Transcranial Doppler-derived indices of cerebrovascular haemodynamics are independent of depth and angle of insonation.

Continuous measurement of cerebral blood flow velocity (CBFV) of the middle cerebral artery (MCA) using transcranial Doppler (TCD) and arterial blood pressure (ABP) monitoring enables assessment of cerebrovascular haemodynamics. Further indices describing cerebrovascular function can be calculated from ABP and CBFV, such as the mean index (Mxa) of cerebrovascular autoregulation, the 'time constant of the cerebral arterial bed' (tau), the 'critical closing pressure' (CrCP) and a 'non-invasive estimator of ICP' (nICP). However, TCD is operator-dependent and changes in angle and depth of MCA insonation result in different readings of CBFV. The effect of differing CBFV readings on the calculated secondary indices remains unknown. The aim of this study was to investigate variation in angle and depth of MCA insonation on these secondary indices. In eight patients continuous ABP and ipsilateral CBFV monitoring was performed using two different TCD probes, resulting in four simultaneous CBFV readings at different angles and depths per patient. From all individual recordings, the K-means clustering algorithm was applied to the four simultaneous longitudinal measurements. The average ratios of the between-clusters, sum-of-squares and total sum-of-squares were significantly higher for CBFV than for the indices Mxa, tau and CrCP (p < 0.001, p = 0.007 and p = 0.016) but not for nICP (p = 0.175). The results indicate that Mxa, tau and CrCP seemed to be not affected by depth and angle of TCD insonation, whereas nICP was

Non-invasive Monitoring of Intracranial Pressure Using Transcranial Doppler Ultrasonography: Is It Possible?

Although intracranial pressure (ICP) is essential to guide management of patients suffering from acute brain diseases, this signal is often neglected outside the neurocritical care environment. This is mainly attributed to the intrinsic risks of the available invasive techniques, which have prevented ICP monitoring in many conditions affecting the intracranial homeostasis, from mild traumatic brain injury to liver encephalopathy. In such scenario, methods for non-invasive monitoring of ICP (nICP) could improve clinical management of these conditions. A review of the literature was performed on PUBMED using the search keywords 'Transcranial Doppler non-invasive intracranial pressure.' Transcranial Doppler (TCD) is a technique primarily aimed at assessing the cerebrovascular dynamics through the cerebral blood flow velocity (FV). Its applicability for nICP assessment emerged from observation that some TCD-derived parameters change during increase of ICP, such as the shape of FV pulse waveform or pulsatility index. Methods were grouped as: based on TCD pulsatility index; aimed at non-invasive estimation of cerebral perfusion pressure and model-based methods. Published studies present with different accuracies, with prediction abilities (AUCs) for detection of ICP ≥20 mmHg ranging from 0.62 to 0.92. This discrepancy could result from inconsistent assessment measures and application in different conditions, from traumatic brain injury to hydrocephalus and stroke. Most of the reports stress a potential advantage of TCD as it provides the possibility to monitor changes of ICP in time. Overall accuracy for TCD-based methods ranges around ±12 mmHg, with a great potential of tracing dynamical changes of ICP in time, particularly those of vasogenic nature.Cambridge Commonwealth, European & International Trust Scholarship (University of Cambridge) provided financial support in the form of Scholarship funding for DC. Woolf Fisher Trust provided financial support in the form of Scholarship funding for JD. Gates Cambridge Trust provided financial support in the form of Scholarship funding for XL. CNPQ provided financial support in the form of Scholarship funding for BCTC (Research Project 203792/2014-9). NIHR Brain Injury Healthcare Technology Co-operative, Cambridge, UK provided financial support in the form of equipment funding for DC, BC and MC. The sponsors had no role in the design or conduct of this manuscript.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s12028-016-0258-

Wavelet pressure reactivity index: a validation study.

