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Carole L. Turner, Susan Tebbs, Piotr Smielewski, and Peter J. Kirkpatrick

Object. Applanation tonometry is a noninvasive method of assessing both peripheral and central arterial blood pressure (BP) profiles. In this study the authors examine whether there are differences in these profiles in patients with intracranial aneurysms when compared with age-matched controls.

Methods. Carotid artery (CA) and derived aortic BP waveforms were obtained using a pulse wave analysis system. The ratio of the pressure wave amplitude above the systolic shoulder to the total systolic BP (augmentation index [AI]) was recorded.

One hundred seventy-three patients with intracranial aneurysms (23 unruptured lesions) and 173 healthy control volunteers were examined. For the patients with aneurysms the right and left CA AIs (mean ± standard deviation) were 125.6 ± 23.1% and 128.3 ± 22.1%, respectively. Corresponding values for the control group were 118.4 ± 22.6% and 119.4 ± 21.8%. The calculated AI for the ascending aorta was 29.8 ± 10.5% and 25.6 ± 12.2% for patients with aneurysms and control volunteers, respectively. Significant asymmetry in CA AI was seen in patients with aneurysms, the left being greater (p = 0.002). No significant differences were seen in mean BP (108 ± 14 mm Hg in patients with aneurysms compared with 106 ± 16 mm Hg in controls; p = 0.2). Multivariate analysis excluded the influence of BP and other potential confounding vascular risk factors for increased AI.

Conclusions. Significant differences in AI, both in magnitude and symmetry, were identified in patients with intracranial aneurysms when compared with matched controls.

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Ivan Timofeev, Marek Czosnyka, Jurgens Nortje, Peter Smielewski, Peter Kirkpatrick, Arun Gupta, and Peter Hutchinson


Decompressive craniectomy is an advanced treatment option for intracranial pressure (ICP) control in patients with traumatic brain injury. The purpose of this study was to evaluate the effect of decompressive craniectomy on ICP and cerebrospinal compensation both within and beyond the first 24 hours of craniectomy.


This study was a retrospective analysis of the physiological parameters from 27 moderately to severely head-injured patients who underwent decompressive craniectomy for progressive brain edema. Of these, 17 patients had undergone prospective digital recording of ICP with estimation of ICP waveform–derived indices. The pressure-volume compensatory reserve (RAP) index and the cerebrovascular pressure reactivity index (PRx) were used to assess those parameters. The values of parameters prior to and during the 72 hours after decompressive craniectomy were included in the analysis.


Decompressive craniectomy led to a sustained reduction in median (interquartile range) ICP values (21.2 mm Hg [18.7; 24.2 mm Hg] preoperatively compared with 15.7 mm Hg [12.3; 19.2 mm Hg] postoperatively; p = 0.01). A similar improvement was observed in RAP. A significantly lower mean arterial pressure (MAP) was needed after decompressive craniectomy to maintain optimum cerebral perfusion pressure (CPP) levels, compared with the preoperative period (99.5 mm Hg [96.2; 102.9 mm Hg] compared with 94.2 mm Hg [87.9; 98.9 mm Hg], respectively; p = 0.017). Following decompressive craniectomy, the PRx had positive values in all patients, suggesting acquired derangement in pressure reactivity.


In this study, decompressive craniectomy led to a sustained reduction in ICP and improvement in cerebral compliance. Lower MAP levels after decompressive craniectomy are likely to indicate a reduced intensity of treatment. Derangement in cerebrovascular pressure reactivity requires further studies to evaluate its significance and influence on outcome.

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Erhard W. Lang, Magdalena Kasprowicz, Peter Smielewski, Edgar Santos, John Pickard, and Marek Czosnyka


The pressure reactivity index (PRx) correlates with outcome after traumatic brain injury (TBI) and is used to calculate optimal cerebral perfusion pressure (CPPopt). The PRx is a correlation coefficient between slow, spontaneous changes (0.003–0.05 Hz) in intracranial pressure (ICP) and arterial blood pressure (ABP). A novel index—the so-called long PRx (L-PRx)—that considers ABP and ICP changes (0.0008–0.008 Hz) was proposed.


The authors compared PRx and L-PRx for 6-month outcome prediction and CPPopt calculation in 307 patients with TBI. The PRx- and L-PRx–based CPPopt were determined and the predictive power and discriminant abilities were compared.


