Cerebral Perfusion Pressure Targets Research Articles

How to Define and Meet Blood Pressure Targets After Traumatic Brain Injury: A Narrative Review.

Traumatic brain injury (TBI) poses a significant challenge to healthcare providers, necessitating meticulous management of hemodynamic parameters to optimize patient outcomes. This article delves into the critical task of defining and meeting continuous arterial blood pressure (ABP) and cerebral perfusion pressure (CPP) targets in the context of severe TBI in neurocritical care settings. We narratively reviewed existing literature, clinical guidelines, and emerging technologies to propose a comprehensive approach that integrates real-time monitoring, individualized cerebral perfusion target setting, and dynamic interventions. Our findings emphasize the need for personalized hemodynamic management, considering the heterogeneity of patients with TBI and the evolving nature of their condition. We describe the latest advancements in monitoring technologies, such as autoregulation-guided ABP/CPP treatment, which enable a more nuanced understanding of cerebral perfusion dynamics. By incorporating these tools into a proactive monitoring strategy, clinicians can tailor interventions to optimize ABP/CPP and mitigate secondary brain injury. Challenges in this field include the lack of standardized protocols for interpreting multimodal neuromonitoring data, potential variability in clinical decision-making, understanding the role of cardiac output, and the need for specialized expertise and customized software to have individualized ABP/CPP targets regularly available. The patient outcome benefit of monitoring-guided ABP/CPP target definitions still needs to be proven in patients with TBI. We recommend that the TBI community take proactive steps to translate the potential benefits of personalized ABP/CPP targets, which have been implemented in certain centers, into a standardized and clinically validated reality through randomized controlled trials.

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.

Exploration of uncertainty of PRx time trends

IntroductionPRx can be used as surrogate measure of Cerebral Autoregulation (CA) in traumatic brain injury (TBI) patients. PRx can provide means for individualising cerebral perfusion pressure (CPP) targets, such as CPPopt. However, a recent Delphi consensus of clinicians concluded that consensus could not be reached on the accuracy, reliability, and validation of any current CA assessment method. Research questionWe aimed to quantify the short-term uncertainty of PRx time-trends and to relate this to other physiological measurements. Material and methodsIntracranial pressure (ICP), arterial blood pressure (ABP), end-tidal CO2 (EtCO2) high-resolution recordings of 911 TBI patients were processed with ICM + software. Hourly values of metrics that describe the variability within modalities derived from ABP, ICP and EtCO2, were calculated for the first 24h of neuromonitoring. Generalized additive models were used to describe the time trend of the variability in PRx. Linear correlations were studied for describing the relationship between PRx variability and the other physiological modalities. ResultsThe time profile of variability of PRx decreases over the first 12h and was higher for average PRx ∼0. Increased variability of PRx was not linearly linked with average ABP, ICP, or CPP. For coherence between slow waves of ABP and ICP >0.7, the variability in PRx decreased (R = −0.47, p < 0.001). Discussion and conclusionPRx is a highly variable parameter. PRx short-term dispersion was not related to average ICP, ABP or CPP. The determinants of uncertainty of PRx should be investigated to improve reliability of individualised CA assessment in TBI patients.

Development of a Randomized Trial Comparing ICP-Monitor-Based Management of Severe Pediatric Traumatic Brain Injury to Management Based on Imaging and Clinical Examination Without ICP Monitoring-Research Algorithms.

