| 1. |
- Froese, Logan, et al.
(författare)
-
The impact of sedative and vasopressor agents on cerebrovascular reactivity in severe traumatic brain injury
- 2023
-
Ingår i: Intensive Care Medicine Experimental. - : Springer. - 2197-425X. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study is to evaluate the impact of commonly administered sedatives (Propofol, Alfentanil, Fentanyl, and Midazolam) and vasopressor (Dobutamine, Ephedrine, Noradrenaline and Vasopressin) agents on cerebrovascular reactivity in moderate/severe TBI patients. Cerebrovascular reactivity, as a surrogate for cerebral autoregulation was assessed using the long pressure reactivity index (LPRx). We evaluated the data in two phases, first we assessed the minute-by-minute data relationships between different dosing amounts of continuous infusion agents and physiological variables using boxplots, multiple linear regression and ANOVA. Next, we assessed the relationship between continuous/bolus infusion agents and physiological variables, assessing pre-/post- dose of medication change in physiology using a Wilcoxon signed-ranked test. Finally, we evaluated sub-groups of data for each individual dose change per medication, focusing on key physiological thresholds and demographics.Results: Of the 475 patients with an average stay of 10 days resulting in over 3000 days of recorded information 367 (77.3%) were male with a median Glasgow coma score of 7 (4-9). The results of this retrospective observational study confirmed that the infusion of most administered agents do not impact cerebrovascular reactivity, which is confirmed by the multiple linear regression components having p value > 0.05. Incremental dose changes or bolus doses in these medications in general do not lead to significant changes in cerebrovascular reactivity (confirm by Wilcoxon signed-ranked p value > 0.05 for nearly all assessed relationships). Within the sub-group analysis that separated the data based on LPRx pre-dose, a significance between pre-/post-drug change in LPRx was seen, however this may be more of a result from patient state than drug impact.Conclusions: Overall, this study indicates that commonly administered agents with incremental dosing changes have no clinically significant influence on cerebrovascular reactivity in TBI (nor do they impair cerebrovascular reactivity). Though further investigation in a larger and more diverse TBI patient population is required.
|
|
| 2. |
- Lindblad, Caroline, et al.
(författare)
-
Current state of high-fidelity multimodal monitoring in traumatic brain injury
- 2022
-
Ingår i: Acta Neurochirurgica. - : Springer Nature. - 0001-6268 .- 0942-0940. ; 164:12, s. 3091-3100
-
Forskningsöversikt (refereegranskat)abstract
- Introduction Multimodality monitoring of patients with severe traumatic brain injury (TBI) is primarily performed in neurocritical care units to prevent secondary harmful brain insults and facilitate patient recovery. Several metrics are commonly monitored using both invasive and non-invasive techniques. The latest Brain Trauma Foundation guidelines from 2016 provide recommendations and thresholds for some of these. Still, high-level evidence for several metrics and thresholds is lacking. Methods Regarding invasive brain monitoring, intracranial pressure (ICP) forms the cornerstone, and pressures above 22 mmHg should be avoided. From ICP, cerebral perfusion pressure (CPP) (mean arterial pressure (MAP)-ICP) and pressure reactivity index (PRx) (a correlation between slow waves MAP and ICP as a surrogate for cerebrovascular reactivity) may be derived. In terms of regional monitoring, partial brain tissue oxygen pressure (PbtO(2)) is commonly used, and phase 3 studies are currently ongoing to determine its added effect to outcome together with ICP monitoring. Cerebral microdialysis (CMD) is another regional invasive modality to measure substances in the brain extracellular fluid. International consortiums have suggested thresholds and management strategies, in spite of lacking high-level evidence. Although invasive monitoring is generally safe, iatrogenic hemorrhages are reported in about 10% of cases, but these probably do not significantly affect long-term outcome. Non-invasive monitoring is relatively recent in the field of TBI care, and research is usually from single-center retrospective experiences. Near-infrared spectrometry (NIRS) measuring regional tissue saturation has been shown to be associated with outcome. Transcranial doppler (TCD) has several tentative utilities in TBI like measuring ICP and detecting vasospasm. Furthermore, serial sampling of biomarkers of brain injury in the blood can be used to detect secondary brain injury development. Conclusions In multimodal monitoring, the most important aspect is data interpretation, which requires knowledge of each metric's strengths and limitations. Combinations of several modalities might make it possible to discern specific pathologic states suitable for treatment. However, the cost-benefit should be considered as the incremental benefit of adding several metrics has a low level of evidence, thus warranting additional research.
|
|
| 3. |
- Mathieu, François, et al.
