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.

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.

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

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

ICP, PRx, CPP, and ∆CPPopt in pediatric traumatic brain injury: the combined effect of insult intensity and duration on outcome.

PURPOSE: The aim was to investigate the combined effect of insult intensity and duration, regarding intracranial pressure (ICP), pressure reactivity index (PRx), cerebral perfusion pressure (CPP), and optimal CPP (CPPopt), on clinical outcome in pediatric traumatic brain injury (TBI). METHOD: This observational study included 61 pediatric patients with severe TBI, treated at the Uppsala University Hospital, between 2007 and 2018, with at least 12 h of ICP data the first 10 days post-injury. ICP, PRx, CPP, and ∆CPPopt (actual CPP-CPPopt) insults were visualized as 2-dimensional plots to illustrate the combined effect of insult intensity and duration on neurological recovery. RESULTS: This cohort was mostly adolescent pediatric TBI patients with a median age at 15 (interquartile range 12-16) years. For ICP, brief episodes (minutes) above 25 mmHg and slightly longer episodes (20 min) of ICP 20-25 mmHg correlated with unfavorable outcome. For PRx, brief episodes above 0.25 as well as slightly lower values (around 0) for longer periods of time (30 min) were associated with unfavorable outcome. For CPP, there was a transition from favorable to unfavorable outcome for CPP below 50 mmHg. There was no association between high CPP and outcome. For ∆CPPopt, there was a transition from favorable to unfavorable outcome when ∆CPPopt went below -10 mmHg. No association was found for positive ∆CPPopt values and outcome. CONCLUSIONS: This visualization method illustrated the combined effect of insult intensity and duration in relation to outcome in severe pediatric TBI, supporting previous notions to avoid high ICP and low CPP for longer episodes of time. In addition, higher PRx for longer episodes of time and CPP below CPPopt more than -10 mmHg were associated with worse outcome, indicating a potential role for autoregulatory-oriented management in pediatric TBI.

Higher intracranial pressure variability is associated with lower cerebrovascular resistance in aneurysmal subarachnoid hemorrhage.

Higher intracranial pressure variability (ICPV) has been associated with a more favorable cerebral energy metabolism, lower rate of delayed ischemic neurologic deficits, and more favorable outcome in aneurysmal subarachnoid hemorrhage (aSAH). We have hypothesized that higher ICPV partly reflects more compliant and active cerebral vessels. In this study, the aim was to further test this by investigating if higher ICPV was associated with lower cerebrovascular resistance (CVR) and higher cerebral blood flow (CBF) after aSAH. In this observational study, 147 aSAH patients were included, all of whom had been treated in the Neurointensive Care (NIC) Unit, Uppsala, Sweden, 2012-2020. They were required to have had ICP monitoring and at least one xenon-enhanced computed tomography (Xe-CT) scan to study cortical CBF within the first 2 weeks post-ictus. CVR was defined as the cerebral perfusion pressure in association with the Xe-CT scan divided by the concurrent CBF. ICPV was defined over three intervals: subminute (ICPV-1m), 30-min (ICPV-30m), and 4 h (ICPV-4h). The first 14 days were divided into early (days 1-3) and vasospasm phase (days 4-14). In the vasospasm phase, but not in the early phase, higher ICPV-4h (ß = - 0.19, p < 0.05) was independently associated with a lower CVR in a multiple linear regression analysis and with a higher global cortical CBF (r = 0.19, p < 0.05) in a univariate analysis. ICPV-1m and ICPV-30m were not associated with CVR or CBF in any phase. This study corroborates the hypothesis that higher ICPV, at least in the 4-h interval, is favorable and may reflect more compliant and possibly more active cerebral vessels.

