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Two novel triads based on a diketopyrrolopyrrole (DPP) central core and two 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) units attached by thiophene rings have been synthesised having high molar extinction coefficients. These triads were characterised and used as donor materials in small molecule, solution processable organic solar cells. Both triads were blended with PC71BM as an acceptor in different ratios by wt % and their photovoltaic properties were studied. For both the triads a modest photovoltaic performance was observed, having an efficiency of 0.65%. Moreover, in order to understand the ground and excited state properties and vertical absorption profile of DPP and BODIPY units within the triads, theoretical DFT and TDDFT calculations were performed.

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2024. The Author(s).)

Background: In neurointensive care, increased intracranial pressure (ICP) is a feared secondary brain insult in traumatic brain injury (TBI). A system that predicts ICP insults before they emerge may facilitate early optimization of the physiology, which may in turn lead to stopping the predicted ICP insult from occurring. The aim of this study was to evaluate the performance of different artificial intelligence models in predicting the risk of ICP insults., Methods: The models were trained to predict risk of ICP insults starting within 30 min, using the Uppsala high frequency TBI dataset. A restricted dataset consisting of only monitoring data were used, and an unrestricted dataset using monitoring data as well as clinical data, demographic data, and radiological evaluations was used. Four different model classes were compared: Gaussian process regression, logistic regression, random forest classifier, and Extreme Gradient Boosted decision trees (XGBoost)., Results: Six hundred and two patients with TBI were included (total monitoring 138,411 h). On the task of predicting upcoming ICP insults, the Gaussian process regression model performed similarly on the Uppsala high frequency TBI dataset (sensitivity 93.2%, specificity 93.9%, area under the receiver operating characteristic curve [AUROC] 98.3%), as in earlier smaller studies. Using a more flexible model (XGBoost) resulted in a comparable performance (sensitivity 93.8%, specificity 94.6%, AUROC 98.7%). Adding more clinical variables and features further improved the performance of the models slightly (XGBoost: sensitivity 94.1%, specificity of 94.6%, AUROC 98.8%)., Conclusions: Artificial intelligence models have potential to become valuable tools for predicting ICP insults in advance during neurointensive care. The fact that common off-the-shelf models, such as XGBoost, performed well in predicting ICP insults opens new possibilities that can lead to faster advances in the field and earlier clinical implementations., (© 2024. The Author(s).)

Background: This single-center, retrospective study investigated the outcome effect of the combined intensity and duration of differences between actual cerebral perfusion pressure (CPP) and optimal cerebral perfusion pressure (CPPopt), and also for absolute CPP, in patients with traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (aSAH)., Methods: A total of 378 TBI and 432 aSAH patients treated in a neurointensive care unit between 2008 and 2018 with at least 24 hours of CPPopt data during the first 10 days following injury, and with 6-month (TBI) or 12-month (aSAH) extended Glasgow Outcome Scale (GOS-E) scores, were included in the study. ∆CPPopt-insults (∆CPPopt=actual CPP-CPPopt) and CPP-insults were visualized as 2-dimensional plots to highlight the combined effect of insult intensity (mm Hg) and duration (min) on patient outcome., Results: In TBI patients, a zone of ∆CPPopt ± 10 mm Hg was associated with more favorable outcome, with transitions towards unfavorable outcome above and below this zone. CPP in the range of 60 to 80 mm Hg was associated with higher GOS-E, whereas CPP outside this range was associated with lower GOS-E. In aSAH patients, there was no clear transition from higher to lower GOS-E for ∆CPPopt-insults; however, there was a transition from favorable to unfavorable outcome when CPP was <80 mm Hg., Conclusions: TBI patients with CPP close to CPPopt exhibited better clinical outcomes, and absolute CPP within the 60 to 80 mm Hg range was also associated with favorable outcome. In aSAH patients, there was no clear transition for ∆CPPopt-insults in relation to outcome, whereas generally high absolute CPP values were associated overall with favorable recovery., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Cerebral perfusion pressure (CPP) management in the developing child with traumatic brain injury (TBI) is challenging. The pressure reactivity index (PRx) may serve as marker of cerebral pressure autoregulation (CPA) and optimal CPP (CPPopt) may be assessed by identifying the CPP level with best (lowest) PRx. To evaluate the potential of CPPopt guided management in children with severe TBI, cerebral microdialysis (CMD) monitoring levels of lactate and the lactate/pyruvate ratio (LPR) (indicators of ischemia) were related to actual CPP levels, autoregulatory state (PRx) and deviations from CPPopt (ΔCPPopt)., Methods: Retrospective study of 21 children ≤ 17 years with severe TBI who had both ICP and CMD monitoring were included. CPP, PRx, CPPopt and ΔCPPopt where calculated, dichotomized and compared with CMD lactate and lactate-pyruvate ratio., Results: Median age was 16 years (range 8-17) and median Glasgow coma scale motor score 5 (range 2-5). Both lactate (p = 0.010) and LPR (p =  < 0.001) were higher when CPP ≥ 70 mmHg than when CPP < 70. When PRx ≥ 0.1 both lactate and LPR were higher than when PRx < 0.1 (p =  < 0.001). LPR was lower (p = 0.012) when CPPopt ≥ 70 mmHg than when CPPopt < 70, but there were no differences in lactate levels. When ΔCPPopt > 10 both lactate (p = 0.026) and LPR (p = 0.002) were higher than when ΔCPPopt < -10., Conclusions: Increased levels of CMD lactate and LPR in children with severe TBI appears to be related to disturbed CPA (PRx). Increased lactate and LPR also seems to be associated with actual CPP levels ≥ 70 mmHg. However, higher lactate and LPR values were also seen when actual CPP was above CPPopt. Higher CPP appears harmful when CPP is above the upper limit of pressure autoregulation. The findings indicate that CPPopt guided CPP management may have potential in pediatric TBI., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