(författare)
-
Relationship Between Measures of Cerebrovascular Reactivity and Intracranial Lesion Progression in Acute TBI Patients : an Exploratory Analysis.
- 2020
-
Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 32:2, s. 373-382
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Failure of cerebral autoregulation and progression of intracranial lesion have both been shown to contribute to poor outcome in patients with acute traumatic brain injury (TBI), but the interplay between the two phenomena has not been investigated. Preliminary evidence leads us to hypothesize that brain tissue adjacent to primary injury foci may be more vulnerable to large fluctuations in blood flow in the absence of intact autoregulatory mechanisms. The goal of this study was therefore to assess the influence of cerebrovascular reactivity measures on radiological lesion expansion in a cohort of patients with acute TBI.METHODS: We conducted a retrospective cohort analysis on 50 TBI patients who had undergone high-frequency multimodal intracranial monitoring and for which at least two brain computed tomography (CT) scans had been performed in the acute phase of injury. We first performed univariate analyses on the full cohort to identify non-neurophysiological factors (i.e., initial lesion volume, timing of scan, coagulopathy) associated with traumatic lesion growth in this population. In a subset analysis of 23 patients who had intracranial recording data covering the period between the initial and repeat CT scan, we then correlated changes in serial volumetric lesion measurements with cerebrovascular reactivity metrics derived from the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC (correlation coefficient between the pulse amplitude of intracranial pressure and cerebral perfusion pressure). Using multivariate methods, these results were subsequently adjusted for the non-neurophysiological confounders identified in the univariate analyses.RESULTS: We observed significant positive linear associations between the degree of cerebrovascular reactivity impairment and progression of pericontusional edema. The strongest correlations were observed between edema progression and the following indices of cerebrovascular reactivity between sequential scans: % time PRx > 0.25 (r = 0.69, p = 0.002) and % time PAx > 0.25 (r = 0.64, p = 0.006). These associations remained significant after adjusting for initial lesion volume and mean cerebral perfusion pressure. In contrast, progression of the hemorrhagic core and extra-axial hemorrhage volume did not appear to be strongly influenced by autoregulatory status.CONCLUSIONS: Our preliminary findings suggest a possible link between autoregulatory failure and traumatic edema progression, which warrants re-evaluation in larger-scale prospective studies.
|
|
| 4. |
- Mathieu, François, et al.
(författare)
-
Relationship between Measures of CerebrovascularReactivity and Intracranial Lesion Progressionin Acute Traumatic Brain Injury Patients:A CENTER-TBI Study
- 2020
-
Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 37:13, s. 1556-1565
-
Tidskriftsartikel (refereegranskat)abstract
- Failure of cerebral autoregulation has been linked to unfavorable outcome after traumatic brain injury (TBI). Preliminary evidence from a small, retrospective, single-center analysis suggests that autoregulatory dysfunction may be associated with traumatic lesion expansion, particularly for pericontusional edema. The goal of this study was to further explore these associations using prospective, multi-center data from the Collaborative European Neurotrauma Effectiveness Research in TBI (CENTER-TBI) and to further explore the relationship between autoregulatory failure, lesion progression, and patient outcome. A total of 88 subjects from the CENTER-TBI High Resolution ICU Sub-Study cohort were included. All patients had an admission computed tomography (CT) scan and early repeat scan available, as well as high-frequency neurophysiological recordings covering the between-scan interval. Using a novel, semiautomated approach at lesion segmentation, we calculated absolute changes in volume of contusion core, pericontusional edema, and extra-axial hemorrhage between the imaging studies. We then evaluated associations between cerebrovascular reactivity metrics and radiological lesion progression using mixed-model regression. Analyses were adjusted for baseline covariates and non-neurophysiological factors associated with lesion growth using multi-variate methods. Impairment in cerebrovascular reactivity was significantly associated with progression of pericontusional edema and, to a lesser degree, intraparenchymal hemorrhage. In contrast, there were no significant associations with extra-axial hemorrhage. The strongest relationships were observed between RAC-based metrics and edema formation. Pulse amplitude index showed weaker, but consistent, associations with contusion growth. Cerebrovascular reactivity metrics remained strongly associated with lesion progression after taking into account contributions from non-neurophysiological factors and mean cerebral perfusion pressure. Total hemorrhagic core and edema volumes on repeat CT were significantly larger in patients who were deceased at 6 months, and the amount of edema was greater in patients with an unfavourable outcome (Glasgow Outcome Scale-Extended 1–4). Our study suggests associations between autoregulatory failure, traumatic edema progression, and poor outcome. This is in keeping with findings from a single-center retrospective analysis, providing multi-center prospective data to support those results.