Association of Arterial Metabolic Content with Cerebral Blood Flow Regulation and Cerebral Energy Metabolism-A Multimodality Analysis in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: In this study, the association of the arterial content of oxygen, carbon dioxide, glucose, and lactate with cerebral pressure reactivity, energy metabolism and clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH) was investigated. METHODS: In this retrospective study, 60 patients with aSAH, treated at the neurointensive care (NIC), Uppsala University Hospital, Sweden, between 2016 and 2021 with arterial blood gas (ABG), intracranial pressure, and cerebral microdialysis (MD) monitoring were included. The first 10 days were divided into an early phase (day 1 to 3) and a vasospasm phase (day 4 to 10). RESULTS: Higher arterial lactate was independently associated with higher/worse pressure reactivity index (PRx) in the early phase (ß = 0.32, P = .02), whereas higher pO2 had the opposite association in the vasospasm phase (ß = -0.30, P = .04). Arterial glucose and pCO2 were not associated with PRx. Higher arterial lactate (ß = 0.29, P = .05) was independently associated with higher MD-glucose in the vasospasm phase, whereas higher pO2 had the opposite association in the vasospasm phase (ß = -0.33, P = .03). Arterial glucose and pCO2 were not associated with MD-glucose. Higher pCO2 in the early phase, lower arterial glucose in both phases, and lower arterial lactate in the vasospasm phase were associated (P < .05) with better clinical outcome. CONCLUSIONS: Arterial variables associated with more vasoconstriction (higher pO2 and lower arterial lactate) were associated with better cerebral pressure reactivity, but worse energy metabolism. In severe aSAH, when cerebral large-vessel vasospasm with exhausted distal vasodilation is common, more vasoconstriction could increase distal vasodilatory reserve and pressure reactivity, but also reduce cerebral blood flow and metabolic supply. The MD may be useful to monitor the net effects on cerebral metabolism in PRx-targeted NIC.

Neurointensive care of traumatic brain injury in the elderly-age-specific secondary insult levels and optimal physiological levels to target need to be defined.

BACKGROUND: Elderly patients with traumatic brain injury increase. Current targets and secondary insult definitions during neurointensive care (NIC) are mostly based on younger patients. The aim was therefore to study the occurrence of predefined secondary insults and the impact on outcome in different ages with particular focus on elderly. METHODS: Patients admitted to Uppsala 2008-2014 were included. Patient characteristics, NIC management, monitoring data, and outcome were analyzed. The percentage of monitoring time for ICP, CPP, MAP, and SBP above-/below-predefined thresholds was calculated. RESULTS: Five hundred seventy patients were included, 151 elderly ≥ 65 years and 419 younger 16-64 years. Age ≥ 65 had significantly higher percentage of CPP > 100, MAP > 120, and SBP > 180 and age 16-64 had higher percentage of ICP ≥ 20, CPP ≤ 60, and MAP ≤ 80. Age ≥ 65 contributed independently to the different secondary insult patterens. When patients in all ages were analyzed, low percentage of CPP > 100 and SBP > 180, respectively, was significant predictors of favorable outcome and high percentage of ICP ≥ 20, CPP > 100, SBP ≤ 100, and SBP > 180, respectively, was predictors of death. Analysis of age interaction showed that patients ≥ 65 differed and had a higher odds for favorable outcome with large proportion of good monitoring time with SBP > 180. CONCLUSIONS: Elderly ≥ 65 have different patterns of secondary insults/physiological variables, which is independently associated to age. The finding that SBP > 180 increased the odds of favorable outcome in the elderly but decreased the odds in younger patients may indicate that blood pressure should be treated differently depending on age.

Prognosis in moderate-severe traumatic brain injury in a Swedish cohort and external validation of the IMPACT models.

