Pressure Autoregulation Research Articles

Optimal target mean arterial pressure for patients with sepsis-associated encephalopathy: a retrospective cohort study

BackgroundSepsis-associated encephalopathy (SAE) patients often experience changes in intracranial pressure and impaired cerebral autoregulation. Mean arterial pressure (MAP) plays a crucial role in cerebral perfusion pressure, but its relationship with mortality in SAE patients remains unclear. This study aims to investigate the relationship between MAP and the risk of 28-day and in-hospital mortality in SAE patients, providing clinicians with the optimal MAP target.MethodsWe retrospectively collected clinical data of patients diagnosed with SAE on the first day of ICU admission from the MIMIC-IV (v2.2) database. Patients were divided into four groups based on MAP quartiles. Kruskal-Wallis H test and Chi-square test were used to compare clinical characteristics among the groups. Restricted cubic spline and segmented Cox regression models, both unadjusted and adjusted for multiple variables, were employed to elucidate the relationship between MAP and the risk of 28-day and in-hospital mortality in SAE patients and to identify the optimal MAP. Subgroup analyses were conducted to assess the stability of the results.ResultsA total of 3,816 SAE patients were included. The Q1 group had higher rates of acute kidney injury and vasoactive drug use on the first day of ICU admission compared to other groups (P < 0.01). The Q1 and Q4 groups had longer ICU and hospital stays (P < 0.01). The 28-day and in-hospital mortality rates were highest in the Q1 group and lowest in the Q3 group. Multivariable adjustment restricted cubic spline curves indicated a nonlinear relationship between MAP and mortality risk (P for nonlinearity < 0.05). The MAP ranges associated with HRs below 1 for 28-day and in-hospital mortality were 74.6–90.2 mmHg and 74.6–89.3 mmHg, respectively.The inflection point for mortality risk, determined by the minimum hazard ratio (HR), was identified at a MAP of 81.5 mmHg. The multivariable adjusted segmented Cox regression models showed that for MAP < 81.5 mmHg, an increase in MAP was associated with a decreased risk of 28-day and in-hospital mortality (P < 0.05). In Model 4, each 5 mmHg increase in MAP was associated with a 15% decrease in 28-day mortality risk (HR: 0.85, 95% CI: 0.79–0.91, p < 0.05) and a 14% decrease in in-hospital mortality risk (HR: 0.86, 95% CI: 0.80–0.93, p < 0.05). However, for MAP ≥ 81.5 mmHg, there was no significant association between MAP and mortality risk (P > 0.05). Subgroup analyses based on age, congestive heart failure, use of vasoactive drugs, and acute kidney injury showed consistent results across different subgroups.Subsequent analysis of SAE patients with septic shock also showed results similar to those of the original cohort.However, for comatose SAE patients (GCS ≤ 8), there was a negative correlation between MAP and the risk of 28-day and in-hospital mortality when MAP was < 81.5 mmHg, but a positive correlation when MAP was ≥ 81.5 mmHg in adjusted models 2 and 4.ConclusionThere is a nonlinear relationship between MAP and the risk of 28-day and in-hospital mortality in SAE patients. The optimal MAP target for SAE patients in clinical practice appears to be 81.5 mmHg.

#2534 Classification of patients with acute kidney damage on the base of blood pressure value as a risk factor using a neural network