The efficacy of our current approach to incorporating intracranial pressure (ICP) data into pediatric severe traumatic brain injury (sTBI) management is incompletely understood, lacking data from multicenter, prospective, randomized studies. The National Institutes of Health-supported Benchmark Evidence from Latin America-Treatment of Raised Intracranial Pressure-Pediatrics trial will compare outcomes from pediatric sTBI of a management protocol based on ICP monitoring vs 1 based on imaging and clinical examination without monitoring. Because no applicable comprehensive management algorithms for either cohort are available, it was necessary to develop them. A consensus conference involving the 21 intensivists and neurosurgeons from the 8 trial sites used Delphi-based methodology to formulate management algorithms for both study cohorts. We included recommendations from the latest Brain Trauma Foundation pediatric sTBI guidelines and the consensus-based adult algorithms (Seattle International Brain Injury Consensus Conference/Consensus Revised Imaging and Clinical Examination) wherever relevant. We used a consensus threshold of 80%. We developed comprehensive management algorithms for monitored and nonmonitored cohort children with sTBI. We defined suspected intracranial hypertension for the nonmonitored group, set minimum number and timing of computed tomography scans, specified minimal age-adjusted mean arterial pressure and cerebral perfusion pressure targets, defined clinical neuroworsening, described minimal requisites for intensive care unit management, produced tiered management algorithms for both groups, and listed treatments not routinely used. We will study these protocols in the Benchmark Evidence from Latin America-Treatment of Raised Intracranial Pressure-Pediatrics trial in low- and middle-income countries. Second, we present them here for consideration as prototype pediatric sTBI management algorithms in the absence of published alternatives, acknowledging their limited evidentiary status. Therefore, herein, we describe our study design only, not recommended treatment protocols.

Critical Care Experience With Clinical Cerebral Autoregulation Testing in Adults With Traumatic Brain Injury.

To describe the setting, feasibility, and safety of static cerebral autoregulation testing in critically injured adults with traumatic brain injury (TBI). Methods: We reviewed static autoregulation testing using transcranial Doppler (TCD) ultrasound in patients > 18 years with TBI ICD codes between January 1, 2014, and December 31, 2021. Adverse events during testing were defined as systemic hypertension (systolic blood pressure (SBP>180 mmHg), bradycardia (HR<40 bpm), and high ICP (>30 mmHg). Impaired and absent cerebral autoregulation was defined as an autoregulatory index (ARI) <0.4 and ARI 0, respectively. We characterized prescribed changes in intracranial pressure (ICP) and cerebral perfusion pressure (CPP) targets by autoregulation testing results. Results: A total of 135 patients, median age 31 (interquartile range (IQR) 24, 43) years, 71.9% male, admission Glasgow coma scale (GCS) score 3 (IQR 3, 5.5), and 70.9% with subdural hematoma from severe (GCS 3-8; 133 (98.5%)) and moderate (GCS 9-12; 2 (1.5%)) TBI, underwent 309 attempted testing. All patients were mechanically ventilated and had ICP monitoring; 246 (80%) had brain tissue oxygen monitoring, and 68 (22%) had an external ventricular drain. The median number of autoregulation tests was two (range 1-3) tests/patient, and the median admission to the first test time was two days (IQR 1, 3). Of 55 (17.8%) tests not completed, systemic hypertension (32, 10.4%), intracranial hypertension (10, 3.2%), and bradycardia (3, 0.9%) were transient. Fifty-three (51%) of the first (n=104) autoregulation tests showed impaired/absent cerebral autoregulation. Impaired/absent autoregulation results at the first test were associated with repeat cerebral autoregulation testing (RR 2.25, 95% CI [1.40-3.60], p=0.0007) than intact cerebral autoregulation results. Pre-testing cerebral hemodynamic targets were maintained (n=131; 86.8%) when cerebral autoregulation was impaired (n=151; RR 1.49, 95% CI [1.25-1.77], p<0.0001). However, 15 (9.9%) test results led to higher ICP targets (from 20 mmHg to 25 mmHg), 5 (3.3%) results led to an increase in CPP target (from 60 mmHg to 70 mmHg), and five out of 131 (3.8%) patients underwent decompressive craniectomy and placement of an external ventricular drain. Intact cerebral autoregulation results (n=43/103, 41.7%) were associated with a change in ICP targets from 20 mmHg to 25 mmHg (RR 3.15, 95% CI [1.97-5.03], p<0.0001). Conclusions: Static cerebral autoregulation testing was feasible, safe, and useful in individualizing the care of patients with moderate-severe TBI receiving multimodal neuromonitoring. Testing results guided future testing, cerebral hemodynamic targets, and procedural decisions. Impaired cerebral autoregulation was very common.

Intracranial Pressure Monitoring and Treatment Thresholds in Acute Neural Injury: A Narrative Review of the Historical Achievements, Current State, and Future Perspectives.