|
|
| 5. |
- Zeiler, Frederick A., et al.
(författare)
-
Association between Physiological Signal Complexity and Outcomes in Moderate and Severe Traumatic Brain Injury : A CENTER-TBI Exploratory Analysis of Multi-Scale Entropy
- 2021
-
Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 38:2, s. 272-282
-
Tidskriftsartikel (refereegranskat)abstract
- In traumatic brain injury (TBI), preliminary retrospective work on signal entropy suggests an association with global outcome. The goal of this study was to provide multi-center validation of the association between multi-scale entropy (MSE) of cardiovascular and cerebral physiological signals, with six-month outcome. Using the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit (ICU) cohort, we selected patients with a minimum of 72 h of physiological recordings and a documented six-month Glasgow Outcome Scale Extended (GOSE) score. The 10-sec summary data for heart rate (HR), mean arterial pressure (MAP), intracranial pressure (ICP), and pulse amplitude of ICP (AMP) were derived across the first 72 h of data. The MSE complexity index (MSE-Ci) was determined for HR, MAP, ICP, and AMP, with the association between MSE and dichotomized six-month outcomes assessed using Mann-Whitney U testing and logistic regression analysis. A total of 160 patients had a minimum of 72 h of recording and a documented outcome. Decreased HR MSE-Ci (7.3 [interquartile range (IQR) 5.4 to 10.2] vs. 5.1 [IQR 3.1 to 7.0]; p = 0.002), lower ICP MSE-Ci (11.2 [IQR 7.5 to 14.2] vs. 7.3 [IQR 6.1 to 11.0]; p = 0.009), and lower AMP MSE-Ci (10.9 [IQR 8.0 to 13.7] vs. 8.7 [IQR 6.6 to 11.0]; p = 0.022), were associated with death. Similarly, lower HR MSE-Ci (8.0 [IQR 6.2 to 10.9] vs. 6.2 [IQR 3.9 to 8.7]; p = 0.003) and lower ICP MSE-Ci (11.4 [IQR 8.6 to 14.4)] vs. 9.2 [IQR 6.0 to 13.5]), were associated with unfavorable outcome. Logistic regression analysis confirmed that lower HR MSE-Ci and ICP MSE-Ci were associated with death and unfavorable outcome at six months. These findings suggest that a reduction in cardiovascular and cerebrovascular system entropy is associated with worse outcomes. Further work in the field of signal complexity in TBI multi-modal monitoring is required.
|
|
| 6. |
- Zeiler, Frederick A, et al.