Abstract Background and Aims In acute kidney damage, the monitoring of hemodynamic status is best achieved by determining the blood pressure value. It is considered that the values of diastolic blood pressure in young and healthy people are constant from the aorta to the periphery, and the values of systolic and pulse pressure increase from the periphery to the aorta. The frequency of hypertension correlates with the presence of a cardiovascular precipitating risk factor in acute kidney injury, hypertension is also a modifying risk factor in the second and third stages of acute kidney injury, while the presence of hypotension on admission can be a clinical indicator of its cause. In patients with acute kidney damage and in patients with sepsis, the mechanism of autoregulation of mean arterial pressure, which is affected by stroke volume and heart rate, is not effective. The aim of the paper is to examine the classification of hospitalized patients with acute kidney injury based on blood pressure as a risk factor. Method The study included 86 patients over 18 years of age of both sexes (39 men 45.3% and 47 women 54.7%) with an average age of 66.85 ± 15.30 years who were diagnosed with acute kidney injury on admission to hospital treatment. Patients were divided into groups according to the stages of renal insufficiency. The study was designed as a cross-sectional comparative study. The assessment of the existence of acute kidney damage, as well as the determination of the stage of the disease, was based on the diagnostic criteria proposed by the K/DIGO expert group for acute kidney damage. The study did not include patients who had disease progression after acute kidney failure and were treated with dialysis for more than three months. Basic clinical, biochemical and hemodynamic parameters were determined in all subjects at the beginning of treatment, except for the analysis of nitrogen status, which was determined both before and at the end of treatment. During the formation of the neural network (pattern recognition Mat Lab), the parameters of systolic arterial pressure, diastolic arterial pressure normalized by min-max normalization to values from 0 to 1 were included. The data were randomly distributed into three categories: 80% for training, 10% for test, 10% for validation, which means that the parameters of 68 patients were used for training, 9 patients for validation and another 9 patients for the test. The number of input parameters is 33 to 39, while the number of output parameters is 2 in relation to treatment. Formed neural networks with different included blood pressure parameters, structures of 25 neurons in the hidden layer, with 55 and 15 epochs and with accuracy of 97.7% and 90.7% of patient classification. Results Our results show that 40.3% of patients in the third stage of acute kidney injury have hypertension. The lowest average values of systolic (108.44 ± 22.81 mmHg) and diastolic (65.56 ± 15.29 mmHg) blood pressure were experienced by patients in the first stage of acute kidney damage, and the lowest values of mean arterial pressure existed in the second stage of acute kidney damage (68.20 ± 44.96 mmHg) .Statistically significant risk factors for the development of the third stage of acute kidney damage in the multivariate analysis were patients older than 65 years, and mean arterial pressure values less than 65 mmHg. The confusion matrices showed that the classifiers adapted to the minimum and maximum values of systolic, diastolic and mean arterial blood pressure are well adapted and achieve satisfactory accuracy with 97.7% and 90.7%. Conclusion By comparing blood pressure parameters in hospitalized patients in relation to the stage of acute kidney damage, no statistically significant deviations were found. Univariate logistic regression analysis showed that age over 65 was a significant independent risk factor for stage three acute kidney injury, while the multivariate model showed that risk factors for the development of stage three acute kidney injury were patients same age and middle arterial blood pressure less than 65 mmHg. Satisfactory accuracy of formed neural networks when classifying patients during validation training and test was also demonstrated.

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.

Sport-related concussion alters cerebral hemodynamic activity during controlled respiration.

Sport-related concussion (SRC) is known to disrupt neurohemodynamic activity, cardiac function, and blood pressure (BP) autoregulation. This study aims to observe changes in cerebrovascular and cardiovascular responses during controlled respiration after sustaining an SRC. University varsity athletes (n = 81) completed a preseason physiological assessment and were followed up within 5 days of sustaining an SRC. During preseason and follow-up assessments, participants' continuous beat-to-beat BP was collected by finger photoplethysmography, and right prefrontal cortex oxygenation was collected using near-infrared spectroscopy (NIRS). Participants completed 5 min of seated rest and 5 min of a 6-breaths per minute controlled breathing protocol (5 s inhale and 5 s exhale; 0.10 Hz). Wavelet transformation was applied to the NIRS and BP signals, separating them into respiratory (0.10-0.6 Hz) and cardiac (0.6-2 Hz) frequency intervals. Of the 81 participants, 74 had a usable BP signal, 43 had usable NIRS signals, and 28 had both usable BP and NIRS signals. Wavelet amplitudes were calculated and coherence between NIRS and BP on the 28 participants were assessed. There was a significant (P < 0.05) decrease in oxygenated hemoglobin amplitude from 0.062 to 0.054 Hz and hemoglobin difference amplitude from 0.059 to 0.051 Hz, both at the respiratory (0.10-0.6 Hz) frequency interval, from preseason to acute SRC, respectively. Therefore, during controlled respiration, there was a reduction in intensity at the respiratory band, suggesting a protective, reduced respiratory contribution to cerebral hemodynamic activity following acute SRC.NEW & NOTEWORTHY This study investigated cerebral hemodynamic activity following sport-related concussion. Prefrontal cortex oxygenation was assessed by near-infrared spectroscopy (NIRS) during a controlled breathing protocol. Wavelet transformation of the NIRS signals showed significant decreases in HbO2 and HbD amplitude at the respiratory frequency interval (0.10-0.6 HZ) from preseason baseline to acute concussion. These results suggest a decreased respiratory contribution to cerebral hemodynamic activity following acute concussion.

