Regulation of the cerebral circulation: bedside assessment and clinical implications

The regulation of the cerebral circulation relies on the complex interplay between cardiovascular, respiratory, and neural physiology. In health, these physiologic systems act to maintain an adequate cerebral blood flow (CBF) through modulation of hydrodynamic parameters; the resistance of cerebral vessels, and the arterial, intracranial, and venous pressures. In critical illness, however, one or more of these parameters can be compromised raising the possibility of disturbed CBF regulation and its pathophysiologic sequelae. The rigorous assessment of the cerebral circulation requires not only measuring CBF and its hydrodynamic determinants but also assessing the stability of CBF in response to changes in arterial pressure (cerebral autoregulation), the reactivity of CBF to a vasodilator (CO₂ reactivity for example), and the dynamic regulation of arterial pressure (baroreceptor sensitivity). Ideally, cerebral circulation monitors in critical care should be continuous, physically robust, allow for both regional and global CBF assessment, and be conducive to application at the bedside. The regulation of the cerebral circulation is impaired not only in primary neurologic conditions that affect the vasculature such as subarachnoid haemorrhage and stroke, but also in conditions that affect the regulation of intracranial pressure (such as traumatic brain injury and hydrocephalus) or arterial blood pressure (sepsis, or cardiac dysfunction). Importantly, this impairment is often associated with poor patient outcome. At present, the assessment of the cerebral circulation is primarily used as a research tool to elucidate pathophysiology or prognosis. However, when combined with other physiologic signals and online analytical techniques, cerebral circulation monitoring has the appealing potential to not only prognosticate patients, but also direct critical care management.JD is supported by a Woolf Fisher scholarship (NZ). MC is partially supported by the NIHR

Application of Robotic Transcranial Doppler for Extended Duration Recording in Moderate/Severe Traumatic Brain Injury: First Experiences

Long duration application of transcranial Doppler (TCD) for recording of middle cerebral artery (MCA) cerebral blood flow velocity (CBFV) has been fraught with difficulties.[1,2] Classically, TCD has been labor intensive, with limited ability to obtain uninterrupted recordings for extended periods. Furthermore, application of TCD within neurocritically ill for long durations has been limited given the complexity of care, regular bedside nursing care/patient manipulations, and presence of various other multi-modal monitoring devices. This is especially the case in traumatic brain injury (TBI) patients, with the adoption of extensive multi-modal monitoring. Within TBI, most TCD recordings, using standard widely available probes and holders, range from 30 minutes to 1-hour duration and are frequently interrupted due to shifting of the probe and signal loss.[3,4] Thus, we are typically left with a “snap-shot” recording with TCD examination, limiting our ability to extract valuable continuous variables, such as autoregulatory capacity.[3-5] Recent advances in robotics have le

Measurement of Intraspinal Pressure After Spinal Cord Injury: Technical Note from the Injured Spinal Cord Pressure Evaluation Study.

Intracranial pressure (ICP) is routinely measured in patients with severe traumatic brain injury (TBI). We describe a novel technique that allowed us to monitor intraspinal pressure (ISP) at the injury site in 14 patients who had severe acute traumatic spinal cord injury (TSCI), analogous to monitoring ICP after brain injury. A Codman probe was inserted subdurally to measure the pressure of the injured spinal cord compressed against the surrounding dura. Our key finding is that it is feasible and safe to monitor ISP for up to a week in patients after TSCI, starting within 72 h of the injury. With practice, probe insertion and calibration take less than 10 min. The ISP signal characteristics after TSCI were similar to the ICP signal characteristics recorded after TBI. Importantly, there were no associated complications. Future studies are required to determine whether reducing ISP improves neurological outcome after severe TSCI

ICP versus Laser Doppler Cerebrovascular Reactivity Indices to Assess Brain Autoregulatory Capacity

