Cerebral Perfusion Pressure Thresholds Research Articles

Intracranial Pressure-Derived Cerebrovascular Reactivity Indices and Their Critical Thresholds: A Canadian High Resolution-Traumatic Brain Injury Validation Study.

Current neurointensive care guidelines recommend intracranial pressure (ICP) and cerebral perfusion pressure (CPP) centered management for moderate-severe traumatic brain injury (TBI) because of their demonstrated associations with patient outcome. Cerebrovascular reactivity metrics, such as the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC index, have also demonstrated significant prognostic capabilities with regard to outcome. However, critical thresholds for cerebrovascular reactivity indices have only been identified in two studies conducted at the same center. In this study, we aim to determine the critical thresholds of these metrics by leveraging a unique multi-center database. The study included a total of 354 patients from the CAnadian High-Resolution TBI (CAHR-TBI) Research Collaborative. Based on 6-month Glasgow Outcome Scores, patients were dichotomized into alive versus dead and favorable versus unfavorable. Chi-square values were then computed for incrementally increasing values of each physiological parameter of interest against outcome. The values that generated the greatest chi-squares for each parameter were considered to be the thresholds with the greatest outcome discriminatory capacity. To confirm that the identified thresholds provide prognostic utility, univariate and multivariable logistical regression analyses were performed adjusting for the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) variables. Through the chi-square analysis, a lower limit CPP threshold of 60 mm Hg and ICP thresholds of 18 mm Hg and 22 mm Hg were identified for both survival and favorable outcome predictions. For the cerebrovascular reactivity metrics, different thresholds were identified for the two outcome dichotomizations. For survival prediction, thresholds of 0.35, 0.25, and 0 were identified for PRx, PAx, and RAC, respectively. For favorable outcome prediction, thresholds of 0.325, 0.20, and 0.05 were found. Univariate logistical regression analysis demonstrated that the time spent above/below thresholds were associated with outcome. Further, multivariable logistical regression analysis found that percent time above/below the identified thresholds added additional variance to the IMPACT core model for predicting both survival and favorable outcome. In this study, we were able to validate the results of the previous two works as well as to reaffirm the ICP and CPP guidelines from the Brain Trauma Foundation (BTF) and the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC).

Severe Traumatic Brain Injury in French-Speaking Pediatric Intensive Care Units: Study of Practices

AbstractBest strategies for managing severe pediatric traumatic brain injury (TBI) are not established, with wide variations among professional practices. The main objective of this study was to assess compliance with updated pediatric TBI management guidelines (2019). A survey was distributed among French-speaking pediatric intensive care physicians from April 1 to June 30, 2019. The survey was based on a clinical case with a total of 70 questions that cover the 15 items of the 2019 TBI guidelines. The questions evaluated the assessment and management of TBI during the acute and intensive care phases. Of 487 e-mails sent, 78 surveys were included. Guidelines were adhered to (> 60%) for 10 of 15 items in the guidelines. Strong adherence to recent guideline changes was achieved for seizure prophylaxis with levetiracetam (n = 21/33, 64%) and partial pressure of carbon dioxide threshold (n = 52, 67%). However, management of the sodium and glucose thresholds and the role of transcranial Doppler were not consistent with the guidelines. Assessment of brain tissue oxygenation (n = 12, 16%) and autoregulation (n = 35, 45%) was not a common practice. There was strong agreement among clinicians on the intracranial pressure (> 80%) and cerebral perfusion pressure (> 70%) thresholds used according to age. Overall, stated practices for the management of TBI appear to be relatively standardized among responders. Variations persist in areas with a lack of evidence and pediatric-specific recommendations.

Implementation of Multimodality Neurologic Monitoring Reporting in Pediatric Traumatic Brain Injury Management

