Malignant middle cerebral artery infarction (MMI) is generally treated with decompressive craniectomy (DC) followed by neurointensive care (NIC). However, prognostic values of autonomic and complexity indices remain unclear. We aimed to explore heart rate variability (HRV), baroreflex sensitivity (BRS), and signal complexity (SC) in patients with MMI during post-DC NIC in relation to demographics, stroke severity, NIC variables [intracranial pressure (ICP), cerebral perfusion pressure (CPP), and Pressure Reactivity index (PRx)], and outcome. This single-center, retrospective study analyzed 70 ICP-monitored, typically sedated, and mechanically ventilated patients with MMI, during NIC after DC (2008–2022). HRV, BRS, and SC [multiscale entropy (MSE)] of heart rate, mean arterial pressure (MAP), ICP, and amplitude of ICP (AMP) were analyzed for the first seven NIC days post-DC. Correlations (Spearman) were explored for HRV, BRS, and SC with demographics, stroke severity, and NIC variables. Associations (multivariable ordinal logistic regression) were evaluated for HRV, BRS, and SC variables in relation to six-month modified Rankin Scale (mRS). Combinations of SC and NIC variables were explored in relation to mRS in heatmaps. Median age was 57 years and 79

Autonomic nervous system (ANS) dysfunction and reduced signal complexity (SC) appear to occur after traumatic brain injury (TBI) and may reflect impaired physiological adaptability. However, their relationships with cerebral physiology and functional outcome during neurointensive care (NIC) remain incompletely understood. This study explores heart rate variability (HRV), baroreflex sensitivity (BRS) and multiscale entropy-derived SC of systemic and cerebral signals in patients with moderate-to-severe TBI during NIC. This retrospective, single-centre study included 649 TBI patients with intracranial pressure (ICP) monitoring for longer than 24 h, treated in the NIC unit at Uppsala University Hospital, Sweden (2008–2024). HRV, BRS and SC (multiscale entropy complexity index) of heart rate (HR), mean arterial pressure (MAP), ICP, ICP pulse amplitude (AMP) and cerebral perfusion pressure (CPP), respectively, were analysed over the first 10 days of NIC. Associations with demographics, injury severity, NIC physiology (ICP, CPP, pressure reactivity index [PRx]) and 6-month Glasgow Outcome Scale-Extended (GOSE) were assessed using Spearman’s correlations, multivariable ordinal logistic regression and two-variable outcome heatmaps. In multivariable regression (adjusted for age, Glasgow Coma Scale motor score [GCS M], pupillary reactivity, ICP, CPP and PRx) higher HRV and SC of each of HR, ICP, AMP and CPP independently correlated with better functional outcome in separate models. Outcome heatmaps demonstrated that reduced SC combined with high ICP, low CPP or high PRx was particularly associated with poor recovery. Lower admission GCS M, barbiturate use and decompressive craniectomy were generally associated with reduced HRV, BRS and SC. Higher ICP and PRx and lower CPP correlated with reduced systemic and cerebral SC. Reduced SC and HRV are independently associated with worse outcome after TBI, even when adjusted for conventional NIC predictors. Reduced SC may co-occur with higher ICP and PRx and lower CPP in TBI.

OBJECTIVE:There is a paucity of studies on the optimal thresholds for neurointensive care (NIC) targets such as intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in spontaneous intracerebral hemorrhage (sICH). There is also a need to clarify the role of cerebral pressure autoregulatory disturbances (pressure reactivity index [PRx]) and to determine if the autoregulatory CPP target (optimal CPP [CPPopt]) is superior to traditional fixed CPP targets in sICH. In this study, the authors aimed to explore the role of ICP, PRx, CPP, and CPPopt insults in sICH patients treated in the NIC unit. METHODS:In this observational study, 184 adults with sICH with intracerebral hemorrhage (ICH) volume above 10 ml who received > 12 hours of ICP monitoring during the first 7 days at the authors' NIC unit, Uppsala University Hospital, Sweden, between 2010 and 2019 (10 years) were included. Demographic characteristics, admission status, radiological examination, and clinical outcome were evaluated. Favorable outcome was defined as conscious at discharge, while unfavorable outcome as unconscious or deceased. ICP, CPP, PRx, and CPPopt during the first 7 days were analyzed in relation to outcome. RESULTS:In total, 138 (75%) patients recovered favorably at discharge. Lower percentage of good monitoring time with ICP above 25 mm Hg was independently associated with favorable outcome. CPP above 80 mm Hg was frequent and independently associated with favorable outcome. Median PRx did not differ between the outcome groups, but there was a trend toward worse outcome when PRx exceeded +0.5. Furthermore, when PRx was analyzed together with the concurrent ICP and CPP values, higher values increased the ICP and CPP interval associated with unfavorable outcome. Lastly, there was no independent correlation between CPP deviation from CPPopt and outcome. CONCLUSIONS:Avoiding ICP elevations above 20 to 25 mm Hg and maintaining CPP above 80 mm Hg may be beneficial in sICH patients with large bleeding volume who require NIC. PRx was not independently associated with outcome, but higher values appeared to narrow the safe zones of ICP and CPP.