(författare)
-
Brain tissue oxygen and cerebrovascular reactivity in traumatic brain injury : a collaborative european neurotrauma effectiveness research in traumatic brain injury exploratory analysis of insult burden
- 2020
-
Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 37:17, s. 1854-1863
-
Tidskriftsartikel (refereegranskat)abstract
- Pressure reactivity index (PRx) and brain tissue oxygen (PbtO2) are associated with outcome in traumatic brain injury (TBI). This study explores the relationship between PRx and PbtO2 in adult moderate/severe TBI. Using the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high resolution intensive care unit (ICU) sub-study cohort, we evaluated those patients with archived high-frequency digital intraparenchymal intracranial pressure (ICP) and PbtO2 monitoring data of, a minimum of 6 h in duration, and the presence of a 6 month Glasgow Outcome Scale -Extended (GOSE) score. Digital physiological signals were processed for ICP, PbtO2, and PRx, with the % time above/below defined thresholds determined. The duration of ICP, PbtO2, and PRx derangements was characterized. Associations with dichotomized 6-month GOSE (alive/dead, and favorable/unfavorable outcome; ≤ 4 = unfavorable), were assessed. A total of 43 patients were included. Severely impaired cerebrovascular reactivity was seen during elevated ICP and low PbtO2 episodes. However, most of the acute ICU physiological derangements were impaired cerebrovascular reactivity, not ICP elevations or low PbtO2 episodes. Low PbtO2 without PRx impairment was rarely seen. % time spent above PRx threshold was associated with mortality at 6 months for thresholds of 0 (area under the curve [AUC] 0.734, p = 0.003), > +0.25 (AUC 0.747, p = 0.002) and > +0.35 (AUC 0.745, p = 0.002). Similar relationships were not seen for % time with ICP >20 mm Hg, and PbtO2 < 20 mm Hg in this cohort. Extreme impairment in cerebrovascular reactivity is seen during concurrent episodes of elevated ICP and low PbtO2. However, the majority of the deranged cerebral physiology seen during the acute ICU phase is impairment in cerebrovascular reactivity, with most impairment occurring in the presence of normal PbtO2 levels. Measures of cerebrovascular reactivity appear to display the most consistent associations with global outcome in TBI, compared with ICP and PbtO2.
|
|
| 7. |
- Zeiler, Frederick A., et al.
(författare)
-
Diffuse intracranial injury patterns are associated with impaired cerebrovascular reactivity in adult traumatic brain injury : a CENTER-TBI validation study
- 2020
-
Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 37:4, s. 1597-1608
-
Tidskriftsartikel (refereegranskat)abstract
- Recent single-center retrospective analysis displayed the association between admission computed tomography (CT) markers of diffuse intracranial injury and worse cerebrovascular reactivity. The goal of this study was to further explore these associations using the prospective multi-center Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) high-resolution intensive care unit (HR ICU) data set. Using the CENTER-TBI HR ICU sub-study cohort, we evaluated those patients with both archived high-frequency digital physiology (100 Hz or higher) and the presence of a digital admission CT scan. Physiological signals were processed for pressure reactivity index (PRx) and both the percent (%) time above defined PRx thresholds and mean hourly dose above threshold. Admission CT injury scores were obtained from the database. Quantitative contusion, edema, intraventricular hemorrhage (IVH), and extra-axial lesion volumes were obtained via semi-automated segmentation. Comparison between admission CT characteristics and PRx metrics was conducted using Mann-U, Jonckheere-Terpstra testing, with a combination of univariate linear and logistic regression techniques. A total of 165 patients were included. Cisternal compression and high admission Rotterdam and Helsinki CT scores, and Marshall CT diffuse injury sub-scores were associated with increased percent (%) time and hourly dose above PRx threshold of 0, +0.25, and +0.35 (p < 0.02 for all). Logistic regression analysis displayed an association between deep peri-contusional edema and mean PRx above a threshold of +0.25. These results suggest that diffuse injury patterns, consistent with acceleration/deceleration forces, are associated with impaired cerebrovascular reactivity. Diffuse admission intracranial injury patterns appear to be consistently associated with impaired cerebrovascular reactivity, as measured through PRx. This is in keeping with the previous single-center retrospective literature on the topic. This study provides multi-center validation for those results, and provides preliminary data to support potential risk stratification for impaired cerebrovascular reactivity based on injury pattern.
|
|
| 8. |
- Zeiler, Frederick A., et al.