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.

Introduction: In this study, we investigated the roles of cerebral blood flow (CBF) and cerebral oxygen delivery (CDO 2 ) in relation to cerebral energy metabolism after aneurysmal subarachnoid hemorrhage (aSAH)., Methods: Fifty-seven adult aSAH patients treated on the neurointensive care unit at Uppsala, Sweden between 2012 and 2020, with at least 1 xenon-enhanced computed tomography (Xe-CT) scan in the first 14 days after ictus and concurrent microdialysis (MD) monitoring, were included in this retrospective study. CBF was measured globally and focally (around the MD catheter) with Xe-CT, and CDO 2 calculated. Cerebral energy metabolites were measured using MD., Results: Focal ischemia (CBF <20 mL/100 g/min around the MD catheter was associated with lower median [interquartile range]) MD-glucose (1.2 [0.7 to 2.2] mM vs. 2.3 [1.3 to 3.5] mM; P =0.05) and higher MD-lactate-pyruvate (LPR) ratio (34 [29 to 66] vs. 25 [21 to 32]; P =0.02). A compensated/normal MD pattern (MD-LPR <25) was observed in the majority of patients (22/23, 96%) without focal ischemia, whereas 4 of 11 (36%) patients with a MD pattern of poor substrate supply (MD-LPR >25, MD-pyruvate <120 µM) had focal ischemia as did 5 of 20 (25%) patients with a pattern of mitochondrial dysfunction (MD-LPR >25, MD-pyruvate >120 µM) ( P =0.04). Global CBF and CDO 2 , and focal CDO 2 , were not associated with the MD variables., Conclusions: While MD is a feasible tool to study cerebral energy metabolism, its validity is limited to a focal area around the MD catheter. Cerebral energy disturbances were more related to low CBF than to low CDO 2 . Considering the high rate of mitochondrial dysfunction, treatments that increase CBF but not CDO 2 , such as hemodilution, may still benefit glucose delivery to drive anaerobic metabolism., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2023. The Author(s).)

