Transcranial Doppler Based Cerebrovascular Reactivity Indices in Adult Traumatic Brain Injury: A Scoping Review of Associations With Patient Oriented Outcomes

Abstract

Background: Disruption in cerebrovascular reactivity following traumatic brain injury (TBI) is a known phenomenon that may hold prognostic value and clinical relevance. Ultimately, improved knowledge of this process and more robust means of continuous assessment may lead to advances in precision medicine following TBI. One such method is transcranial Doppler (TCD), which has been employed to evaluate cerebrovascular reactivity following injury utilizing a continuous time-series approach.Objective: The present study undertakes a scoping review of the literature on the association of continuous time-domain TCD based indices of cerebrovascular reactivity, with global functional outcomes, cerebral physiologic correlates, and imaging evidence of lesion change.Design: Multiple databases were searched from inception to November 2020 for articles relevant to the association of continuous time-domain TCD based indices of cerebrovascular reactivity with global functional outcomes, cerebral physiologic correlates, and imaging evidence of lesion change.Results: Thirty-six relevant articles were identified. There was significant evidence supporting an association with continuous time-domain TCD based indices and functional outcomes following TBI. Indices based on mean flow velocity, as measured by TCD, were most numerous while more recent studies point to systolic flow velocity-based indices encoding more prognostic utility. Physiologic parameters such as intracranial pressure, cerebral perfusion pressure, Carbon Dioxide (CO2) reactivity as well as more established indices of cerebrovascular reactivity have all been associated with these TCD based indices. The literature has been concentrated in a few centres and is further limited by the lack of multivariate analysis.Conclusions: This systematic scoping review of the literature identifies that there is a substantial body of evidence that cerebrovascular reactivity as measured by time-domain TCD based indices have prognostic utility following TBI. Indices based on mean flow velocities have the largest body of literature for their support. However, recent studies indicate that indices based on systolic flow velocities may contain the most prognostic utility and more closely follow more established measures of cerebrovascular reactivity. To a lesser extent, the literature supports some associations between these indices and cerebral physiologic parameters. These indices provide a more complete picture of the patient’s physiome following TBI and may ultimately lead to personalized and precise clinical care. Further validation in multi-institution studies is required before these indices can be widely adopted clinically.

Multimodal and autoregulation monitoring in the neurointensive care unit

“…Similar findings have been described in patients presenting with spontaneous intracerebral hemorrhage (ICH) where a gradual decline in CA capacity ipsilateral to the hemorrhage location over the first 5 days was associated with a decline in clinical exam and worse 90-day outcomes (180). In SAH, increases in Mx_a and Sx_a have been associated with the development of vasospasm in the ipsilateral hemisphere and combining radiographic vasospasm with increasing Mx_a from baseline over the first 7 days from ictus has been correlated with the development of DCI (181,182).…”

“…Furthermore, unlike PRx, which is based on changes in ICP as a surrogate of CBV and relies on the intracranial pressure-volume relationship, TCD more directly measures CBF and can provide insights into dynamic CA changes even in the setting of highly compliant intracranial systems where PRx may not demonstrate significant fluctuations ( 35 , 47 ). Despite these reasons for optimism, much work still needs to be done to validate TCD as a feasible continuous or semi-continuous monitoring technique as the majority of published studies report only snap-shots in time with no study reporting monitoring durations longer than 4 h ( 183 ). Furthermore, the vast majority of TCD derived CA reports are from data generated at the Addenbrooke’s Hospital in Cambridge United Kingdom, highlighting the need for external validation in different hospital settings and patient populations ( 183 ).…”

“…Despite these reasons for optimism, much work still needs to be done to validate TCD as a feasible continuous or semi-continuous monitoring technique as the majority of published studies report only snap-shots in time with no study reporting monitoring durations longer than 4 h ( 183 ). Furthermore, the vast majority of TCD derived CA reports are from data generated at the Addenbrooke’s Hospital in Cambridge United Kingdom, highlighting the need for external validation in different hospital settings and patient populations ( 183 ). Recently, a proposed protocol was published for a prospective multicenter study in severe TBI patients utilizing TCD with ICP/PbtO 2 monitors with the goal of obtaining high-fidelity continuous data and correlate TCD based indices such as Mx/Mx_a, Sx/Sx_a, and CrCP with invasive parameters ( 94 ).…”

Systemic immune inflammation index and peripheral blood carbon dioxide concentration at admission predict poor prognosis in patients with severe traumatic brain injury

“…Previous studies have shown that patients with severe TBI may experience hyperventilation at early stages, thus decreasing peripheral blood CO 2 levels. The decreases in peripheral blood CO 2 concentrations and partial pressure of CO 2 lead to intracranial vasoconstriction, decreased cerebral blood flow and decreased intracranial pressure (ICP), thus further aggravating the occurrence of brain metabolic disorders and inflammation after TBI ( 20 – 22 ). Peripheral blood CO 2 concentrations have been found to influence the development of inflammation in mammalian innate immune and inflammatory experiments: elevated CO 2 concentrations eliminate the NF-Kb activity induced by LPS in a manner independent of the IKKβ pathway.…”

Curcumin-Impregnated Drug Delivery Systems May Show Promise in the Treatment of Diseases Secondary to Traumatic Brain Injury: Systematic Review

“…10, 11 Cerebrovascular autoregulation and CO 2 reactivity, which are vital mechanisms that provide cerebral blood flow, are partially or completely impaired following TBI. 12 Chronic depolarization of vascular smooth muscle cells and cerebral vasospasm resulting in TBI are also seen in most cases. 13 Oxygen and glucose consumption are affected in the brain, 14 and the amount of phosphocreatine and ATP in the tissue decreases.…”