KEY POINTS: The brain is vulnerable to damage from too little or too much blood flow. A physiological mechanism termed cerebral autoregulation (CA) exists to maintain stable blood flow even if cerebral perfusion pressure (CPP) is changing. A robust method for assessing CA is not yet available. There are still some problems with the traditional measure, the pressure reactivity index (PRx). We introduce a new method, the wavelet transform method (wPRx), to assess CA using data from two sets of controlled hypotension experiments in piglets: one set had artificially manipulated arterial blood pressure (ABP) oscillations; the other group were spontaneous ABP waves. A significant linear relationship was found between wPRx and PRx in both groups, with wPRx providing a more stable result for the spontaneous waves. Although both methods showed similar accuracy in distinguishing intact and impaired CA, it seems that wPRx tends to perform better than PRx, although not significantly so. ABSTRACT: We present a novel method to monitor cerebral autoregulation (CA) using the wavelet transform (WT). The new method is validated against the pressure reactivity index (PRx) in two piglet experiments with controlled hypotension. The first experiment (n = 12) had controlled haemorrhage with artificial stationary arterial blood pressure (ABP) and intracranial pressure (ICP) oscillations induced by sinusoidal slow changes in positive end-expiratory pressure ('PEEP group'). The second experiment (n = 17) had venous balloon inflation during spontaneous, non-stationary ABP and ICP oscillations ('non-PEEP group'). The wavelet transform phase shift (WTP) between ABP and ICP was calculated in the frequency range 0.0067-0.05 Hz. Wavelet semblance, the cosine of WTP, was used to make the values comparable to PRx, and the new index was termed wavelet pressure reactivity index (wPRx). The traditional PRx, the running correlation coefficient between ABP and ICP, was calculated. The result showed a significant linear relationship between wPRx and PRx in the PEEP group (R = 0.88) and non-PEEP group (R = 0.56). In the non-PEEP group, wPRx showed better performance than PRx in distinguishing cerebral perfusion pressure (CPP) above and below the lower limit of autoregulation (LLA). When CPP was decreased below LLA, wPRx increased from 0.43 ± 0.28 to 0.69 ± 0.12 (P = 0.003) while PRx increased from 0.07 ± 0.21 to 0.27 ± 0.37 (P = 0.04). Moreover, wPRx provided a more stable result than PRx (SD of PRx was 0.40 ± 0.07, and SD of wPRx was 0.28 ± 0.11, P = 0.001). Assessment of CA using wavelet-derived phase shift between ABP and ICP is feasible

Cerebral haemodynamics during experimental intracranial hypertension.

Intracranial hypertension is a common final pathway in many acute neurological conditions. However, the cerebral haemodynamic response to acute intracranial hypertension is poorly understood. We assessed cerebral haemodynamics (arterial blood pressure, intracranial pressure, laser Doppler flowmetry, basilar artery Doppler flow velocity, and vascular wall tension) in 27 basilar artery-dependent rabbits during experimental (artificial CSF infusion) intracranial hypertension. From baseline (∼9 mmHg; SE 1.5) to moderate intracranial pressure (∼41 mmHg; SE 2.2), mean flow velocity remained unchanged (47 to 45 cm/s; p = 0.38), arterial blood pressure increased (88.8 to 94.2 mmHg; p < 0.01), whereas laser Doppler flowmetry and wall tension decreased (laser Doppler flowmetry 100 to 39.1% p < 0.001; wall tension 19.3 to 9.8 mmHg, p < 0.001). From moderate to high intracranial pressure (∼75 mmHg; SE 3.7), both mean flow velocity and laser Doppler flowmetry decreased (45 to 31.3 cm/s p < 0.001, laser Doppler flowmetry 39.1 to 13.3%, p < 0.001), arterial blood pressure increased still further (94.2 to 114.5 mmHg; p < 0.001), while wall tension was unchanged (9.7 to 9.6 mmHg; p = 0.35).This animal model of acute intracranial hypertension demonstrated two intracranial pressure-dependent cerebroprotective mechanisms: with moderate increases in intracranial pressure, wall tension decreased, and arterial blood pressure increased, while with severe increases in intracranial pressure, an arterial blood pressure increase predominated. Clinical monitoring of such phenomena could help individualise the management of neurocritical patients.The authors would acknowledge Dr Hugh Richards and Dr Stefan Piechnik who contributed to data collection. JD is supported by a Woolf Fisher scholarship. GVV is supported by an A.G. Leventis Foundation Scholarship, and a Charter Studentship from St Edmund’s College, Cambridge. XYL is supported by Bill Gates Scholarship, and DC is supported by a Cambridge Commonwealth, European & International Trust Scholarship (University of Cambridge).This is the author accepted manuscript. The final version is available from SAGE via https://doi.org/10.1177/0271678X1663906

Effects of Age and Sex on Optic Nerve Sheath Diameter in Healthy Volunteers and Patients With Traumatic Brain Injury.