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.

The effect of passive leg raising test on intracranial pressure and cerebral autoregulation in brain injured patients: a physiological observational study

BackgroundThe use of the passive leg raising (PLR) is limited in acute brain injury (ABI) patients with increased intracranial pressure (ICP) since the postural change of the head may impact on ICP and cerebral autoregulation. However, the PLR use may prevent a positive daily fluid balance, which had been recently associated to worse neurological outcomes. We therefore studied early and delayed effects of PLR on the cerebral autoregulation of patients recovering from ABI.Materials and methodsThis is a Prospective, observational, single-center study conducted in critically ill patients admitted with stable ABI and receiving invasive ICP monitoring, multimodal neuromonitoring and continuous hemodynamic monitoring. The fluid challenge consisted of 500 mL of crystalloid over 10 min; fluid responsiveness was defined as cardiac index increase ≥ 10%. Comparisons between different variables at baseline and after PLR were made by paired Wilcoxon signed-rank test. The correlation coefficients between hemodynamic and neuromonitoring variables were assessed using Spearman’s rank test.ResultsWe studied 23 patients [12 patients (52.2%) were fluid responders]. The PLR significantly increased ICP [from 13.7 (8.3–16.4) to 15.4 (12.0–19.2) mmHg; p < 0.001], cerebral perfusion pressure (CPP) [from 51.1 (47.4–55.6) to 56.4 (49.6–61.5) mmHg; p < 0.001] and the pressure reactivity index (PRx) [from 0.12 (0.01–0.24) to 0.43 (0.34–0.46) mmHg; p < 0.001]. Regarding Near Infrared Spectroscopy (NIRS)-derived parameters, PLR significantly increased the arterial component of regional cerebral oxygen saturation (O2Hbi) [from 1.8 (0.8–3.7) to 4.3 (2.5–5.6) μM cm; p < 0.001], the deoxygenated hemoglobin (HHbi) [from 1.6 (0.2–2.9) to 2.7 (1.4–4.0) μM cm; p = 0.007] and total hemoglobin (cHbi) [from 3.6 (1.9–5.3) to 7.8 (5.2–10.3): p < 0.001]. In all the patients who had altered autoregulation after PLR, these changes persisted ten minutes afterwards. After the PLR, we observed a significant correlation between MAP and CPP and PRx.ConclusionsIn ABI patient with stable ICP, PLR test increased ICP, but mostly within safety values and thresholds. Despite this, cerebral autoregulation was importantly impaired, and this persisted up to 10 min after the end of the maneuvre. Our results discourage the use of PLR test in ABI even when ICP is stable.

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.

Tissue-specific expression of senescence biomarkers in spontaneously hypertensive rats: evidence of premature aging in hypertension.

Cellular senescence is an age-related physiological process that contributes to tissue dysfunction and accelerated onset of chronic metabolic diseases including hypertension. Indeed, elevation of blood pressure in hypertension coincides with premature vascular aging and dysfunction. In addition, onsets of metabolic disturbance and osteopenia in patients with hypertension have also been reported. It is possible that hypertension enhances premature aging and causes progressive loss of function in multiple organs. However, the landscape of cellular senescence in critical tissues affected by hypertension remains elusive. Heart, liver, bone, hypothalamus, and kidney were collected from spontaneously hypertensive rats (SHR) and age- and sex-matched normotensive Wistar rats (WT) at 6, 12, 24 and 36 weeks of age (n = 10 animals/group). Changes in mRNA levels of senescence biomarkers namely cyclin-dependent kinase (CDK) inhibitors (CDKIs), i.e., Cdkn2a (encoding p16Ink4a) and Cdkn1a (encoding p21cip1) as well as senescence-associated secretory phenotypes (SASPs), i.e., Timp1, Mmp12, Il6 and Cxcl1, were determined. Additionally, bone collagen alignment and hydroxy apatite crystal dimensions were determined by synchrotron radiation small- and wide-angle X-ray scattering (SAXS/WAXS) techniques. Real-time PCR revealed that transcript levels of genes encoding CDKIs and SASPs in the heart and liver were upregulated in SHR from 6 to 36 weeks of age. Expression of Timp1 and Cxcl1 was increased in bone tissues isolated from 36-week-old SHR. In contrast, we found that expression levels of Timp1 and Il6 mRNA were decreased in hypothalamus and kidney of SHR in all age groups. Simultaneous SAXS/WAXS analysis also revealed misalignment of bone collagen fibers in SHR as compared to WT. Premature aging was identified in an organ directly affected by high blood pressure (i.e., heart) and those with known functional defects in SHR (i.e., liver and bone). Cellular senescence was not evident in organs with autoregulation of blood pressure (i.e., brain and kidney). Our study suggested that cellular senescence is induced by persistently elevated blood pressure and in part, leading to organ dysfunction. Therefore, interventions that can both lower blood pressure and prevent cellular senescence should provide therapeutic benefits for treatment of cardiovascular and metabolic consequences.

