Intraoperative clonidine in endometriosis and spine surgery: A protocol for two randomised, blinded, placebo-controlled trials.

BACKGROUND: A high proportion of patients who undergo surgery continue to suffer from moderate to severe pain in the early postoperative period despite advances in pain management strategies. Previous studies suggest that clonidine, an alpha2 adrenergic agonist, administered during the perioperative period could reduce acute postoperative pain intensity and opioid consumption. However, these studies have several limitations related to study design and sample size and hence, further studies are needed. AIM: To investigate the effect of a single intravenous (IV) dose of intraoperative clonidine on postoperative opioid consumption, pain intensity, nausea, vomiting and sedation after endometriosis and spine surgery. METHODS: Two separate randomised, blinded, placebo-controlled trials are planned. Patients scheduled for endometriosis (CLONIPAIN) will be randomised to receive either 150 µg intraoperative IV clonidine or placebo (isotonic saline). Patients undergoing spine surgery (CLONISPINE) will receive 3 µg/kg intraoperative IV clonidine or placebo. We aim to include 120 patients in each trial to achieve power of 90% at an alpha level of 0.05. OUTCOMES: The primary outcome is opioid consumption within the first three postoperative hours. Secondary outcomes include pain intensity at rest and during coughing, nausea, vomiting and sedation within the first two postoperative hours and opioid consumption within the first six postoperative hours. Time to discharge from the PACU will be registered. CONCLUSION: This study is expected to provide valuable information on the efficacy of intraoperative clonidine in acute postoperative pain management in patients undergoing endometriosis and spine surgery.

Blood-brain Barrier Permeability May Influence Vasopressor Effects in Anesthetized Patients With Brain Tumor: An Analysis of Magnetic Resonance Imaging Data.

OBJECTIVE: This is a secondary analysis of data from a previous study of anesthetized brain tumor patients receiving ephedrine or phenylephrine infusions. 18 patients with magnetic imaging verified tumor contrast enhancement were included. We hypothesized that vasopressors induce microcirculatory flow changes, characterized by increased capillary transit time heterogeneity (CTH) and decreased mean transit time (MTT), in brain regions exhibiting BBB leakage. METHODS: This is a secondary analysis of data from a previous study of anesthetized brain tumor patients receiving ephedrine or phenylephrine infusions. 18 patients with magnetic imaging verified tumor contrast enhancement were included. Postvasopressor to prevasopressor ratios of CTH, MTT, relative transit time heterogeneity (RTH), cerebral blood flow (CBF), cerebral blood volume, and oxygen extraction fraction (OEF) were calculated in tumor, peritumoral, hippocampal, and contralateral grey matter regions. Comparisons were made between brain regions and vasopressors. RESULTS: During phenylephrine infusion, ratios of CTH, RTH, and CBF were greater, and ratios of MTT and OEF were lower, in the tumor region with contrast leakage compared with corresponding contralateral grey matter ratios. During ephedrine infusion, ratios of CTH, MTT, RTH, CBF, and cerebral blood volume were higher in the tumor region with leakage compared with contralateral grey matter ratios. In addition, the ratio of CBF was higher in all regions, the ratio of RTH was lower in the leaking tumor region, and the ratio of OEF was lower in peritumoral, hippocampal, and grey matter regions with ephedrine compared with phenylephrine. CONCLUSIONS: Vasopressors can induce distinct microcirculatory flow alterations in regions with compromised brain tumor barrier or BBB. Ephedrine, a combined α and ß-adrenergic agonist, appears to result in fewer flow alterations and less impact on tissue oxygenation compared with phenylephrine, a pure α-adrenergic agonist.

Allocating operating room capacity to non-elective neurosurgical patients improves access and safety for elective patients at Aarhus University Hospital.

