Cerebral Pressure Autoregulation Research Articles

The Optimal pressure reactivity index range is disease-specific: A comparison between aneurysmal subarachnoid hemorrhage and traumatic brain injury

PurposeImpaired cerebral pressure autoregulation is common and detrimental after acute brain injuries. Based on the prevalence of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage (aSAH) patients compared to traumatic brain injury (TBI), we hypothesized that the type of autoregulatory disturbance and the optimal PRx range may differ between these two conditions. The aim of this study was to determine the optimal PRx ranges in relation to functional outcome following aSAH and TBI, respectively.MethodsIn this observational study, 487 aSAH patients and 413 TBI patients, treated in the neurointensive care, Uppsala, Sweden, between 2008 and 2018, were included. The percentage of good monitoring time (%GMT) of PRx was calculated within 8 intervals covering the range from -1.0 to + 1.0, and analyzed in relation to favorable outcome (GOS-E 5 to 8).ResultsIn multiple logistic regressions, a higher %GMTs of PRx in the intervals -1.0 to -0.5 and + 0.75 to + 1.0 were independently associated with a lower rate of favorable outcome in the aSAH cohort. In a similar analysis in the TBI cohort, only positive PRx in the interval + 0.75 to + 1.0 was independently associated with a lower rate of favorable outcome.ConclusionExtreme PRx values in both directions were unfavorable in aSAH, possibly as high PRx could indicate proximal vasospasm with exhausted distal vasodilatory reserve, while very negative PRx could reflect myogenic hyperreactivity with suppressed cerebral blood flow. Only elevated PRx was unfavorable in TBI, possibly as pressure passive vessels may be a more predominant pathomechanism in this disease.

The effects of cerebral pressure autoregulation status and CPP levels on cerebral metabolism in pediatric traumatic brain injury

BackgroundCerebral perfusion pressure (CPP) management in the developing child with traumatic brain injury (TBI) is challenging. The pressure reactivity index (PRx) may serve as marker of cerebral pressure autoregulation (CPA) and optimal CPP (CPPopt) may be assessed by identifying the CPP level with best (lowest) PRx. To evaluate the potential of CPPopt guided management in children with severe TBI, cerebral microdialysis (CMD) monitoring levels of lactate and the lactate/pyruvate ratio (LPR) (indicators of ischemia) were related to actual CPP levels, autoregulatory state (PRx) and deviations from CPPopt (ΔCPPopt).MethodsRetrospective study of 21 children ≤ 17 years with severe TBI who had both ICP and CMD monitoring were included. CPP, PRx, CPPopt and ΔCPPopt where calculated, dichotomized and compared with CMD lactate and lactate-pyruvate ratio.ResultsMedian age was 16 years (range 8–17) and median Glasgow coma scale motor score 5 (range 2–5). Both lactate (p = 0.010) and LPR (p = < 0.001) were higher when CPP ≥ 70 mmHg than when CPP < 70. When PRx ≥ 0.1 both lactate and LPR were higher than when PRx < 0.1 (p = < 0.001). LPR was lower (p = 0.012) when CPPopt ≥ 70 mmHg than when CPPopt < 70, but there were no differences in lactate levels. When ΔCPPopt > 10 both lactate (p = 0.026) and LPR (p = 0.002) were higher than when ΔCPPopt < –10.ConclusionsIncreased levels of CMD lactate and LPR in children with severe TBI appears to be related to disturbed CPA (PRx). Increased lactate and LPR also seems to be associated with actual CPP levels ≥ 70 mmHg. However, higher lactate and LPR values were also seen when actual CPP was above CPPopt. Higher CPP appears harmful when CPP is above the upper limit of pressure autoregulation. The findings indicate that CPPopt guided CPP management may have potential in pediatric TBI.

Visualization of Cerebral Pressure Autoregulatory Insults in Traumatic Brain Injury.