BACKGROUND: A major challenge in management of traumatic brain injury (TBI) is to assess the heterogeneity of TBI pathology and outcome prediction. A reliable outcome prediction would have both great value for the healthcare provider, but also for the patients and their relatives. A well-known prediction model is the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) prognostic calculator. The aim of this study was to externally validate all three modules of the IMPACT calculator on TBI patients admitted to Uppsala University hospital (UUH). METHOD: TBI patients admitted to UUH are continuously enrolled into the Uppsala neurointensive care unit (NICU) TBI Uppsala Clinical Research (UCR) quality register. The register contains both clinical and demographic data, radiological evaluations, and outcome assessments based on the extended Glasgow outcome scale extended (GOSE) performed at 6 months to 1 year. In this study, we included 635 patients with severe TBI admitted during 2008-2020. We used IMPACT core parameters: age, motor score, and pupillary reaction. RESULTS: The patients had a median age of 56 (range 18-93), 142 female and 478 male. Using the IMPACT Core model to predict outcome resulted in an AUC of 0.85 for mortality and 0.79 for unfavorable outcome. The CT module did not increase AUC for mortality and slightly decreased AUC for unfavorable outcome to 0.78. However, the lab module increased AUC for mortality to 0.89 but slightly decreased for unfavorable outcome to 0.76. Comparing the predicted risk to actual outcomes, we found that all three models correctly predicted low risk of mortality in the surviving group of GOSE 2-8. However, it produced a greater variance of predicted risk in the GOSE 1 group, denoting general underprediction of risk. Regarding unfavorable outcome, all models once again underestimated the risk in the GOSE 3-4 groups, but correctly predicts low risk in GOSE 5-8. CONCLUSIONS: The results of our study are in line with previous findings from centers with modern TBI care using the IMPACT model, in that the model provides adequate prediction for mortality and unfavorable outcome. However, it should be noted that the prediction is limited to 6 months outcome and not longer time interval.

Intracranial pressure- and cerebral perfusion pressure threshold-insults in relation to cerebral energy metabolism in aneurysmal subarachnoid hemorrhage.

BACKGROUND: The aim was to investigate the association between intracranial pressure (ICP)- and cerebral perfusion pressure (CPP) threshold-insults in relation to cerebral energy metabolism and clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: In this retrospective study, 75 aSAH patients treated in the neurointensive care unit, Uppsala, Sweden, 2008-2018, with ICP and cerebral microdialysis (MD) monitoring were included. The first 10 days were divided into early (day 1-3), early vasospasm (day 4-6.5), and late vasospasm phase (day 6.5-10). The monitoring time (%) of ICP insults (> 20 mmHg and > 25 mmHg), CPP insults (< 60 mmHg, < 70 mmHg, < 80 mmHg, and < 90 mmHg), and autoregulatory CPP optimum (CPPopt) insults (∆CPPopt = CPP-CPPopt < - 10 mmHg, ∆CPPopt > 10 mmHg, and within the optimal interval ∆CPPopt ± 10 mmHg) were calculated in each phase. RESULTS: Higher percent of ICP above the 20 mmHg and 25 mmHg thresholds correlated with lower MD-glucose and increased MD-lactate-pyruvate ratio (LPR), particularly in the vasospasm phases. Higher percentage of CPP below all four thresholds (60/70/80//90 mmHg) also correlated with a MD pattern of poor cerebral substrate supply (MD-LPR > 40 and MD-pyruvate < 120 µM) in the vasospasm phase and higher burden of CPP below 60 mmHg was independently associated with higher MD-LPR in the late vasospasm phase. Higher percentage of CPP deviation from CPPopt did not correlate with worse cerebral energy metabolism. Higher burden of CPP-insults below all fixed thresholds in both vasospasm phases were associated with worse clinical outcome. The percentage of ICP-insults and CPP close to CPPopt were not associated with clinical outcome. CONCLUSIONS: Keeping ICP below 20 mmHg and CPP at least above 60 mmHg may improve cerebral energy metabolism and clinical outcome.

Cerebral Blood Flow and Oxygen Delivery in Aneurysmal Subarachnoid Hemorrhage: Relation to Neurointensive Care Targets.

