Latent trajectories of cerebral perfusion pressure and risk prediction models among patients with traumatic brain injury: based on an interpretable artificial neural network.

OBJECTIVE: This study aimed to characterize long-term cerebral perfusion pressure (CPP) trajectory in traumatic brain injury (TBI) patients and construct an interpretable prediction model to assess the risk of unfavorable CPP evolution patterns. METHODS: TBI patients with CPP records were identified from the Medical Information Mart for the Intensive Care (MIMIC)-IV 2.1, eICU Collaborative Research Database (eICU-CRD) 2.0 and HiRID dataset 1.1.1. The research process consisted of two stages. First, group-based trajectory modeling (GBTM) was used to identify different CPP trajectories. Second, different ANN algorithms were employed to predict the trajectories of CPP. RESULTS: A total of 331 eligible patients' records from MIMIC-IV 2.1 and eICU-CRD 2.0 were used for trajectory analysis and model development. Additionally, 310 patients' data from HiRID were used for external validation. The GBTM identified 5 CPP trajectory groups, group 1 and group 5 were merged into class 1 based on unfavorable in-hospital mortality. The best 6 predictors were invasive systolic blood pressure coefficient of variation (ISBPCV), venous blood chloride ion concentration, PaCO2, PT (Prothrombin Time), CPP coefficient of variation (CPPCV), and mean CPP. Compared with other algorithms, Scaled Conjugate Gradient (SCG) performed relatively better in identifying class 1. CONCLUSION: This study identified 2 CPP trajectory groups associated with elevated risk and 3 with reduced risk. PaCO2 might be a strong predictor for the unfavorable CPP class. The ANN model achieved the primary goal of risk stratification, which is conducive to early intervention and individualized treatment.

The effects of bolus compared to continuous administration of adrenaline on cerebral oxygenation during experimental cardiopulmonary resuscitation.

Background: Bolus administration of adrenaline during cardiopulmonary resuscitation (CPR) results in only short-term increases in systemic and cerebral perfusion pressure (CePP) with unclear effects on cerebral oxygenation. The aim of this study was to investigate the effects of bolus compared to continuous adrenaline administration on cerebral oxygenation in a porcine CPR model. Methods: After five minutes of cardiac arrest, mechanical CPR was performed for 15 min. Adrenaline (45 µg/kg) was administered either as a bolus every five minutes or continuously over the same period via an infusion pump. Main outcome parameter was brain tissue oxygen tension (PbtO2), secondary outcome parameters included mean arterial pressure (MAP), intracranial pressure (ICP), CePP and cerebral regional oxygen saturation (rSO2) as well as arterial and cerebral venous blood gases. Results: During CPR, mean MAP (45 ± 8 mmHg vs. 38 ± 8 mmHg; p = 0.0827), mean ICP (27 ± 7 mmHg vs. 20 ± 7 mmHg; p = 0.0653) and mean CePP (18 ± 8 mmHg vs. 18 ± 8 mmHg; p = 0.9008) were similar in the bolus and the continuous adrenaline group. Also, rSO2 (both 24 ± 6 mmHg; p = 0.9903) and cerebral venous oxygen saturation (18 ± 12% versus 27.5 ± 12%; p = 0.1596) did not differ. In contrast, relative PbtO2 reached higher values in the continuous group after five minutes of CPR and remained significantly higher than in the bolus group until the end of resuscitation. Conclusion: Continuous administration of adrenaline improved brain tissue oxygen tension compared with bolus administration during prolonged CPR.

The Effects of Head Elevation on Intracranial Pressure, Cerebral Perfusion Pressure, and Cerebral Oxygenation Among Patients with Acute Brain Injury: A Systematic Review and Meta-Analysis.