Monitoring Mean Arterial Preasur (MAP) in Traumatic Brain Injury Patients during The Initial 60 Minutes of Manitol 20%

The effect of manitol 20% on changes in blood pressure after traumatic brain injury is unknown. The purpose of this study was to analyze the differences in blood pressure before and after the administration of 20% mannitol in traumatic brain injury patients at the Intensive Care Unit. This study is a quasi experimental research which uses a pre-post test without control one group design, a method used in observational analytic techniques. The population of this study were all traumatic brain injury patients who were given a manitol infusion of 20% 100ml, with consecutive sampling technique, obtained 12 samples. With a significance threshold of p 0.05, the test was performed using the Paired T test on systolic and MAP data and the post hoc Wilcoxon test on diastolic data.  paired t-test systolic p=0.000, MAP p=0,000. Wilcoxon test diastolic p=0,002. Decreasing blood pressure 15 minutes after administration of 20% mannitol occurs because half live mannitol which lowers blood pressure and responds to decreased blood pressure autoregulation, at 30 minutes resulting in decreased intra-cranial pressure, improves cerebral perfusion and brain autoregulation that affects systemic blood pressure 60 changes in blood pressure may be due to diuresis effects. During the administration of mannitol there is a change in blood pressure that needs to be monitored

Applications of near-infrared spectroscopy in neurocritical care.

Acute brain injuries are commonly encountered in the intensive care unit. Alterations in cerebrovascular physiology triggered by the initial insult can lead to neurological worsening, further brain injury, and poor outcomes. Robust methods for assessing cerebrovascular physiology continuously at the bedside are limited. In this review, we aim to assess the potential of near-infrared spectroscopy (NIRS) as a bedside tool to monitor cerebrovascular physiology in critically ill patients with acute brain injury as well as those who are at high risk for developing brain injury. We first review basic principles of cerebral blood flow regulation and how these are altered after brain injury. We then discuss the potential role for NIRS in different acute brain injuries. We pay specific attention to the potential for NIRS to (1)identify new brain injuries and clinical worsening, (2)non-invasively measure intracranial pressure (ICP) and cerebral autoregulation, and (3)identify optimal blood pressure (BP) targets that may improve patient outcomes. A growing body of work supports the use of NIRS in the care of brain injured patients. NIRS is routinely used during cardiac surgeries to identify acute neurologic events, and there is some evidence that treatment algorithms using cerebral oximetry may result in improved outcomes. In acute brain injury, NIRS can be used to measure autoregulation to identify an "optimum" BP where autoregulation status is best preserved. Finally, NIRS has been utilized to identify oximetry thresholds that correlate with poor outcome as well as identify new focal intracranial hemorrhages. NIRS is emerging as a tool that can non-invasively measure brain function in critically ill patients. Future work will be aimed at technical refinements to improve diagnostic accuracy, as well as larger scale clinical trials that can establish a definitive impact on patient outcomes.

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.

