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Background: Haemorrhagic shock (HS) is frequently associated with secondary cerebral injury due to compromised cerebral perfusion. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an effective haemorrhage control strategy; however, concerns persist regarding its cerebral effects, particularly in the presence of elevated intracranial pressure (ICP). Cerebral microdialysis (CMD) derived glycerol (CGly) is a recognised marker of cellular membrane stress and injury.

Objective: To investigate CGly dynamics during prolonged total REBOA (tREBOA) in HS and to compare cerebral cellular responses between animals with normal and elevated ICP.

Methods: In this experimental porcine study, eighteen pigs were subjected to controlled HS and resuscitated with tREBOA for 90 min. Animals were allocated to either a normal ICP group (NICPG, n = 9) or an elevated ICP group (EICPG, n = 9). Continuous monitoring of proximal arterial pressure, ICP, and cerebral perfusion pressure was performed. CGly concentrations were measured using CMD throughout the experimental protocol.

Results: tREBOA effectively restored proximal arterial pressure and cerebral perfusion pressure in both groups. CGly concentrations remained relatively stable during the haemorrhage phase and increased progressively during prolonged aortic occlusion. Importantly, CGly responses did not differ significantly between animals with normal and elevated ICP. The observed increases in CGly during prolonged occlusion were consistent with cellular membrane perturbation rather than irreversible neuronal injury.

Conclusions: In this experimental model of HS, prolonged total REBOA restored macrocirculatory parameters but was associated with time-dependent increases in CGly. Elevated ICP was not associated with exacerbation of cerebral cellular membrane stress during total aortic occlusion under the conditions studied. These findings suggest that intracranial hypertension alone does not worsen cerebral cellular responses during tREBOA, while highlighting the importance of occlusion duration and the need for further studies to optimise cerebral protection during prolonged aortic occlusion.

How the brain generates conscious experiences remains profoundly mysterious. Pharmacological interventions that alter the state of consciousness have been proposed as a tool to investigate the neural mechanisms of consciousness. However, we have recently demonstrated that the sedative Propofol influences both conscious and unconscious neural processing. Altered arousal, and other pharmacological effects, therefore cannot be assumed a priori to provide information specifically on conscious neural processes. Instead, effects on both conscious and unconscious processes need to be considered. Here we investigated the role of noradrenergic activity in conscious and unconscious visuospatial processing. In Study 1 we used Dexmedetomidine, a sedative that specifically targets α2A noradrenergic receptors. In Study 2, we used sleep deprivation as a natural state of altered arousal, which exerts partially overlapping effects on noradrenaline levels. Unlike Propofol, both Dexmedetomidine and sleep deprivation selectively altered brain activity (fMRI BOLD signal change) during conscious processing. However, the two methods produced distinct effects on visuospatial bias during low arousal: while Dexmedetomidine reduced leftward bias, sleep deprivation increased leftward bias. These differential effects on spatial bias were explained by an unexpected increase in sympathetic drive, as indexed by increased activity in the central autonomic network and in heart rate, from sleep deprivation, that indicate increased rather than decreased noradrenaline levels during task performance. Together, these findings emphasize noradrenergic activity as a target for pharmacological manipulations of consciousness, which could open a window to its neurophysiological underpinnings.

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used as an adjunct in haemorrhagic shock (HS) to restore proximal perfusion. Its cerebral metabolic effects during haemorrhagic shock, particularly in the presence of elevated intracranial pressure (ICP), remain incompletely characterised.

Methods: In a controlled porcine model, HS was induced by controlled bleeding to a mean arterial pressure of approximately 40 mmHg. Animals were allocated to a normal ICP group or an experimentally elevated ICP group. Total REBOA (zone 1) was applied for 90 min. Cerebral metabolism was assessed using intracerebral microdialysis with measurements of lactate, pyruvate, and lactate–pyruvate ratio (LPR). Cerebral haemodynamics and ICP were continuously monitored.

Results: HS was associated with a statistically significant increase in LPR in both groups, indicating cerebral metabolic disturbance. Following aortic occlusion, LPR gradually decreased toward baseline in both groups. Animals with elevated ICP demonstrated a transient delay in metabolic normalisation during the early post-occlusion phase. Statistically significant differences between groups were limited to the first 10 min following occlusion. Overall metabolic trajectories were similar thereafter.

Conclusions: Total REBOA restored cerebral metabolic markers of ischaemia during haemorrhagic shock, as reflected by normalisation of LPR, even in the presence of experimentally elevated ICP. These findings indicate acute metabolic recovery and so suggest that the use of tREBOA in the setting of elevated ICP is not contra indicated and can be a bridge to further treatment. Our findings do not demonstrate absence of tissue injury, or long-term neurological recovery. Further studies incorporating complementary physiological and structural outcome measures would be recommended.