Objectives: RESCUEicp studied decompressive craniectomy (DC) applied as third-tier option in severe traumatic brain injury (TBI) patients in a randomized controlled setting and demonstrated a decrease in mortality with similar rates of favorable outcome in the DC group compared to the medical management group. In many centers, DC is being used in combination with other second/third-tier therapies. The aim of the present study is to investigate outcomes from DC in a prospective non-RCT context., Methods: This is a prospective observational study of 2 patient cohorts: one from the University Hospitals Leuven (2008-2016) and one from the Brain-IT study, a European multicenter database (2003-2005). In thirty-seven patients with refractory elevated intracranial pressure who underwent DC as a second/third-tier intervention, patient, injury and management variables including physiological monitoring data and administration of thiopental were analysed, as well as Extended Glasgow Outcome score (GOSE) at 6 months., Results: In the current cohorts, patients were older than in the surgical RESCUEicp cohort (mean 39.6 vs. 32.3; p < 0.001), had higher Glasgow Motor Score on admission (GMS < 3 in 24.3% vs. 53.0%; p = 0.003) and 37.8% received thiopental (vs. 9.4%; p < 0.001). Other variables were not significantly different. GOSE distribution was: death 24.3%; vegetative 2.7%; lower severe disability 10.8%; upper severe disability 13.5%; lower moderate disability 5.4%; upper moderate disability 2.7%, lower good recovery 35.1%; and upper good recovery 5.4%. The outcome was unfavorable in 51.4% and favorable in 48.6%, as opposed to 72.6% and 27.4% respectively in RESCUEicp (p = 0.02)., Conclusion: Outcomes in DC patients from two prospective cohorts reflecting everyday practice were better than in RESCUEicp surgical patients. Mortality was similar, but fewer patients remained vegetative or severely disabled and more patients had a good recovery. Although patients were older and injury severity was lower, a potential partial explanation may be in the pragmatic use of DC in combination with other second/third-tier therapies in real-life cohorts. The findings underscore that DC maintains an important role in managing severe TBI., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: It was recently reported that lower intracranial pressure variability (ICPV) is associated with delayed ischemic neurological deficits and unfavorable outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to determine whether lower ICPV also correlated with worse cerebral energy metabolism after aSAH., Methods: A total of 75 aSAH patients treated in the neurointensive care unit at Uppsala University Hospital, Sweden between 2008 and 2018 and with both intracranial pressure and cerebral microdialysis (MD) monitoring during the first 10 days after ictus were included in this retrospective study. ICPV was calculated with a bandpass filter limited to intracranial pressure slow waves with a wavelength of 55 to 15 seconds. Cerebral energy metabolites were measured hourly with MD. The monitoring period was divided into 3 phases; early (days 1 to 3), early vasospasm (days 4 to 6.5), and late vasospasm (days 6.5 to 10)., Results: Lower ICPV was associated with lower MD-glucose in the late vasospasm phase, lower MD-pyruvate in the early vasospasm phases, and higher MD-lactate-pyruvate ratio (LPR) in the early and late vasospasm phases. Lower ICPV was associated with poor cerebral substrate supply (LPR >25 and pyruvate <120 µM) rather than mitochondrial failure (LPR >25 and pyruvate >120 µM). There was no association between ICPV and delayed ischemic neurological deficit, but lower ICPV in both vasospasm phases correlated with unfavorable outcomes., Conclusion: Lower ICPV was associated with an increased risk for disturbed cerebral energy metabolism and worse clinical outcomes in aSAH patients, possibly explained by a vasospasm-related decrease in cerebral blood volume dynamics and cerebral ischemia., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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 (β =  - 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., (© 2022. The Author(s).)

Critical care is complex and stressful. It is difficult to register in real time data not recorded by automatic systems. Time-specific knowledge of manual measures is important for understanding pathophysiology and for analyzing treatment and quality of care. Therefore, a novel iPad-based method for registration of manual measures was developed, which many can build themselves. Using a configuration for intracranial pressure (ICP) management, the methodology was validated, ICP treatment captured, and the quality of ICP management evaluated. Twenty-two patients with acute brain injuries were studied. The iPad-system was totally used for 2538 h. Thirteen-hundred-five manual measures were entered. Thirty-nine episodes of predefined ICP insults were identified. During 16/39 episodes, ICP treatments were registered. For 4/39 episodes treatments were registered within 90 s before or after the episode. For 3/39 episodes it was registered that treatment was intentionally refrained. In 15/16 episodes without registered treatment, the insult was mild or reasonable explanations were found when medical records and the Patient data management system were reviewed. In one situation without particular circumstances, morphine and clonidine were given to decrease ICP but not registered. No episodes of downtime or loss of data occurred. The developed methodology appears to be stable and robust as well as feasible and user-friendly. It was possible to capture the treatment of ICP insults with high temporal resolution, and to evaluate the quality of ICP management. An own developed novel tablet-based system like our system may be a promising potential tool useful in various future intensive care applications., (© 2022. The Author(s).)

Purpose: To investigate the association between two cardiac biomarkers, NT-proBNP and TnI, with intracranial pressure (ICP)-/cerebral perfusion pressure (CPP)-insults, cerebral pressure autoregulation, delayed ischemic neurological deficits (DIND), and clinical outcome after aneurysmal subarachnoid hemorrhage (aSAH)., Methods: In this retrospective study, 196 aSAH patients treated at the neurointensive care unit, Uppsala University Hospital, Sweden, 2011-2018, with ICP-monitoring and serial NT-proBNP and TnI measurements were included. The first 10 days were divided into early phase (day 1-3) and vasospasm phase (day 4-10)., Results: NT-proBNP and TnI were elevated above the reference interval at least once the first 10 days in 175 (89%) and 116 (59%) patients, respectively. In the vasospasm phase, higher NT-proBNP and TnI were associated with increased percentage of CPP below 60 mmHg. Higher TnI also correlated with more ICP-insults above 20 mmHg. NT-proBNP and TnI did not predict worse pressure autoregulation and DIND. Higher NT-proBNP and TnI were associated with mortality and unfavorable outcome in univariate, but not multivariate, analyses., Conclusion: Elevated NT-proBNP and TnI correlated with an increased burden of secondary ICP-/CPP-insults, but not with worse pressure autoregulation, DIND, and without independent association with clinical outcome., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