The first aim was to investigate the combined effect of insult intensity and duration of the pressure reactivity index (PRx) and deviation from the autoregulatory cerebral perfusion pressure target (∆CPPopt = actual CPP - optimal CPP [CPPopt]) on outcome in traumatic brain injury. The second aim was to determine if PRx influenced the association between intracranial pressure (ICP), CPP, and ∆CPPopt with outcome. Observational cohort study. Neurocritical care unit, Cambridge, United Kingdom. Five hundred fifty-three traumatic brain injury patients with ICP and arterial blood pressure monitoring and 6-month outcome data (Glasgow Outcome Scale [GOS]). None. The insult intensity (mm Hg or PRx coefficient) and duration (minutes) of ICP, PRx, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In these plots, there was a transition from favorable to unfavorable outcome when PRx remained positive for 30 minutes and this was also the case for shorter durations when the intensity was higher. In a similar plot of ∆CPPopt, there was a gradual transition from favorable to unfavorable outcome when ∆CPPopt went below -5 mm Hg for 30-minute episodes of time and for shorter durations for more negative ∆CPPopt. Furthermore, the percentage of monitoring time with certain combinations of PRx with ICP, CPP, and ∆CPPopt were correlated with GOS and visualized in heatmaps. In the combined PRx/ICP heatmap, ICP above 20 mm Hg together with PRx above 0 correlated with unfavorable outcome. In a PRx/CPP heatmap, CPP below 70 mm Hg together with PRx above 0.2-0.4 correlated with unfavorable outcome. In the PRx-/∆CPPopt heatmap, ∆CPPopt below 0 together with PRx above 0.2-0.4 correlated with unfavorable outcome. Higher intensities for longer durations of positive PRx and negative ∆CPPopt correlated with worse outcome. Elevated ICP, low CPP, and negative ∆CPPopt were particularly associated with worse outcomes when the cerebral pressure autoregulation was concurrently impaired.

Should Patients with Traumatic Brain Injury with Significant Contusions be Treated with Different Neurointensive Care Targets?

BackgroundPatients with traumatic brain injury (TBI) with large contusions make up a specific TBI subtype. Because of the risk of brain edema worsening, elevated cerebral perfusion pressure (CPP) may be particularly dangerous. The pressure reactivity index (PRx) and optimal cerebral perfusion pressure (CPPopt) are new promising perfusion targets based on cerebral autoregulation, but they reflect the global brain state and may be less valid in patients with predominant focal lesions. In this study, we aimed to investigate if patients with TBI with significant contusions exhibited a different association between PRx, CPP, and CPPopt in relation to functional outcome compared to those with small/no contusions.MethodsThis observational study included 385 patients with moderate to severe TBI treated at a neurointensive care unit in Uppsala, Sweden. The patients were classified into two groups: (1) significant contusions (> 10 mL) and (2) small/no contusions (but with extra-axial or diffuse injuries). The percentage of good monitoring time (%GMT) with intracranial pressure > 20 mm Hg; PRx > 0.30; CPP < 60 mm Hg, within 60–70 mm Hg, or > 70 mm Hg; and ΔCPPopt less than − 5 mm Hg, ± 5 mm Hg, or > 5 mm Hg was calculated. Outcome (Glasgow Outcome Scale-Extended) was assessed after 6 months.ResultsAmong the 120 (31%) patients with significant contusions, a lower %GMT with CPP between 60 and 70 mm Hg was independently associated with unfavorable outcome. The %GMTs with PRx and ΔCPPopt ± 5 mm Hg were not independently associated with outcome. Among the 265 (69%) patients with small/no contusions, a higher %GMT of PRx > 0.30 and a lower %GMT of ΔCPPopt ± 5 mm Hg were independently associated with unfavorable outcome.ConclusionsIn patients with TBI with significant contusions, CPP within 60–70 mm Hg may improve outcome. PRx and CPPopt, which reflect global cerebral pressure autoregulation, may be useful in patients with TBI without significant focal brain lesions but seem less valid for those with large contusions. However, this was an observational, hypothesis-generating study; our findings need to be validated in prospective studies before translating them into clinical practice.

Cerebrovascular reactivity (PRx) and optimal cerebral perfusion pressure in elderly with traumatic brain injury

PurposeCerebral perfusion pressure (CPP) guidance by cerebral pressure autoregulation (CPA) status according to PRx (correlation mean arterial blood pressure (MAP) and intracranial pressure (ICP)) and optimal CPP (CPPopt = CPP with lowest PRx) is promising but little is known regarding this approach in elderly. The aim was to analyze PRx and CPPopt in elderly TBI patients.MethodsA total of 129 old (≥ 65 years) and 342 young (16–64 years) patients were studied using monitoring data for MAP and ICP. CPP, PRx, CPPopt, and ΔCPPopt (difference between actual CPP and CPPopt) were calculated. Logistic regression analyses with PRx and ΔCPPopt as explanatory variables for outcome. The combined effects of PRx/CPP and PRx/ΔCPPopt on outcome were visualized as heatmaps.ResultsThe elderly had higher PRx (worse CPA), higher CPPopt, and different temporal patterns. High PRx influenced outcome negatively in the elderly but less so than in younger patients. CPP close to CPPopt correlated to favorable outcome in younger, in contrast to elderly patients. Heatmap interaction analysis of PRx/ΔCPPopt in the elderly showed that the region for favorable outcome was centered around PRx 0 and ranging between both functioning and impaired CPA (PRx range − 0.5–0.5), and the center of ΔCPPopt was − 10 (range − 20–0), while in younger the center of PRx was around − 0.5 and ΔCPPopt closer to zero.ConclusionsThe elderly exhibit higher PRx and CPPopt. High PRx influences outcome negatively in the elderly but less than in younger patients. The elderly do not show better outcome when CPP is close to CPPopt in contrast to younger patients.