The PRx and L-PRx correlation was good (R = 0.7, p < 0.00001; Spearman test). The PRx, age, CPP, and Glasgow Coma Scale score but not L-PRx were significant fatal outcome predictors (death and persistent vegetative state). There was a significant difference between the areas under the receiver operating characteristic curves calculated for PRx and L-PRx (0.61 ± 0.04 vs 0.51 ± 0.04; z-statistic = −3.26, p = 0.011), which indicates a better ability by PRx than L-PRx to predict fatal outcome. The CPPopt was higher for L-PRx than for PRx, without a statistical difference (median CPPopt for L-PRx: 76.9 mm Hg, interquartile range [IQR] ± 10.1 mm Hg; median CPPopt for PRx: 74.7 mm Hg, IQR ± 8.2 mm Hg). Death was associated with CPP below CPPopt for PRx (χ2 = 30.6, p < 0.00001), and severe disability was associated with CPP above CPPopt for PRx (χ2 = 7.8, p = 0.005). These relationships were not statistically significant for CPPopt for L-PRx.


The PRx is superior to the L-PRx for TBI outcome prediction. Individual CPPopt for L-PRx and PRx are not statistically different. Deviations between CPP and CPPopt for PRx are relevant for outcome prediction; those between CPP and CPPopt for L-PRx are not. The PRx uses the entire B-wave spectrum for index calculation, whereas the L-PRX covers only one-third of it. This may explain the performance discrepancy.

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Peter J. Kirkpatrick, Joseph Lam, Pippa Al-Rawi, Piotr Smielewski, and Marek Czosnyka

Object. Signal changes in adult extracranial tissues may have a profound effect on cerebral near-infrared spectroscopy (NIRS) measurements. During carotid surgery NIRS signals provide the opportunity to determine the relative contributions from the intra- and extracranial vascular territories, allowing for a more accurate quantification. In this study the authors applied multimodal monitoring methods to patients undergoing carotid endarterectomy and explored the hypothesis that NIRS can define thresholds for cerebral ischemia, provided extracranial NIRS signal changes are identified and removed. Relative criteria for intraoperative severe cerebral ischemia (SCI) were applied to 103 patients undergoing carotid endarterectomy.

Methods. One hundred three patients underwent carotid endarterectomy. An intraoperative fall in transcranial Doppler—detected middle cerebral artery flow velocity (%ΔFV) of greater than 60% accompanied by a sustained fall in cortical electrical activity were adopted as criteria for SCI. Ipsilateral frontal NIRS recorded the total difference in concentrations of oxyhemoglobin and deoxyhemoglobin (Total ΔHbdiff). Interrupted time series analysis following clamping of the external carotid artery (ECA) and the internal carotid artery (ICA) allowed the different vascular components of Total ΔHbdiff (ECA ΔHbdiff and ICA ΔHbdiff) to be identified.

Data obtained in 76 patients were deemed suitable. A good correlation between %ΔFV and ICA ΔHbdiff (r = 0.73, p < 0.0001) was evident. Sixteen patients (21%) fulfilled the criteria for SCI. All patients who demonstrated an ICA ΔHbdiff of greater than 6.8 µmol/L showed SCI, and in two patients within this group nondisabling watershed infarction developed, as seen on postoperative computerized tomography scans. No patient with an ICA ΔHbdiff less than 5 µmol/L exhibited SCI or suffered a stroke. Within the resolution of the criteria used an ICA ΔHbdiff threshold of 6.8 µmol/L provided 100% specificity for SCI, whereas an ICA ΔHbdiff less than 5 µmol/L was 100% sensitive for excluding SCI. When Total ΔHbdiff was used without removing the ECA component, no thresholds for SCI were apparent.

Conclusions. Carotid endarterectomy provides a stable environment for exploring NIRS-quantified thresholds for SCI in the adult head.

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Piotr Smielewski, Marek Czosnyka, Peter Kirkpatrick, and John D. Pickard

✓ The transient hyperemic response test has been shown to provide an index of cerebral autoregulation in healthy individuals and in patients who have suffered a subarachnoid hemorrhage. In this study, the test was applied to patients who had received a severe head injury, and the value of the test was assessed by comparing its result with the individual's clinical condition (Glasgow Coma Scale [GCS] score), cerebral perfusion pressure (CPP), transcranial Doppler wave form—derived index for cerebral autoregulation (relationship between the CPP and the middle cerebral artery flow velocity), and outcome (Glasgow Outcome Scale [GOS] score).