(författare)
-
Evaluation of the relationship between slow-waves of intracranial pressure, mean arterial pressure and brain tissue oxygen in TBI : a CENTER-TBI exploratory analysis
- 2021
-
Ingår i: Journal of clinical monitoring and computing. - : Springer Berlin/Heidelberg. - 1387-1307 .- 1573-2614. ; 35:4, s. 711-722
-
Tidskriftsartikel (refereegranskat)abstract
- Brain tissue oxygen (PbtO2) monitoring in traumatic brain injury (TBI) has demonstrated strong associations with globaloutcome. Additionally, PbtO2 signals have been used to derive indices thought to be associated with cerebrovascular reactivityin TBI. However, their true relationship to slow-wave vasogenic fuctuations associated with cerebral autoregulation remainsunclear. The goal of this study was to investigate the relationship between slow-wave fuctuations of intracranial pressure(ICP), mean arterial pressure (MAP) and PbtO2 over time. Using the Collaborative European NeuroTrauma EfectivenessResearch in Traumatic Brain Injury (CENTER-TBI) high resolution ICU sub-study cohort, we evaluated those patients withrecorded high-frequency digital intra-parenchymal ICP and PbtO2 monitoring data of a minimum of 6 h in duration. Digitalphysiologic signals were processed for ICP, MAP, and PbtO2 slow-waves using a moving average flter to decimate the highfrequency signal. The frst 5 days of recording were analyzed. The relationship between ICP, MAP and PbtO2 slow-wavesover time were assessed using autoregressive integrative moving average (ARIMA) and vector autoregressive integrativemoving average (VARIMA) modelling, as well as Granger causality testing. A total of 47 patients were included. The ARIMAstructure of ICP and MAP were similar in time, where PbtO2 displayed diferent optimal structure. VARIMA modellingand IRF plots confrmed the strong directional relationship between MAP and ICP, demonstrating an ICP response to MAPimpulse. PbtO2 slow-waves, however, failed to demonstrate a defnite response to ICP and MAP slow-wave impulses. Theseresults raise questions as to the utility of PbtO2 in the derivation of cerebrovascular reactivity measures in TBI. There isa reproducible relationship between slow-wave fuctuations of ICP and MAP, as demonstrated across various time-seriesanalytic techniques. PbtO2 does not appear to reliably respond in time to slow-wave fuctuations in MAP, as demonstratedon various VARIMA models across all patients. These fndings suggest that PbtO2 should not be utilized in the derivationof cerebrovascular reactivity metrics in TBI, as it does not appear to be responsive to changes in MAP in the slow-waves.These fndings corroborate previous results regarding PbtO2 based cerebrovascular reactivity indices.
|
|
| 9. |
- Zeiler, Frederick A., et al.
(författare)
-
Patient-specific ICP Epidemiologic Thresholds in Adult Traumatic Brain Injury : A CENTER-TBI Validation Study
- 2019
-
Ingår i: Journal of Neurosurgical Anesthesiology. - : Wolters Kluwer. - 0898-4921 .- 1537-1921.
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patient-specific epidemiologic intracranial pressure (ICP) thresholds in adult traumatic brain injury (TBI) have emerged, using the relationship between pressure reactivity index (PRx) and ICP, displaying stronger association with outcome over existing guideline thresholds. The goal of this study was to explore this relationship in a multi-center cohort in order to confirm the previous finding.METHODS: Using the Collaborative European Neuro Trauma Effectiveness Research in TBI (CENTER-TBI) high-resolution intensive care unit cohort, we derived individualized epidemiologic ICP thresholds for each patient using the relationship between PRx and ICP. Mean hourly dose of ICP was calculated for every patient for the following thresholds: 20, 22 mm Hg and the patient's individual ICP threshold. Univariate logistic regression models were created comparing mean hourly dose of ICP above thresholds 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).RESULTS: Individual thresholds were identified in 65.3% of patients (n=128), in keeping with previous results (23.0±11.8 mm Hg [interquartile range: 14.9 to 29.8 mm Hg]). Mean hourly dose of ICP above individual threshold provides superior discrimination (area under the receiver operating curve [AUC]=0.678, P=0.029) over mean hourly dose above 20 mm Hg (AUC=0.509, P=0.03) or above 22 mm Hg (AUC=0.492, P=0.035) on univariate analysis for alive/dead outcome at 6 to 12 months. The AUC for mean hourly dose above individual threshold trends to higher values for favorable/unfavorable outcome, but fails to reach statistical significance (AUC=0.610, P=0.060). This was maintained when controlling for baseline admission characteristics.CONCLUSIONS: Mean hourly dose of ICP above individual epidemiologic ICP threshold has stronger associations with mortality compared with the dose above Brain Trauma Foundation defined thresholds of 20 or 22 mm Hg, confirming prior findings. Further studies on patient-specific epidemiologic ICP thresholds are required.
|
|
| 10. |
- Åkerlund, Cecilia, et al.
(författare)
-
Impact of duration and magnitude of raised intracranial pressure on outcome after severe traumatic brain injury : A CENTER-TBI high-resolution group study
- 2020
-
Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 15:12
-
Tidskriftsartikel (refereegranskat)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.
|
|