INTRODUCTION: This study addresses surgical scheduling within the Department of Neurosurgery at Aarhus University Hospital (AUH). The department provides neurosurgical care to a population of 1.3 million in central Denmark, and has treatment obligations for specific neurosurgical diseases for the entire country, which has a population of 5.8 million. Efficient utilisation of the department's four operating suites is crucial to ensure that patients have timely access to both non-elective and elective neurosurgical procedures. Historically, the elective operating room (OR) schedule was made without consideration of the possible arrival of non-elective patients; consequently, elective surgeries were often cancelled to accommodate those with more urgent indications. The challenge was thus to introduce a structured way of planning for these non-elective surgical procedures that would minimise the need for cancelling elective surgeries without decreasing overall productivity. METHODS: Using a mathematical model developed in a previous study at Leiden University Medical Center, the effect of allocating OR time during regular working hours for non-elective neurosurgical procedures at AUH was analysed, so that a weighted trade-off could be made between cancellations of elective patients due to an overflow of non-elective patients and unused OR time due to excessive reservation of time for non-elective patients. This allocation was tested in a six-week pilot study during weeks 24 & 25 and weeks 34-37 of 2020 before being implemented in 2021. RESULTS: In the 35 weeks following the implementation, the new allocation strategy resulted in a significant 77% decrease in the cancellation of elective neurosurgical procedures when compared with the same time period in 2019, with a significant 16% increase in surgical productivity. CONCLUSIONS: This study shows that with mathematical modelling complex problems in the distribution of neurosurgical OR capacity can be solved, improving both patient safety and the working environment of neurosurgeons and OR staff.

Temporal Changes in Serum S100B Levels From Prehospital to Early In-Hospital Sampling in Patients Suffering Traumatic Brain Injury.

Background: The biomarker S100B is used for the rule-out of intracranial lesions in patients with mild traumatic brain injury (TBI) and is suggested for prehospital use in Europe. Early kinetics of S100B are not exhaustively investigated in human TBI. This post hoc descriptive study of the data from the PreTBI studies aimed to characterize the early temporal changes of S100B using two-sample timepoints. Materials and Methods: Two consecutive blood samples were taken prehospital and in-hospital after injury and assayed for S100B. The endpoint adjudication of the outcome intracranial lesion was done by the evaluation of electronic medical patient journals. The data were analyzed using descriptive statistics, scatterplots, and temporal changes estimated by the locally weighted scatterplot smoothing (LOWESS) regression line. Results: A total of 592 adult patients with TBI were included; 566 with Glasgow Coma Scale (GCS) 14-15, 20 with GCS 9-13, and 6 with GCS 3-8. Intracranial lesions were diagnosed in 44/566 (7.4%) of patients. In 90% of patients, S100B concentrations decreased from prehospital to in-hospital sampling. The mean decrease was-0.34 µg/L. S100B concentrations seem to decline already within 60 min. Patients sampled very close to trauma and patients suffering intracranial lesions may express a slight incline before this decline. Temporal changes of S100B did not differ in patients >65 years of age, in antiplatelet/-coagulant treatment, alcohol intoxicated, or suffering extra-cranial injuries. Conclusion: S100B concentrations may peak earlier than expected from previous studies of temporal changes in human TBI. Patterns of S100B stand robust to parameters stated as limiting factors to the use for early rule-out of intracranial lesions in the current guidelines. Further studies are needed to investigate the ultra-early temporal profiles of other novel TBI biomarkers to assess prehospital applicability and optimal diagnostic performance in TBI.

Cerebral Macro- and Microcirculation during Ephedrine versus Phenylephrine Treatment in Anesthetized Brain Tumor Patients: A Randomized Clinical Trial Using Magnetic Resonance Imaging.

BACKGROUND: This study compared ephedrine versus phenylephrine treatment on cerebral macro- and microcirculation, measured by cerebral blood flow, and capillary transit time heterogeneity, in anesthetized brain tumor patients. The hypothesis was that capillary transit time heterogeneity in selected brain regions is greater during phenylephrine than during ephedrine, thus reducing cerebral oxygen tension. METHODS: In this single-center, double-blinded, randomized clinical trial, 24 anesthetized brain tumor patients were randomly assigned to ephedrine or phenylephrine. Magnetic resonance imaging of peritumoral and contralateral hemispheres was performed before and during vasopressor infusion. The primary endpoint was between-group difference in capillary transit time heterogeneity. Secondary endpoints included changes in cerebral blood flow, estimated oxygen extraction fraction, and brain tissue oxygen tension. RESULTS: Data from 20 patients showed that mean (± SD) capillary transit time heterogeneity in the contralateral hemisphere increased during phenylephrine from 3.0 ± 0.5 to 3.2 ± 0.7 s and decreased during ephedrine from 3.1 ± 0.8 to 2.7 ± 0.7 s (difference phenylephrine versus difference ephedrine [95% CI], -0.6 [-0.9 to -0.2] s; P = 0.004). In the peritumoral region, the mean capillary transit time heterogeneity increased during phenylephrine from 4.1 ± 0.7 to 4.3 ± 0.8 s and decreased during ephedrine from 3.5 ± 0.9 to 3.3 ± 0.9 s (difference phenylephrine versus difference ephedrine [95%CI], -0.4[-0.9 to 0.1] s; P = 0.130). Cerebral blood flow (contralateral hemisphere ratio difference [95% CI], 0.3 [0.06 to 0.54]; P = 0.018; and peritumoral ratio difference [95% CI], 0.3 [0.06 to 0.54; P = 0.018) and estimated brain tissue oxygen tension (contralateral hemisphere ratio difference [95% CI], 0.34 [0.09 to 0.59]; P = 0.001; and peritumoral ratio difference [95% CI], 0.33 [0.09 to 0.57]; P = 0.010) were greater during ephedrine than phenylephrine in both regions. CONCLUSIONS: Phenylephrine caused microcirculation in contralateral tissue, measured by the change in capillary transit time heterogeneity, to deteriorate compared with ephedrine, despite reaching similar mean arterial pressure endpoints. Ephedrine improved cerebral blood flow and tissue oxygenation in both brain regions and may be superior to phenylephrine in improving cerebral macro- and microscopic hemodynamics and oxygenation.