Limitation of cerebral blood flow by increased venous outflow resistance in elevated ICP.

Extensive investigation and modeling efforts have been dedicated to cerebral pressure autoregulation, which is primarily regulated by the ability of the cerebral arterioles to change their resistance and modulate cerebral blood flow (CBF). However, the mechanisms by which elevated intracranial pressure (ICP) leads to increased resistance to venous outflow have received less attention. We modified our previously described model of intracranial fluid interactions with a newly developed model of a partially collapsed blood vessel, which we termed the "flow control zone" (FCZ). We sought to determine the degree to which ICP elevation causing venous compression at the FCZ becomes the main parameter limiting CBF. The FCZ component was designed using nonlinear functions representing resistance as a function of cross-sectional area and the pressure-volume relations of the vessel wall. We used our previously described swine model of cerebral edema with graduated elevation of ICP to calculate venous outflow resistance and a newly defined parameter, the cerebral resistance index (CRI), which is the ratio between venous outflow resistance and cerebrovascular resistance. Model simulations of cerebral edema and increased ICP led to increased venous outflow resistance. There was a close similarity between model predictions of venous outflow resistance and experimental results in the swine model (cross-correlation coefficient of 0.97, a mean squared error of 0.087, and a mean absolute error of 0.15). CRI was strongly correlated to ICP in the swine model (r2 = 0.77, P = 0.00012, 95% confidence interval [0.15, 0.45]). A CRI value of 0.5 was associated with ICP values above clinically significant thresholds (24 mmHg) in the swine model and a diminished capacity of changes in arteriolar resistance to influence flow in the mathematical model. Our results demonstrate the importance of venous compression at the FCZ in determining CBF when ICP is elevated. The cerebral resistance index may provide an indication of when compression of venous outflow becomes the dominant factor in limiting CBF following brain injury.NEW & NOTEWORTHY The goal of this study was to investigate the effects of venous compression caused by elevated intracranial pressure (ICP) due to cerebral edema, validated through animal experiments. The flow control zone model highlights the impact of cerebral venous compression on cerebral blood flow (CBF) during elevated ICP. The cerebral venous outflow resistance-to-cerebrovascular resistance ratio may indicate when venous outflow compression becomes the dominant factor limiting CBF. CBF regulation descriptions should consider how arterial or venous factors may predominantly influence flow in different clinical scenarios.

The role of intracranial pressure variability as a predictor of intracranial hypertension and mortality in critically ill patients.

Intracranial pressure (ICP) monitoring is a widely utilized and essential tool for tracking neurosurgical patients, but there are limitations to the use of a solely ICP-based paradigm for guiding management. It has been suggested that ICP variability (ICPV), in addition to mean ICP, may be a useful predictor of neurological outcomes, as it represents an indirect measure of intact cerebral pressure autoregulation. However, the current literature regarding the applicability of ICPV shows conflicting associations between ICPV and mortality. Thus, the authors aimed to investigate the effect of ICPV on intracranial hypertensive episodes and mortality using the eICU Collaborative Research Database version 2.0. The authors extracted from the eICU database 1,815,676 ICP readings from 868 patients with neurosurgical conditions. ICPV was computed using two methods: the rolling standard deviation (RSD) and the absolute deviation from the rolling mean (DRM). An episode of intracranial hypertension was defined as at least 25 minutes of ICP > 22 mm Hg in any 30-minute window. The effects of mean ICPV on intracranial hypertension and mortality were computed using multivariate logistic regression. A recurrent neural network with long short-term memory was used for time-series predictions of ICP and ICPV to prognosticate future episodes of intracranial hypertension. A higher mean ICPV was significantly associated with intracranial hypertension using both ICPV definitions (RSD: aOR 2.82, 95% CI 2.07-3.90, p < 0.001; DRM: aOR 3.93, 95% CI 2.77-5.69, p < 0.001). ICPV was significantly associated with mortality in patients with intracranial hypertension (RSD: aOR 1.28, 95% CI 1.04-1.61, p = 0.026, DRM: aOR 1.39, 95% CI 1.10-1.79, p = 0.007). In the machine learning models, both definitions of ICPV achieved similarly good results, with the best F1 score of 0.685 ± 0.026 and an area under the curve of 0.980 ± 0.003 achieved with the DRM definition over 20 minutes. ICPV may be useful as an adjunct for the prognostication of intracranial hypertensive episodes and mortality in neurosurgical critical care as part of neuromonitoring. Further research on predicting future intracranial hypertensive episodes with ICPV may help clinicians react expediently to ICP changes in patients.