Since its introduction in the 1960s, intracranial pressure (ICP) monitoring has become an indispensable tool in neurocritical care practice and a key component of the management of moderate/severe traumatic brain injury (TBI). The primary utility of ICP monitoring is to guide therapeutic interventions aimed at maintaining physiological ICP and preventing intracranial hypertension. The rationale for such ICP maintenance is to prevent secondary brain injury arising from brain herniation and inadequate cerebral blood flow. There exists a large body of evidence indicating that elevated ICP is associated with mortality and that aggressive ICP control protocols improve outcomes in severe TBI patients. Therefore, current management guidelines recommend a cerebral perfusion pressure (CPP) target range of 60-70 mm Hg and an ICP threshold of >20 or >22 mm Hg, beyond which therapeutic intervention should be initiated. Though our ability to achieve these thresholds has drastically improved over the past decades, there has been little to no change in the mortality and morbidity associated with moderate-severe TBI. This is a result of the "one treatment fits all" dogma of current guideline-based care that fails to take individual phenotype into account. The way forward in moderate-severe TBI care is through the development of continuously derived individualized ICP thresholds. This narrative review covers the topic of ICP monitoring in TBI care, including historical context/achievements, current monitoring technologies and indications, treatment methods, associations with patient outcome and multi-modal cerebral physiology, present controversies surrounding treatment thresholds, and future perspectives on personalized approaches to ICP-directed therapy.

Autoregulatory Management in Traumatic Brain Injury: The Role of Absolute Pressure Reactivity Index Values and Optimal Cerebral Perfusion Pressure Curve Shape.

The aim of this study was to investigate if the absolute pressure reactivity index (PRx) value influenced the association between cerebral perfusion pressure (CPP) and outcome and if the optimal CPP (CPPopt) curve shape influenced the association between deviation from CPPopt and outcome in traumatic brain injury (TBI). We included 383 TBI patients treated at the neurointensive care in Uppsala between 2008 and 2018 with at least 24 h of CPP data. To determine the influence of absolute PRx values on the association between absolute CPP and outcome, the percentage of monitoring time for combinations of CPP and PRx were correlated with outcome (Extended Glasgow Outcome Scale [GOS-E]) in a heatmap. To determine the association between CPP and the relatively best PRx (CPPopt), the percentage of monitoring time of ΔCPPopt (actual CPP-CPPopt) ±5 mm Hg was analyzed in relation to GOS-E. To determine the association between CPP and the relatively best PRx within a certain absolute PRx range (curve shape), both the percentage of ΔCPPopt within the absolute limits of reactivity (PRx <0.00, < 0.15, etc.) and within certain confidence intervals of PRx-deterioration (+0.025, +0.05 etc.) from CPPopt were analyzed in relation to GOS-E. The heatmap of PRx and absolute CPP versus outcome indicated that the CPP range (55-75 mm Hg) associated with favorable outcome was wider when PRx was below 0, whereas the upper CPP-threshold decreased as PRx increased. CPPopt could be calculated during 53% of the monitoring time. Higher percentage of monitoring time with ΔCPPopt ±5 mm Hg, ΔCPPopt within the reactivity-thresholds (PRx <0.30), and ΔCPPopt within the PRx-confidence interval +0.025 were all independently associated with favorable outcome in separate logistic regressions. These regressions had similar area under receiver operating curve and were not superior to a similar regression when the CPPopt-target was replaced by the percentage of monitoring time within the traditional fixed CPP-targets 60 to 70 mm Hg. Individualized CPPopt-targets exhibited a comparable outcome association as traditional CPP targets and different definitions of the best CPPopt range based on the PRx value had a limited effect on the association between deviation from CPPopt and outcome. Since CPPopt could only be calculated during half of the time, an alternative approach would be to assess the absolute PRx to anticipate a safe CPP range.