BACKGROUND: Head elevation is recommended as a tier zero measure to decrease high intracranial pressure (ICP) in neurocritical patients. However, its quantitative effects on cerebral perfusion pressure (CPP), jugular bulb oxygen saturation (SjvO2), brain tissue partial pressure of oxygen (PbtO2), and arteriovenous difference of oxygen (AVDO2) are uncertain. Our objective was to evaluate the effects of head elevation on ICP, CPP, SjvO2, PbtO2, and AVDO2 among patients with acute brain injury. METHODS: We conducted a systematic review and meta-analysis on PubMed, Scopus, and Cochrane Library of studies comparing the effects of different degrees of head elevation on ICP, CPP, SjvO2, PbtO2, and AVDO2. RESULTS: A total of 25 articles were included in the systematic review. Of these, 16 provided quantitative data regarding outcomes of interest and underwent meta-analyses. The mean ICP of patients with acute brain injury was lower in group with 30° of head elevation than in the supine position group (mean difference [MD] - 5.58 mm Hg; 95% confidence interval [CI] - 6.74 to - 4.41 mm Hg; p < 0.00001). The only comparison in which a greater degree of head elevation did not significantly reduce the ICP was 45° vs. 30°. The mean CPP remained similar between 30° of head elevation and supine position (MD - 2.48 mm Hg; 95% CI - 5.69 to 0.73 mm Hg; p = 0.13). Similar findings were observed in all other comparisons. The mean SjvO2 was similar between the 30° of head elevation and supine position groups (MD 0.32%; 95% CI - 1.67% to 2.32%; p = 0.75), as was the mean PbtO2 (MD - 1.50 mm Hg; 95% CI - 4.62 to 1.62 mm Hg; p = 0.36), and the mean AVDO2 (MD 0.06 µmol/L; 95% CI - 0.20 to 0.32 µmol/L; p = 0.65).The mean ICP of patients with traumatic brain injury was also lower with 30° of head elevation when compared to the supine position. There was no difference in the mean values of mean arterial pressure, CPP, SjvO2, and PbtO2 between these groups. CONCLUSIONS: Increasing degrees of head elevation were associated, in general, with a lower ICP, whereas CPP and brain oxygenation parameters remained unchanged. The severe traumatic brain injury subanalysis found similar results.

A Comprehensive Perspective on Intracranial Pressure Monitoring and Individualized Management in Neurocritical Care: Results of a Survey with Global Experts.

BACKGROUND: Numerous trials have addressed intracranial pressure (ICP) management in neurocritical care. However, identifying its harmful thresholds and controlling ICP remain challenging in terms of improving outcomes. Evidence suggests that an individualized approach is necessary for establishing tolerance limits for ICP, incorporating factors such as ICP waveform (ICPW) or pulse morphology along with additional data provided by other invasive (e.g., brain oximetry) and noninvasive monitoring (NIM) methods (e.g., transcranial Doppler, optic nerve sheath diameter ultrasound, and pupillometry). This study aims to assess current ICP monitoring practices among experienced clinicians and explore whether guidelines should incorporate ancillary parameters from NIM and ICPW in future updates. METHODS: We conducted a survey among experienced professionals involved in researching and managing patients with severe injury across low-middle-income countries (LMICs) and high-income countries (HICs). We sought their insights on ICP monitoring, particularly focusing on the impact of NIM and ICPW in various clinical scenarios. RESULTS: From October to December 2023, 109 professionals from the Americas and Europe participated in the survey, evenly distributed between LMIC and HIC. When ICP ranged from 22 to 25 mm Hg, 62.3% of respondents were open to considering additional information, such as ICPW and other monitoring techniques, before adjusting therapy intensity levels. Moreover, 77% of respondents were inclined to reassess patients with ICP in the 18-22 mm Hg range, potentially escalating therapy intensity levels with the support of ICPW and NIM. Differences emerged between LMIC and HIC participants, with more LMIC respondents preferring arterial blood pressure transducer leveling at the heart and endorsing the use of NIM techniques and ICPW as ancillary information. CONCLUSIONS: Experienced clinicians tend to personalize ICP management, emphasizing the importance of considering various monitoring techniques. ICPW and noninvasive techniques, particularly in LMIC settings, warrant further exploration and could potentially enhance individualized patient care. The study suggests updating guidelines to include these additional components for a more personalized approach to ICP management.

Brain tissue oxygen partial pressure monitoring and prognosis of patients with traumatic brain injury: a meta-analysis.