Association Between Disrupted Cerebral Autoregulation and Radiographic Neurologic Injury for Children on Extracorporeal Membrane Oxygenation: A Prospective Pilot Study.

Validation of a real-time monitoring device to evaluate the risk or occurrence of neurologic injury while on extracorporeal membrane oxygenation (ECMO) may aid clinicians in prevention and treatment. Therefore, we performed a pilot prospective cohort study of children under 18 years old on ECMO to analyze the association between cerebral blood pressure autoregulation as measured by diffuse correlation spectroscopy (DCS) and radiographic neurologic injury. DCS measurements of regional cerebral blood flow were collected on enrolled patients and correlated with mean arterial blood pressure to determine the cerebral autoregulation metric termed DCSx. The primary outcome of interest was radiographic neurologic injury on eligible computed tomography (CT) or magnetic resonance imaging (MRI) scored by a blinded pediatric neuroradiologist utilizing a previously validated scale. Higher DCSx scores, which indicate disruption of cerebral autoregulation, were associated with higher radiographic neurologic injury score (slope, 11.0; 95% confidence interval [CI], 0.29-22). Patients with clinically significant neurologic injury scores of 10 or more had higher median DCSx measures than patients with lower neurologic injury scores (0.48 vs . 0.13; p = 0.01). Our study indicates that obtaining noninvasive DCS measures for children on ECMO is feasible and disruption of cerebral autoregulation determined from DCS is associated with higher radiographic neurologic injury score.

Cerebral pressure autoregulation and optimal cerebral perfusion pressure during neurocritical care of children with traumatic brain injury.

The management of cerebral perfusion pressure (CPP) is a challenge in children with traumatic brain injury (TBI) because the normal blood pressure is age dependent and the role of cerebral pressure autoregulation (CPA) is unclear. In this study, the authors aimed to examine the pressure reactivity index (PRx), CPP, optimal CPP (CPPopt), and deviations from CPPopt (ΔCPPopt) in a series of children with TBI generally and regarding age relations, temporal changes, and the influence on outcome. Intracranial pressure (ICP) and mean arterial pressure (MAP) monitoring data were collected during neurointensive care in 57 children who sustained a TBI and were ≤ 17 years of age. CPP, PRx, CPPopt, and ΔCPPopt (actual CPP - CPPopt) were calculated. Clinical outcomes at 6 months postinjury were dichotomized into favorable outcomes (Glasgow Outcome Scale [GOS] score 4 or 5) and unfavorable outcomes (GOS scores 1-3). The median patient age was 15 (range 0.5-17) years, and the median Glasgow Coma Scale motor score at admission was 5 (range 2-5). Forty-nine (86%) of the 57 patients had favorable outcomes. For the entire group, lower PRx (better preserved CPA) was associated with a more favorable outcome (p = 0.023, ANCOVA adjusted for age). When the children were divided into age groups, this finding was statistically significant in children ≤ 15 years of age (p = 0.016), but not in children ≥ 16 years (p = 0.528). In children ≤ 15 years, a lower proportion of time with ΔCPPopt < -10% was significantly associated with a favorable outcome (p = 0.038), but not in the older age group. Temporal analysis indicated that PRx was higher (more impaired CPA) from day 4 and CPPopt was higher from day 6 in the unfavorable outcome group compared with the favorable outcome group, although those findings were not significant. Impaired CPA is related to poor outcome, particularly in children ≤ 15 years of age. In that age group, actual CPP below the CPPopt level contributed significantly to unfavorable outcome, while levels close to or above the CPPopt were unrelated to outcome. CPPopt appears to be higher during the time period when CPA is most impaired.

Plasma Biomarkers of Evolving Encephalopathy and Brain Injury in Neonates with Hypoxic-Ischemic Encephalopathy

The objective of the study was to evaluate the relationship between a panel of candidate plasma biomarkers and (1) death or severe brain injury on magnetic resonance imaging (MRI) and (2) dysfunctional cerebral pressure autoregulation as a measure of evolving encephalopathy. Neonates with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) at 2 level IV neonatal intensive care units were enrolled into this observational study. Patients were treated with therapeutic hypothermia (TH) and monitored with continuous blood pressure monitoring and near-infrared spectroscopy. Cerebral pressure autoregulation was measured by the hemoglobin volume phase (HVP) index; a higher HVP index indicates poorer autoregulation. Serial blood samples were collected during TH and assayed for Tau, glial fibrillary acidic protein, and neurogranin. MRIs were assessed using National Institutes of Child Health and Human Development scores. The relationships between the candidate biomarkers and (1) death or severe brain injury on MRI (defined as a National Institutes of Child Health and Human Development score of ≥ 2B) and (2) autoregulation were evaluated using bivariate and adjusted logistic regression models. Sixty-two patients were included. Elevated Tau levels on days 2-3 of TH were associated with death or severe injury on MRI (aOR: 1.06, 95% CI: 1.03-1.09; aOR: 1.04, 95% CI: 1.01-1.06, respectively). Higher Tau was also associated with poorer autoregulation (higher HVP index) on the same day (P=.022). Elevated plasma levels of Tau are associated with death or severe brain injury by MRI and dysfunctional cerebral autoregulation in neonates with HIE. Larger-scale validation of Tau as a biomarker of brain injury in neonates with HIE is warranted.