The lower limit of reactivity as a potential individualised cerebral perfusion pressure target in traumatic brain injury: a CENTER-TBI high-resolution sub-study analysis

BackgroundA previous retrospective single-centre study suggested that the percentage of time spent with cerebral perfusion pressure (CPP) below the individual lower limit of reactivity (LLR) is associated with mortality in traumatic brain injury (TBI) patients. We aim to validate this in a large multicentre cohort.MethodsRecordings from 171 TBI patients from the high-resolution cohort of the CENTER-TBI study were processed with ICM+ software. We derived LLR as a time trend of CPP at a level for which the pressure reactivity index (PRx) indicates impaired cerebrovascular reactivity with low CPP. The relationship with mortality was assessed with Mann-U test (first 7-day period), Kruskal–Wallis (daily analysis for 7 days), univariate and multivariate logistic regression models. AUCs (CI 95%) were calculated and compared using DeLong’s test.ResultsAverage LLR over the first 7 days was above 60 mmHg in 48% of patients. %time with CPP < LLR could predict mortality (AUC 0.73, p = < 0.001). This association becomes significant starting from the third day post injury. The relationship was maintained when correcting for IMPACT covariates or for high ICP.ConclusionsUsing a multicentre cohort, we confirmed that CPP below LLR was associated with mortality during the first seven days post injury.

Towards autoregulation-oriented management after traumatic brain injury: increasing the reliability and stability of the CPPopt algorithm

PurposeCPPopt denotes a Cerebral Perfusion Pressure (CPP) value at which the Pressure-Reactivity index, reflecting the global state of Cerebral Autoregulation, is best preserved. CPPopt has been investigated as a potential dynamically individualised CPP target in traumatic brain injury patients admitted in intensive care unit. The prospective bedside use of the concept requires ensured safety and reliability of the CPP recommended targets based on the automatically-generated CPPopt. We aimed to: Increase stability and reliability of the CPPopt automated algorithm by fine-tuning; perform outcome validation of the adjusted algorithm in a multi-centre TBI cohort.MethodsICM + software was used to derive CPPopt and fine-tune the algorithm. Parameters for improvement of the algorithm were selected based on qualitative and quantitative assessment of stability and reliability metrics. Patients enrolled in the Collaborative European Neuro Trauma Effectiveness Research in TBI (CENTER-TBI) high-resolution cohort were included for retrospective validation. Yield and stability of the new algorithm were compared to the previous algorithm using Mann–U test. Area under the curves for mortality prediction at 6 months were compared with the DeLong Test.ResultsCPPopt showed higher stability (p < 0.0001), but lower yield compared to the previous algorithm [80.5% (70—87.5) vs 85% (75.7—91.2), p < 0.001]. Deviation of CPPopt could predict mortality with an AUC of [AUC = 0.69 (95% CI 0.59–0.78), p < 0.001] and was comparable with the previous algorithm.ConclusionThe CPPopt calculation algorithm was fine-tuned and adapted for prospective use with acceptable lower yield, improved stability and maintained prognostic power.

ICP, CPP, and PRx in traumatic brain injury and aneurysmal subarachnoid hemorrhage: association of insult intensity and duration with clinical outcome.

The primary aim of this study was to determine the combined effect of insult intensity and duration of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and pressure reactivity index (PRx) on outcome measured with the Glasgow Outcome Scale-Extended (GOS-E) in patients with traumatic brain injury (TBI) or aneurysmal subarachnoid hemorrhage (aSAH). This observational study included all TBI and aSAH patients treated in the neurointensive care unit in Uppsala, Sweden, 2008-2018, with at least 24 hours of ICP monitoring during the first 10 days following injury and available long-term clinical outcome data. ICP, CPP, and PRx insults were visualized as 2D plots to highlight the effects of both insult intensity and duration on patient outcome. Of 950 included patients, 436 were TBI and 514 aSAH patients. The TBI patients were younger, more often male, and exhibited worse neurological status at admission, but recovered more favorably than the aSAH patients. There was a transition from good to poor outcome with ICP above 15-20 mm Hg in both TBI and aSAH. The two diagnoses had opposite CPP patterns. In TBI patients, CPP episodes at or below 80 mm Hg were generally favorable, whereas CPP episodes above 80 mm Hg were favorable in the aSAH patients. In the TBI patients there was a transition from good to poor outcome when PRx exceeded zero, but no evident transition was found in the aSAH cohort. The insult intensity and duration plots formulated in this study illustrate the similarities and differences between TBI and aSAH patients. In particular, aSAH patients may benefit from much higher CPP targets than TBI patients.