Objective: To explore the relationship between various autoregulatory indices in order to determine which approximate small-vessel/microvascular autoregulatory capacity most accurately. Methods: Utilizing a retrospective cohort of traumatic brain injury (TBI) patients (N=41) with: transcranial Doppler (TCD), intracranial pressure (ICP) and cortical laser Doppler flowmetry (LDF), we calculated various continuous indices of autoregulation and cerebrovascular responsiveness: A. ICP derived (pressure reactivity index (PRx) – correlation between ICP and mean arterial pressure (MAP), PAx – correlation between pulse amplitude of ICP (AMP) and MAP, RAC – correlation between AMP and cerebral perfusion pressure (CPP)), B. TCD derived (Mx – correlation between mean flow velocity (FVm) and CPP, Mx_a – correlation betrween FVm and MAP, Sx – correlation between systolic flow velocity (FVs) and CPP, Sx_a – correlation between FVs and MAP, Dx – correlation between diastolic flow index (FVd) and CPP, Dx_a – correlation between FVd and MAP), and LDF derived (Lx – correlation between LDF cerebral blood flow (CBF) and CPP, Lx_a – correlation between LDF-CBF and MAP). We assessed the relationship between these indices via Pearson correlation, Friedman test, principal component analysis (PCA), agglomerative hierarchal clustering (AHC) and k-means cluster analysis (KMCA). Results: LDF based autoregulatory index (Lx) was most associated with TCD based Mx/Mx_a and Dx/Dx_a across Pearson correlation, PCA, AHC and KMCA. Lx was only remotely associated with ICP based indices (PRx, PAx, RAC). TCD based Sx/Sx_a were more closely associated with ICP derived PRx, PAx and RAC. This indicates that vascular derived indices of autoregulatory capacity (ie. TCD and LDF based) co-vary, with Sx/Sx_a being the exception. Whereas, indices of cerebrovascular reactivity derived from pulsatile CBV (ie. ICP indices) appear to not be closely related to those of vascular origin. Conclusions: Transcranial Doppler Mx is the most closely associated with LDF based Lx/Lx_a. Both Sx/Sx-a and the ICP derived indices appear to be dissociated with LDF based cerebrovascular reactivity, leaving Mx/Mx-a as a better surrogate for the assessment of cortical small vessel/microvascular cerebrovascular reactivity. Sx/Sx_a co-cluster/co-vary with ICP derived indices, as seen in our previous work.This work was made possible through salary support through the Cambridge Commonwealth Trust Scholarship, the Royal College of Surgeons of Canada – Harry S. Morton Travelling Fellowship in Surgery, the University of Manitoba Clinician Investigator Program, R. Samuel McLaughlin Research and Education Award, the Manitoba Medical Service Foundation, and the University of Manitoba Faculty of Medicine Dean’s Fellowship Fund. These studies were supported by National Institute for Healthcare Research (NIHR, UK) through the Acute Brain Injury and Repair theme of the Cambridge NIHR Biomedical Research Centre, an NIHR Senior Investigator Award to DKM. Authors were also supported by a European Union Framework Program 7 grant (CENTER-TBI; Grant Agreement No. 602150) MC is supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI17C1790). JD is supported by a Woolf Fisher Scholarship (NZ)

Transcranial Doppler Monitoring of Intracranial Pressure Plateau Waves

$\textbf{BACKGROUND}$: Transcranial Doppler (TCD) has been used to estimate ICP noninvasively (nICP); however, its accuracy varies depending on different types of intracranial hypertension. Given the high specificity of TCD to detect cerebrovascular events, this study aimed to compare four TCD-based nICP methods during plateau waves of ICP. $\textbf{METHODS}$: A total of 36 plateau waves were identified in 27 patients (traumatic brain injury) with TCD, ICP, and ABP simultaneous recordings. The nICP methods were based on: (1) interaction between flow velocity (FV) and ABP using a "black-box" mathematical model (\textit{nICP_BB}); (2) diastolic FV (\textit{nICP_FV}$_{d}$); (3) critical closing pressure (\textit{nICP_CrCP}), and (4) pulsatility index (\textit{nICP_PI}). Analyses focused on relative changes in time domain between ICP and noninvasive estimators during plateau waves and the magnitude of changes ($\textit{∆}$ between baseline and plateau) in real ICP and its estimators. A ROC analysis for an ICP threshold of 35 mmHg was performed. $\textbf{RESULTS}$: In time domain, \textit{nICP_PI, nICP_BB,} and \textit{nICP_CrCP} presented similar correlations: 0.80 ± 0.24, 0.78 ± 0.15, and 0.78 ± 0.30, respectively. \textit{nICP_FV}$_{d}$ presented a weaker correlation (R = 0.62 ± 0.46). Correlations between ∆ICP and ∆nICP were better represented by \textit{nICP_CrCP} and BB, R = 0.48, 0.44 (p < 0.05), respectively. \textit{nICP_FV}$_{d}$ and $\textit{PI}$ presented nonsignificant $\textit{∆}$ correlations. ROC analysis showed moderate to good areas under the curve for all methods: \textit{nICP_BB}, 0.82; \textit{nICP_FV}$_{d}$, 0.77; \textit{nICP_CrCP}, 0.79; and \textit{nICP_PI}, 0.81. $\textbf{CONCLUSIONS}$: Changes of ICP in time domain during plateau waves were replicated by nICP methods with strong correlations. In addition, the methods presented high performance for detection of intracranial hypertension. However, absolute accuracy for noninvasive ICP assessment using TCD is still low and requires further improvement

Can interhemispheric desynchronization of cerebral blood flow anticipate upcoming vasospasm in aneurysmal subarachnoid haemorrhage patients?