Malignant middle cerebral artery infarction (MMI) is a severe neurological condition. Decompressive craniectomy (DC) is an established lifesaving surgical treatment. However, the role of neurocritical care with monitoring and management of the intracranial pressure (ICP), pressure reactivity index (PRx), cerebral perfusion pressure (CPP), and optimal perfusion pressure (CPPopt) remain unclear. This study aims to examine the dynamics of these variables post-DC in relation to clinical outcome. This retrospective study included 70 MMI patients who underwent DC with ICP monitoring of at least 12 hours and available data of clinical outcome (modified Rankin Scale [mRS] at 6 months). The associations between mRS and cerebral physiology (ICP, PRx, CPP, and ∆CPPopt) was analysed and presented in different outcome heatmaps over the first 7 days following DC. ICP above 15 mmHg was associated with unfavourable outcome, particularly for longer durations. As PRx exceeded zero, outcome worsened progressively, and values above 0.5 correlated to poor outcome regardless of duration. As CPP dropped below 80 mmHg, there was a transition from favourable to unfavourable outcome. Negative ∆CPPopt, particularly below -20 mmHg, corresponded to unfavourable outcome. In two-variable heatmaps, elevated PRx combined with high ICP, low CPP or negative ∆CPPopt correlated with worse outcome. Invasive ICP-monitoring may provide prognostic information for long-term recovery in MMI patients post-DC. The study highlighted disease-specific optimal physiological intervals for ICP, PRx, CPP, and ΔCPPopt. Of particular interest, the autoregulatory variable, PRx, influenced the safe and dangerous ICP, CPP, and ∆CPPopt intervals.

This study compared the roles of extraparenchymal autonomic nervous system (ANS) control of cerebral blood flow (CBF) versus intraparenchymal cerebrovascular autoregulation in 487 patients with aneurysmal subarachnoid hemorrhage (SAH) and 413 patients with traumatic brain injury (TBI). Vasomotion intensity of extraparenchymal and intraparenchymal vessels were quantified as the amplitude of oscillations of arterial blood pressure (ABP) and intracranial pressure (ICP) in the very low frequency range of 0.02-0.07 Hz, or periods of 55-15 sec, computed with a bandpass filter. A version of the pressure reactivity index (PRx-55-15) was computed as the correlation of the filtered waveforms, ABP-55-15 and ICP-55-15. Since ABP-55-15 is measured in the radial artery, any influence of cerebral factors must be mediated by the ANS. ICP-55-15 is measured in the brain and is influenced by intraparenchymal chemical and metabolic factors in addition to the ANS. Patient outcome was assessed using the Extended Glasgow Outcome Score (GOSe). Ten-day mean cerebral perfusion pressure (CPP) was negatively correlated with GOSe in the TBI cohort (R = -0.13, p = 0.01) but positively correlated with GOSe in the SAH cohort, (R = 0.32, p < 0.00001), indicating a much greater dependence on ANS support in the form of elevated CPP in SAH. The optimal CPP range for TBI was 60-70 mmHg, but for SAH it was 110-120 mmHg. The percentage of monitoring time with PRx-55-15 < 0.8, indicating very pressure-active cerebral vessels that resist ANS influence via systemic ABP, is positively correlated with GOSe in the TBI cohort (R = 0.14, p = 0.003), but negatively correlated with GOSe in the SAH cohort (R = -0.10, p = 0.004). The TBI cohort optimal PRx-55-15 for patient outcome was -1.0, while the SAH optimum was 0.3. For the TBI cohort, the correlation of ABP-55-15 amplitude with 10-day mean ICP-55-15 amplitude was 0.29. For the SAH cohort the correlation was 0.51, which is stronger (p = 0.0001). The TBI cohort had a median GOSe of 5 (interquartile range [IQR] 3-7), while SAH had a median of 3 (IQR 3-5), which is worse (p < 0.00001). The higher optimal CPP in patients with SAH, more passive optimal pressure reactivity, and greater dependence of cerebral on systemic vasomotion indicate that they require more active support by the ANS and systemic circulation for CBF than patients with TBI. CBF in patients with TBI is more reliant on cerebrovascular autoregulation based on metabolic demand. This appears to be deficient following SAH, making the heightened ANS support necessary. Although this support is beneficial, it does not fully compensate for the loss of cerebrovascular autoregulation, as reflected in the problems in the SAH cohort with delayed cerebral ischemia and poor outcome.

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.

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.

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. 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). 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

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.

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.

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.

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 & UDelta;CPPopt (actual CPP-CPPopt) & PLUSMN;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 & UDelta;CPPopt 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 & UDelta;CPPopt & PLUSMN;5 mm Hg, & UDelta;CPPopt within the reactivity-thresholds (PRx <0.30), and & UDelta;CPPopt within the PRx-confidence interval +0.025 were all independently associated with favorable outcome in separate logistic regressions. These regressions had similar area under receiver operating curve and were not superior to a similar regression when the CPPopt-target was replaced by the percentage of monitoring time within the traditional fixed CPP-targets 60 to 70 mm Hg. Individualized CPPopt-targets exhibited a comparable outcome association as traditional CPP targets and different definitions of the best CPPopt range based on the PRx value had a limited effect on the association between deviation from CPPopt and outcome. Since CPPopt could only be calculated during half of the time, an alternative approach would be to assess the absolute PRx to anticipate a safe CPP range.

The 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). 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. 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. 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.

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.

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.

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: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 pO2 had the opposite association in the vasospasm phase (β = -0.30, P = .04). Arterial glucose and pCO2 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 pO2 had the opposite association in the vasospasm phase (β = -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.

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 Univer-sity Hospital, Sweden, 2011-2018, with ICP-monitoring and serial NT-proBNP and TnI measurements were in-cluded. 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.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).

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 mu M [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] mu M vs. 5 [3-10] mu M, p < 0.05) on days 2 to 5, and higher biomarker levels of cellular injury (MD-glycerol median [interquartile range]; 103 [66-193] mu M vs. 68 [49-106] mu M, 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.

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.