Kidney Dysfunction After Traumatic Brain Injury: Pathophysiology and General Management.

Traumatic brain injury (TBI) remains a major cause of mortality and morbidity, and almost half of these patients are admitted to the intensive care unit. Of those, 10% develop acute kidney injury (AKI) and 2% even need kidney replacement therapy (KRT). Although clinical trials in patients with TBI who have AKI are lacking, some general principles in this population may apply. The present review is an overview on the epidemiology and pathophysiology of AKI in patients with TBI admitted to the intensive care unit who are at risk for or who have developed AKI. A cornerstone in severe TBI management is preventing secondary brain damage, in which reducing the intracranial pressure (ICP) and optimizing the cerebral perfusion pressure (CPP) remain important therapeutic targets. To treat episodes of elevated ICP, osmolar agents such as mannitol and hypertonic saline are frequently administered. Although we are currently awaiting the results of a prospective randomized controlled trial that compares both agents, it is important to realize that both agents have been associated with an increased risk of developing AKI which is probably higher for mannitol compared with hypertonic saline. For the brain, as well as for the kidney, targeting an adequate perfusion pressure is important. Hemodynamic management based on the combined use of intravascular fluids and vasopressors is ideally guided by hemodynamic monitoring. Hypotonic albumin or crystalloid resuscitation solutions may increase the risk of brain edema, and saline-based solutions are frequently used but have a risk of hyperchloremia, which might jeopardize kidney function. In patients at risk, frequent assessment of serum chloride might be advised. Maintenance of an adequate CPP involves the optimization of circulating blood volume, often combined with vasopressor agents. Whether individualized CPP targets based on cerebrovascular autoregulation monitoring are beneficial needto be further investigated. Interestingly, such individualized perfusion targets are also under investigation in patients as a strategy to mitigate the risk for AKI in patients with chronic hypertension. In the small proportion of patients with TBI who need KRT, continuous techniques are advised based on pathophysiology and expert opinion. The need for KRT is associated with a higher risk of intracranial hypertension, especially if osmolar clearance occurs fast, which can even occur in continuous techniques. Precise ICP and CPP monitoring is mandatory, especially at the initiation of KRT.

Continuous Time-Domain Cerebrovascular Reactivity Metrics and Discriminate Capacity for the Upper and Lower Limits of Autoregulation: A Scoping Review of the Animal Literature.

Over a wide range of systemic arterial pressures, cerebral blood flow (CBF) is regulated fairly constantly by the cerebral vessels in a process termed cerebral autoregulation (CA), which is depicted by the Lassen autoregulatory curve. After traumatic brain injury (TBI), CA can get impaired and these impairments manifest in changes of the Lassen autoregulatory curve. Continuous surrogate metrics of pressure-based CA, termed cerebrovascular reactivity (CVR) metrics, evaluate the relationship between slow vasogenic fluctuations in a driving pressure for cerebral blood flow, and the most commonly studied and utilized measures are based in the time domain and have been increasingly applied in bedside TBI care and have sparked the investigation of individualized cerebral perfusion pressure targets. However, not all CVR metrics have been validated as true measures of autoregulation in the pre-clinical setting. We reviewed all available pre-clinical animal literature that assessed the association between continuous time-domain metrics of CVR and some aspect of the Lassen autoregulatory curve. All 15 articles found associated the evaluated continuous metrics to the lower limit of autoregulation curve whereas none looked at the upper limit. Most of the evaluated metrics showed the ability to discriminate the lower limit of autoregulation with various methods of perturbation. Further work is required to evaluate the utility of such surrogate measures against the upper limit of autoregulation, while also providing validation to the existing literature supporting specific indices and their ability to discriminate the lower limit.

Optimal Cerebral Perfusion Pressure Guided by Brain Oxygen Pressure Measurement.