BACKGROUND: The primary aim was to determine to what extent continuously monitored neurointensive care unit (neuro-ICU) targets predict cerebral blood flow (CBF) and delivery of oxygen (CDO2) after aneurysmal subarachnoid hemorrhage. The secondary aim was to determine whether CBF and CDO2 were associated with clinical outcome. METHODS: In this observational study, patients with aneurysmal subarachnoid hemorrhage treated at the neuro-ICU in Uppsala, Sweden, from 2012 to 2020 with at least one xenon-enhanced computed tomography (Xe-CT) obtained within the first 14 days post ictus were included. CBF was measured with the Xe-CT and CDO2 was calculated based on CBF and arterial oxygen content. Regional cerebral hypoperfusion was defined as CBF < 20 mL/100 g/min, and poor CDO2 was defined as CDO2 < 3.8 mL O2/100 g/min. Neuro-ICU variables including intracranial pressure (ICP), pressure reactivity index, cerebral perfusion pressure (CPP), optimal CPP, and body temperature were assessed in association with the Xe-CT. The acute phase was divided into early phase (day 1-3) and vasospasm phase (day 4-14). RESULTS: Of 148 patients, 27 had underwent a Xe-CT only in the early phase, 74 only in the vasospasm phase, and 47 patients in both phases. The patients exhibited cerebral hypoperfusion and poor CDO2 for medians of 15% and 30%, respectively, of the cortical brain areas in each patient. In multiple regressions, higher body temperature was associated with higher CBF and CDO2 in the early phase. In a similar regression for the vasospasm phase, younger age and longer pulse transit time (lower peripheral resistance) correlated with higher CBF and CDO2, whereas lower hematocrit only correlated with higher CBF but not with CDO2. ICP, CPP, and pressure reactivity index exhibited no independent association with CBF and CDO2. R2 of these regressions were below 0.3. Lower CBF and CDO2 in the early phase correlated with poor outcome, but this only held true for CDO2 in multiple regressions. CONCLUSIONS: Systemic and cerebral physiological variables exhibited a modest association with CBF and CDO2. Still, cerebral hypoperfusion and low CDO2 were common and low CDO2 was associated with poor outcome. Xe-CT imaging could be useful to help detect secondary brain injury not evident by high ICP and low CPP.

Low intracranial pressure variability is associated with delayed cerebral ischemia and unfavorable outcome in aneurysmal subarachnoid hemorrhage.

PURPOSE: High intracranial pressure variability (ICPV) is associated with favorable outcome in traumatic brain injury, by mechanisms likely involving better cerebral blood flow regulation. However, less is known about ICPV in aneurysmal subarachnoid hemorrhage (aSAH). In this study, we investigated the explanatory variables for ICPV in aSAH and its association with delayed cerebral ischemia (DCI) and clinical outcome. METHODS: In this retrospective study, 242 aSAH patients, treated at the neurointensive care, Uppsala, Sweden, 2008-2018, with ICP monitoring the first ten days post-ictus were included. ICPV was evaluated on three time scales: (1) ICPV-1 m-ICP slow wave amplitude of wavelengths between 55 and 15 s, (2) ICPV-30 m-the deviation from the mean ICP averaged over 30 min, and (3) ICPV-4 h-the deviation from the mean ICP averaged over 4 h. The ICPV measures were analyzed in the early phase (day 1-3), in the early vasospasm phase (day 4-6.5), and the late vasospasm phase (day 6.5-10). RESULTS: High ICPV was associated with younger age, reduced intracranial pressure/volume reserve (high RAP), and high blood pressure variability in multiple linear regression analyses for all ICPV measures. DCI was associated with reduced ICPV in both vasospasm phases. High ICPV-1 m in the post-ictal early phase and the early vasospasm phase predicted favorable outcome in multiple logistic regressions, whereas ICPV-30 m and ICPV-4 h in the late vasospasm phase had a similar association. CONCLUSIONS: Higher ICPV may reflect more optimal cerebral vessel activity, as reduced values are associated with an increased risk of DCI and unfavorable outcome after aSAH.

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

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

Temporal effects of barbiturate coma on intracranial pressure and compensatory reserve in children with traumatic brain injury.

