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. 2019 Jul;161(7):1275-1284.
doi: 10.1007/s00701-019-03915-3. Epub 2019 May 3.

Compensatory-reserve-weighted intracranial pressure versus intracranial pressure for outcome association in adult traumatic brain injury: a CENTER-TBI validation study

Frederick A Zeiler  1   2   3 , Ari Ercole  4 , Manuel Cabeleira  5 , Erta Beqiri  5   6 , Tommaso Zoerle  7 , Marco Carbonara  7 , Nino Stocchetti  6   7 , David K Menon  4 , Peter Smielewski  5 , Marek Czosnyka  5   8 ; CENTER-TBI High Resolution ICU Sub-Study Participants and Investigators
Collaborators, Affiliations

Compensatory-reserve-weighted intracranial pressure versus intracranial pressure for outcome association in adult traumatic brain injury: a CENTER-TBI validation study

Frederick A Zeiler et al. Acta Neurochir (Wien). 2019 Jul.

Abstract

Background: Compensatory-reserve-weighted intracranial pressure (wICP) has recently been suggested as a supplementary measure of intracranial pressure (ICP) in adult traumatic brain injury (TBI), with a single-center study suggesting an association with mortality at 6 months. No multi-center studies exist to validate this relationship. The goal was to compare wICP to ICP for association with outcome in a multi-center TBI cohort.

Methods: Using the Collaborative European Neuro Trauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit (ICU) cohort, we derived ICP and wICP (calculated as wICP = (1 - RAP) × ICP; where RAP is the compensatory reserve index derived from the moving correlation between pulse amplitude of ICP and ICP). Various univariate logistic regression models were created comparing ICP and wICP to dichotomized outcome at 6 to 12 months, based on Glasgow Outcome Score-Extended (GOSE) (alive/dead-GOSE ≥ 2/GOSE = 1; favorable/unfavorable-GOSE 5 to 8/GOSE 1 to 4, respectively). Models were compared using area under the receiver operating curves (AUC) and p values.

Results: wICP displayed higher AUC compared to ICP on univariate regression for alive/dead outcome compared to mean ICP (AUC 0.712, 95% CI 0.615-0.810, p = 0.0002, and AUC 0.642, 95% CI 0.538-746, p < 0.0001, respectively; no significant difference on Delong's test), and for favorable/unfavorable outcome (AUC 0.627, 95% CI 0.548-0.705, p = 0.015, and AUC 0.495, 95% CI 0.413-0.577, p = 0.059; significantly different using Delong's test p = 0.002), with lower wICP values associated with improved outcomes (p < 0.05 for both). These relationships on univariate analysis held true even when comparing the wICP models with those containing both ICP and RAP integrated area under the curve over time (p < 0.05 for all via Delong's test).

Conclusions: Compensatory-reserve-weighted ICP displays superior outcome association for both alive/dead and favorable/unfavorable dichotomized outcomes in adult TBI, through univariate analysis. Lower wICP is associated with better global outcomes. The results of this study provide multi-center validation of those seen in a previous single-center study.

Keywords: Compensatory reserve; Intracranial pressure; Outcome; Weighted ICP.

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Conflict of interest statement

Funding was obtained from the Hannelore Kohl Stiftung (Germany), from OneMind (USA) and from Integra LifeSciences Corporation (USA). PS and MC receive part of licensing fees for the software ICM+ (Cambridge Enterprise Ltd., UK) used for data collection and analysis in this study. All other authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Figures

Fig. 1
Fig. 1
a, b ICP and wICP across GOSE categories. GOSE = Glasgow Outcome Score—Extended, ICP = intracranial pressure, mmHg = millimeters of Mercury, wICP = compensatory-reserve-weighted ICP (wICP = (1 − RAP) × ICP). *p values reported are for the Jonckheere-Terpstra test, which was set to assess for statistically significant decreases in mean values of ICP and wICP, with increase GOSE category
Fig. 2
Fig. 2
ICP and wICP across dichotomized 6 to 12 month outcomes. GOSE = Glasgow Outcome Score—Extended, ICP = intracranial pressure, mmHg = millimeters of mercury, wICP = compensatory-reserve-weighted ICP (wICP = (1 − RAP) × ICP). a Mean ICP for alive and dead outcomes. b Mean ICP for favorable and unfavorable outcomes. c Mean wICP for alive and dead outcomes. d Mean wICP for favorable and unfavorable outcomes. Alive/dead dichotomization (alive = GOSE ≥ 2, dead = GOSE 1). Favorable/unfavorable dichotomization (favorable = GOSE 5 to 8, unfavorable = GOSE 1 to 4). *p values reported are for Mann-Whitney U test, comparing mean values between dichotomized groupings
Fig. 3
Fig. 3
Univariate logistic regression—ICP, ICP + RAP AUC above + 0.4, and wICP receiver operating curves. GOSE = Glasgow Outcome Scale Extended, ICP = intracranial pressure, ULR = univariate logistic regression, wICP = compensatory-reserve-weighted ICP (wICP = (1 − RAP) × ICP). a ICP ULR for alive/dead outcome. b ICP ULR for favorable/unfavorable outcome. c ICP + RAP AUC above + 0.4 ULR for alive/dead outcome. d ICP + RAP AUC above + 0.4 for favorable/unfavorable outcome. e wICP ULR for alive/dead outcome. f wICP ULR for favorable/unfavorable outcome. Alive/dead dichotomization (alive = GOSE ≥ 2, dead = GOSE 1). Favorable/unfavorable dichotomization (favorable = GOSE 5 to 8, unfavorable = GOSE 1 to 4). *Indicates AUC reported failed to reach statistical significance in the ULR model
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