Background/ObjectiveMultimodality neurologic monitoring (MMM) is an emerging technique for management of traumatic brain injury (TBI). An increasing array of MMM-derived biomarkers now exist that are associated with injury severity and functional outcomes after TBI. A standardized MMM reporting process has not been well described, and a paucity of evidence exists relating MMM reporting in TBI management with functional outcomes or adverse events.MethodsProspective implementation of standardized MMM reporting at a single pediatric intensive care unit (PICU) is described that included monitoring of intracranial pressure (ICP), cerebral oxygenation and electroencephalography (EEG). The incidence of clinical decisions made using MMM reporting is described, including timing of neuroimaging, ICP monitoring discontinuation, use of paralytic, hyperosmolar and pentobarbital therapies, neurosurgical interventions, ventilator and CPP adjustments and neurologic prognostication discussions. Retrospective analysis was performed on the association of MMM reporting with initial Glasgow Coma Scale (GCS) and Pediatric Risk of Mortality III (PRISM III) scores, duration of total hospitalization and PICU hospitalization, duration of mechanical ventilation and invasive ICP monitoring, inpatient complications, time with ICP > 20 mmHg, time with cerebral perfusion pressure (CPP) < 40 mmHg and 12-month Glasgow Outcome Scale—Extended Pediatrics (GOSE-Peds) scores. Association of outcomes with MMM reporting was investigated using the Wilcoxon rank-sum test or Fisher’s exact test, as appropriate.ResultsEighty-five children with TBI underwent MMM over 6 years, among which 18 underwent daily MMM reporting over a 21-month period. Clinical decision-making influenced by MMM reporting included timing of neuroimaging (100.0%), ICP monitoring discontinuation (100.0%), timing of extubation trials of surviving patients (100.0%), body repositioning (11.1%), paralytic therapy (16.7%), hyperosmolar therapy (22.2%), pentobarbital therapy (33.3%), provocative cerebral autoregulation testing (16.7%), adjustments in CPP thresholds (16.7%), adjustments in PaCO2 thresholds (11.1%), neurosurgical interventions (16.7%) and neurologic prognostication discussions (11.1%). The implementation of MMM reporting was associated with a reduction in ICP monitoring duration (p = 0.0017) and mechanical ventilator duration (p = 0.0018). No significant differences were observed in initial GCS or PRISM III scores, total hospitalization length, PICU hospitalization length, total complications, time with ICP > 20 mmHg, time with CPP < 40 mmHg, use of tier 2 therapy, or 12-month GOS-E Peds scores.ConclusionImplementation of MMM reporting in pediatric TBI management is feasible and can be impactful in tailoring clinical decisions. Prospective work is needed to understand the impact of MMM and MMM reporting systems on functional outcomes and clinical care efficacy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12028-021-01190-8.

Abstract P447: Intracranial Pressure and Cerebral Perfusion Pressure Monitoring in Spontaneous Intracranial Hemorrhage: A Secondary Analysis of the Mistie III Trial

Introduction: Intracerebral hemorrhage (ICH) management guidelines recommend maintaining intracranial pressure (ICP) &lt;20 and cerebral perfusion pressure (CPP) between 50-70 mmHg. We did subgroup analyses of MISTIE III trial to explore whether minimally invasive surgery (MIS) improves ICP or CPP and whether thresholds are associated with long term outcomes. Methods: MISTIE III was a randomized clinical trial including 499 patients with spontaneous ICH randomized to MIS+Alteplase or standard medical care (SMC). Primary outcomes were any threshold event of ICP &gt;20 and CPP &lt;60/70 mmHg. Secondary outcomes were poor modified Rankin Scale at one year and mortality at 30/365 days. We used multivariable models to investigate factors associated with ICP/CPP events and outcomes. Results: Of 72 patients with ICP monitored for median 92 (72-96) hours, 31 (43.1%) had at least one ICP reading &gt;20 and 52/35 (72.2/34.7%) had at least one CPP reading &lt;70/60 mmHg. Lower intraventricular hemorrhage volume and SMC group were associated with having any ICP threshold event &gt;20 and CPP event &lt;70 mmHg whereas CPP&lt;60 mmHg was associated with end of treatment (EOT) ICH volume, hydrocephalus on diagnostic CT and no prior antiplatelet agent use. On adjusted analyses, percentage of ICP readings &gt;20 were significantly less likely in patients undergoing MIS vs SMC (Coefficient -0.79, 95% Confidence Interval [CI] [(-)1.46-(-)0.11]; p=0.02). Percentage of CPP readings &lt;70 were significantly less frequent in MIS group (Coefficient -1.59 [(-)2.58-(-)0.59]; p=0.002). Patients who underwent successful MIS with EOT ICH volume &lt;15mL also had significantly lower percentage of readings at ICP&lt;20 (p=0.02), and CPP&lt;70 (p=0.05). Lower percentage of CPP readings &lt;60 mmHg was independently associated with lower mortality at 30 and 365 days (p=0.02 and 0.04) and CPP &lt;70 was associated with lower one-year mortality (p=0.04). There were no significant associations with one-year functional outcome. Conclusion: Elevated ICP and inadequate CPP are not infrequent during ICP monitoring for large ICH. Burden of low CPP events predict higher short and long term mortality, but not functional outcomes. CPP may be more significant than ICP. MIS appears to mitigate ICP and CPP threshold events.