Diagnostic accuracy of prehospital serum S100B and GFAP in patients with mild traumatic brain injury: a prospective observational multicenter cohort study - "the PreTBI I study".

BACKGROUND: The biomarker serum S100 calcium-binding protein B (S100B) is used in in-hospital triage of adults with mild traumatic brain injury to rule out intracranial lesions. The biomarker glial fibrillary acidic protein (GFAP) is suggested as a potential diagnostic biomarker for traumatic brain injury. The aim of this study was to investigate the diagnostic accuracy of early prehospital S100B and GFAP measurements to rule out intracranial lesions in adult patients with mild traumatic brain injury. METHODS: Prehospital and in-hospital blood samples were drawn from 566 adult patients with mild traumatic brain injury (Glasgow Coma Scale Score 14-15). The index test was S100B and GFAP concentrations. The reference standard was endpoint adjudication of the traumatic intracranial lesion based on medical records. The primary outcome was prehospital sensitivity of S100B in relation to the traumatic intracranial lesion. RESULTS: Traumatic intracranial lesions were found in 32/566 (5.6%) patients. The sensitivity of S100B > 0.10 µg/L was 100% (95%CI: 89.1;100.0) in prehospital samples and 100% (95% CI 89.1;100.0) in in-hospital samples. The specificity was 15.4% (95%CI: 12.4;18.7) in prehospital samples and 31.5% (27.5;35.6) in in-hospital samples. GFAP was only detected in less than 2% of cases with the assay used. CONCLUSION: Early prehospital and in-hospital S100B levels < 0.10 µg/L safely rules out traumatic intracranial lesions in adult patients with mild traumatic brain injury, but specificity is lower with early prehospital sampling than with in-hospital sampling. The very limited cases with values detectable with our assay do not allow conclusions to be draw regarding the diagnostic accuracy of GFAP. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02867137 .

Effect of tranexamic acid on markers of inflammation in children undergoing craniofacial surgery.

BACKGROUND: Tranexamic acid (TXA) reduces blood loss and transfusion requirements during craniosynostosis surgery in small children. Possible interaction from TXA on the inflammatory system is unknown. OBJECTIVE: To evaluate the effect of TXA on a wide range of inflammatory markers in children receiving TXA in a randomized, blinded, and placebo controlled study design. METHODS: Thirty children undergoing craniosynostosis surgery with significant blood loss received TXA (bolus dose of 10 mg kg-1 followed by 8 hours continuous infusion of 3 mg kg-1  h-1 ) or placebo in a randomized, double-blinded study design. Using a new proximity extension assays employing a panel of inflammatory biomarkers samples was used for analysis of blood samples obtained pre-operatively, 4 and 24 hours after operation. RESULTS: Ninety-two inflammatory parameters were measured. TXA did not affect any of the measured parameters as compared with placebo. Among 34 of the 92 pro- and antiinflammatory parameters investigated changes were observed between pre-operative, 4 or 24 hours, respectively, reflecting immune activation during surgical stress. CONCLUSION: TXA administration in a low-dose regimen including bolus followed by 8 hours infusion during craniosynostosis surgery did not change any of 92 inflammatory markers as compared with placebo.

Ephedrine versus Phenylephrine Effect on Cerebral Blood Flow and Oxygen Consumption in Anesthetized Brain Tumor Patients: A Randomized Clinical Trial.

