The white lines represent the mean transition line +2 SD, while the grey line represents the mean transition line -2 SD. Above, and to the right, of the white line, there is a high degree of statistical certainty of events being associated with worse outcome, whereas below the grey line, the statistical certainty is high that events are not associated with harm.

Fig 4. Correlation between number of events above thresholds of intracranial pressure intensity and duration and outcome, stratified by cerebral autoregulatory status.

Orange / red areas indicates areas where ICP levels and event durations are associated with worse outcomes. The transition line, i.e. where there is no correlation between number of events and outcome, is drawn in black. All patients contribute some data to both plots, the degree however depending on the extent of their intact vs. impaired autoregulation. A) Intact autoregulation (mean PRx <= 0.3), B) Impaired autoregulation (mean PRx > 0.3).

Fig 5. Fraction of monitoring time with intact autoregulation, per patient.

All patients had both episodes of impaired and intact autoregulation, but to different extents.

Fig 6. Total pressure and time dose (PTD) above ICP thresholds stratified by outcome at 6 months.

The group mean PTD was higher for patients who had died within 6 months post injury, while the mean doses were similar for GOS-E 3 to 8 outcomes.

Fig 7. Group mean PTD (mmHg·h) above thresholds of ICP, median for A) favourable vs unfavourable outcome, B) dead vs alive at 6 months post injury.

Fig 8. A) Intact vs B) impaired autoregulation, mean PTD for favourable and unfavourable outcome, C) Intact vs D) Impaired autoregulation for 6 month mortality.