To assess whether monitoring brain tissue oxygen partial pressure (PbtO2) or employing intracranial pressure (ICP)/cerebral perfusion pressure (CCP)-guided management improves patient outcomes, including mortality, hospital length of stay (LOS), mean daily ICP and mean daily CCP during the intensive care unit(ICU)stay. We searched the Web of Science, EMBASE, PubMed, Cochrane Library, and MEDLINE databases until December 12, 2023. Prospective randomized controlled and cohort studies were included. A meta-analysis was performed for the primary outcome measure, mortality, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eleven studies with a total of 37,492 patients were included. The mortality in the group with PbtO2 was 29.0% (odds ratio: 0.73;95% confidence interval [CI]:0.56-0.96; P = 0.03; I = 55%), demonstrating a significant benefit. The overall hospital LOS was longer in the PbtO2 group than that in the ICP/CPP group (mean difference:2.03; 95% CI:1.03-3.02; P<0.0001; I = 39%). The mean daily ICP in the PbtO2 monitoring group was lower than that in the ICP/CPP group (mean difference:-1.93; 95% CI: -3.61 to -0.24; P = 0.03; I = 41%). Moreover, PbtO2 monitoring did not improve the mean daily CPP (mean difference:2.43; 95%CI: -1.39 to 6.25;P = 0.21; I = 56%).Compared with ICP/CPP monitoring, PbtO2 monitoring reduced the mortality and the mean daily ICP in patients with severe traumatic brain injury; however, no significant effect was noted on the mean daily CPP. In contrast, ICP/CPP monitoring alone was associated with a short hospital stay.

Individualized Autoregulation-Derived Cerebral Perfusion Targets in Aneurysmal Subarachnoid Hemorrhage: A New Therapeutic Avenue?

Background: Cerebral perfusion pressure (CPP) is an important target in aneurysmal subarachnoid hemorrhage (aSAH), but it does not take into account autoregulatory disturbances. The pressure reactivity index (PRx) and the CPP with the optimal PRx (CPPopt) are new variables that may capture these pathomechanisms. In this study, we investigated the effect on the outcome of certain combinations of CPP or ΔCPPopt (actual CPP-CPPopt) with the concurrent autoregulatory status (PRx) after aSAH. Methods: This observational study included 432 aSAH patients, treated in the neurointensive care unit, at Uppsala University Hospital, Sweden. Functional outcome (GOS-E) was assessed 1-year postictus. Heatmaps of the percentage of good monitoring time (%GMT) of PRx/CPP and PRx/ΔCPPopt combinations in relation to GOS-E were created to visualize the association between these variables and outcome. Results: In the heatmap of the %GMT of PRx/CPP, the combination of lower CPP with higher PRx values was more strongly associated with lower GOS-E. The tolerance for lower CPP values increased with lower PRx values until a threshold of -0.50. However, for decreasing PRx below -0.50, there was a gradual reduction in the tolerance for lower CPP. In the heatmap of the %GMT of PRx/ΔCPPopt, the combination of negative ΔCPPopt with higher PRx values was strongly associated with lower GOS-E. In particular, negative ΔCPPopt together with PRx above +0.50 correlated with worse outcomes. In addition, there was a transition toward an unfavorable outcome when PRx went below -0.50, particularly if ΔCPPopt was negative. Conclusions: The PRx levels influenced the association between CPP/ΔCPPopt and outcome. Thus, this variable could be used to individualize a safe CPP-/ΔCPPopt-range.

Optimal cerebral perfusion pressure in aneurysmal subarachnoid hemorrhage and its relation to perfusion deficits on CT-perfusion.

Preservation of optimal cerebral perfusion is a crucial part of the acute management after aneurysmal subarachnoid hemorrhage (aSAH). A few studies indicated possible benefits of maintaining a cerebral perfusion pressure (CPP) near the calculated optimal CPP (CPPopt), representing an individually optimal condition at which cerebral autoregulation functions at its best. This retrospective observational monocenter study was conducted to investigate, whether "suboptimal" perfusion with actual CPP deviating from CPPopt correlates with perfusion deficits detected by CT-perfusion (CTP). A consecutive cohort of aSAH-patients was reviewed and patients with available parameters for CPPopt-calculation, who simultaneously received CTP, were analyzed. By plotting the pressure reactivity index (PRx) versus CPP, CPP correlating the lowest PRx value was identified as CPPopt. Perfusion deficits on CTP were documented. In 86 out of 324 patients, the inclusion criteria were met. Perfusion deficits were detected in 47% (40/86) of patients. In 43% of patients, CPP was lower than CPPopt, which correlated with detected perfusion deficits (r = 0.23, p = 0.03). Perfusion deficits were found in 62% of patients with CPPCPPopt (OR 3, p = 0.01). These findings support the hypothesis, that a deviation of CPP from CPPopt is an indicator of suboptimal cerebral perfusion.