BACKGROUND: Asymmetry of cerebral autoregulation (CA) was demonstrated in patients after aneurysmal subarachnoid haemorrhage (aSAH). A classical method for CA assessment requires simultaneous measurement of both arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV). In this study, we have proposed a cerebral blood flow asymmetry index based only on CBFV and analysed its association with the occurrence of vasospasm after aSAH. NEW METHOD: The phase shifts (PS) between slow oscillations in left and right CBFV (side-to-side PS) and between ABP and CBFV (CBFV-ABP PS) were estimated using multichannel matching pursuit (MMP) and cross-spectral analysis. RESULTS: We retrospectively analysed data collected from 45 aSAH patients (26 with vasospasm). Data were analysed up to 7th day after aSAH unless the vasospasm was detected earlier. A progressive asymmetry, manifested by a gradual increase in side-to-side PS on consecutive days after aSAH, was observed in patients who developed vasospasm (Radj2 = 0.14, p = 0.009). In these patients, early side-to-side PS was more positive than in patients without vasospasm (2.8° ± 5.6° vs -1.7° ± 5.7°, p = 0.011). No such a difference was found in CBFV-ABP PS. Patients with positive side-to-side PS were more likely to develop vasospasm than patients with negative side-to-side PS (21/7 vs 5/12, p = 0.0047). COMPARISON WITH EXISTING METHOD: MMP, in contrast to the spectral approach, accounts for non-stationarity of analysed signals. MMP applied to the PS estimation reflects the cerebral blood flow asymmetry in aSAH better than the spectral analysis. CONCLUSIONS: Changes in side-to-side PS might be helpful to identify patients who are at risk of vasospasm

Association of transcranial Doppler blood flow velocity slow waves with delayed cerebral ischemia in patients suffering from subarachnoid hemorrhage: a retrospective study.

BACKGROUND: Cerebral vasospasm (VS) and delayed cerebral ischemia (DCI) constitute major complications following subarachnoid hemorrhage (SAH). A few studies have examined the relationship between different indices of cerebrovascular dynamics with the occurrence of VS. However, their potential association with the development of DCI remains elusive. In this study, we investigated the pattern of changes of different transcranial Doppler (TCD)-derived indices of cerebrovascular dynamics during vasospasm in patients suffering from subarachnoid hemorrhage, dichotomized by the presence of delayed cerebral ischemia. METHODS: A retrospective analysis was performed using recordings from 32 SAH patients, diagnosed with VS. Patients were divided in two groups, depending on development of DCI. Magnitude of slow waves (SWs) of cerebral blood flow velocity (CBFV) was measured. Cerebral autoregulation was estimated using the moving correlation coefficient Mxa. Cerebral arterial time constant (tau) was expressed as the product of resistance and compliance. Complexity of CBFV was estimated through measurement of sample entropy (SampEn). RESULTS: In the whole population (N = 32), magnitude of SWs of ipsilateral to VS side CBFV was higher during vasospasm (4.15 ± 1.55 vs before: 2.86 ± 1.21 cm/s, p < 0.001). Ipsilateral SWs of CBFV before VS had higher magnitude in DCI group (N = 19, p < 0.001) and were strongly predictive of DCI, with area under the curve (AUC) = 0.745 (p = 0.02). Vasospasm caused a non-significant shortening of ipsilateral values of tau and increase in SampEn in all patients related to pre-VS measurements, as well as an insignificant increase of Mxa in DCI related to non-DCI group (N = 13). CONCLUSIONS: In patients suffering from subarachnoid hemorrhage, TCD-detected VS was associated with higher ipsilateral CBFV SWs, related to pre-VS measurements. Higher CBFV SWs before VS were significantly predictive of delayed cerebral ischemia

Are we ready for Optimal CPP-oriented management of TBI patients?