Temporal Dynamics of ICP, CPP, PRx, and CPPopt in High-Grade Aneurysmal Subarachnoid Hemorrhage and the Relation to Clinical Outcome

BackgroundHigh intracranial pressure (ICP) and low cerebral perfusion pressure (CPP) may induce secondary brain injury following aneurysmal subarachnoid hemorrhage (aSAH). In the current study, we aimed to determine the temporal incidence of insults above/below certain ICP/CPP thresholds, the role of pressure autoregulation in CPP management (PRx and CPPopt), and the relation to clinical outcome.MethodsIn this retrospective study, 242 patients were included with aSAH, who were treated in the neurointensive care unit, Uppsala University Hospital, Sweden, 2008–2018, with ICP monitoring the first 10 days post-ictus. Data from ICP, pressure autoregulation (PRx), CPP, and CPPopt (the CPP with the lowest/optimal PRx) were analyzed the first 10 days. The percentage of good monitoring time (GMT) above/below various ICP and CPP thresholds was calculated, e.g., ICP > 20 mm Hg (%), CPP < 60 mm Hg (%), and ∆CPPopt (CPP–CPPopt) < − 10 mm Hg (%).ResultsOf the 242 patients, 63 (26%) had favorable (GOS-E 5–8) and 179 (74%) had unfavorable (GOS-E 1–4) outcome at 12 months. Higher proportion (GMT) of ICP insults above 20 mm Hg was most common the first 3 days post-ictus and was then independently associated with unfavorable outcome. CPP gradually increased throughout the 10 days post-ictus, and higher proportion of GMT with CPP < 90 mm Hg was independently associated with unfavorable outcome in the late vasospasm phase (days 6.5–10). PRx was above 0 throughout the 10 days and deteriorated in the late vasospasm phase. Higher values were then independently associated with unfavorable outcome. There was no difference in GMT of CPP deviations from CPPopt between the outcome groups.ConclusionsAvoiding intracranial hypertension early and maintaining a high CPP in the vasospasm phase when the pressure autoregulation is most disturbed may improve clinical outcome after aSAH.

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.

The Limited Impact of Current Therapeutic Interventions on Cerebrovascular Reactivity in Traumatic Brain Injury: A Narrative Overview

Current intensive care unit (ICU) treatment strategies for traumatic brain injury (TBI) care focus on intracranial pressure (ICP)- and cerebral perfusion pressure (CPP)-directed therapeutics, dictated by guidelines. Impaired cerebrovascular reactivity in moderate/severe TBI is emerging as a major associate with poor outcome and appears to dominate the landscape of physiologic derangement over the course of a patient's ICU stay. Within this article, we review the literature on the known drivers of impaired cerebrovascular reactivity in adult TBI, highlight the current knowledge surrounding the impact of guideline treatment strategies on continuously monitored cerebrovascular reactivity, and discuss current treatment paradigms for impaired reactivity. Finally, we touch on the areas of future research, as we strive to develop specific therapeutics for impaired cerebrovascular reactivity in TBI. There exists limited literature to suggest advanced age, intracranial injury patterns of diffuse injury, and sustained ICP elevations may drive impaired cerebrovascular reactivity. To date, the literature suggests there is a limited impact of such ICP/CPP guideline-based therapies on cerebrovascular reactivity, with large portions of a given patients ICU period spent with impaired cerebrovascular reactivity. Emerging treatment paradigms focus on the targeting individualized CPP and ICP thresholds based on cerebrovascular reactivity, without directly targeting the pathways involved in its dysfunction. Further work involved in uncovering the molecular pathways involved in impaired cerebrovascular reactivity is required, so that we can develop therapeutics directed at its prevention and treatment.

Temporal Neurophysiological Dynamics in Traumatic Brain Injury: Role of Pressure Reactivity and Optimal Cerebral Perfusion Pressure for Predicting Outcome.

