Analysis of high-frequency PbtO2 measures in traumatic brain injury: insights into the treatment threshold

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OBJECTIVE

Brain tissue hypoxia is common after traumatic brain injury (TBI). Technology now exists that can detect brain hypoxia and guide corrective therapy. Current guidelines for the management of severe TBI recommend maintaining partial pressure of brain tissue oxygen (PbtO2) > 15–20 mm Hg; however, uncertainty persists as to the optimal treatment threshold. The object of this study was to better inform the relationship between PbtO2 values and outcome for patients with TBI.

METHODS

PbtO2 measurements were prospectively and automatically collected every minute from consecutive patients admitted to the San Francisco General Hospital neurological ICU during a 6-year period. Mean PbtO2 values in TBI patients as well as the proportion of PbtO2 values below each of 75 thresholds between 0 mm Hg and 75 mm Hg over various epochs up to 30 days from the time of admission were analyzed. Patient outcomes were determined using the Glasgow Outcome Scale. The authors explored putative treatment thresholds by generating 675 separate receiver operating characteristic curves and 675 generalized linear models to examine each 1–mm Hg threshold for various epochs.

RESULTS

A total of 1,380,841 PbtO2 values were recorded in 190 TBI patients. A high proportion of PbtO2 measures were below 20 mm Hg irrespective of the examined epoch. Time below treatment thresholds was more strongly associated with outcome than mean PbtO2. A treatment window was suggested: a threshold of 19 mm Hg most robustly distinguished patients by outcome, especially from days 3–5; however, benefit was suggested from maintaining values at least as high as 33 mm Hg.

CONCLUSIONS

This analysis of high-frequency physiological data substantially informs the relationship between PbtO2 values and outcome. The results suggest a therapeutic window for PbtO2 in TBI patients along with minimum and preferred PbtO2 treatment thresholds, which may be examined in future studies. Traditional treatment thresholds that have the strongest association with outcome may not be optimal.

ABBREVIATIONS AUC = area under the curve; BTF = Brain Trauma Foundation; GCS = Glasgow Coma Scale; GLM = generalized linear model; GOS = Glasgow Outcome Scale; TBI = traumatic brain injury; PbtO2 = partial pressure of oxygen in brain tissue; ROC = receiver operating characteristic.

Article Information

Correspondence Gregory W. J. Hawryluk: University of Utah, Salt Lake City, UT. gregory.hawryluk@hsc.utah.edu.

INCLUDE WHEN CITING Published online October 12, 2018; DOI: 10.3171/2018.4.JNS172604.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Analysis of inclusion criteria and flowchart. Patients with PbtO2 data and GOS scores at discharge with a confirmed TBI were included in the analyses. A first wave of conservative data-driven analyses was performed using ROC/AUC to test whether specific treatment thresholds predicted mortality (GOS score 1 vs > 1). A second wave of liberal data-driven analyses was performed using GLM to test the same hypothesis, followed by post hoc testing using the least significant difference (LSD) for thresholds with significant predictors on GOS scores.

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    Distribution of PbtO2 values demonstrating that a high proportion of measures were consistently below treatment threshold throughout the first 30 days after ICU admission. PbtO2 values were measured using the Licox system, and measures are plotted within 1–mm Hg ranges. A: Individual days. B: Multiday epochs. The vertical red line indicates a possible treatment threshold of 19 mm Hg. The blue line includes patients recovering specifically from TBI (n = 190). The indicated time is in reference to the time of ICU admission.

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    Patient outcome is more strongly associated with the proportion of time spent below treatment thresholds than it is with mean PbtO2 values. The proportion of PbtO2 values < 19 mm Hg is associated with outcome from days 1 to 4 in TBI patients. A: Values were measured using the Licox system, and average PbtO2 values are plotted in relation to time after ICU admission. B: The proportion of PbtO2 values below a potential threshold of 19 mm Hg are plotted. The “n” used in statistical testing in (A) is the number of PbtO2 measures, while the “n” in (B) is the number of patients. Mean values are shown. The error bars represent SEM. *Significant on analysis.

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    The amount of time spent at lower PbtO2 (< 45 mm Hg) values is associated with poorer neurological outcome after injury. Plots display thresholds at 1–mm Hg increments. All TBI patients with GOS values (n = 185) are reported. Values were measured using the Licox PbtO2 monitoring system and time is relative to ICU admission. A: Individual days. B: Multiday epochs. The vertical red line at 19 mm Hg indicates counts below a proposed threshold of 19 mm Hg.

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    Data-driven identification of potential treatment thresholds to predict mortality of TBI patients based on PbtO2 proportions below each value using ROC analysis. PbtO2 data for each TBI patient were analyzed using the ROC curve to calculate the AUC to test whether the proportion of events below each 1–mm Hg threshold could predict mortality (GOS score 1 vs GOS scores 2–4). p values from AUC results are plotted on the y-axis and 1–mm Hg thresholds on the x-axis to identify windows of vulnerability in the ICU for 7 days after admission to the ICU post-TBI (A–G). Patient numbers drop off each day, most likely due to discharge or death. The increase in patients on day 2 indicates that Licox monitoring was not initiated until 2 days after coming into the hospital for some patients. Data for all days, either 3–5 (H) or 1–7 (I), were combined to calculate proportions below each threshold for each duration, highlighting the average dip in p values that occurs between 15 and 40 mm Hg on days 3–5.

  • View in gallery

    Data-driven identification of potential treatment thresholds to predict mortality of TBI patients based on PbtO2 proportions below each value using GLM analysis. PbtO2 data for each TBI patient were analyzed using GLM to test whether the proportion of events below each 1–mm Hg threshold could predict the GOS score at discharge (all groups combined/main effect). p values from GLM are plotted on the y-axis and 1–mm Hg thresholds on the x-axis, similar to Fig. 5, to identify windows of vulnerability in the ICU for 7 days after admission to the ICU post-TBI (A–G). Data for all days, either 3–5 (H) or 1–7 (I), were combined to calculate proportions below each threshold. The y-axis is plotted to emphasize the locations where the p values fall into significance (p < 0.05), with red arrows indicating the lowest point of the drop in p values.

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