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 (β = 0.32, P  = .02), whereas higher pO 2 had the opposite association in the vasospasm phase (β = -0.30, P  = .04). Arterial glucose and pCO 2 were not associated with PRx. Higher arterial lactate (β = 0.29, P  = .05) was independently associated with higher MD-glucose in the vasospasm phase, whereas higher pO 2 had the opposite association in the vasospasm phase (β = -0.33, P  = .03). Arterial glucose and pCO 2 were not associated with MD-glucose. Higher pCO 2 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 pO 2 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.

The aim of the study was to investigate sex-related differences in intracranial pressure (ICP) dynamics, cerebral pressure autoregulation (PRx55-15), cerebral energy metabolism, and clinical outcome after severe traumatic brain injury (TBI). One-hundred sixty-nine adult patients with TBI, treated at the Neurointensive Care (NIC) Unit at Uppsala University Hospital between 2008 and 2020 with ICP and cerebral microdialysis (MD) monitoring were included. Of the 169 patients with TBI, 131 (78%) were male and 38 (22%) female. Male patients were more often injured by motor vehicle accidents and less often by bicycle accidents ( p  < 0.05). There were otherwise no differences in age, neurological status at admission, and types of intracranial hemorrhages between the sexes. The percent of monitoring time with ICP above 20 mm Hg and cerebral perfusion pressure (CPP) below 60 mm Hg were similar for both sexes. Males exhibited more disturbed cerebral pressure autoregulation (PRx55-15 [mean ± standard deviation (SD)]; 0.28 ± 0.18 vs. 0.17 ± 0.23, p  < 0.05) on day 1, worse cerebral energy metabolism (MD-lactate-/pyruvate-ratio [median (interquartile range)]; 25 [19-31] vs. 20 [17-25], p  < 0.01) and mitochondrial dysfunction (higher burden of MD-lactate-/pyruvate-ratio >25 and MD-pyruvate >120 μM [median (interquartile range)]; 13 [0-58] % vs. 3 [0-17] %, p  < 0.05) on days 2 to 5, increased excitotoxicity (MD-glutamate median [interquartile range]; 9 [4-32] μM vs. 5 [3-10] μM, p  < 0.05) on days 2 to 5, and higher biomarker levels of cellular injury (MD-glycerol median [interquartile range]; 103 [66-193] μM vs. 68 [49-106] μM, p  < 0.01) most pronounced on days 6 to 10. There was no difference in mortality or the degree of favorable outcome between the sexes. Altogether, females exhibited more favorable cerebral physiology post-TBI, particularly better mitochondrial function and reduced excitotoxicity, but this did not translate into better clinical outcome compared with males. Future studies are needed to further explore potential sex differences in secondary injury mechanisms in TBI.

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 (CDO 2 ) after aneurysmal subarachnoid hemorrhage. The secondary aim was to determine whether CBF and CDO 2 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 CDO 2 was calculated based on CBF and arterial oxygen content. Regional cerebral hypoperfusion was defined as CBF < 20 mL/100 g/min, and poor CDO 2 was defined as CDO 2  < 3.8 mL O 2 /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 CDO 2 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 CDO 2 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 CDO 2 , whereas lower hematocrit only correlated with higher CBF but not with CDO 2 . ICP, CPP, and pressure reactivity index exhibited no independent association with CBF and CDO 2 . R 2 of these regressions were below 0.3. Lower CBF and CDO 2 in the early phase correlated with poor outcome, but this only held true for CDO 2 in multiple regressions., Conclusions: Systemic and cerebral physiological variables exhibited a modest association with CBF and CDO 2 . Still, cerebral hypoperfusion and low CDO 2 were common and low CDO 2 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., (© 2022. The Author(s).)

Objective: 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)., Methods: 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., Results: 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., Conclusions: 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.

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., (© 2022. The Author(s).)

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., (© 2021. The Author(s).)