BACKGROUND: The aim was to study the effects of barbiturate coma treatment (BCT) on intracranial pressure (ICP) and intracranial compensatory reserve (RAP index) in children (< 17 years of age) with traumatic brain injury (TBI) and refractory intracranial hypertension (RICH). METHODS: High-resolution monitoring data were used to study the effects of BCT on ICP, mean arterial pressure (MAP), cerebral perfusion pressure (CPP), and RAP index. Four half hour long periods were studied: before bolus injection and at 5, 10, and 24 hours thereafter, respectively, and a fifth tapering period with S-thiopental between < 100 and < 30 µmol/L. S-thiopental concentrations and administered doses were registered. RESULTS: Seventeen children treated with BCT 2007-2017 with high-resolution data were included; median age 15 (range 6-17) and median Glasgow coma score 7 (range 3-8). Median time from trauma to start of BCT was 44.5 h (range 2.5-197.5) and from start to stop 99.0 h (range 21.0-329.0). Median ICP was 22 (IQR 20-25) in the half hour period before onset of BCT and 16 (IQR 11-20) in the half hour period 5 h later (p = 0.011). The corresponding figures for CPP were 65 (IQR 62-71) and 63 (57-71) (p > 0.05). The RAP index was in the half hour period before onset of BCT 0.6 (IQR 0.1-0.7), in the half hour period 5 h later 0.3 (IQR 0.1-0.7) (p = 0.331), and in the whole BCT period 0.3 (IQR 0.2-0.4) (p = 0.004). Eighty-two percent (14/17) had favorable outcome (good recovery = 8 patients and moderate disability = 6 patients). CONCLUSION: BCT significantly reduced ICP and RAP index with preserved CPP. BCT should be considered in case of RICH.

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

BACKGROUND: High 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. METHODS: In 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 (%). RESULTS: Of 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. CONCLUSIONS: Avoiding 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 pressure variability: relation to clinical outcome, intracranial pressure-volume index, cerebrovascular reactivity and blood pressure variability.

It was recently found in traumatic brain injury (TBI) that ICP variability (ICPV) predicted favorable outcome. We hypothesized that ICPV may depend on intracranial compliance, unstable blood pressure and cerebral vasomotion. In this study, we aimed to further investigate the explanatory variables for ICPV and its relation to outcome. Data from 362 TBI patients were retrospectively analyzed day 2 to 5 post-injury. ICPV was evaluated in three ways. First, variability in the sub-minute time interval (similar to B waves) was calculated as the amplitude of the ICP slow waves using a bandpass filter, limiting the analysis to oscillations of 55 to 15 s (ICP AMP 55-15). The second and third ICPV measures were calculated as the deviation from the mean ICP averaged over 30 min (ICPV-30m) and 4 h (ICPV-4h), respectively. All ICPV measures were associated with a reduced intracranial pressure/volume state (high ICP and RAP) and high blood pressure variability in multiple linear regression analyses. Higher ICPV was associated with better pressure reactivity in the univariate, but not the multiple analyses. All ICPV measures were associated with favorable outcome in univariate analysis, but only ICP AMP 55-15 and ICPV-30m did so in the multiple logistic regression analysis. Higher ICPV can be explained by a reduced intracranial compliance and variations in cerebral blood volume due to the vessel response to unstable blood pressure. As ICP AMP 55-15 and ICPV-30m independently predicted favorable outcome, it may represent general cerebral vessel activity, associated with better cerebral blood flow regulation and less secondary insults.

High Arterial Glucose is Associated with Poor Pressure Autoregulation, High Cerebral Lactate/Pyruvate Ratio and Poor Outcome Following Traumatic Brain Injury.