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

BACKGROUND: Cerebral 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). METHODS: Retrospective 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. RESULTS: Median 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. CONCLUSIONS: Increased 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.

Preliminary Study on Application of Combined Monitoring of Neuroelectrophysiology-Intracranial Pressure-Cerebral Perfusion Pressure in Craniotomy for Intracranial Aneurysm Clipping: An Anatomical and Clinical Study

SUMMARY: Intracranial aneurysm is a common cerebrovascular disease with high mortality. Neurosurgical clipping for the treatment of intracranial aneurysms can easily lead to serious postoperative complications. Studies have shown that intraoperative monitoring of the degree of cerebral ischemia is extremely important to ensure the safety of operation and improve the prognosis of patients. Aim of this study was to probe the application value of combined monitoring of intraoperative neurophysiological monitoring (IONM)-intracranial pressure (ICP)-cerebral perfusion pressure (CPP) in craniotomy clipping of intracranial aneurysms. From January 2020 to December 2022, 126 patients in our hospital with intracranial aneurysms who underwent neurosurgical clipping were randomly divided into two groups. One group received IONM monitoring during neurosurgical clipping (control group, n=63), and the other group received IONM-ICP-CPP monitoring during neurosurgical clipping (monitoring group, n=63). The aneurysm clipping and new neurological deficits at 1 day after operation were compared between the two groups. Glasgow coma scale (GCS) score and national institutes of health stroke scale (NIHSS) score were compared before operation, at 1 day and 3 months after operation. Glasgow outcome scale (GOS) and modified Rankin scale (mRS) were compared at 3 months after operation. All aneurysms were clipped completely. Rate of new neurological deficit at 1 day after operation in monitoring group was 3.17 % (2/63), which was markedly lower than that in control group of 11.11 % (7/30) (P0.05). Combined monitoring of IONM-ICP-CPP can monitor the cerebral blood flow of patients in real time during neurosurgical clipping, according to the monitoring results, timely intervention measures can improve the consciousness state of patients in early postoperative period and reduce the occurrence of early postoperative neurological deficits.

El aneurisma intracraneal es una enfermedad cerebrovascular común con alta mortalidad. El clipaje neuroquirúrgico para el tratamiento de aneurismas intracraneales puede provocar complicaciones posoperatorias graves. Los estudios han demostrado que la monitorización intraoperatoria del grado de isquemia cerebral es extremadamente importante para garantizar la seguridad de la operación y mejorar el pronóstico de los pacientes. El objetivo de este estudio fue probar el valor de la aplicación de la monitorización combinada de la monitorización neurofisiológica intraoperatoria (IONM), la presión intracraneal (PIC) y la presión de perfusión cerebral (CPP) en el clipaje de craneotomía de aneurismas intracraneales. Desde enero de 2020 hasta diciembre de 2022, 126 pacientes de nuestro hospital con aneurismas intracraneales que se sometieron a clipaje neuroquirúrgico se dividieron aleatoriamente en dos grupos. Un grupo recibió monitorización IONM durante el clipaje neuroquirúrgico (grupo de control, n=63) y el otro grupo recibió monitorización IONM-ICP-CPP durante el clipaje neuroquirúrgico (grupo de monitorización, n=63). Se compararon entre los dos grupos el recorte del aneurisma y los nuevos déficits neurológicos un día después de la operación. La puntuación de la escala de coma de Glasgow (GCS) y la puntuación de la escala de accidentes cerebrovasculares de los institutos nacionales de salud (NIHSS) se compararon antes de la operación, 1 día y 3 meses después de la operación. La escala de resultados de Glasgow (GOS) y la escala de Rankin modificada (mRS) se compararon 3 meses después de la operación. Todos los aneurismas fueron cortados por completo. La tasa de nuevo déficit neurológico 1 día después de la operación en el grupo de seguimiento fue del 3,17 % (2/63), que fue notablemente inferior a la del grupo de control del 11,11 % (7/30) (P 0,05). La monitorización combinada de IONM-ICP-CPP puede controlar el flujo sanguíneo cerebral de los pacientes en tiempo real durante el corte neuroquirúrgico; de acuerdo con los resultados de la monitorización, las medidas de intervención oportunas pueden mejorar el estado de conciencia de los pacientes en el período postoperatorio temprano y reducir la aparición de problemas postoperatorios tempranos y déficits neurológicos.