The measurement of optic nerve sheath diameter (ONSD) has been reported as a non-invasive marker for intracranial pressure (ICP). Nevertheless, it is uncertain whether possible ONSD differences occur with age and sex in healthy and brain-injured populations. The aim of this study was to investigate the effects of sex and age on ONSD in healthy volunteers and patients with traumatic brain injury. We prospectively included 122 healthy adult volunteers (Galliera Hospital, Genova, Italy), and compared age/sex dependence of ONSD to 95 adult patients (Addenbrooke's Hospital, Cambridge, UK) with severe traumatic brain injury (TBI) requiring intubation and invasive ICP monitoring. The two groups were stratified for sex and age. Age was divided into 3 subgroups: (1) young adults: 18-44 years; (2) middle-aged adults: 45-64 years; (3) old adults: >65 years. In healthy volunteers, ONSD was significantly different between males and females [median (interquartile range): 4.2 (3.9-4.6) mm vs. 4.1 (3.6-4.2) mm (p = 0.01), respectively] and was correlated with age (R = 0.50, p < 0.0001). ONSD was significantly increased in group 3 compared to groups 2 and 1, indicating that ONSD values are higher in elderly subjects. In TBI patients, no differences in ONSD were found for sex and the correlation between ONSD and age was non-significant (R = 0.13, p = 0.20). ONSD increases with age and is significantly larger for males in healthy volunteers but not in TBI patients. Different ONSD cut-off values need not be age- or sex-adjusted for the assessment of increased ICP in TBI patients

Effects of Prone Position and Positive End-Expiratory Pressure on Noninvasive Estimators of ICP: A Pilot Study.

BACKGROUND: Prone positioning and positive end-expiratory pressure can improve pulmonary gas exchange and respiratory mechanics. However, they may be associated with the development of intracranial hypertension. Intracranial pressure (ICP) can be noninvasively estimated from the sonographic measurement of the optic nerve sheath diameter (ONSD) and from the transcranial Doppler analysis of the pulsatility (ICPPI) and the diastolic component (ICPFVd) of the velocity waveform. METHODS: The effect of the prone positioning and positive end-expiratory pressure on ONSD, ICPFVd, and ICPPI was assessed in a prospective study of 30 patients undergoing spine surgery. One-way repeated measures analysis of variance, fixed-effect multivariate regression models, and receiver operating characteristic analyses were used to analyze numerical data. RESULTS: The mean values of ONSD, ICPFVd, and ICPPI significantly increased after change from supine to prone position. Receiver operating characteristic analyses demonstrated that, among the noninvasive methods, the mean ONSD measure had the greatest area under the curve signifying it is the most effective in distinguishing a hypothetical change in ICP between supine and prone positioning (0.86±0.034 [0.79 to 0.92]). A cutoff of 0.43 cm was found to be a best separator of ONSD value between supine and prone with a specificity of 75.0 and a sensitivity of 86.7. CONCLUSIONS: Noninvasive ICP estimation may be useful in patients at risk of developing intracranial hypertension who require prone positioning.DC and MC are partially supported by NIHR Brain Injury Healthcare Technology Co-operative, Cambridge, UK. JD is supported by a Woolf Fisher Scholarship (NZ)

The Burden of Brain Hypoxia and Optimal Mean Arterial Pressure in Patients With Hypoxic Ischemic Brain Injury After Cardiac Arrest.