BACKGROUND: Arterial hyperglycemia is associated with poor outcome in traumatic brain injury (TBI), but the pathophysiology is not completely understood. Previous preclinical and clinical studies have indicated that arterial glucose worsens pressure autoregulation. The aim of this study was to evaluate the relationship of arterial glucose to both pressure reactivity and cerebral energy metabolism. METHOD: This retrospective study was based on 120 patients with severe TBI treated at the Uppsala University hospital, Sweden, 2008-2018. Data from cerebral microdialysis (glucose, pyruvate, and lactate), arterial glucose, and pressure reactivity index (PRx55-15) were analyzed the first 3 days post-injury. RESULTS: High arterial glucose was associated with poor outcome/Glasgow Outcome Scale-Extended at 6-month follow-up (r = - 0.201, p value = 0.004) and showed a positive correlation with both PRx55-15 (r = 0.308, p = 0.001) and cerebral lactate/pyruvate ratio (LPR) days 1-3 (r = 0. 244, p = 0.014). Cerebral lactate-to-pyruvate ratio and PRx55-15 had a positive association day 2 (r = 0.219, p = 0.048). Multivariate linear regression analysis showed that high arterial glucose predicted poor pressure autoregulation on days 1 and 2. CONCLUSIONS: High arterial glucose was associated with poor outcome, poor pressure autoregulation, and cerebral energy metabolic disturbances. The latter two suggest a pathophysiological mechanism for the negative effect of arterial hyperglycemia, although further studies are needed to elucidate if the correlations are causal or confounded by other factors.

Multivariate projection method to investigate inflammation associated with secondary insults and outcome after human traumatic brain injury: a pilot study.

BACKGROUND: Neuroinflammation has been proposed as a possible mechanism of brain damage after traumatic brain injury (TBI), but no consensus has been reached on the most relevant molecules. Furthermore, secondary insults occurring after TBI contribute to worsen neurological outcome in addition to the primary injury. We hypothesized that after TBI, a specific pattern of cytokines is related to secondary insults and outcome. METHODS: A prospective observational clinical study was performed. Secondary insults by computerized multimodality monitoring system and systemic value of different cytokines were collected and analysed in the first week after intensive care unit admission. Neurological outcome was assessed at 6 months (GOSe). Multivariate projection technique was applied to analyse major sources of variation and collinearity within the cytokines dataset without a priori selecting potential relevant molecules. RESULTS: Twenty-nine severe traumatic brain injury patients undergoing intracranial pressure monitoring were studied. In this pilot study, we demonstrated that after TBI, patients who suffered of prolonged and severe secondary brain damage are characterised by a specific pattern of cytokines. Patients evolving to brain death exhibited higher levels of inflammatory mediators compared to both patients with favorable and unfavorable neurological outcome at 6 months. Raised ICP and low cerebral perfusion pressure occurred in 21 % of good monitoring time. Furthermore, the principal components selected by multivariate projection technique were powerful predictors of neurological outcome. CONCLUSIONS: The multivariate projection method represents a valuable methodology to study neuroinflammation pattern occurring after secondary brain damage in severe TBI patients, overcoming multiple putative interactions between mediators and avoiding any subjective selection of relevant molecules.

Telemetric intracranial pressure monitoring: a noninvasive method to follow up children with complex craniosynostoses. A case report.

INTRODUCTION: There are no reliable noninvasive methods of monitoring ICP. Most assessments are made by indirect measures and are difficult to follow over time. Invasive studies can be used but up until now have required in-hospital transcutaneous measurements. Accurate ICP recordings over longer periods of time can be very valuable in timing different surgical procedures in syndromal cases. This case shows that telemetric ICP monitoring can be used for long-term follow-up in patients that may need repeated surgeries related to their craniosynostosis condition. CASE REPORT: In this report, the telemetric ICP probe (Raumedic Neurovent-P-tel) was implanted before surgery and was used for repeated "noninvasive" ICP recordings pre- and postoperatively in a patient with craniosynostosis. The patient was an eight-year-old girl with pansynostosis with only the right lambdoid suture open. A telemetric ICP probe was implanted the day before cranial vault remodeling and the ICP was monitored pre- and postoperatively. The ICP was above 15 mmHg 72.2 % of the monitoring time before surgery, and the amplitude of the curve was greater than normal suggesting impaired compliance. Direct postoperative ICP was normal, and the amplitude was lower. The ICP was then monitored both in out-patient clinic and in four longer hospital stays. Both the values and the curves were analyzed, and the time with ICP above 15 mmHg decreased over time, and the waveform amplitude of the curves improved. CONCLUSION: This "noninvasive" way of recording ICP is a feasible and helpful tool in decision-making and intervening in patients with craniosynostosis.

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

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