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

BACKGROUND: Patients 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. METHODS: This 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. RESULTS: Among 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. CONCLUSIONS: In 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.

Monitoring of cerebral blood flow autoregulation: physiologic basis, measurement, and clinical implications.

Cerebral blood flow (CBF) autoregulation is the physiologic process whereby blood supply to the brain is kept constant over a range of cerebral perfusion pressures ensuring a constant supply of metabolic substrate. Clinical methods for monitoring CBF autoregulation were first developed for neurocritically ill patients and have been extended to surgical patients. These methods are based on measuring the relationship between cerebral perfusion pressure and surrogates of CBF or cerebral blood volume (CBV) at low frequencies (<0.05 Hz) of autoregulation using time or frequency domain analyses. Initially intracranial pressure monitoring or transcranial Doppler assessment of CBF velocity was utilised relative to changes in cerebral perfusion pressure or mean arterial pressure. A more clinically practical approach utilising filtered signals from near infrared spectroscopy monitors as an estimate of CBF has been validated. In contrast to the traditional teaching that 50 mm Hg is the autoregulation threshold, these investigations have found wide interindividual variability of the lower limit of autoregulation ranging from 40 to 90 mm Hg in adults and 20-55 mm Hg in children. Observational data have linked impaired CBF autoregulation metrics to adverse outcomes in patients with traumatic brain injury, ischaemic stroke, subarachnoid haemorrhage, intracerebral haemorrhage, and in surgical patients. CBF autoregulation monitoring has been described in both cardiac and noncardiac surgery. Data from a single-centre randomised study in adults found that targeting arterial pressure during cardiopulmonary bypass to above the lower limit of autoregulation led to a reduction of postoperative delirium and improved memory 1 month after surgery compared with usual care. Together, the growing body of evidence suggests that monitoring CBF autoregulation provides prognostic information on eventual patient outcomes and offers potential for therapeutic intervention. For surgical patients, personalised blood pressure management based on CBF autoregulation data holds promise as a strategy to improve patient neurocognitive outcomes.

The prediction of estimated cerebral perfusion pressure with trans-systolic time in preterm and term infants.

It is important to monitor cerebral perfusion in infants because hypo- and hyperperfusion can contribute to neurological injury. This study aimed to clarify the relationship between trans-systolic time (TST) and critical closing pressure (CrCP) or estimated cerebral perfusion pressure (CPPe) in neonates. Moreover, we aimed to determine the TST values in preterm and term infants with stable cerebral perfusion to clarify normative reference data. This multicentre prospective study included infants with arterial lines admitted to the neonatal intensive care units between December 2021 and August 2023. TST, CrCP, and CPPe were calculated using middle cerebral artery waveforms recorded using transcranial Doppler ultrasonography when clinicians collected arterial blood samples. Three hundred and sixty samples were obtained from 112 infants with a gestational age of 32 (interquartile range, 27-37) weeks and a birth weight of 1481 (956-2355) g. TST was positively correlated with CPPe (r = 0.60, p < 0.001), but not with CrCP (r = 0.08, p = 0.10). The normative reference values of TST in preterm and term infants without samples of hyper- or hypocapnia and/or hyper- or hypotension, which may affect cerebral perfusion, were as follows: ≤ 29 weeks, 0.12 (0.11-0.14) s; 30-36 weeks, 0.14 (0.12-0.15) s; and ≥ 37 weeks, 0.16 (0.14-0.17) s, respectively.  Conclusion: TST in neonates significantly correlated with CPPe, but not with CrCP. TST may be a good predictor of cerebral perfusion and potentially have wider clinical applications. What is Known: • Trans-systolic time (TST) is used in evaluating the effects of increased intracranial pressure on cerebral haemodynamics. However, little is known about the efficacy of TST in predicting neonatal cerebral perfusion pressure. What is New: • This study added evidence that TST correlated with estimated cerebral perfusion pressure, but not with critical closing pressure. Additionally, we showed the normative reference values of the TST in preterm and term infants.