Objective: Monitoring cerebral autoregulation (CA) is important for TBI patients, 1 as impaired CA correlates with poor outcome. 2 3 Today, automated algorithms allow to assess CPP for which autoregulation is best preserved (CPPopt) continuously and present it at the bedside 5 6 . Individualising CPP treatment using CPPopt is attractive and this has been recognised in published guidelines. However there are no specifications for its use clinically and it has therefore never been prospectively evaluated 1 . Numerous logistic, technical, feasibility and safety questions remain before the idea of selecting individual CPP treatment targets based on the state of CA 4 can be incorporated into clinical practice. How far are we from strict guidelines on the incorporation of this methodology into TBI protocols? Design: Literature review Subjects: Methods: Systematic review Results: The feasibility of CPPot-guided therapy has only been evaluated retrospectively and in non-clinical ways, whereas no studies exist on its safety. A prospective investigation of CPPopt-guided therapy has been initiated with ‘CppOpt Guided Therapy: Assessment of Target Effectiveness’ (COGiTATE), a multicenter randomized trial assessing feasibility and safety of a continuous CA monitoring-based therapy in adult TBI patients. Conclusions: COGiTATE seems to be the first step to define the physiological effect of targeting CPPopt and should pave the way toward establishing the exact protocol of CPPopt-oriented therapy and the phase III study. References: 1. Carney N, Totten AM, OʼReilly C, et al. Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition. Neurosurgery. 2016;80(1):1. doi:10.1227/NEU.0000000000001432. 2. Hlatky R, Furuya Y, Valadka AB, et al. Dynamic autoregulatory response after severe head injury. J Neurosurg. 2002;97(5):1054-1061. doi:10.3171/jns.2002.97.5.1054. 3. Czosnyka M, Czosnyka Z, Smielewski P. Pressure reactivity index: journey through the past 20 years. doi:10.1007/s00701-017-3310-1. 4. Steiner LA, Czosnyka M, Piechnik SK, et al. Continuous monitoring of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury. Crit Care Med. 2002;30(4):733-738. http://www.ncbi.nlm.nih.gov/pubmed/11940737. Accessed December 28, 2017. 5. Aries MJH, Czosnyka M, Budohoski KP, et al. Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury*. Crit Care Med. 2012. doi:10.1097/CCM.0b013e3182514eb6. 6. Liu X, Maurits NM, Aries MJH, et al. Monitoring of Optimal Cerebral Perfusion Pressure in Traumatic Brain Injured Patients Using a Multi-Window Weighting Algorithm. J Neurotrauma. 2017;34(22):3081-3088. doi:10.1089/neu.2017.5003. 7. Depreitere B, Güiza F, Berghe G Van Den, et al. Pressure autoregulation monitoring and cerebral perfusion pressure target recommendation in patients with severe traumatic brain injury based on minute-by-minute monitoring data. J Neurosurg. 2014;120(120):1451-1457. doi:10.3171/2014.3.JNS131500. 8. Güiza F, Meyfroidt G, Piper I, et al. Cerebral Perfusion Pressure Insults and Associations with Outcome in Adult Traumatic Brain Injury. doi:10.1089/neu.2016.4807. 9. Oshorov A V, Savin IA, Goriachev AS, Popugaev KA, Potapov AA, Gavrilov AG. [The first experience in monitoring the cerebral vascular autoregulation in the acute period of severe brain injury]. Anesteziol Reanimatol. (2):61-64. http://www.ncbi.nlm.nih.gov/pubmed/18540464. Accessed January 1, 2018. 10. Donnelly J, Czosnyka M, Adams H, et al. Individualizing Thresholds of Cerebral Perfusion Pressure Using Estimated Limits of Autoregulation. Crit Care Med. 2017;45(9):1464-1471. doi:10.1097/CCM.0000000000002575. 11. Dias C, Silva MJ, Pereira E, et al. Optimal Cerebral Perfusion Pressure Management at Bedside: A Single-Center Pilot Study. Neurocrit Care. 2015;23(1):92-102. doi:10.1007/s12028-014-0103-8. 12. Jaeger M, Dengl M, J&#252, Schuhmann MU. Effects of cerebrovascular pressure reactivity-guided optimization of cerebral perfusion pressure on brain tissue oxygenation after traumatic brain injury*. Crit Care Med. 2010;38(5):1343-1347. doi:10.1097/ccm.0b013e3181d45530

Baroreflex sensitivity and heart rate variability are predictors of mortality in patients with aneurysmal subarachnoid haemorrhage.

OBJECT: We aimed to investigate the link between the autonomic nervous system (ANS) impairment, assessed using baroreflex sensitivity (BRS) and heart rate variability (HRV) indices, and mortality after aneurysmal subarachnoid haemorrhage (aSAH). METHODS: A total of 57 patients (56 ± 18 years) diagnosed with aSAH were retrospectively enrolled in the study, where 25% of patients died in the hospital. BRS was calculated using a modified cross-correlation method. Time- and frequency-domain HRV indices were calculated from a time-series of systolic peak intervals of arterial blood pressure signals. Additionally, cerebral autoregulation (CA) was assessed using the mean velocity index (Mxa), where Mxa > 0 indicates impaired CA. RESULTS: Both BRS and HRV indices were lower in non-survivors than in survivors. The patients with disturbed BRS and HRV had more extensive haemorrhage in the H-H scale (p = .040) and were more likely to die (p = .013) when compared to patients with the intact ANS. The logistic regression model for mortality included: the APACHE II score (p = .002; OR 0.794) and the normalised high frequency power of the HRV (p < <.001; OR 0.636). A positive relationship was found between the Mxa and BRS (R = 0.48, p = .003), which suggests that increasing BRS is moderately strongly associated with worsening CA. CONCLUSION: Our results indicated that lower values of HRV indices and BRS correlate with mortality and that there is a link between cerebral dysautoregulation and the analysed estimates of the ANS in aSAH patients