NT-proBNP and troponin I in high-grade aneurysmal subarachnoid hemorrhage: Relation to clinical course and outcome

PurposeTo investigate the association between two cardiac biomarkers, NT-proBNP and TnI, with intracranial pressure (ICP)−/cerebral perfusion pressure (CPP)-insults, cerebral pressure autoregulation, delayed ischemic neurological deficits (DIND), and clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). MethodsIn this retrospective study, 196 aSAH patients treated at the neurointensive care unit, Uppsala University Hospital, Sweden, 2011–2018, with ICP-monitoring and serial NT-proBNP and TnI measurements were included. The first 10 days were divided into early phase (day 1–3) and vasospasm phase (day 4–10). ResultsNT-proBNP and TnI were elevated above the reference interval at least once the first 10 days in 175 (89%) and 116 (59%) patients, respectively. In the vasospasm phase, higher NT-proBNP and TnI were associated with increased percentage of CPP below 60 mmHg. Higher TnI also correlated with more ICP-insults above 20 mmHg. NT-proBNP and TnI did not predict worse pressure autoregulation and DIND. Higher NT-proBNP and TnI were associated with mortality and unfavorable outcome in univariate, but not multivariate, analyses. ConclusionElevated NT-proBNP and TnI correlated with an increased burden of secondary ICP-/CPP-insults, but not with worse pressure autoregulation, DIND, and without independent association with clinical outcome.

Females Exhibit Better Cerebral Pressure Autoregulation, Less Mitochondrial Dysfunction, and Reduced Excitotoxicity after Severe Traumatic Brain Injury.

The aim of the study was to investigate sex-related differences in intracranial pressure (ICP) dynamics, cerebral pressure autoregulation (PRx55-15), cerebral energy metabolism, and clinical outcome after severe traumatic brain injury (TBI). One-hundred sixty-nine adult patients with TBI, treated at the Neurointensive Care (NIC) Unit at Uppsala University Hospital between 2008 and 2020 with ICP and cerebral microdialysis (MD) monitoring were included. Of the 169 patients with TBI, 131 (78%) were male and 38 (22%) female. Male patients were more often injured by motor vehicle accidents and less often by bicycle accidents (p < 0.05). There were otherwise no differences in age, neurological status at admission, and types of intracranial hemorrhages between the sexes. The percent of monitoring time with ICP above 20 mm Hg and cerebral perfusion pressure (CPP) below 60 mm Hg were similar for both sexes. Males exhibited more disturbed cerebral pressure autoregulation (PRx55-15 [mean ± standard deviation (SD)]; 0.28 ± 0.18 vs. 0.17 ± 0.23, p < 0.05) on day 1, worse cerebral energy metabolism (MD-lactate-/pyruvate-ratio [median (interquartile range)]; 25 [19-31] vs. 20 [17-25], p < 0.01) and mitochondrial dysfunction (higher burden of MD-lactate-/pyruvate-ratio >25 and MD-pyruvate >120 μM [median (interquartile range)]; 13 [0-58] % vs. 3 [0-17] %, p < 0.05) on days 2 to 5, increased excitotoxicity (MD-glutamate median [interquartile range]; 9 [4-32] μM vs. 5 [3-10] μM, p < 0.05) on days 2 to 5, and higher biomarker levels of cellular injury (MD-glycerol median [interquartile range]; 103 [66-193] μM vs. 68 [49-106] μM, p < 0.01) most pronounced on days 6 to 10. There was no difference in mortality or the degree of favorable outcome between the sexes. Altogether, females exhibited more favorable cerebral physiology post-TBI, particularly better mitochondrial function and reduced excitotoxicity, but this did not translate into better clinical outcome compared with males. Future studies are needed to further explore potential sex differences in secondary injury mechanisms in TBI.

Characterising the dynamics of cerebral metabolic dysfunction following traumatic brain injury: A microdialysis study in 619 patients.