Visualization of the Intracranial Pressure and Time Burden in Childhood Brain Trauma: What We Have Learned One Decade on With KidsBrainIT.

To validate the intracranial pressure (ICP) dose-response visualization plot for the first time in a novel prospectively collected pediatric traumatic brain injury (pTBI) data set from the multi-center, multi-national KidsBrainIT consortium. Prospectively collected minute-by-minute ICP and mean arterial blood pressure time series of 104 pTBI patients were categorized in ICP intensity-duration episodes. These episodes were correlated with the 6-month Glasgow Outcome Score (GOS) and displayed in a color-coded ICP dose-response plot. The influence of cerebrovascular reactivity and cerebral perfusion pressure (CPP) were investigated. The generated ICP dose-response plot on the novel data set was similar to the previously published pediatric plot. This study confirmed that higher ICP episodes were tolerated for a shorter duration of time, with an approximately exponential decay curve delineating the positive and negative association zones. ICP above 20 mm Hg for any duration in time was associated with poor outcome in our patients. Cerebrovascular reactivity state did not influence their respective transition curves above 10 mm Hg ICP. CPP below 50 mm Hg was not tolerated, regardless of ICP and duration, and was associated with worse outcome. The ICP dose-response plot was reproduced in a novel and independent pTBI data set. ICP above 20 mm Hg and CPP below 50 mm Hg for any duration in time were associated with worse outcome. This highlighted a pressing need to reduce pediatric ICP therapeutic thresholds used at the bedside.

A Case Report of Spontaneous Vaginal Delivery Under General Anesthesia in a Patient With a Large Cerebral Aneurysm.

Cerebral aneurysms are rarely encountered in pregnancy. Their antepartum and intrapartum management remain clinically challenging, primarily due to concern regarding potential rupture. We present a case of a patient in preterm labor at risk for imminent delivery with a 10mm cerebral aneurysm. She was recommended for cesarean section (CS), yet delivered via spontaneous vaginal delivery in the operating room after induction of general anesthesia for the intended CS. Her aneurysm and neurologic function remained intact postpartum. Cerebral aneurysms <5mm are unlikely to undergo significant growth during pregnancy. The presence of a cerebral aneurysm is not automatically a contraindication to the Valsalva maneuver. The recommendation for which patients with unruptured cerebral aneurysms should deliver by CS, operative vaginal delivery, or unassisted vaginal delivery (i.e., which patients should avoid Valsalva maneuver intrapartum), is complex and requires multidisciplinary discussion.

Cerebral perfusion and metabolism with mild hypercapnia vs. normocapnia in a porcine post cardiac arrest model with and without targeted temperature management.

Aim: To determine whether targeting mild hypercapnia (PaCO2 7 kPa) would yield improved cerebral blood flow and metabolism compared to normocapnia (PaCO2 5 kPa) with and without targeted temperature management to 33 °C (TTM33) in a porcine post-cardiac arrest model. Methods: 39 pigs were resuscitated after 10 minutes of cardiac arrest using cardiopulmonary bypass and randomised to TTM33 or no-TTM, and hypercapnia or normocapnia. TTM33 was managed with intravasal cooling. Animals were stabilized for 30 minutes followed by a two-hour intervention period. Hemodynamic parameters were measured continuously, and neuromonitoring included intracranial pressure (ICP), pressure reactivity index, cerebral blood flow, brain-tissue pCO2 and microdialysis. Measurements are reported as proportion of baseline, and areas under the curve during the 120 min intervention period were compared. Results: Hypercapnia increased cerebral flow in both TTM33 and no-TTM groups, but also increased ICP (199% vs. 183% of baseline, p = 0.018) and reduced cerebral perfusion pressure (70% vs. 84% of baseline, p < 0.001) in no-TTM animals. Cerebral lactate (196% vs. 297% of baseline, p < 0.001), pyruvate (118% vs. 152% of baseline, p < 0.001), glycerol and lactate/pyruvate ratios were lower with hypercapnia in the TTM33 group, but only pyruvate (133% vs. 150% of baseline, p = 0.002) was lower with hypercapnia among no-TTM animals. Conclusion: In this porcine post-arrest model, hypercapnia led to increased cerebral flow both with and without hypothermia, but also increased ICP and reduced cerebral perfusion pressure in no-TTM animals. The effects of hypercapnia were different with and without TTM.(Institutional protocol number: FOTS, id 14931).