Forty-seven patients, aged 16 to 63 years, with head injuries were included in the study. Signals of intracranial pressure, arterial blood pressure, flow velocity, and cortical microcirculatory flux were digitized and recorded for a period of 30 minutes using special computer software. Two carotid compressions were performed at the beginning of each recording. The transient hyperemic response ratio (THRR: the ratio of the hyperemic flow velocity recorded after carotid release and the precompression baseline flow velocity) was calculated, as was the correlation coefficient Sx used to describe the relationship between slow fluctuations in the systolic flow velocity and CPP throughout the period of recording.

No significant changes in CPP were found during compression. There was a significant correlation between the THRR and the Sx (r = 0.49, p < 0.0001). The hyperemic response proved to be lower in patients who exhibited a poor clinical grade at presentation (GCS scores < 6, p = 0.01) and lower in patients achieving a poor outcome (GOS scores of 3, 4, and 5, p = 0.003). Loss of postcompression hyperemia occurred when the CPP fell below 50 mm Hg.

The carotid compression test provides a simple index of cerebral autoregulation that is relevant to the clinical condition and outcome of the severely head injured patient.

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Marek Czosnyka, Peter Smielewski, Ivan Timofeev, Andrea Lavinio, Eric Guazzo, Peter Hutchinson, and John D. Pickard

✓Many doctors involved in the critical care of head-injured patients understand intracranial pressure (ICP) as a number, characterizing the state of the brain pressure–volume relationships. However, the dynamics of ICP, its waveform, and secondarily derived indices portray useful information about brain homeostasis. There is circumstantial evidence that this information can be used to modify and optimize patients' treatment. Secondary variables, such as pulse amplitude and the magnitude of slow waves, index of compensatory reserve, and pressure–reactivity index (PRx), look promising in clinical practice. The optimal cerebral perfusion pressure (CPP) derived using the PRx is a new concept that may help to avoid excessive use of vasopressors in CPP-oriented therapy. However, the use of secondary ICP indices remains to be confirmed in clinical trials.

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Peter J. Kirkpatrick, Pietr Smielewski, Peter C. Whitfield, Marik Czosnyka, David Menon, and John D. Pickard

✓ Near-infrared spectroscopy was used to monitor changes in the cerebral oxygenation state in 13 patients during carotid endarterectomy. Variations in the levels of the chromophores (oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (Hb), and oxidized cytochrome (CytO2)), and the total hemoglobin content (tHb) were compared with changes in middle cerebral artery flow velocity measured using transcranial Doppler ultrasonography. Of eight patients who showed a fall in flow velocity on application of the internal carotid artery cross-clamp, seven demonstrated a rapid and closely correlated fall in HbO2 signal, and an increase in Hb. Levels of CytO2 and tHb remained unchanged. During endarterectomy, recovery of the HbO2 and Hb levels toward preclamp baseline values occurred in three of these patients. Intraoperative shunts accelerated recovery of HbO2 and Hb signals in two of three individuals. Release of the internal carotid cross-clamp resulted in a rapid increase in HbO2 and decrease in Hb signal in those patients in whom spontaneous recovery had not occurred; in five instances, a hyperemia evolved with raised flow velocity and HbO2 to above baseline values. Cross-clamping and subsequent reperfusion of the external carotid artery had no effect on any parameter measured. The authors conclude that near-infrared spectroscopy can register changes in cerebral oxygenation during carotid endarterectomy without significant contamination from extracranial tissues.

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Seung-Bo Lee, Hakseung Kim, Young-Tak Kim, Frederick A. Zeiler, Peter Smielewski, Marek Czosnyka, and Dong-Joo Kim


Monitoring intracranial and arterial blood pressure (ICP and ABP, respectively) provides crucial information regarding the neurological status of patients with traumatic brain injury (TBI). However, these signals are often heavily affected by artifacts, which may significantly reduce the reliability of the clinical determinations derived from the signals. The goal of this work was to eliminate signal artifacts from continuous ICP and ABP monitoring via deep learning techniques and to assess the changes in the prognostic capacities of clinical parameters after artifact elimination.