Traumatic brain injury (TBI) is a major cause of death and disability, particularly amongst young people. Current intensive care management of TBI patients is targeted at maintaining normal brain physiology and preventing secondary injury. Microdialysis is an invasive monitor that permits real-time assessment of derangements in cerebral metabolism and responses to treatment. We examined the prognostic value of microdialysis parameters, and the inter-relationships with other neuromonitoring modalities to identify interventions that improve metabolism. This was an analysis of prospective data in 619 adult TBI patients requiring intensive care treatment and invasive neuromonitoring at a tertiary UK neurosciences unit. Patients had continuous measurement of intracranial pressure (ICP), arterial blood pressure (ABP), brain tissue oxygenation (PbtO2), and cerebral metabolism and were managed according to a standardized therapeutic protocol. Microdialysate was assayed hourly for metabolites including glucose, pyruvate, and lactate. Cerebral perfusion pressure (CPP) and cerebral autoregulation (PRx) were derived from the ICP and ABP. Outcome was assessed with the Glasgow Outcome Score (GOS) at 6 months. Relationships between monitoring variables was examined with generalized additive mixed models (GAMM). Lactate/Pyruvate Ratio (LPR) over the first 3 to 7 days following injury was elevated amongst patients with poor outcome and was an independent predictor of ordinal GOS (p<0.05). Significant non-linear associations were observed between LPR and cerebral glucose, CPP, and PRx (p<0.001 to p<0.05). GAMM models suggested improved cerebral metabolism (i.e. reduced LPR with CPP >70mmHg, PRx <0.1, PbtO2 >18mmHg, and brain glucose >1mM. Deranged cerebral metabolism is an important determinant of patient outcome following TBI. Variations in cerebral perfusion, oxygenation and glucose supply are associated with changes in cerebral LPR and suggest therapeutic interventions to improve cerebral metabolism. Future prospective studies are required to determine the efficacy of these strategies.

Transcranial color Doppler ultrasonography: methodology and usefulness for the study of patent foramen ovale in cryptogenic stroke

Non-invasive Doppler ultrasonographic study of cerebral arteries (transcranial Doppler, TCD) has been extensively applied on both outpatient and inpatient settings. It is performed placing a low-frequency (≤2 MHz) transducer on the scalp of the patient over specific acoustic windows, in order to visualize the intracranial arterial vessels and to evaluate the cerebral blood flow velocity and its alteration in many different conditions. Nowadays a valid indication for TCD in the outpatient setting is the research of right-to-left shunting, responsible for the so-called "paradoxical embolism", most often due to patency of foramen ovale, which is responsible for the majority of cryptogenic strokes occurring in patients younger than 55 years. TCD also allows to classify the grade of severity of such shunts using the so-called "microembolic signal grading score". Therefore, TCD is an essential cardiological exam for the detection of patent foramen ovale, assuming an important role as a first-level examination to guide the subsequent diagnostic-therapeutic management. In addition, TCD has found many useful applications in neurocritical care practice. It is useful for the identification of intracranial vascular stenosis and for the assessment of critical conditions including vasospasm in subarachnoid hemorrhage, traumatic brain injury and brain stem death. It is also used to evaluate cerebral hemodynamic changes after stroke, to investigate cerebral pressure autoregulation, and for the clinical evaluation of cerebral vasomotor reactivity.

Effect of Intraoperative Arterial Hypotension on the Risk of Perioperative Stroke After Noncardiac Surgery: A Retrospective Multicenter Cohort Study.

Intraoperative cerebral blood flow is mainly determined by cerebral perfusion pressure and cerebral autoregulation of vasomotor tone. About 1% of patients undergoing noncardiac surgery develop ischemic stroke. We hypothesized that intraoperative hypotension within a range frequently observed in clinical practice is associated with an increased risk of perioperative ischemic stroke within 7 days after surgery. Adult noncardiac surgical patients undergoing general anesthesia at Beth Israel Deaconess Medical Center and Massachusetts General Hospital between 2005 and 2017 were included in this retrospective cohort study. The primary exposure was intraoperative hypotension, defined as a decrease in mean arterial pressure (MAP) below 55 mm Hg, categorized into no intraoperative hypotension, short (<15 minutes, median [interquartile range {IQR}], 2 minutes [1-5 minutes]) and prolonged (≥15 minutes, median [IQR], 21 minutes [17-31 minutes]) durations. The primary outcome was a new diagnosis of early perioperative ischemic stroke within 7 days after surgery. In secondary analyses, we assessed the effect of a MAP decrease by >30% from baseline on perioperative stroke. Analyses were adjusted for the preoperative STRoke After Surgery (STRAS) prediction score, work relative value units, and duration of surgery. Among 358,391 included patients, a total of 1553 (0.4%) experienced an early perioperative ischemic stroke. About 42% and 3% of patients had a MAP of below 55 mm Hg for a short and a prolonged duration, and 49% and 29% had a MAP decrease by >30% from baseline for a short and a prolonged duration, respectively. In an adjusted analysis, neither a MAP <55 mm Hg (short duration: adjusted odds ratio [ORadj], 0.95; 95% confidence interval [CI], 0.85-1.07; P = .417 and prolonged duration: ORadj, 1.18; 95% CI, 0.91-1.55; P = .220) nor a MAP decrease >30% (short duration: ORadj, 0.97; 95% CI, 0.67-1.42; P = .883 and prolonged duration: ORadj, 1.30; 95% CI, 0.89-1.90; P = .176) was associated with early perioperative stroke. A high a priori stroke risk quantified based on preoperatively available risk factors (STRAS prediction score) was associated with longer intraoperative hypotension (adjusted incidence rate ratio, 1.04; 95% CI, 1.04-1.05; P < .001 per 5 points of the STRAS prediction score). This study found no evidence to conclude that intraoperative hypotension within the range studied was associated with early perioperative stroke within 7 days after surgery. These findings emphasize the importance of perioperative cerebral blood flow autoregulation to prevent ischemic stroke.