Background: Although increasing cerebral perfusion pressure (CPP) is commonly accepted to improve brain tissue oxygen pressure (PbtO2), it remains unclear whether recommended CPP targets (i. e., >60 mmHg) would result in adequate brain oxygenation in brain injured patients. The aim of this study was to identify the target of CPP associated with normal brain oxygenation.Methods: Prospectively collected data including patients suffering from acute brain injury and monitored with PbtO2, in whom daily CPP challenge using vasopressors was performed. Initial CPP target was >60 mmHg; norepinephrine infusion was modified to have an increase in CPP of at least 10 mmHg at two different steps above the baseline values. Whenever possible, the same CPP challenge was performed for the following days, for a maximum of 5 days. CPP “responders” were patients with a relative increase in PbtO2 from baseline values > 20%.Results: A total of 53 patients were included. On the first day of assessment, CPP was progressively increased from 73 (70–76) to 83 (80–86), and 92 (90–96) mmHg, which resulted into a significant PbtO2 increase [from 20 (17–23) mmHg to 22 (20–24) mmHg and 24 (22–26) mmHg, respectively; p < 0.001]. Median CPP value corresponding to PbtO2 values > 20 mmHg was 79 (74–87) mmHg, with 2 (4%) patients who never achieved such target. Similar results of CPP targets were observed the following days. A total of 25 (47%) were PbtO2 responders during the CPP challenge on day 1, in particular if low PbtO2 was observed at baseline.Conclusions: PbtO2 monitoring can be an effective way to individualize CPP values to avoid tissue hypoxia. Low PbtO2 values at baseline can identify the responders to the CPP challenge.

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.

Escalating Mean Arterial Pressure in Severe Traumatic Brain Injury: A Prospective, Observational Study.

To investigate cerebral autoregulatory status in patients with severe traumatic brain injury (TBI), guidelines now suggest active manipulation of mean arterial pressure (MAP). There is a paucity of data, however, describing the effect on intracranial pressure (ICP) when MAP is raised. Consecutive patients with TBI requiring ICP monitoring were enrolled from November 2019 to April 2020. The MAP and ICP were recorded continuously, and clinical annotations were made whenever intravenous vasopressors were commenced or adjusted to defend cerebral perfusion pressure (CPP) targets. A significant change in MAP burden was defined as MAP >100min.mm Hg over 15 min. The primary outcome was the change in ICP burden over the same 15-min period. Bedside and clinical parameters were then compared between these groups. Twenty-eight patients were enrolled, providing 212 clinical events, of which 60 were deemed significant. Over the first 15 min, 65% were associated with a net negative ICP burden. A greater reduction in ICP burden was observed with events occurring in patients without a history of hypotension at scene (p = 0.016), after three days post-injury (p = 0.0018), and where the pressure-reactivity index (PRx) was <0.25 (p = 0.0005) or the ICP amplitude to CPP correlation coefficient (RAC) was <-0.10 (p = 0.0036) at the initiation of vasopressor changes. The ICP burden in the first 15 min was highly correlated with the next 15-min period. In patients with severe TBI requiring ICP monitoring, increasing MAP to pursue a CPP target was followed by a net negative ICP burden in approximately two-thirds of events. These data suggest a MAP challenge may be a useful adjunct in managing intracranial hypertension.

Cerebrovascular Autoregulation Monitoring in the Management of Adult Severe Traumatic Brain Injury: A Delphi Consensus of Clinicians

BackgroundSeveral methods have been proposed to measure cerebrovascular autoregulation (CA) in traumatic brain injury (TBI), but the lack of a gold standard and the absence of prospective clinical data on risks, impact on care and outcomes of implementation of CA-guided management lead to uncertainty.AimTo formulate statements using a Delphi consensus approach employing a group of expert clinicians, that reflect current knowledge of CA, aspects that can be implemented in TBI management and CA research priorities.MethodsA group of 25 international academic experts with clinical expertise in the management of adult severe TBI patients participated in this consensus process. Seventy-seven statements and multiple-choice questions were submitted to the group in two online surveys, followed by a face-to-face meeting and a third online survey. Participants received feedback on average scores and the rationale for resubmission or rephrasing of statements. Consensus on a statement was defined as agreement of more than 75% of participants.ResultsConsensus amongst participants was achieved on the importance of CA status in adult severe TBI pathophysiology, the dynamic non-binary nature of CA impairment, its association with outcome and the inadvisability of employing universal and absolute cerebral perfusion pressure targets. Consensus could not be reached on the accuracy, reliability and validation of any current CA assessment method. There was also no consensus on how to implement CA information in clinical management protocols, reflecting insufficient clinical evidence.ConclusionThe Delphi process resulted in 25 consensus statements addressing the pathophysiology of impaired CA, and its impact on cerebral perfusion pressure targets and outcome. A research agenda was proposed emphasizing the need for better validated CA assessment methods as well as the focused investigation of the application of CA-guided management in clinical care using prospective safety, feasibility and efficacy studies.