OBJECTIVES: In patients at risk of hypoxic ischemic brain injury following cardiac arrest, we sought to: 1) characterize brain oxygenation and determine the prevalence of brain hypoxia, 2) characterize autoregulation using the pressure reactivity index and identify the optimal mean arterial pressure, and 3) assess the relationship between optimal mean arterial pressure and brain tissue oxygenation. DESIGN: Prospective interventional study. SETTING: Quaternary ICU. PATIENTS: Adult patients with return of spontaneous circulation greater than 10 minutes and a postresuscitation Glasgow Coma Scale score under 9 within 72 hours of cardiac arrest. INTERVENTIONS: All patients underwent multimodal neuromonitoring which included: 1) brain tissue oxygenation, 2) intracranial pressure, 3) jugular venous continuous oximetry, 4) regional saturation of oxygen using near-infrared spectroscopy, and 5) pressure reactivity index-based determination of optimal mean arterial pressure, lower and upper limit of autoregulation. We additionally collected mean arterial pressure, end-tidal CO2, and temperature. All data were captured at 300 Hz using ICM+ (Cambridge Enterprise, Cambridge, United Kingdom) brain monitoring software. MEASUREMENTS AND MAIN RESULTS: Ten patients (7 males) were included with a median age 47 (range 20-71) and return to spontaneous circulation 22 minutes (12-36 min). The median duration of monitoring was 47 hours (15-88 hr), and median duration from cardiac arrest to inclusion was 15 hours (6-44 hr). The mean brain tissue oxygenation was 23 mm Hg (SD 8 mm Hg), and the mean percentage of time with a brain tissue oxygenation below 20 mm Hg was 38% (6-100%). The mean pressure reactivity index was 0.23 (0.27), and the percentage of time with a pressure reactivity index greater than 0.3 was 50% (12-91%). The mean optimal mean arterial pressure, lower and upper of autoregulation were 89 mm Hg (11), 82 mm Hg (8), and 96 mm Hg (9), respectively. There was marked between-patient variability in the relationship between mean arterial pressure and indices of brain oxygenation. As the patients' actual mean arterial pressure approached optimal mean arterial pressure, brain tissue oxygenation increased (p < 0.001). This positive relationship did not persist when the actual mean arterial pressure was above optimal mean arterial pressure. CONCLUSIONS: Episodes of brain hypoxia in hypoxic ischemic brain injury are frequent, and perfusion within proximity of optimal mean arterial pressure is associated with increased brain tissue oxygenation. Pressure reactivity index can yield optimal mean arterial pressure, lower and upper limit of autoregulation in patients following cardiac arrest

Prospective study on non-invasive assessment of ICP in head injured patients: comparison of four methods

Elevation of intracranial pressure (ICP) may occur in many diseases and therefore the ability to measure it non-invasively would be useful. Flow velocity signals from Transcranial Doppler (TCD) have been used to estimate ICP, however the relative accuracy of these methods is unclear. This study aimed to compare 4 previously described TCD-based methods with directly measured ICP in a prospective cohort of head injured patients. Non-invasive ICP (nICP) was obtained using the following methods: I) a mathematical “black-box” model based on interaction between TCD and ABP (nICP_BB); II) based on diastolic FV (nICP_FVd); III) based on critical closing pressure (nICP_CrCP) and IV) based on TCD-derived pulsatility index (nICP_PI). In time domain, for recordings including spontaneous changes in ICP greater than 7 mmHg, nICP_PI showed the best correlation with measured ICP (R=0.61). Considering every TCD recording as an independent event, nICP_BB generally showed to be the best estimator of measured ICP (R=0.39, p0.05). nICP_PI was not related to measured ICP using any of the above statistical indicators. We also introduced a new estimator (nICP_Av) based on the average of 3 methods (nICP_BB, nICP_FVd and nICP_CrCP), which overall presented improved statistical indicators (R=0.47, p<0.05; 95% CI=9.17 mmHg; AUC= 0.73, p<0.05). nICP_PI appeared to reflect changes in ICP in time most accurately. nICP_BB was the best estimator for ICP ‘as a number’. nICP_Av demonstrated to improve the accuracy of measured ICP estimation.DC is supported by a Cambridge Commonwealth, European & International Trust Scholarship, University of Cambridge. JD is supported by a Woolf Fisher Trust Scholarship. XL is supported by a Gates Cambridge Scholarship. GVV is supported by an A. G. Leventis Foundation Scholarship, and a Charter Studentship from St Edmund’s College, Cambridge. SM and GF are supported by the Pan-American Health Organization. DC and MC are partially supported by NIHR Brain Injury Healthcare Technology Co-operative, Cambridge, UK.This is the author accepted manuscript. The final version is available from Mary Ann Liebert via http://dx.doi.org/10.1089/neu.2015.413