A scoping review of the literature was performed systematically on commonly described continuous autoregulation measurement techniques in adult traumatic brain injury (TBI) to provide an overview of methodology and comprehensive reference library of the available literature for each technique. Five separate small systematic reviews were conducted for each of the continuous techniques: pressure reactivity index (PRx), laser Doppler flowmetry (LDF), near infrared spectroscopy (NIRS) techniques, brain tissue oxygen tension (PbtO), and thermal diffusion (TD) techniques. Articles from MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to December 2016), and reference lists of relevant articles were searched. A two-tier filter of references was conducted. The literature base identified from the individual searches was limited, except for PRx. The total number of articles using each of the five searched techniques for continuous autoregulation in adult TBI were: PRx (28), LDF (4), NIRS (9), PbtO (10), and TD (8). All continuous techniques described in adult TBI are based on moving correlation coefficients. The premise behind the calculation of these moving correlation coefficients focuses on the impact of slow fluctuations in either mean arterial pressure (MAP) or cerebral perfusion pressure (CPP) on some indirect measure of cerebral blood flow (CBF), such as: intracranial pressure (ICP), LDF, NIRS signals, PbtO, or TD CBF. The thought is the correlation between a hemodynamic driving factor, such as MAP or CPP, and a surrogate for CBF or cerebral perfusion sheds insight on the state of cerebral autoregulation. Both PRx and NIRS indices were validated experimentally against the "gold standard" static autoregulatory curve (Lassen curve) at least around the lower threshold of autoregulation. The PRx has the largest literature base supporting the association with patient outcome. Various methods of continuous autoregulation assessment are described within the adult TBI literature. Many studies exist on these various indices, suggesting an association between their values and patient morbidity/death.

Impaired cerebrovascular reactivity has been associated with outcome following traumatic brain injury (TBI), but it is unknown how it is affected by trauma severity. Thus, we aimed to explore the relationship between intracranial (IC) and extracranial (EC) injury burden and cerebrovascular reactivity in TBI patients. We retrospectively included critically ill TBI patients. IC injury burden included detailed lesion and computerized tomography (CT) scoring (i.e., Marshall, Rotterdam, Helsinki, and Stockholm Scores) on admission. EC injury burden was characterized using the injury severity score (ISS) and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score. Pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC were used to assess autoregulation/cerebrovascular reactivity. We used univariate and multi-variate logistic regression techniques to explore relationships between IC and EC injury burden and autoregulation indices. A total of 358 patients were assessed. ISS and all IC CT scoring systems were poor predictors of impaired cerebrovascular reactivity. Only subdural hematomas and thickness of subarachnoid hemorrhage (SAH; p < 0.05, respectively) were consistently associated with dysfunctional cerebrovascular reactivity. High age (p < 0.01 for all) and admission APACHE II scores (p < 0.05 for all) were the two variables most strongly associated with abnormal cerebrovascular reactivity. In summary, diffuse IC injury markers (thickness of SAH and the presence of a subdural hematoma) and APACHE II were most associated with dysfunction in cerebrovascular reactivity after TBI. Standard CT scoring systems and evidence of macroscopic parenchymal damage are poor predictors, implicating potentially both microscopic injury patterns and host response as drivers of dysfunctional cerebrovascular reactivity. Age remains a major variable associated with cerebrovascular reactivity.