Context: Too many people living with chronic kidney disease are opting for and starting on hospital-based dialysis compared to a home-based kidney replacement therapy. Dialysis services are becoming financially unsustainable., Objective: This study aimed to assess the efficacy of coproductive research in chronic kidney disease service improvement to achieve greater sustainability., Design: A 2-year coproductive service improvement study was conducted with multiple stakeholders with the specific intention of maximizing engagement with the national health kidney services, patients and public., Setting and Participants: A national health kidney service (3 health boards, 18 dialysis units), patients and families (n = 50), multidisciplinary teams including doctors, nurses, psychologists, social workers, and so forth (n = 68), kidney charities, independent dialysis service providers and wider social services were part of this study., Findings: Coproductive research identified underutilized resources (e.g., patients on home dialysis and social services) and their potential, highlighted unmet social care needs for patients and families and informed service redesign. Education packages were reimagined to support the home dialysis agenda including opportunities for wider service input. The impacts of one size fits all approaches to dialysis on specialist workforce skills were made clearer and also professional, patient and public perceptions of key sustainability policies., Discussion and Conclusions: Patient and key stakeholders mapped out new ways to link services to create more sustainable models of kidney health and social care. Maintaining principles of knowledge coproduction could help achieve financial sustainability and move towards more prudent adult chronic kidney disease services., Patient or Public Contribution: Involved in developing research questions, study design, management and conduct, interpretation of evidence and dissemination., (© 2021 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

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., (© 2021. The Author(s).)

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., (© 2021. The Author(s).)

Background: Systemic hyperthermia is common after traumatic brain injury (TBI) and may induce secondary brain injury, although the pathophysiology is not fully understood. In this study, our aim was to determine the incidence and temporal course of hyperthermia after TBI and its relation to intracranial pressure dynamics, cerebral metabolism, and clinical outcomes., Materials and Methods: This retrospective study included 115 TBI patients. Data from systemic physiology (body temperature, blood pressure, and arterial glucose), intracranial pressure dynamics (intracranial pressure, cerebral perfusion pressure, compliance, and pressure reactivity), and cerebral microdialysis (glucose, pyruvate, lactate, glycerol, glutamate, and urea) were analyzed during the first 10 days after injury., Results: Overall, 6% of patients did not have hyperthermia (T>38°C) during the first 10 days after injury, whereas 20% had hyperthermia for >50% of the time. Hyperthermia increased from 21% (±27%) of monitoring time on day 1 to 36% (±29%) on days 6 to 10 after injury. In univariate analyses, higher body temperature was not associated with higher intracranial pressure nor lower cerebral perfusion pressure, but was associated with lower cerebral glucose concentration (P=0.001) and higher percentage of lactate-pyruvate ratio>25 (P=0.02) on days 6 to 10 after injury. Higher body temperature and lower arterial glucose concentration were associated with lower cerebral glucose in a multiple linear regression analysis (P=0.02 for both). There was no association between hyperthermia and worse clinical outcomes., Conclusion: Hyperthermia was most common between days 6 and 10 following TBI, and associated with disturbances in cerebral energy metabolism but not worse clinical outcome., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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 pO 2 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 pO 2 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.

Objective: Community-acquired bacterial meningitis (CABM) is a severe condition associated with high mortality. In this study the first aim was to evaluate the incidence of intracranial pressure (ICP) insults and disturbances in cerebral vasomotor reactivity and the second aim was to evaluate the management and clinical outcome of CABM patients treated in the neurointensive care unit (NICU)., Methods: CABM patients who were treated in the NICU of Uppsala University Hospital, Sweden, during 2008-2020 were included in the study. Data on demographics, admission variables, treatment, ICP dynamics, vasomotor reactivity, and short-term clinical outcome were evaluated in these patients., Results: Of 97 CABM patients, 81 (84%) received ICP monitoring, of whom 22% had ICP > 20 mm Hg during 5% or more of the monitoring time on day 1, which decreased to 9% on day 3. For those patients with ICP monitoring, 46% required CSF drainage, but last-tier ICP treatment, including thiopental (4%) and decompressive craniectomy (1%), was rare. Cerebral vasomotor reactivity was disturbed, with a mean pressure reactivity index (PRx) above 0.2 in 45% of the patients on day 1, and remained high for the first 3 days. In total, 81 (84%) patients had a favorable outcome (Glasgow Coma Scale motor score [GCS M] 6) at discharge, 9 (9%) patients had an unfavorable outcome (GCS M < 6) at discharge, and 7 (7%) patients died in the NICU. Those with favorable outcome had significantly better cerebral vasomotor reactivity (lower PRx) than the two other outcome groups (p < 0.01)., Conclusions: Intracranial hypertension was frequent following severe CABM and CSF drainage was often sufficient to control ICP. Cerebral vasomotor reactivity was commonly disturbed and associated with poor outcome. Clinical outcome was slightly better than in earlier studies.