Effects of Norepinephrine, Propofol, and Hemoglobin Concentration on Dynamic Measurements of Cerebrovascular Reactivity in Acute Brain Injury

Abstract

Effects of treatment-associated variables on cerebrovascular autoregulation (CA) in acute brain injury patients remain unclear. As deficient CA is associated with worse outcomes and ideas about CA-steered management are emerging, this question is relevant. We investigated effects of norepinephrine and propofol infusion rates and hemoglobin concentration on dynamic measurements of cerebrovascular reactivity as surrogate for CA. A retrospective analysis of 91 traumatic brain injury (TBI) and 13 stroke patients admitted to the intensive care unit (ICU) of the Leuven University Hospitals was performed. Low-resolution autoregulation index (LAx) and high-frequency pressure reactivity index (PRx) were calculated as measurements of cerebrovascular reactivity. Data was binned into 5-, 15-, and 60-min intervals. Bivariate time-series analysis using lagged cross-correlations were calculated after pre-whitening and differencing. Linear mixed models evaluated effects of age, gender, cardiovascular risk, brain comorbidity, Glasgow Coma Scale (GCS), pupil reactivity, and type of injury. Median dose of norepinephrine, propofol and hemoglobin concentration was 7.8 μg/kg/h (Q1 3.6-Q3 13.8), 3 mg/kg/h (Q1 1.9-Q3 4.3), and 9.2 gꞏdL −1 (Q1 8.2-Q3 10.5), respectively. Mean crosscorrelations for 24 lags were close to zero and not significant for all variables. No significant differences as function of age, gender, cardiovascular risk, brain comorbidity, GCS, pupil reactivity, and type of injury were found. Dynamic intracranial pressure-based measurements of cerebrovascular reactivity in acute brain injured patients are not affected by gradually adjusted norepinephrine or propofol infusion rates or slow changes in hemoglobin concentration within the typical ranges during ICU admission. Future trials on cerebrovascular reactivity-steered management and treatment of CA impairment may not have to take these variables into account.

The Impact of Vasopressor and Sedative Agents on Cerebrovascular Reactivity and Compensatory Reserve in Traumatic Brain Injury: An Exploratory Analysis

“…As such, variation in vasopressor dosing appears to provide some support for the ability to target optimal CPP targets. Such prospective work on optimal CPP targeting is the focus of collaborative groups in Europe and Canada, 12,27,32,33 and the subject of an ongoing phase 2 randomized controlled trial. 22 Third, cerebrovascular reactivity appears to remain relatively unaffected by sedative agents and changes in dosing.…”

“…24,25 Currently, our understanding of the impact of guideline-based therapeutics, including the effects of sedatives and vasopressors, is limited to a small number of studies using aggregate data. 10,13,26,27 A recent 25year retrospective analysis by Donnelly and associates suggested that, despite changes in TBI management guidelines over various epochs, cerebrovascular reactivity remained essentially unchanged, with mortality rates in patients with moderate/severe TBI being relatively fixed. 10 Similarly, a recent multi-center study from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study found no significant association between therapeutic intensity levels (TIL), and impaired cerebrovascular reactivity.…”

The impact of hypertonic saline on cerebrovascular reactivity and compensatory reserve in traumatic brain injury: an exploratory analysis

“…Predictors of ICP response to the various BTF guideline-based therapeutics are crucial, as they would allow for clinical end-users to stratify patients pre-treatment into suspected responders vs. non-responders, which may facilitate alternative treatments or increase in aggressiveness of therapies applied. Much further work, using highfrequency physiological responses, is required in this regard, and will be the focus of ongoing work from European [2,6,33] and Canadian [8] collaborative research groups.…”

“…With only 15 patients with 69 HTS administration events, our data set is small, yet relatively unique globally with high-frequency physiology linked with treatment information. Similar methodologies for the exploration of the relationships between TBI therapeutics and continuous physiological responses have been employed by other centers globally [12,13,17,32,33,41,42]. As these types of data sets are rare, we are left with exploring such treatmentrelated impacts on small patient numbers.…”

Hypertonic Saline for Moderate Traumatic Brain Injury: A Scoping Review of Impact on Neurological Deterioration

“…Multi-center and international groups are exploring such work, including those in Europe [34][35][36] and Canada. [37][38][39] Our group in particular, the Winnipeg Acute TBI Laboratories, has recently led some of the preliminary work in this field, through the development of non-invasive techniques for continuous cerebrovascular reactivity assessments, and through interrogation of the impacts of HTS, sedation, and vasopressor agents on multi-modal cerebral physiological monitoring.…”