Cerebral perfusion pressure and autoregulation in eclampsia—a case control study

Dynamic cerebral autoregulation and cerebral perfusion pressure are altered in pregnancies complicated by preeclampsia compared with normotensive pregnancies, but the connections of dynamic cerebral autoregulation, cerebral perfusion pressure, and cerebral complications in preeclampsia remain unclear. This study aimed to assess dynamic cerebral autoregulation and cerebral perfusion pressure after delivery in women with eclampsia, in women with preeclampsia both with and without severe features, and in normotensive women. This was a prospective case control study at a large referral hospital in Cape Town, South Africa. The recruitment of participants was done at diagnosis (cases) or at admission for delivery (controls). Transcranial Doppler examinations with continuous noninvasive blood pressure measurements and end-tidal CO2 monitoring were conducted for cases and controls after delivery. Cerebral perfusion pressure and dynamic cerebral autoregulation index were calculated, and values were compared among groups. We included 16 women with eclampsia, 18 women with preeclampsia with severe features, 32 women with preeclampsia without severe features, and 21 normotensive women with uncomplicated pregnancies. Dynamic cerebral autoregulation was depressed in pregnant women with eclampsia; (autoregulation index, 3.9; interquartile range, 3.1-5.2) compared with all other groups (those with preeclampsia with severe features, autoregulation index, 5.6 [interquartile range, 4.4-6.8]; those with preeclampsia without severe features, autoregulation index, 6.8 [interquartile range, 5.1-7.4]; and normotensive controls, autoregulation index, 7.1 [interquartile range, 6.1-7.9]). Pregnant women with eclampsia had increased cerebral perfusion pressure (109.5 mm Hg; interquartile range, 91.2-130.9) compared with those with preeclampsia without severe features and those with normal blood pressure (84 mm Hg [interquartile range, 73.0-122.0] and 80.0 mm Hg [interquartile range, 67.5-92.0], respectively); furthermore, there was no difference in cerebral perfusion pressure between pregnant women with eclampsia and pregnant women with preeclampsia with severe features (109.5 mm Hg [interquartile range, 91.2-130.9] vs 96.5 mm Hg [interquartile range, 75.8-110.5]). Cerebral perfusion pressure and dynamic cerebral autoregulation are altered in eclampsia and may be important in the pathophysiological pathway and constitute a therapeutic target in the prevention of cerebral complications in preeclampsia.

Autoregulatory or Fixed Cerebral Perfusion Pressure Targets in Traumatic Brain Injury: Determining Which Is Better in an Energy Metabolic Perspective.

Current guidelines in traumatic brain injury (TBI) recommend a cerebral perfusion pressure (CPP) within the fixed interval of 60-70 mm Hg. However, the autoregulatory, optimal CPP target (CPPopt) might yield better cerebral blood flow (CBF) regulation. In this study, we investigated fixed versus autoregulatory CPP targets in relation to cerebral energy metabolism and clinical outcome after TBI. Ninety-eight non-craniectomized patients with severe TBI treated in the neurointensive care unit, Uppsala University Hospital, Sweden, 2008-2018, were included. Data from cerebral microdialysis (MD), intracranial pressure (ICP), pressure autoregulation, CPP and CPPopt55-15 (a variant of CPPopt based on filtered slow waves from 15-55 sec range) were analyzed the first 10 days. The good monitoring time (GMT %) below/within/above the fixed and autoregulatory CPP targets were calculated. CPPopt55-15 was >70 mm Hg 74% of the time the first 10 days. Higher GMT (%) ΔCPPopt55-15 ± 10 mm Hg correlated with lower lactate/pyruvate ratio (LPR) on day 1 and lower cerebral glycerol on days 6-10, and predicted favorable clinical outcome. Higher GMT (%) CPP within 60-70 mm Hg correlated with lower cerebral glucose on days 2-10 and higher LPR on days 6-10, but predicted favorable clinical outcome. Higher GMT (%) CPP >70 mm Hg had the opposite associations; that is, with higher cerebral glucose and lower LPR, but unfavorable clinical outcome. Autoregulatory CPP targets may be beneficial, because patients with CPP values close to the optimal CPP had both better cerebral energy metabolism and better clinical outcome, but this needs to be evaluated in randomized trials.