The first 24 hours of monitoring ICP and ABP in a total of 309 patients with TBI was retrospectively analyzed. An artifact elimination model for ICP and ABP was constructed via a stacked convolutional autoencoder (SCAE) and convolutional neural network (CNN) with 10-fold cross-validation tests. The prevalence and prognostic capacity of ICP- and ABP-related clinical events were compared before and after artifact elimination.


The proposed SCAE-CNN model exhibited reliable accuracy in eliminating ABP and ICP artifacts (net prediction rates of 97% and 94%, respectively). The prevalence of ICP- and ABP-related clinical events (i.e., systemic hypotension, intracranial hypertension, cerebral hypoperfusion, and poor cerebrovascular reactivity) all decreased significantly after artifact removal.


The SCAE-CNN model can be reliably used to eliminate artifacts, which significantly improves the reliability and efficacy of ICP- and ABP-derived clinical parameters for prognostic determinations after TBI.

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Hakseung Kim, Hack-Jin Lee, Young-Tak Kim, Yunsik Son, Peter Smielewski, Marek Czosnyka, and Dong-Joo Kim


Failure of cerebral autoregulation and subsequent hypoperfusion is common during the acute phase of traumatic brain injury (TBI). The cerebrovascular pressure-reactivity index (PRx) indirectly reflects cerebral autoregulation and has been used to derive optimal cerebral perfusion pressure (CPP). This study provides a method for the use of a combination of PRx, CPP, and intracranial pressure (ICP) to better evaluate the extent of cerebral hypoperfusion during the first 24 hours after TBI, allowing for a more accurate prediction of mortality risk.


Continuous ICP and arterial blood pressure (ABP) signals acquired from 295 TBI patients during the first 24 hours after admission were retrospectively analyzed. The CPP at the lowest PRx was determined as the optimal CPP (CPPopt). The duration of a severe hypoperfusion event (dHP) was defined as the cumulative time that the PRx was > 0.2 and the CPP was < 70 mm Hg with the addition of intracranial hypertension (ICP > 20 or > 22 mm Hg). The outcome was determined as 6-month mortality.


The cumulative duration of PRx > 0.2 and CPP < 70 mm Hg exhibited a significant association with mortality (p < 0.001). When utilized with basic clinical information available during the first 24 hours after admission (i.e., Glasgow Coma Scale score, age, and mean ICP), a dHP > 25 minutes yielded a significant predictive capacity for mortality (p < 0.05, area under the curve [AUC] = 0.75). The parameter was particularly predictive of mortality for patients with a mean ICP > 20 or > 22 mm Hg (AUC = 0.81 and 0.87, respectively).


A short duration (25 minutes) of severe hypoperfusion, evaluated as lowered CPP during worsened cerebrovascular reactivity during the 1st day after TBI, is highly indicative of mortality.

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Marek Czosnyka, Marcella Balestreri, Luzius Steiner, Piotr Smielewski, Peter J. Hutchinson, Basil Matta, and John D. Pickard

Object. The object of this study was to investigate whether a failure of cerebrovascular autoregulation contributes to the relationship between age and outcome in patients following head injury.

Methods. Data obtained from continuous bedside monitoring of intracranial pressure (ICP), arterial blood pressure (ABP), and cerebral perfusion pressure (CPP = ABP — ICP) in 358 patients with head injuries and intermittent monitoring of transcranial Doppler blood flow velocity (FV) in the middle cerebral artery in 237 patients were analyzed retrospectively. Indices used to describe cerebral autoregulation and pressure reactivity were calculated as correlation coefficients between slow waves of systolic FV and CPP (autoregulation index [ARI]) and between ABP and ICP (pressure reactivity index [PRI]).

Older patients had worse outcomes after brain trauma than younger patients (p = 0.00001), despite the fact that the older patients had higher initial Glasgow Coma Scale scores (p = 0.006). When age was considered as an independent variable, it appeared that ICP decreased with age (p = 0.005), resulting in an increasing mean CPP (p = 0.0005). Blood FV was not dependent on age (p = 0.58). Indices of autoregulation and pressure reactivity demonstrated a deterioration in cerebrovascular control with advancing age (PRI: p = 0.003; ARI: p = 0.007).

Conclusions. An age-related decline in cerebrovascular autoregulation was associated with a relative deterioration in outcome in elderly patients following head trauma.