Background: Dysphagia is independently associated with adverse outcomes in intensive care units (ICU). Early identification through dysphagia screening does not occur routinely, negatively impacting optimal patient management. This study aimed to validate the Swedish version of the Gugging Swallowing Screen—Intensive Care Unit (GUSS-IVA).

Methods: This is a prospective multicentre study of 56 adult ICU patients with endotracheal intubation exceeding 48 h at three hospitals in Sweden. The GUSS-ICU was translated into Swedish (GUSS-IVA) and used to screen all prolonged intubated patients (>48 h) once extubated. The GUSS-IVA screen was conducted by ICU nursing staff and then compared with a gold standard Flexible Endoscopic Evaluation of Swallowing (FEES) within 2 h of the GUSS-IVA screen. Fifty-one of 56 patients underwent FEES (where assessors were blinded to the GUSS-IVA screen results). Sensitivity and specificity were calculated, as was the area under the receiver operating characteristic curves (AUC) with 95% confidence intervals (CI). For inter-rater reliability, within 2 h of the initial screen, 29/56 patients were GUSS-IVA screened a second time by a nursing staff blinded to the first GUSS-IVA results.

Results: Among the 56 patients, 38 (67.9%) were identified as dysphagic using the GUSS-IVA screen. With FEES, 42 of 51 patients (82.4%) were diagnosed with dysphagia; of these, 16 (31.4%) were classified as aspirating. Compared to FEES, GUSS-IVA showed high sensitivity and specificity values (81% and 89%, respectively) with an AUC of 0.85 (95% CI: 0.71–0.95) and a positive predictive value of 97%. High convergent validity was obtained for GUSS-IVA compared with the Dysphagia Outcome Severity Scale (ɸ = 0.57, p <.001) and the Functional Oral Intake Scale (ɸ = 0.52, p <.001) and moderate validity with the Penetration-Aspiration Scale (ɸ = 0.30, p =.033). The inter-rater reliability showed moderate agreement (Cohen's kappa κ = 0.501, p =.006).

Conclusions: This study indicates that the Swedish GUSS-IVA is a valid and reliable screen to identify dysphagic ICU patients. Given the negative impact of dysphagia on short and long-term patient outcomes, the Swedish GUSS-IVA is recommended as an essential first step by nursing staff for early identification of dysphagia for further diagnostics and subsequent patient management.

Purpose: To assess changes of cerebral haemodynamic and intracranial pressure (ICP) in animals, with or without elevated ICP, during controlled haemorrhagic shock and resuscitation with Total REBOA (tREBOA).

Method: In 22 anaesthetized and normoventilated pigs, after placement of catheters for monitoring invasive proximal blood pressure (pMAP), ICP, and vital parameters, and 60 min stabilisation phase, a controlled haemorrhagic shock (HS), was conducted. In 11 pigs (EICPG), an elevated ICP of 25–30 mmHg at the end HS was achieved by simulating an epidural mass. In 11 pigs (NICPG), the ICP was normal. tREBOA was then applied for 120 min. The changes of pMAP and ICP were followed, and cerebral perfusion pressure (CPP) calculated. The integrity of the autoregulation was estimated using a calculated Modified-Long Pressure Reactivity Index (mL-PRx).

Results: After stabilisation, hemodynamics and physiological parameters were similar and normal in both groups. At the end of the HS, ICP was 16 mmHg in NICPG vs. 32 in EICPG (p = 0.0010). CPP was 30 mmHg in NICPG vs. 6 mmHg in EICPG (p = 0.0254). After aorta occlusion CPP increased immediately in both groups reaching after 15 min up to104 mmHg in NICPG vs. 126 mmHg in EICPG. Cerebrovascular reactivity seems to be altered during bleeding and occlusion phases in both groups with positive mL-PRx. The alteration was more pronounced in EICPG, but reversible in both groups.

Conclusion: tREBOA is lifesaving by restoration the cerebral circulation defined as CPP in animals with HS with normal or elevated ICP. Despite the observation of short episodes of cerebral autoregulation impairment during the occlusion, mainly in EICPG, tREBOA seems to be an effective tool for improving cerebral perfusion in HS that extends the crucial early window sometimes known as the “golden hour” for resuscitation even after a traumatic brain injury.

Background: Olfactory dysfunction together with neurological and cognitive symptoms are common after COVID-19. We aimed to study whether performance on olfactory and neuropsychological tests following infection predict post-COVID condition (PCC), persisting symptoms, and reduced health-related quality of life.