BACKGROUND: Studies in anesthetized patients suggest that phenylephrine reduces regional cerebral oxygen saturation compared with ephedrine. The present study aimed to quantify the effects of phenylephrine and ephedrine on cerebral blood flow and cerebral metabolic rate of oxygen in brain tumor patients. The authors hypothesized that phenylephrine reduces cerebral metabolic rate of oxygen in selected brain regions compared with ephedrine. METHODS: In this double-blinded, randomized clinical trial, 24 anesthetized patients with brain tumors were randomly assigned to ephedrine or phenylephrine treatment. Positron emission tomography measurements of cerebral blood flow and cerebral metabolic rate of oxygen in peritumoral and normal contralateral regions were performed before and during vasopressor infusion. The primary endpoint was between-group difference in cerebral metabolic rate of oxygen. Secondary endpoints included changes in cerebral blood flow, oxygen extraction fraction, and regional cerebral oxygen saturation. RESULTS: Peritumoral mean ± SD cerebral metabolic rate of oxygen values before and after vasopressor (ephedrine, 67.0 ± 11.3 and 67.8 ± 25.7 µmol · 100 g · min; phenylephrine, 68.2 ± 15.2 and 67.6 ± 18.0 µmol · 100 g · min) showed no intergroup difference (difference [95% CI], 1.5 [-13.3 to 16.3] µmol · 100 g · min [P = 0.839]). Corresponding contralateral hemisphere cerebral metabolic rate of oxygen values (ephedrine, 90.8 ± 15.9 and 94.6 ± 16.9 µmol · 100 g · min; phenylephrine, 100.8 ± 20.7 and 96.4 ± 17.7 µmol · 100 g · min) showed no intergroup difference (difference [95% CI], 8.2 [-2.0 to 18.5] µmol · 100 g · min [P = 0.118]). Ephedrine significantly increased cerebral blood flow (difference [95% CI], 3.9 [0.7 to 7.0] ml · 100 g · min [P = 0.019]) and regional cerebral oxygen saturation (difference [95% CI], 4 [1 to 8]% [P = 0.024]) in the contralateral hemisphere compared to phenylephrine. The change in oxygen extraction fraction in both regions (peritumoral difference [95% CI], -0.6 [-14.7 to 13.6]% [P = 0.934]; contralateral hemisphere difference [95% CI], -0.1 [- 12.1 to 12.0]% [P = 0.989]) were comparable between groups. CONCLUSIONS: The cerebral metabolic rate of oxygen changes in peritumoral and normal contralateral regions were similar between ephedrine- and phenylephrine-treated patients. In the normal contralateral region, ephedrine was associated with an increase in cerebral blood flow and regional cerebral oxygen saturation compared with phenylephrine.

Neuroanesthesia Practice During the COVID-19 Pandemic: Recommendations From Society for Neuroscience in Anesthesiology and Critical Care (SNACC).

The pandemic of coronavirus disease 2019 (COVID-19) has several implications relevant to neuroanesthesiologists, including neurological manifestations of the disease, impact of anesthesia provision for specific neurosurgical procedures and electroconvulsive therapy, and health care provider wellness. The Society for Neuroscience in Anesthesiology and Critical Care appointed a task force to provide timely, consensus-based expert guidance for neuroanesthesiologists during the COVID-19 pandemic. The aim of this document is to provide a focused overview of COVID-19 disease relevant to neuroanesthesia practice. This consensus statement provides information on the neurological manifestations of COVID-19, advice for neuroanesthesia clinical practice during emergent neurosurgery, interventional radiology (excluding endovascular treatment of acute ischemic stroke), transnasal neurosurgery, awake craniotomy and electroconvulsive therapy, as well as information about health care provider wellness. Institutions and health care providers are encouraged to adapt these recommendations to best suit local needs, considering existing practice standards and resource availability to ensure safety of patients and providers.

Influence of Simulated Pre-Hospital Transport, Time to Analysis, and Storage Temperature on S100 Calcium-Binding Protein B Values.