Intracranial pressure (ICP), cerebral perfusion pressure (CPP), and the pressure reactivity index (PRx) have been shown to correlate with outcome after traumatic brain injury (TBI), but their temporal evolution is less studied. Optimal CPP (CPPopt; i.e., the CPP with the lowest [optimal] PRx value) has been proposed as a dynamic, individualized CPP target. Our aim was to map the temporal course of these parameters and their relation to outcome, in particular the extent and impact of CPP insults based both on fixed CPP thresholds and on divergence from CPPopt. Data from 362 TBI patients with ICP-monitoring treated at the neurointensive care unit of Uppsala University Hospital, Uppsala, Sweden, between 2008-2016 were retrospectively analyzed for the temporal course of ICP, mean arterial blood pressure, CPP, PRx, PRx55-15 (a variant of PRx), and CPPopt the first 10 days post-injury. PRx and PRx55-15 showed significantly lower/better values for those with favorable outcome, most pronounced on Days 2 to 5. PRx55-15 gave better separation between the two groups. In the univariate analysis, CPP insults (both fixed and CPPopt-thresholds) were significantly correlated with outcome on these days. Multi-variate logistic regression showed that age, Glasgow Coma Score Motor, pupillary abnormality at admission, CPP > CPPopt, and PRx55-15 were significant independent outcome predictors. PRx was significant when PRx55-15 was excluded. High PRx55-15 and high grade of monitoring time with CPP > CPPopt, but not the traditional fixed CPP thresholds, were strong predictors for worse clinical outcome. The study supports the concept that CPPopt is an important parameter in TBI management.

Cerebral perfusion pressure threshold to prevent delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

ObjectiveTo seek a cerebral perfusion pressure (CPP) threshold that can reduce the occurrence of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). MethodsWe analyzed the clinical data of patients with the diagnosis of aSAH and underwent CPP monitoring in our department from February 2014 to December 2015. CPP was divided into four specified thresholds by every 10 mmHg increments, which were from 50 mmHg to 80 mmHg. The totally time ratio of CPP below each threshold was calculated. The correlation between the time ratio and DCI were analyzed using binary logistic regression. And receiver operating characteristic curve was performed to identify the cutoff time ratios at higher risk of DCI. ResultsFinally, 17 patients developed DCI from 60 patients who were recruited. The time ratios of CPP which was below 50 mmHg, 60 mmHg and 70 mmHg were found predictors of DCI by the binary logistic regression. The cutoff time ratios were 0.4% (AUC = 0.777), 7.0% (AUC = 0.702), 28.7% (AUC = 0.696) respectively. While at the level of 80 mmHg, the cutoff time ratio was 65% (AUC = 0.595). It was not related to DCI (P = 0.167). Patients suffered from DCI had a worse outcome than who did not at 3 month after aSAH (P = 0.018). ConclusionTime ratios at higher risk of DCI had a positive relationship with the CPP thresholds. Keeping CPP above 70 mmHg may be helpful to prevent DCI after aSAH, but it still needs further investigation.

Critical thresholds for intracranial pressure vary over time in non-craniectomised traumatic brain injury patients

BackgroundIntracranial pressure (ICP)- and cerebral perfusion pressure (CPP)-guided therapy is central to neurocritical care for traumatic brain injury (TBI) patients. We sought to identify time-dependent critical thresholds for mortality and unfavourable outcome for ICP and CPP in non-craniectomised TBI patients.MethodsThis is a retrospective cohort study of 355 patients with moderate-to-severe TBI who received ICP monitoring and were managed without decompressive craniectomy in a tertiary hospital neurocritical care unit. Patients were grouped in 2 × 2 tables according to survival/death or favourable/unfavourable outcomes at 6 months and serial thresholds of mean ICP and CPP, using increments of 0.1 and 0.5 mmHg respectively. Sequential chi-square analysis was performed, and the thresholds yielding the highest chi-square test statistic were taken as having the best discriminative value for outcome. This process was repeated over monitoring periods of 1, 3, 5 and 7 days and for each day of recording to establish time-dependent thresholds. The same analysis was performed for age and sex subgroups.ResultsGlobal ICP thresholds were 21.3 and 20.5 mmHg for mortality and unfavourable outcome respectively (p < 0.001). After the first day of ICP monitoring, ICP thresholds fell to between 15 and 20 mmHg and remained significant (p < 0.05). Significant time-dependent CPP thresholds for mortality or unfavourable outcome were often not identified, and no identifiable trends were produced.ConclusionCritical ICP thresholds in non-craniectomised TBI patients vary with time and fall below established ICP targets after the first day of monitoring.