Methods: Both hospitalized (N = 10) and non-hospitalized individuals (N = 56) were enrolled in this prospective cohort study. Participants were evaluated 1–3 months after infection with an olfactory threshold test and neuropsychological tests, which was used as predictors of PCC. A questionnaire outlining persisting symptoms and the validated instrument EuroQol five-dimension five-level for health-related quality of life assessment were used as outcome data 1 year after infection (N = 59). Principal component analysis was used to identify relevant predictors for PCC at 1 year.

Results: Objectively assessed olfactory dysfunction at 1–3 months post infection, but not subjective olfactory symptoms, predicted post-COVID condition with reduced health-related quality of life (PCC+) at 1 year. The PCC+ group scored more often below the cut off for mild cognitive impairment on the Montreal Cognitive Assessment (61.5% vs. 21.7%) and higher on the Multidimensional Fatigue Inventory-20, compared to the group without PCC+.

Conclusion: Our results indicate that objectively assessed, olfactory dysfunction is a predictor for PCC+. These findings underscore the importance of objective olfactory testing. We propose that olfactory screening in the early post-acute phase of COVID-19 infection might identify individuals that are at higher risk of developing long-term health sequalae.

BACKGROUND: Limited evidence existed on the comparative effectiveness of decompressive craniectomy (DC) versus craniotomy for evacuation of traumatic acute subdural hematoma (ASDH) until the recently published randomised clinical trial RESCUE-ASDH. In this study, that ran concurrently, we aimed to determine current practice patterns and compare outcomes of primary DC versus craniotomy.

METHODS: We conducted an analysis of centre treatment preference within the prospective, multicentre, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (known as CENTER-TBI) and NeuroTraumatology Quality Registry (known as Net-QuRe) studies, which enrolled patients throughout Europe and Israel (2014-2020). We included patients with an ASDH who underwent acute neurosurgical evacuation. Patients with severe pre-existing neurological disorders were excluded. In an instrumental variable analysis, we compared outcomes between centres according to treatment preference, measured by the case-mix adjusted proportion DC per centre. The primary outcome was functional outcome rated by the 6-months Glasgow Outcome Scale Extended, estimated with ordinal regression as a common odds ratio (OR), adjusted for prespecified confounders. Variation in centre preference was quantified with the median odds ratio (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582).

FINDINGS: Between December 19, 2014 and December 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI of whom 336 (7%) underwent acute surgery for ASDH evacuation; 91 (27%) underwent DC and 245 (63%) craniotomy. The proportion primary DC within total acute surgery cases ranged from 6 to 67% with an interquartile range (IQR) of 12-26% among 46 centres; the odds of receiving a DC for prognostically similar patients in one centre versus another randomly selected centre were trebled (adjusted median odds ratio 2.7, p < 0.0001). Higher centre preference for DC over craniotomy was not associated with better functional outcome (adjusted common odds ratio (OR) per 14% [IQR increase] more DC in a centre = 0.9 [95% CI 0.7-1.1], n = 200). Primary DC was associated with more follow-on surgeries and complications [secondary cranial surgery 27% vs. 18%; shunts 11 vs. 5%]; and similar odds of in-hospital mortality (adjusted OR per 14% IQR more primary DC 1.3 [95% CI (1.0-3.4), n = 200]).

INTERPRETATION: We found substantial practice variation in the employment of DC over craniotomy for ASDH. This variation in treatment strategy did not result in different functional outcome. These findings suggest that primary DC should be restricted to salvageable patients in whom immediate replacement of the bone flap is not possible due to intraoperative brain swelling.

FUNDING: Hersenstichting Nederland for the Dutch NeuroTraumatology Quality Registry and the European Union Seventh Framework Program.