Optimal Cerebral Perfusion Pressure Assessed with a Multi-Window Weighted Approach Adapted for Prospective Use: A Validation Study.

Pressure reactivity index (PRx)-cerebral perfusion pressure (CPP) relationships over a given time period can be used to detect a value of CPP at which PRx shows the best autoregulation (optimal CPP, or CPPopt). Algorithms for continuous assessment of CPPopt in traumatic brain injury (TBI) patients reached the desired high yield with a multi-window approach (CPPopt_MA). However, the calculations were tested on retrospective manually cleaned datasets. Moreover, CPPopt false-positive values can be generated from non-physiological variations of intracranial pressure (ICP) and arterial blood pressure (ABP). Therefore, the algorithm robustness was improved, making it suitable for prospective bedside application (COGiTATE trial). To validate the CPPopt revised algorithm in a large single-centre retrospective cohort of TBI patients. 840 TBI patients were included. CPPopt yield, stability and ability to discriminate outcome groups were compared to CPPopt_MA and the Brain Trauma Foundation (BTF) guideline reference. CPPopt yield was lower than CPPopt_MA yield (85% and 90%, p<0.001), but, importantly, with increased stability (p<0.0001). The ∆(CPP-CPPopt) could distinguish the mortality and survival outcome (t=-6.7, p<0.0001) with a statistical significance higher than the ∆CPP calculated with the guideline reference (CPP-60) (t=-4.5, p<0.0001). This study validates, on a large cohort of patients, the new algorithm proposed for prospective use of CPPopt as a CPP target at bedside.

Influence of Patient Demographics on Optimal Cerebral Perfusion Pressure Following Traumatic Brain Injury.

The relationship between optimal cerebral perfusion pressure (CPPopt) and patient characteristics has yet to be defined but could have significant implications for future guidelines recommending cerebral perfusion pressure (CPP) targets.Data from 36 traumatic brain injured patients admitted to neurological intensive care were analysed retrospectively. Linear mixed effects (LME) analysis was performed using an unadjusted-adjusted approach.Clinical characteristics with p<0.10 were included in the adjusted model. A second adjusted model which included all variables of interest was created. Model fit was assessed using the root-mean-square error (RMSE).The adjusted model included time from initiation of intracranial pressure (ICP) monitoring (estimate=0.00292, p<0.001), age (estimate=-0.211, p=0.0750) and the presence of diffuse axonal injury (DAI) (estimate=-35.5, p<0.001). The RMSE of this model was 8.11mmHg. The RMSE of the model containing all variables was 8.09mmHg.Time, age and the presence of DAI may be important predictors of CPPopt. The models were too inaccurate at predicting CPPopt for employment in clinical practice but warrant further investigation. CPPopt is a dynamic measurement influenced by many factors, supporting the utility of investigating the feasibility of CPPopt-guided therapy.

Intracranial and Cerebral Perfusion Pressure Thresholds Associated With Inhospital Mortality Across Pediatric Neurocritical Care.