Early Craniectomy Improves Intracranial and Cerebral Perfusion Pressure after Severe Traumatic Brain Injury

After traumatic brain injury, decompressive craniectomy (DC) is a second-tier, late therapy for refractory intracranial hypertension. We hypothesize that early DC, based on CT evidence of intracranial hypertension, improves intracranial pressure (ICP) and cerebral perfusion pressure (CPP). From September 2008 to January 2015, 286 traumatic brain injury patients requiring invasive ICP monitoring at a single Level I trauma center were reviewed. DC and non-DC patients were propensity score matched 1:1, based on demographics, hemodynamics, injury severity score (ISS), Glasgow Coma Scale (GCS), transfusion requirements, and need for vasopressor therapy. Data are presented as M ± SD or median (IQR) and compared at P ≤ 0.05. The study population was 42 ± 17 years, 84 per cent male, ISS = 29 ± 11, GCS = 6(5), length of stay (LOS) = 32(40) days, and 28 per cent mortality. There were 116/286 (41%) DC, of which 105/116 (91%) were performed at the time of ICP placement. For 50 DC propensity matched to 50 non-DC patients, the midline shift was 7(11) versus 0(5) mm (P < 0.001), abnormal ICP (hours > 20 mm Hg) was 1(10) versus 8(16) (P = 0.017), abnormal CPP (hours < 60 mm Hg) was 0(6) versus 4(9) (P = 0.008), daily minimum CPP (mm Hg) was 67(13) versus 62(17) (P = 0.010), and daily maximum ICP (mm Hg) was 18(9) versus 22(11) (P < 0.001). However, LOS [33(37) versus 25(34) days], mortality (24 versus 30%), and Glasgow Outcome Score Extended [3.0(3.0) versus 3.0(4.0)] did not improve significantly. Early DC for CT evidence of intracranial hypertension decreased abnormal ICP and CPP time and improved ICP and CPP thresholds, but had no obvious effect on the outcome.

Cerebral Perfusion Pressure Variability Between Patients and Between Centres.

The aim of this analysis was to investigate to what extent median cerebral perfusion pressure (CPP) differs between severe traumatic brain injury (TBI) patients and between centres, and whether the 2007 change in CPP threshold in the Brain Trauma Foundation guidelines is reflected in patient data collected at several centres over different time periods. Data were collected from the Brain-IT database, a multi-centre project between 2003 and 2005, and from a recent project in four centres between 2009 and 2013. For patients nursed with their head up at 30° and with the blood pressure transducer at atrium level, CPP was corrected by 10 mmHg. Median CPP, interquartile ranges and total CPP ranges over the monitoring time were calculated per patient and per centre. Per-centre medians pre-2007 were situated between 50 and 70 mmHg in 6 out of 16 centres, while 10 centres had medians above 70 mmHg and 4 above 80 mmHg. Post-2007, three out of four centres had medians between 60 and 70 mmHg and one above 80 mmHg. One out of two centres with data pre- and post-2007 shifted from a median CPP of 76 mmHg to 60 mmHg, while the other remained at 68-67 mmHg. CPP data are characterised by a high inter-individual variability, but the data also suggest differences in CPP policies between centres. The 2007 guideline change may have affected policies towards lower CPP in some centres. Deviations from the guidelines occur in the direction of CPP > 70 mmHg.

Anatomical and Physiological Differences between Children and Adults Relevant to Traumatic Brain Injury and the Implications for Clinical Assessment and Care.

General and central nervous system anatomy and physiology in children is different to that of adults and this is relevant to traumatic brain injury (TBI) and spinal cord injury. The controversies and uncertainties in adult neurotrauma are magnified by these differences, the lack of normative data for children, the scarcity of pediatric studies, and inappropriate generalization from adult studies. Cerebral metabolism develops rapidly in the early years, driven by cortical development, synaptogenesis, and rapid myelination, followed by equally dramatic changes in baseline and stimulated cerebral blood flow. Therefore, adult values for cerebral hemodynamics do not apply to children, and children cannot be easily approached as a homogenous group, especially given the marked changes between birth and age 8. Their cranial and spinal anatomy undergoes many changes, from the presence and disappearance of the fontanels, the presence and closure of cranial sutures, the thickness and pliability of the cranium, anatomy of the vertebra, and the maturity of the cervical ligaments and muscles. Moreover, their systemic anatomy changes over time. The head is relatively large in young children, the airway is easily compromised, the chest is poorly protected, the abdominal organs are large. Physiology changes—blood volume is small by comparison, hypothermia develops easily, intracranial pressure (ICP) is lower, and blood pressure normograms are considerably different at different ages, with potentially important implications for cerebral perfusion pressure (CPP) thresholds. Mechanisms and pathologies also differ—diffuse injuries are common in accidental injury, and growing fractures, non-accidental injury and spinal cord injury without radiographic abnormality are unique to the pediatric population. Despite these clear differences and the vulnerability of children, the amount of pediatric-specific data in TBI is surprisingly weak. There are no robust guidelines for even basics aspects of care in children, such as ICP and CPP management. This is particularly alarming given that TBI is a leading cause of death in children. To address this, there is an urgent need for pediatric-specific clinical research. If this goal is to be achieved, any clinician or researcher interested in pediatric neurotrauma must be familiar with its unique pathophysiological characteristics.