Correlation between early intracranial pressure and cerebral perfusion pressure with 28-day intensive care unit mortality in patients with hemorrhagic stroke.

INTRODUCTION: Hemorrhagic stroke may cause changes in intracranial pressure (ICP) and cerebral perfusion pressure (CPP), which may influence the prognosis of patients. The aim of this study was to investigate the relationship between early ICP, CPP, and 28-day mortality in the intensive care unit (ICU) of patients with hemorrhagic stroke. PATIENTS AND METHODS: A retrospective study was performed using the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD), including hemorrhagic stroke patients in the ICU with recorded ICP monitoring. The median values of ICP and CPP were collected for the first 24 h of the patient's monitoring. The primary outcome was 28-day ICU mortality. Multivariable Cox proportional hazards models were used to analyze the relationship between ICP, CPP, and 28-day ICU mortality. Restricted cubic regression splines were used to analyze nonlinear relationships. RESULTS: The study included 837 patients with a 28-day ICU mortality rate of 19.4%. Multivariable analysis revealed a significant correlation between early ICP and 28-day ICU mortality (HR 1.08, 95% CI 1.04-1.12, p < 0.01), whereas early CPP showed no correlation with 28-day ICU mortality (HR 1.00, 95% CI 0.98-1.01, p = 0.57), with a correlation only evident when CPP < 60 mmHg (HR 1.99, 95% CI 1.14-3.48, p = 0.01). The study also identified an early ICP threshold of 16.5 mmHg. DISCUSSION AND CONCLUSION: Early ICP shows a correlation with 28-day mortality in hemorrhagic stroke patients, with a potential intervention threshold of 16.5 mmHg. In contrast, early CPP showed no correlation with patient prognosis.

Variations in Autoregulation-Based Optimal Cerebral Perfusion Pressure Determination Using Two Integrated Neuromonitoring Platforms in a Trauma Patient.

BACKGROUND: Neuromonitoring devices are often used in traumatic brain injury. The objective of this report is to raise awareness concerning variations in optimal cerebral perfusion pressure (CPPopt) determination using exploratory information provided by two neuromonitoring monitors that are part of research programs (Moberg CNS Monitor and RAUMED NeuroSmart LogO). METHODS: We connected both monitors simultaneously to a parenchymal intracranial pressure catheter and recorded the pressure reactivity index (PRx) and the derived CPPopt estimates for a patient with a severe traumatic brain injury. These estimates were available at the bedside and were updated at each minute. RESULTS: Using the Bland and Altman method, we found a mean variation of - 3.8 (95% confidence internal from - 8.5 to 0.9) mm Hg between the CPPopt estimates provided by the two monitors (limits of agreement from - 26.6 to 19.1 mm Hg). The PRx and CPPopt trends provided by the two monitors were similar over time, but CPPopt trends differed when PRx values were around zero. Also, almost half of the CPPopt estimates differed by more than 10 mm Hg. CONCLUSIONS: These wide variations recorded in the same patient are worrisome and reiterate the importance of understanding and standardizing the methodology and algorithms behind commercial neuromonitoring devices prior to incorporating them in clinical use.

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

PURPOSE: Cerebral 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. METHODS: A 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. RESULTS: The 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. CONCLUSIONS: The 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.

Evaluation of Cerebral Perfusion Pressure, Cerebral Blood Flow, and Cerebral Oxygenation at Different Head of Bed Positions Using Transcranial Doppler and Near-Infrared Spectroscopy in Postoperative Neurosurgical Patients.