Targets for treatment of raised intracranial pressure or decreased cerebral perfusion pressure in pediatric neurocritical care are not well defined. Current pediatric guidelines, based on traumatic brain injury, suggest an intracranial pressure target of less than 20 mm Hg and cerebral perfusion pressure minimum of 40-50 mm Hg, with possible age dependence of cerebral perfusion pressure. We sought to define intracranial pressure and cerebral perfusion pressure thresholds associated with inhospital mortality across a large single-center pediatric neurocritical care cohort. Retrospective chart review. PICU, single quaternary-care center. Individuals receiving intracranial pressure monitoring from January 2012 to December 2016. None. Intracranial pressure and cerebral perfusion pressure measurements from 262 neurocritical care patients (87 traumatic brain injury and 175 nontraumatic brain injury; 63% male; 8.3 ± 5.8 yr; mortality 11.1%). Mean intracranial pressure and cerebral perfusion pressure had area under the receiver operating characteristic curves of 0.75 and 0.64, respectively, for association of inhospital mortality. Cerebral perfusion pressure cut points increased with age (< 2 yr = 47, 2 to < 8 yr = 58 mm Hg, ≥ 8 yr = 73 mm Hg). In the traumatic brain injury subset, mean intracranial pressure and cerebral perfusion pressure had area under the receiver operating characteristic curves of 0.70 and 0.78, respectively, for association of inhospital mortality. Traumatic brain injury cerebral perfusion pressure cut points increased with age (< 2 yr = 45, 2 to < 8 yr = 57, ≥ 8 yr = 68 mm Hg). Mean intracranial pressure greater than 15 mm Hg, male sex, and traumatic brain injury status were independently associated with inhospital mortality (odds ratio, 14.23 [5.55-36.46], 2.77 [1.04-7.39], and 2.57 [1.03-6.38], respectively; all p < 0.05). Mean cerebral perfusion pressure less than 67 mm Hg and traumatic brain injury status were independently associated with inhospital mortality (odds ratio, 5.16 [2.05-12.98] and 3.71 [1.55-8.91], respectively; both p < 0.01). In the nontraumatic brain injury subset, mean intracranial pressure had an area under the receiver operating characteristic curve 0.77 with an intracranial pressure cut point of 15 mm Hg, whereas mean cerebral perfusion pressure was not predictive of inhospital mortality. We identified mean intracranial pressure thresholds, utilizing receiver operating characteristic and regression analyses, associated with inhospital mortality that is below current guidelines-based treatment targets in both traumatic brain injury and nontraumatic brain injury patients, and age-dependent cerebral perfusion pressure thresholds associated with inhospital mortality that were above current guidelines-based targets in traumatic brain injury patients. Further study is warranted to identify data-driven intracranial pressure and cerebral perfusion pressure targets in children undergoing intracranial pressure monitoring, whether for traumatic brain injury or other indications.

Traumatic Brain Injury Practice Guidelines: Variability in U.K. PICUs.

Traumatic brain injury in children is a leading cause of morbidity and mortality. Lack of high-quality evidence may lead to variation in management within and between PICUs. We examined U.K. pediatric traumatic brain injury management guidelines for extent of variability. Analysis of U.K. PICU traumatic brain injury guidelines for areas of consistency and variation among each other and against the second edition of Brain Trauma Foundation pediatric traumatic brain injury guidelines. Not applicable. Not applicable. Textual analysis of U.K. PICU guidelines. Twelve key clinical topics in three traumatic brain injury management domains were identified. We performed textual analysis of recommendations from anonymized local guidelines and compared them against each other and the Brain Trauma Foundation pediatric traumatic brain injury guidelines. Fifteen guidelines used by 16 of the 20 U.K. PICUs that manage traumatic brain injury were analyzed. Relatively better consistency was observed for intracranial pressure treatment thresholds (10/15), avoiding prophylactic hyperventilation (15/15), cerebrospinal fluid drainage (13/15), barbiturate (14/15), and decompressive craniectomy (12/15) for intracranial hypertension. There was less consistency in indications for intracranial pressure monitoring (3/15), cerebral perfusion pressure targets (2/15), target osmolarities (7/15), and hyperventilation for intracranial hypertension (2/15). Variability in choice and hierarchy of the interventions for intracranial hypertension were observed, albeit with some points of consistency. Significant variability in pediatric traumatic brain injury management guidelines exists. Despite the heterogeneity, we have highlighted a few points of consistency within the key topic areas of pediatric traumatic brain injury management. We anticipate that this provides impetus for further work around standardization.