Individualizing Thresholds of Cerebral Perfusion Pressure Using Estimated Limits of Autoregulation.

In severe traumatic brain injury, cerebral perfusion pressure management based on cerebrovascular pressure reactivity index has the potential to provide a personalized treatment target to improve patient outcomes. So far, the methods have focused on identifying "one" autoregulation-guided cerebral perfusion pressure target-called "cerebral perfusion pressure optimal". We investigated whether a cerebral perfusion pressure autoregulation range-which uses a continuous estimation of the "lower" and "upper" cerebral perfusion pressure limits of cerebrovascular pressure autoregulation (assessed with pressure reactivity index)-has prognostic value. Single-center retrospective analysis of prospectively collected data. The neurocritical care unit at a tertiary academic medical center. Data from 729 severe traumatic brain injury patients admitted between 1996 and 2016 were used. Treatment was guided by controlling intracranial pressure and cerebral perfusion pressure according to a local protocol. None. Cerebral perfusion pressure-pressure reactivity index curves were fitted automatically using a previously published curve-fitting heuristic from the relationship between pressure reactivity index and cerebral perfusion pressure. The cerebral perfusion pressure values at which this "U-shaped curve" crossed the fixed threshold from intact to impaired pressure reactivity (pressure reactivity index = 0.3) were denoted automatically the "lower" and "upper" cerebral perfusion pressure limits of reactivity, respectively. The percentage of time with cerebral perfusion pressure below (%cerebral perfusion pressure < lower limit of reactivity), above (%cerebral perfusion pressure > upper limit of reactivity), or within these reactivity limits (%cerebral perfusion pressure within limits of reactivity) was calculated for each patient and compared across dichotomized Glasgow Outcome Scores. After adjusting for age, initial Glasgow Coma Scale, and mean intracranial pressure, percentage of time with cerebral perfusion pressure less than lower limit of reactivity was associated with unfavorable outcome (odds ratio %cerebral perfusion pressure < lower limit of reactivity, 1.04; 95% CI, 1.02-1.06; p < 0.001) and mortality (odds ratio, 1.06; 95% CI, 1.04-1.08; p < 0.001). Individualized autoregulation-guided cerebral perfusion pressure management may be a plausible alternative to fixed cerebral perfusion pressure threshold management in severe traumatic brain injury patients. Prospective randomized research will help define which autoregulation-guided method is beneficial, safe, and most practical.

Further Controversies About Brain Tissue Oxygenation Pressure-Reactivity After Traumatic Brain Injury

Continuous monitoring of cerebral autoregulation is considered clinically useful due to its ability to warn against brain ischemic insults, which may translate to a relationship with adverse outcome. It is typically performed using the pressure reactivity index (PRx) based on mean arterial pressure and intracranial pressure. A new ORx index based on brain tissue oxygenation and cerebral perfusion pressure (CPP) has been proposed that similarly allows for evaluation of cerebrovascular reactivity. Conflicting results exist concerning its clinical utility. Retrospective analysis was performed in 85 patients with traumatic brain injury (TBI). ORx was calculated using three time windows of 5, 20, and 60min. Correlation coefficients and individual "optimal CPP" (CPPopt) were calculated using both PRx and ORx, and relation to patient outcome investigated. Correlation coefficients for all comparisons between PRx and ORx indicated poor association between these indices (range from -0.04 to 0.07). PRx was significantly lower in patients with good outcome (p=0.01), while none of the ORx indices proved to be significantly different in the two outcome groups. Higher mortality related to average CPP<CPPopt was found regardless of which index was used to calculate CPPopt. In the TBI setting, ORx does not appear to correlate with vascular pressure reactivity as assessed with PRx. Its potential use for individualizing CPP thresholds remains unclear.