The purpose of this study was to perform a systematic, scoping review of commonly described intermittent/semi-intermittent autoregulation measurement techniques in adult traumatic brain injury (TBI). Nine separate systematic reviews were conducted for each intermittent technique: computed tomographic perfusion (CTP)/Xenon-CT (Xe-CT), positron emission tomography (PET), magnetic resonance imaging (MRI), arteriovenous difference in oxygen (AVDO) technique, thigh cuff deflation technique (TCDT), transient hyperemic response test (THRT), orthostatic hypotension test (OHT), mean flow index (Mx), and transfer function autoregulation index (TF-ARI). MEDLINE, BIOSIS, EMBASE, Global Health, Scopus, Cochrane Library (inception to December 2016), and reference lists of relevant articles were searched. A two tier filter of references was conducted. The total number of articles utilizing each of the nine searched techniques for intermittent/semi-intermittent autoregulation techniques in adult TBI were: CTP/Xe-CT (10), PET (6), MRI (0), AVDO (10), ARI-based TCDT (9), THRT (6), OHT (3), Mx (17), and TF-ARI (6). The premise behind all of the intermittent techniques is manipulation of systemic blood pressure/blood volume via either chemical (such as vasopressors) or mechanical (such as thigh cuffs or carotid compression) means. Exceptionally, Mx and TF-ARI are based on spontaneous fluctuations of cerebral perfusion pressure (CPP) or mean arterial pressure (MAP). The method for assessing the cerebral circulation during these manipulations varies, with both imaging-based techniques and TCD utilized. Despite the limited literature for intermittent/semi-intermittent techniques in adult TBI (minus Mx), it is important to acknowledge the availability of such tests. They have provided fundamental insight into human autoregulatory capacity, leading to the development of continuous and more commonly applied techniques in the intensive care unit (ICU). Numerous methods of intermittent/semi-intermittent pressure autoregulation assessment in adult TBI exist, including: CTP/Xe-CT, PET, AVDO technique, TCDT-based ARI, THRT, OHT, Mx, and TF-ARI. MRI-based techniques in adult TBI are yet to be described, with the main focus of MRI techniques on metabolic-based cerebrovascular reactivity (CVR) and not pressure-based autoregulation.

The purpose of this study was to provide validation of intracranial pressure (ICP) derived continuous indices of cerebrovascular reactivity against the lower limit of autoregulation (LLA). Utilizing an intracranial hypertension model within white New Zealand rabbits, ICP, transcranial Doppler (TCD), laser Doppler flowmetry (LDF), and arterial blood pressure were recorded. Data were retrospectively analyzed in a cohort of 12 rabbits with adequate signals for interrogating the LLA. We derived continuous indices of cerebrovascular reactivity: PRx (correlation between ICP and mean arterial pressure [MAP]), PAx (correlation between pulse amplitude of ICP [AMP] and MAP), and Lx (correlation between LDF-based cerebral blood flow [CBF] and cerebral perfusion pressure [CPP]). LLA was derived via piecewise linear regression of CPP versus LDF or CPP versus systolic flow velocity (FVs) plots. We then produced error bar plots for PRx, PAx, and Lx against 2.5 mm Hg bins of CPP, to display the relationship between these indices and the LLA. We compared the CPP values at clinically relevant thresholds of PRx and PAx, to the CPP defined at the LLA. Receiver operating curve (ROC) analysis was performed for each index across the LLA using 2.5 mm Hg bins for CPP. The mean LLA was 51.5 ± 8.2 mm Hg. PRx and PAx error bar plots demonstrate that each index correlates with the LLA, becoming progressively more positive below the LLA. Similarly, CPP values at clinically relevant thresholds of PRx and PAx were not statistically different from the CPP derived at the LLA. Finally, ROC analysis indicated that PRx and PAx predicted the LAA, with areas under the curve (AUCs) of 0.795 (95% confidence interval [CI]: 0.731-0.857, p < 0.0001) and 0.703 (95% CI: 0.631-0.775, p < 0.0001), respectively. Both PRx and PAx generally agree with LLA within this experimental model of intracranial hypertension. Further analysis of clinically used indices of autoregulation across the LLA within pure arterial hypotension models is required.

The proposed variable shows a significant association with mortality following head injury. It is sensitive to both the rising absolute ICP and to the critical deterioration of pressure-volume compensation.

