Anders Hånell

Although hyperglycemia is associated with worse outcome following acute brain injury, the pathomechanisms remain elusive. In this experimental pig study, we explored the effects of hyperglycemia on brain physiology. Six pigs were anesthetized and received multimodal neuromonitoring of intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral autoregulatory metrics (PRx, CBFx, ORx, and with transfer function analysis), cerebral blood flow (CBF), partial brain tissue oxygenation (pbtO ₂ ), and cerebral microdialysis (MD). The effect of hyperglycemia was studied in the healthy brain after injection of intravenous glucose injections, which increased MD-glucose, while ICP, CPP, PRx, CBFx, ORx pbtO ₂ , and cerebral energy metabolism remained unchanged. After normalization of arterial glucose, an intracranial balloon was inflated to increase ICP, followed by an intravenous glucose injection to study the effect of hyperglycemia in the injured brain. The latter induced a significant CBF elevation, but no changes in PRx, pbtO ₂ , or cerebral energy metabolism (but a trend towards higher glucose). Hyperglycemia led to favorable short-term effects on cerebral physiology and the immediate increase in arterial glucose that usually follows acute brain injury may be physiologically neuroprotective and the detrimental role of hyperglycemia is more likely related to cellular and molecular pathophysiological mechanisms or merely a confounder.

Accurate measurement of traumatic intracranial hematoma volume is important for assessing disease progression and prognosis, as well as for serving as an important end-point in clinical trials aimed at preventing hematoma expansion. While the ABC/2 formula has traditionally been used for volume estimation in spontaneous intracerebral hemorrhage, its adaptation to traumatic hematomas lacks validation. This study aimed to compare the accuracy of ABC/2 with computer-assisted volumetric analysis (CAVA) in estimating the volumes of traumatic intracranial hematomas. We performed a dual-center observational study that included adult patients with moderate-to-severe traumatic brain injury. Volumes of intracerebral, subdural (SDHs), and epidural hematomas from admission computed tomography scans were measured using ABC/2 and CAVA, and compared using the Wilcoxon signed-rank test, Spearman’s rank correlation, Lin’s concordance correlation coefficient (CCC), and Bland–Altman plots. Prognostic significance for outcomes was evaluated through logistic and linear regression models. In total, 1,179 patients with 1,543 hematomas were included. Despite a high correlation (Spearman coefficients between 0.95 and 0.98) and excellent concordance (Lin’s CCC from 0.89 to 0.96) between ABC/2 and CAVA, ABC/2 overestimated hematoma volumes compared with CAVA, in some instances exceeding 50 ml. Bland–Altman analysis highlighted wide limits of agreement, especially in SDH. While both methods demonstrated comparable accuracy in predicting outcomes, CAVA was slightly better at predicting craniotomies and midline shift. We conclude that while ABC/2 provides a generally reliable volumetric assessment suitable for descriptive purposes and as baseline variables in studies, CAVA should be the gold standard in clinical situations and studies requiring more precise volume estimations, such as those using hematoma expansion as an outcome.

Purpose: This study explores the association of the American Society of Anesthesiologists (ASA) score with 90-day mortality in complicated mild traumatic brain injury (mTBI) patients, and in trauma patients without a TBI. Methods: This retrospective study was conducted using a cohort of trauma patients treated at a level III trauma center in Stockholm, Sweden from January to December 2019. The primary endpoint was 90-day mortality. The population was identified using the Swedish Trauma registry. The Trauma and Injury Severity Score (TRISS) was used to estimate the likelihood of survival. Trauma patients without TBI (NTBI) were used for comparison. Data analysis was conducted using R software, and statistical analysis included univariate and multivariate logistic regression. Results: A total of 244 TBI patients and 579 NTBI patients were included, with a 90-day mortality of 8.2% (n = 20) and 5.4% (n = 21), respectively. Deceased patients in both cohorts were generally older, with greater comorbidities and higher injury severity. Complicated mTBI constituted 97.5% of the TBI group. Age and an ASA score of 3 or higher were independently associated with increased mortality risk in the TBI group, with odds ratios of 1.04 (95% 1.00–1.09) and 3.44 (95% CI 1.10–13.41), respectively. Among NTBI patients, only age remained a significant mortality predictor. TRISS demonstrated limited predictive utility across both cohorts, yet a significant discrepancy was observed between the outcome groups within the NTBI cohort. Conclusion: This retrospective cohort study highlights a significant association between ASA score and 90-day mortality in elderly patients with complicated mTBI, something that could not be observed in comparative NTBI cohort. These findings suggest the benefit of incorporating ASA score into prognostic models to enhance the accuracy of outcome prediction models in these populations, though further research is warranted.

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.

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.

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 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.

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.

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.