Posterior Reversible Encephalopathy Syndrome: Nitroglycerine a Friend or a Foe?

Posterior reversible encephalopathy syndrome (PRES) refers to a clinico-radiological entity with characteristic features on neuroimaging and rapid onset of nonspecific symptoms including headache, seizure, altered consciousness and visual disturbance. It is a neurotoxic state in response to the acute changes in blood pressure leading to vasogenic oedema. It is often but not always associated with hypertension. However, control blood pressure is one of the mainstays of management in such cases. Nitroglycerine (NTG) is a potent vasodilator and is one of the drugs for treatment of hypertensive emergencies. It is found to worsen the cerebral oedema in PRES which is considered due to failure of cerebral blood pressure autoregulation. Here, we report two such cases where patients with PRES deteriorated with NTG infusion. However, the neurological condition of the patients improved drastically the next day. NTG could have further enhanced vasodilation, thus aggravating developing PRES, after autoregulation was lost because of high blood pressure.

Intraoperative hypotension and neurological outcomes.

Intraoperative hypotension (IOH) may render patients at a risk of cerebral hypoperfusion with decreasing cerebral blood flow (CBF), and lead to postoperative neurological injury. On the basis of the literature in recent years, this review attempts to refine the definition of IOH and evaluate its impact on neurological outcomes. Although both absolute and relative blood pressure (BP) thresholds, with or without a cumulative period, have been used in collective clinical studies, no definitive threshold of IOH has been established for neurological complications, including perioperative stroke, postoperative cognitive disorder and delirium. The CBF is jointly modulated by multiple pressure processes (i.e. cerebral pressure autoregulation) and nonpressure processes, including patient, surgical and anaesthesia-related confounding factors. The confounding factors and variability in cerebral pressure autoregulation might impede evaluating the effect of IOH on the neurological outcomes. Furthermore, the majority of the evidence presented in this review are cohort studies, which are weak in demonstrating a cause--effect relationship between IOH and neurological complications. The maintenance of target BP based on the monitoring of regional cerebral oxygen saturation (rScO2) or cerebral pressure autoregulation seems to be associated with the decreased incidence of postoperative neurological complications. Despite the lack of a known threshold value, IOH is a modifiable risk factor targeted to improve neurological outcomes. Ideal BP management is recommended in order to maintain target BP based on the monitoring of rScO2 or cerebral pressure autoregulation.

Arterial Oxygenation in Traumatic Brain Injury-Relation to Cerebral Energy Metabolism, Autoregulation, and Clinical Outcome.

Background:Ischemic and hypoxic secondary brain insults are common and detrimental in traumatic brain injury (TBI). Treatment aims to maintain an adequate cerebral blood flow with sufficient arterial oxygen content. It has been suggested that arterial hyperoxia may be beneficial to the injured brain to compensate for cerebral ischemia, overcome diffusion barriers, and improve mitochondrial function. In this study, we investigated the relation between arterial oxygen levels and cerebral energy metabolism, pressure autoregulation, and clinical outcome.Methods:This retrospective study was based on 115 patients with severe TBI treated in the neurointensive care unit, Uppsala university hospital, Sweden, 2008 to 2018. Data from cerebral microdialysis (MD), arterial blood gases, hemodynamics, and intracranial pressure were analyzed the first 10 days post-injury. The first day post-injury was studied in particular.Results:Arterial oxygen levels were higher and with greater variability on the first day post-injury, whereas it was more stable the following 9 days. Normal-to-high mean pO2 was significantly associated with better pressure autoregulation/lower pressure reactivity index (P = .02) and lower cerebral MD-lactate (P = .04) on day 1. Patients with limited cerebral energy metabolic substrate supply (MD-pyruvate below 120 µM) and metabolic disturbances with MD-lactate-/pyruvate ratio (LPR) above 25 had significantly lower arterial oxygen levels than those with limited MD-pyruvate supply and normal MD-LPR (P = .001) this day. Arterial oxygenation was not associated with clinical outcome.Conclusions:Maintaining a pO2 above 12 kPa and higher may improve oxidative cerebral energy metabolism and pressure autoregulation, particularly in cases of limited energy substrate supply in the early phase of TBI. Evaluating the cerebral energy metabolic profile could yield a better patient selection for hyperoxic treatment in future trials.