Cerebral Perfusion Pressure Insults and Associations with Outcome in Adult Traumatic Brain Injury.

The definition of cerebral perfusion pressure (CPP) secondary insults in severe traumatic brain injury remains unclear. The purpose of the present study is to visualize the association of intensity and duration of episodes below or above CPP thresholds and outcome. The analysis was based on prospectively collected minute-by-minute intracranial pressure (ICP) and blood pressure data and outcome from 259 adult patients. The relationship of episodes of CPP below or above a certain threshold for certain duration with the 6-month Glasgow Outcome Score was visualized separately for episodes of active or deficient autoregulation (AR). In adults ≤65 years, an almost exponential transition curve separates the episodes of CPP associated with better outcomes from the episodes of low CPP associated with worse outcomes, indicating that lower CPP could only be tolerated for a brief time. Analysis of episodes of high CPP again showed a time-intensity dependent association with outcome. When combining the two plots, a safe CPP zone between 60 and 70 mm Hg could be delineated—however, only for AR active insults. The AR status predominantly affected the transition curve for insults of low CPP. Episodes with ICP >25 mm Hg were associated with poor outcome regardless of CPP. In the present study, the CPP pressure-time burden associated with poor outcome was visualized. A safe zone between 60 and 70 mm Hg could be identified for adults ≤65 years, provided AR was active and ICP was ≤25 mm Hg. Deficient AR reduces the tolerability for low CPP.

Interpretation of guidelines for the acute medical management of severe traumatic brain injury in infants,children,and adolescents——second edition

New guideline for the acute medical management of severe traumatic brain injury in infants, children, and adolescents was published in Pediatric Critical Care Medicine in 2012. This guideline made relevant recommendations and suggestions on intracranial pressure monitoring, threshold for treatment of intracranial hypertension, cerebral perfusion pressure thresholds, advanced neuromonitoring, neuroimaging and therapy for intracranial hypertension in pediatric patients with severe traumatic brain injury. This guideline was simply interpretated in order to improve the treatment of severe traumatic brain injury. Key words: Children; Severe traumatic brain injury; Intracranial pressure monitoring; Cerebral perfusion pressure; Moderate hypothermia

ABSTRACT 351

Background and aims: A minimum cerebral perfusion pressure (CPP) of 40 mm Hg is acceptable in children with traumatic brain injury. Optimal CPP threshold in acute CNS infections remain undefined. Aims: To identify the impact of different CPP thresholds on mortality in children with acute CNS infections. Methods: Design: Retrospective analysis of prospectively collected data in level-III PICU. Subjects: 231 children, aged 1–12 years, with raised ICP and modified-GCS Score ≤ 8. Interventions: ICP monitoring using intraparenchymal microtransducer (Codman®). CPP was targeted by fluid boluses, vasopressors and anti-raised-ICP measures. Based on mean CPP in first 72 hours, patients were divided into Groups I (30–40) (n=25), II (41–50) (n=31), III (51–60) (n=56) and IV (≥60) (n=119). Outcomes: Primary: 90-day mortality. Secondary: 72-hour m-GCS score, length of mechanical ventilation, PICU stay, and functional status at 3 months. Statistics: Cox-regression adjusted for age, sex, diagnosis, PRISM-III, opening ICP, PRBC transfusion and osmotherapy. Department review committee approved the study. Results: 90-day-mortality was lower in Group IV (13.4%) than Groups I (96.2%; adjusted HR=16.75, 95% CI 8.75–32, p<0.001), II (64.5%; adjusted HR=7.38, 95% CI 3.8–14.35, p<0.001), III (32.7%; adjusted HR=2.4, 95% CI 1.41–5.37, p=0.003). Median m-GCS score was higher in Group IV (10; IQR 8–11) than others (<8) (p<0.001). Length of mechanical ventilation (Log-rank p<0.001) and PICU stay (Log-rank p<0.001) were lower in Group IV. Intact survival at 3 months was higher in Group-IV (54/103, 52.4%) than others (p<0.001). Conclusions: CPP ≥ 60 mm Hg is independently associated with lower mortality in children with acute CNS infections.

Age-specific cerebral perfusion pressure thresholds and survival in children and adolescents with severe traumatic brain injury*.