Mild traumatic brain injury (mTBI) can be accompanied by structural damage to the brain. Here, we investigated how the presence of intracranial traumatic computed tomography (CT) pathologies relates to the global functional outcome in young patients one year after mTBI. All patients with mTBI (Glasgow Coma Scale: 13-15) ≤24 years in the multi-center, prospective, observational Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study were included. Patient demographics and CT findings were assessed at admission, and the Glasgow Outcome Scale Extended (GOSE) was evaluated at 12 months follow-up. The association between a "positive CT" (at least one of the following: epidural hematoma, subdural hematoma, traumatic subarachnoid hemorrhage (tSAH), intraventricular hemorrhage, subdural collection mixed density, contusion, traumatic axonal injury) and functional outcome (GOSE) was assessed using multi-variable mixed ordinal and logistic regression models. A total of 462 patients with mTBI and initial brain CT from 46 study centers were included. The median age was 19 (17-22) years, and 322 (70%) were males. CT imaging showed a traumatic intracranial pathology in 171 patients (37%), most commonly tSAH (48%), contusions (40%), and epidural hematomas (37%). Patients with a positive CT scan were less likely to achieve a complete recovery 12 months post-injury. The presence of any CT abnormality was associated with both lower GOSE scores (odds ratio [OR]: 0.39 [0.24-0.63]) and incomplete recovery (GOSE <8; OR: 0.41 [0.25-0.68]), also when adjusted for demographical and clinical baseline factors. The presence of intracranial traumatic CT pathologies was predictive of outcome 12 months after mTBI in young patients, which might help to identify candidates for early follow-up and additional care.

Background: Anesthesia preinduction anxiety in children can according to some studies lead to long-term anxiety and negative behavioral changes (NBC), while other studies have not found this effect. This secondary analysis from a recent premedication trial comparing clonidine and midazolam aimed to test the relation between preoperative anxiety assessed with modified Yale Preoperative Anxiety Scale (mYPAS) and postoperative NBCs assessed with Post Hospital Behavior Questionnaire (PHBQ), regardless of premedication type.

Methods: This is a planned secondary analysis from a published premedication comparison trial in an outpatient surgery cohort, children aged 2–7 years. Participant and preoperative factors, particularly preoperative anxiety as mYPAS scores, were assessed for association with development of postoperative NBCs.

Results: Fifty-four of the 115 participants had high preinduction anxiety (mYPAS >30), and 19 of 115 developed >3 postoperative NBCs 1 week after surgery. There was no association between preinduction anxiety level as mYPAS scores and the development of postoperative NBCs at 1 week after surgery (10 of 19 had both, p =.62) nor after 4- or 26-weeks post-surgery. Only lower age was associated with development of NBCs postoperatively.

Conclusions: Based on the findings from this cohort, high preinduction anxiety does not appear to be associated with NBCs postoperatively in children premedicated with clonidine or midazolam.

After mild traumatic brain injury (mTBI), a substantial proportion of individuals do not fully recover on the Glasgow Outcome Scale Extended (GOSE) or experience persistent post-concussion symptoms (PPCS). We aimed to develop prognostic models for the GOSE and PPCS at 6 months after mTBI and to assess the prognostic value of different categories of predictors (clinical variables; questionnaires; computed tomography [CT]; blood biomarkers). From the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study, we included participants aged 16 or older with Glasgow Coma Score (GCS) 13-15. We used ordinal logistic regression to model the relationship between predictors and the GOSE, and linear regression to model the relationship between predictors and the Rivermead Post-concussion Symptoms Questionnaire (RPQ) total score. First, we studied a pre-specified Core model. Next, we extended the Core model with other clinical and sociodemographic variables available at presentation (Clinical model). The Clinical model was then extended with variables assessed before discharge from hospital: early post-concussion symptoms, CT variables, biomarkers, or all three categories (extended models). In a subset of patients mostly discharged home from the emergency department, the Clinical model was extended with 2-3-week post-concussion and mental health symptoms. Predictors were selected based on Akaike's Information Criterion. Performance of ordinal models was expressed as a concordance index (C) and performance of linear models as proportion of variance explained (R2). Bootstrap validation was used to correct for optimism. We included 2376 mTBI patients with 6-month GOSE and 1605 patients with 6-month RPQ. The Core and Clinical models for GOSE showed moderate discrimination (C = 0.68 95% confidence interval 0.68 to 0.70 and C = 0.70[0.69 to 0.71], respectively) and injury severity was the strongest predictor. The extended models had better discriminative ability (C = 0.71[0.69 to 0.72] with early symptoms; 0.71[0.70 to 0.72] with CT variables or with blood biomarkers; 0.72[0.71 to 0.73] with all three categories). The performance of models for RPQ was modest (R2 = 4% Core; R2 = 9% Clinical), and extensions with early symptoms increased the R2 to 12%. The 2-3-week models had better performance for both outcomes in the subset of participants with these symptoms measured (C = 0.74 [0.71 to 0.78] vs. C = 0.63[0.61 to 0.67] for GOSE; R2 = 37% vs. 6% for RPQ). In conclusion, the models based on variables available before discharge have moderate performance for the prediction of GOSE and poor performance for the prediction of PPCS. Symptoms assessed at 2-3 weeks are required for better predictive ability of both outcomes. The performance of the proposed models should be examined in independent cohorts.