OBJECTIVES: Nursing postoperative neurosurgical patients with head of bed (HOB) elevation beyond 30° might be desired at times to prevent pulmonary complications. Due to the paucity of studies determining the effect of HOB beyond 30° on cerebral perfusion pressure (CPP), cerebral blood flow (CBF), and regional cerebral oxygenation (rSO2), this study was designed. METHODS: A total of 40 patients following elective neurosurgery for supratentorial tumors were studied in the neurosurgical intensive care unit three hours following admission. They were assessed for CBF velocities of middle cerebral arteries on either side using transcranial color Doppler (TCCD), rSO2 using near-infrared spectroscopy (NIRS), and mean arterial pressure measured at tragus level at various HOB positions. The estimated cerebral perfusion pressure (CPPe) was calculated from TCCD parameters, and the estimated intracranial pressure (ICPe) was then derived. Their variations at different HOB positions were noted. RESULTS: TCCD parameters such as peak systolic velocity (PSV) and mean flow velocity (MFV) did not significantly vary upon elevating HOB from 0° to 30° but reduced significantly when HOB was further elevated to 60° (p < 0.05). ICPe reduced significantly with a change of HOB positions from 0° to 60° (p < 0.001), and a significant reduction in CPPe was noticed when HOB was elevated to 60° (67.2 ± 10.1 mmHg vs. 74.7 ± 11.2 mmHg at 0°). However, none of these HOB positions affected rSO2 values. CONCLUSION: Postoperative nursing with positions up to 60° HOB can be tried in indicated patients following elective neurosurgery when complemented with CBF velocity and rSO2 monitoring and in whom CPP-guided therapy is not preferred.

Cerebral autoregulation in traumatic brain injury: ultra-low-frequency pressure reactivity index and intracranial pressure across age groups.

BACKGROUND: The ultra-low-frequency pressure reactivity index (UL-PRx) has been established as a surrogate method for bedside estimation of cerebral autoregulation (CA). Although this index has been shown to be a predictor of outcome in adult and pediatric patients with traumatic brain injury (TBI), a comprehensive evaluation of low sampling rate data collection (0.0033 Hz averaged over 5 min) on cerebrovascular reactivity has never been performed. OBJECTIVE: To evaluate the performance and predictive power of the UL-PRx for 12-month outcome measures, alongside all International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) models and in different age groups. To investigate the potential for optimal cerebral perfusion pressure (CPPopt). METHODS: Demographic data, IMPACT variables, in-hospital mortality, and Glasgow Outcome Scale Extended (GOSE) at 12 months were extracted. Filtering and processing of the time series and creation of the indices (cerebral intracranial pressure (ICP), cerebral perfusion pressure (CPP), UL-PRx, and deltaCPPopt (ΔCPPopt and CPPopt-CPP)) were performed using an in-house algorithm. Physiological parameters were assessed as follows: mean index value, % time above threshold, and mean hourly dose above threshold. RESULTS: A total of 263 TBI patients were included: pediatric (17.5% aged ≤ 16 y) and adult (60.5% aged > 16 and < 70 y and 22.0% ≥ 70 y, respectively) patients. In-hospital and 12-month mortality were 25.9% and 32.7%, respectively, and 60.0% of patients had an unfavorable outcome at 12 months (GOSE). On univariate analysis, ICP, CPP, UL-PRx, and ΔCPPopt were associated with 12-month outcomes. The cutoff of ~ 20-22 for mean ICP and of ~ 0.30 for mean UL-PRx were confirmed in all age groups, except in patients older than 70 years. Mean UL-PRx remained significantly associated with 12-month outcomes even after adjustment for IMPACT models. This association was confirmed in all age groups. UL-PRx resulted associate with CPPopt. CONCLUSIONS: The study highlights UL-PRx as a tool for assessing CA and valuable outcome predictor for TBI patients. The results emphasize the potential clinical utility of the UL-PRx and its adaptability across different age groups, even after adjustment for IMPACT models. Furthermore, the correlation between UL-PRx and CPPopt suggests the potential for more targeted treatment strategies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05043545, principal investigator Paolo Gritti, date of registration 2021.08.21.