Evidence-based traumatic brain injury guidelines support cerebral perfusion pressure thresholds for adults at a class 2 level, but evidence is lacking in younger patients. The purpose of this study is to identify the impact of age-specific cerebral perfusion pressure thresholds on short-term survival among patients with severe traumatic brain injury. Institutional review board-approved, prospective, observational cohort study. Level I or II trauma centers in New York State. Data on all patients with a postresuscitation Glasgow Coma Score less than 9 were added in the Brain Trauma Foundation prospective New York State TBI-trac database. We calculated the survival rates and relative risks of mortality for patients with severe traumatic brain injury based on predefined age-specific cerebral perfusion pressure thresholds. A higher threshold and a lower threshold were defined for each age group: 60 and 50 mm Hg for 12 years old or older, 50 and 35 mm Hg for 6-11 years, and 40 and 30 mm Hg for 0-5 years. Patients were stratified into age groups of 0-11, 12-17, and 18 years old or older. Three exclusive groups of CPP-L (events below low cerebral perfusion pressure threshold), CPP-B (events between high and low cerebral perfusion pressure thresholds), and CPP-H (events above high cerebral perfusion pressure threshold) were defined. As an internal control, we evaluated the associations between cerebral perfusion pressure events and events of hypotension and elevated intracranial pressure. Survival was significantly higher in 0-11 and 18 years old or older age groups for patients with CPP-H events compared with those with CPP-L events. There was a significant decrease in survival with prolonged exposure to CPP-B events for the 0-11 and 18 years old and older age groups when compared with the patients with CPP-H events (p = 0.0001 and p = 0.042, respectively). There was also a significant decrease in survival with prolonged exposure to CPP-L events in all age groups compared with the patients with CPP-H events (p< 0.0001 for 0- to 11-yr olds, p = 0.0240 for 12- to 17-yr olds, and p < 0.0001 for 18-yr old and older age groups). The 12- to 17-year olds had a significantly higher likelihood of survival compared with adults with prolonged exposure to CPP-L events (< 50 mm Hg). CPP-L events were significantly related to systemic hypotension for the 12- to 17-year-old group (p = 0.004) and the 18-year-old and older group (p < 0.0001). CPP-B events were significantly related to systemic hypotension in the 0- to 11-year-old group (p = 0.014). CPP-B and CPP-L events were significantly related to elevated intracranial pressure in all age groups. Our data provide new evidence that cerebral perfusion pressure targets should be age specific. Furthermore, cerebral perfusion pressure goals above 50 or 60 mm Hg in adults, above 50 mm Hg in 6- to 17-year olds, and above 40 mm Hg in 0- to 5-year olds seem to be appropriate targets for treatment-based studies. Systemic hypotension had an inconsistent relationship to events of low cerebral perfusion pressure, whereas elevated intracranial pressure was significantly related to all low cerebral perfusion pressure events across all age groups. This may impart a clinically important difference in care, highlighting the necessity of controlling intracranial pressure at all times, while targeting systolic blood pressure in specific instances.

Confusion with cerebral perfusion pressure in a literature review of current guidelines and survey of clinical practise

BackgroundCerebral perfusion pressure (CPP) is defined as the difference between the mean arterial pressure (MAP) and the intracranial pressure (ICP). However, since patients with traumatic brain injury (TBI) are usually treated with head elevation, the recorded CPP values depends on the zero level used for calibration of the arterial blood pressure. Although international guidelines suggest that target values of optimal CPP are within the range of 50 – 70 mmHg in patients with TBI, the calibration of blood pressure, which directly influences CPP, is not described in the guidelines.The aim of this study was to review the literature used to support the CPP recommendations from the Brain Trauma Foundation, and to survey common clinical practice with respect to MAP, CPP targets and head elevation in European centres treating TBI patients.MethodsA review of the literature behind CPP threshold recommendations was performed. Authors were contacted if the publications did not report how MAP or CPP was measured. A short questionnaire related to measurement and treatment targets of MAP and CPP was sent to European neurosurgical centres treating patients with TBI.ResultsAssessment methods for CPP measurement were only retrieved from 6 of the 11 studies cited in the TBI guidelines. Routines for assessment of CPP varied between these 6 publications. The 58 neurosurgical centres that answered our survey reported diverging routines on how to measure MAP and target CPP values. Higher CPP threshold were not observed if blood pressure was calibrated at the heart level (p = 0.51).ConclusionsThe evidence behind the recommended CPP thresholds shows no consistency on how blood pressure is calibrated and clinical practice for MAP measurements and CPP target values seems to be highly variable. Until a consensus is reached on how to measure CPP, confusion will prevail.