Aim: Increased intracranial pressure (ICP) in hypoxic ischaemic brain injury (HIBI) can cause secondary ischaemic brain injury and culminate in brain death. Invasive ICP monitoring is limited by associated risks in HIBI patients. We sought to evaluate the agreement between invasive ICP measurements and non-invasive estimators of ICP (nICP) in HIBI patients. Methods: Eligible consecutive adult (age > 18) cardiac arrest patients with HIBI were included as part of a single center prospective interventional study. Invasive ICP monitoring was undertaken and nICP measurements were undertaken using: a) transcranial Doppler ultrasonography (TCD), b) optic nerve sheet diameter ultrasound (ONSD) and c) jugular venous bulb pressure (JVP). Multiple measurements applied in linear mixed-effects models were considered to obtain the correlation coefficient between ICP and nICP as well as their prediction ability to detect intracranial hypertension (ICP ≥20 mm Hg). Results: Eleven patients were included (median age of 47 [range 20-71], 8 male and 3 female). There was a linear relationship between ICP and nICP with ONSD (R=0.53 [p<0.0001]), JVP (R=0.38 [p<0.001]) and TCD (R=0.30 [p<0.01]). The ability to predict intracranial hypertension was highest for ONSD and TCD (AUC=0.96 [95% CI: 0.90-1.00] and AUC=0.91 [95% CI: 0.83-1.00], respectively). JVP presented the weakest prediction ability (AUC=0.75 [95% CI: 0.56-0.94]). Conclusions: ONSD and TCD methods demonstrated agreement with invasively-monitored ICP, suggesting their potential roles in the detection of intracranial hypertension in HIBI after cardiac arrest.

BackgroundContinuous assessment of cerebral compensatory reserve is possible using the moving correlation between pulse amplitude of intra-cranial pressure (AMP) and intra-cranial pressure (ICP), called RAP. Little is known about the behavior and associations of this index in adult traumatic brain injury (TBI). The goal of this study is to evaluate the association between admission cerebral imaging findings and RAP over the course of the acute intensive care unit stay.MethodsWe retrospectively reviewed 358 adult TBI patients admitted to the Addenbrooke’s Hospital, University of Cambridge, from March 2005 to December 2016. Only non-craniectomy patients were studied. Using archived high frequency physiologic signals, RAP was derived and analyzed over the first 48 h and first 10 days of recording in each patient, using grand mean, percentage of time above various thresholds, and integrated area under the curve (AUC) of RAP over time. Associations between these values and admission computed tomography (CT) injury characteristics were evaluated.ResultsThe integrated AUC, based on various thresholds of RAP, was statistically associated with admission CT markers of diffuse TBI and cerebral edema. Admission CT findings of cortical gyral effacement, lateral ventricle compression, diffuse cortical subarachnoid hemorrhage (SAH), thickness of cortical SAH, presence of bilateral contusions, and subcortical diffuse axonal injury (DAI) were all associated with AUC of RAP over time. Joncheere-Terpstra testing indicated a statistically significant increase in mean RAP AUC across ordinal categories of the abovementioned associated CT findings.ConclusionsRAP is associated with cerebral CT injury patterns of diffuse injury and edema, providing some confirmation of its potential measurement of cerebral compensatory reserve in TBI.Electronic supplementary materialThe online version of this article (10.1007/s00701-018-3681-y) contains supplementary material, which is available to authorized users.

BackgroundIntracranial pressure (ICP)- and cerebral perfusion pressure (CPP)-guided therapy is central to neurocritical care for traumatic brain injury (TBI) patients. We sought to identify time-dependent critical thresholds for mortality and unfavourable outcome for ICP and CPP in non-craniectomised TBI patients.MethodsThis is a retrospective cohort study of 355 patients with moderate-to-severe TBI who received ICP monitoring and were managed without decompressive craniectomy in a tertiary hospital neurocritical care unit. Patients were grouped in 2 × 2 tables according to survival/death or favourable/unfavourable outcomes at 6 months and serial thresholds of mean ICP and CPP, using increments of 0.1 and 0.5 mmHg respectively. Sequential chi-square analysis was performed, and the thresholds yielding the highest chi-square test statistic were taken as having the best discriminative value for outcome. This process was repeated over monitoring periods of 1, 3, 5 and 7 days and for each day of recording to establish time-dependent thresholds. The same analysis was performed for age and sex subgroups.ResultsGlobal ICP thresholds were 21.3 and 20.5 mmHg for mortality and unfavourable outcome respectively (p < 0.001). After the first day of ICP monitoring, ICP thresholds fell to between 15 and 20 mmHg and remained significant (p < 0.05). Significant time-dependent CPP thresholds for mortality or unfavourable outcome were often not identified, and no identifiable trends were produced.ConclusionCritical ICP thresholds in non-craniectomised TBI patients vary with time and fall below established ICP targets after the first day of monitoring.Electronic supplementary materialThe online version of this article (10.1007/s00701-018-3555-3) contains supplementary material, which is available to authorized users.