Influence of hydrodynamic and functional nonlinearities of blood flow in the cerebral vasculature on cerebral perfusion and autoregulation pressure reserve

Ensuring the transport of oxygenated blood to the brain is one of the priorities of the human body. In the literature, there are many models of cerebral circulation with different levels of complexity used to assess pathological conditions, support clinical decisions, and learn about the relationships governing cerebral circulation. This paper presents a zero-dimensional cerebral circulation model that considers hydrodynamic nonlinearities and autoregulation mechanisms. The model has been verified using a computational fluid dynamics (CFD) model of the Circle of Willis (CoW) and its supplying and outgoing branches. Despite the considerable simplicity, the presented model captured the dominant features of cerebral circulation and provides good agreement with the CFD model. The errors in relation to the CFD model did not exceed 2.6% and 9.9% for the symmetrical and highly asymmetrical CoW configurations, respectively. The practical application of the model was demonstrated for predicting the autoregulation pressure reserve for different diameters of natural anastomoses: Posterior and Anterior Communicating Arteries. The advantages and limitations of the model were discussed.

Reversible Malignant Cerebral Edema Following Cranioplasty

AbstractA 44‐year‐old female underwent cranioplasty 6 months after a malignant right MCA stroke. Three hours later, she became unresponsive, with new left‐gaze deviation and right‐side hemiparesis. CT head showed new right MCA hypodensity and diffuse edema. After aggressive medical management, she returned to baseline. A brain MRI showed no stroke. Malignant cerebral edema after uneventful cranioplasty is a rare and often fatal complication related to sudden intracranial negative pressure and altered cerebral autoregulation. This is a rare case in which a patient developed malignant cerebral edema and status epilepticus after cranioplasty and survived.

Remote Diffusion-Weighted Imaging Lesions and Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

Remote diffusion-weighted imaging lesions (RDWILs) in the context of spontaneous intracerebral hemorrhage (ICH) are associated with an increased risk of recurrent stroke, worse functional outcome, and death. To update current knowledge on RDWILs, we conducted a systematic review and meta-analysis of the prevalence, associated factors and presumed causes of RDWILs. We searched Pubmed, Embase, and Cochrane up to June 2022 for studies reporting RDWILs in adults with symptomatic ICH of no-identified-cause, assessed by magnetic resonance imaging, and analyzed associations between baseline variables and RDWILs in random-effects meta-analyses. Eighteen observational studies (7 prospective), reporting 5211 patients were included, of whom 1386 had ≥1 RDWIL (pooled prevalence: 23.5% [19.0-28.6]). RDWIL presence was associated with neuroimaging features of microangiopathy, atrial fibrillation (odds ratio, 3.67 [1.80-7.49]), clinical severity (mean difference in National Institutes of Health Stroke Scale score, 1.58 points [0.50-2.66]), elevated blood pressure (mean difference, 14.02 mmHg [9.44-18.60]), ICH volume (mean difference, 2.78 mL [0.97-4.60]), and subarachnoid (odds ratio, 1.80 [1.00-3.24]) or intraventricular (odds ratio, 1.53 [1.28-1.83]) hemorrhage. RDWIL presence was associated with poor 3-month functional outcome (odds ratio, 1.95 [1.48-2.57]). RDWILs are detected in approximately 1-in-4 patients with acute ICH. Our results suggest that most RDWILs result from disruption of cerebral small vessel disease by ICH-related precipitating factors such as elevated intracranial pressure and cerebral autoregulation impairment. Their presence is associated with worse initial presentation and outcome. However, given the mostly cross-sectional designs and heterogeneity in study quality, further studies are needed to investigate whether specific ICH treatment strategies may reduce the incidence of RDWILs and in turn improve outcome and reduce stroke recurrence.

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.

Cerebral Blood Flow Monitoring with Piezoeletric Film, Photoplethysmogram and an LSTM Neural Network

To improve monitoring of cerebral blood flow and arterial response to clinical interventions following acute traumatic brain injury, we have created a small sensor suite that can be mounted around the diameter of a typical intracranial catheter. This instrument is driven by the need to prevent subsequent ischemic injury after a traumatic brain injury, due to elevated intracranial pressure and compromised cerebral autoregulation. To minimize effects on clinician workflow, our sensors can be integrated into catheters that are currently being used in accordance with accepted standards of care. This paper describes the use of a combination of thin piezoelectric material, a photoplethysmogram, and a long short-term memory regression network to track cerebral blood flow fluctuations. The results show a correlation (R2 = 0.76) between beat-to-beat waveform features collected using our sensor suite and reference blood flow measurements by ultrasound imaging. This method we introduce may help give medical professionals timely data on patients’ cerebral hemodynamic status and how well patients responded to clinical interventions.