According to in-hospital guidelines, the biomarker, S100 calcium-binding protein B (S100B), is used to rule out intracranial lesions in mild-moderate traumatic brain injury (TBI). It is currently investigated whether S100B is applicable in a pre-hospital setting. The aim was to compare S100B values and hemolysis index in blood samples drawn and stored under simulated pre-hospital conditions to standardized blood samples. Thirty patients undergoing craniotomy at Department of Neurosurgery, Aarhus University Hospital (Aarhus, Denmark) each had six blood samples drawn. Two samples, drawn in in-hospital standardized Beckton Dickinson tubes and pre-hospital Monovette tubes, respectively, were stored as references at 21°C for 30 min. Two samples were stored at 15°C and 29°C, respectively, one sample was stored at prolonged time (60 min), and one sample was transported for 30 min before centrifugation. S100B values were compared by equivalence test with a pre-defined equivalence margin of ±8.5%. There was no clinically relevant difference between samples stored in different tubes, at various temperatures, or time to analysis compared to reference samples. Transported samples had an 11.5% (90% confidence interval [CI], 6.55; 16.61) higher median S100B value and a 430% (95% CI, 279.6; 661.4) higher median hemolysis index compared to reference samples. Three of 30 (10%) patients had an S100B value above guideline cutoff in the transported sample, which was not found in reference samples (false positive). There were no false negatives. In conclusion, S100B values were not influenced by different tubes, temperatures, and time to analysis. Transported samples had higher median S100B values and hemolysis, icterus, and lipemia index compared to reference samples.

Effect of Tranexamic Acid on Coagulation and Fibrin Clot Properties in Children Undergoing Craniofacial Surgery.

OBJECTIVE: Craniosynostosis surgery in small children is very often associated with a high blood loss. Tranexamic acid (TXA) reduces blood loss during this procedure, although the potential underlying coagulopathy in these children is not known in detail. Objective was to determine the nature of any coagulopathy found during and after craniosynostosis surgery and to characterize the effect of TXA on fibrin clot formation, clot strength, and fibrinolysis. MATERIALS AND METHODS: Thirty children received either TXA (bolus dose of 10 mg/kg followed by 8 hours continuous infusion of 3 mg/kg/h) or placebo. Dynamic whole blood clot formation assessed by thromboelastometry, platelet count, dynamic thrombin generation/thrombin-antithrombin, clot lysis assay, and fibrinogen/factor XIII (FXIII) levels were measured. Additionally, clot structure was investigated by real-time live confocal microscopy and topical data analysis. RESULTS: Increased ability of thrombin generation was observed together with a tendency toward shortened activated partial thromboplastin time and clotting time. Postoperative maximum clot firmness was higher among children receiving TXA. FXIII decreased significantly during surgery in both groups.Resistance toward tissue plasminogen activator-induced fibrinolysis was higher in children that received TXA, as evidenced by topical data analysis and by a significant longer lysis time. Fibrinogen levels were higher in the TXA group at 24 hours. CONCLUSION: A significant coagulopathy mainly characterized by changes in clot stability and not parameters of thrombin generation was reported. Tranexamic acid improved clot strength and reduced fibrinolysis, thereby avoiding reduction in fibrinogen levels.

Blood Pressure Thresholds and Neurologic Outcomes After Endovascular Therapy for Acute Ischemic Stroke: An Analysis of Individual Patient Data From 3 Randomized Clinical Trials.

Importance: The optimal blood pressure targets during endovascular therapy (EVT) for acute ischemic stroke (AIS) are unknown. Objective: To study whether procedural blood pressure parameters, including specific blood pressure thresholds, are associated with neurologic outcomes after EVT. Design, Setting, and Participants: This retrospective cohort study included adults with anterior-circulation AIS who were enrolled in randomized clinical trials assessing anesthetic strategy for EVT between February 2014 and February 2017. The trials had comparable blood pressure protocols, and patients were followed up for 90 days. A total of 3630 patients were initially approached, and 3265 patients were excluded. Exposure: Endovascular therapy. Main Outcomes and Measures: The primary efficacy variable was functional outcome as defined by the modified Rankin Scale (mRS) score at 90 days. Associations of blood pressure parameters and time less than and greater than mean arterial blood pressure (MABP) thresholds with outcome were analyzed. Results: Of the 365 patients included in the analysis, the mean (SD) age was 71.4 (13.0) years, 163 were women (44.6%), and the median National Institutes of Health Stroke Scale score was 17 (interquartile range [IQR], 14-21). For the entire cohort, 182 (49.9%) received general anesthesia and 183 (50.1%) received procedural sedation. A cumulated period of minimum 10 minutes with less than 70 mm Hg MABP (adjusted OR, 1.51; 95% CI, 1.02-2.22) and a continuous episode of minimum 20 minutes with less than 70 mm Hg MABP (adjusted OR, 2.30; 95% CI, 1.11-4.75) were associated with a shift toward higher 90-day mRS scores, corresponding to a number needed to harm of 10 and 4, respectively. A cumulated period of minimum 45 minutes with greater than 90 mm Hg MABP (adjusted OR, 1.49; 95% CI, 1.11-2.02) and a continuous episode of minimum 115 minutes with greater than 90 mm Hg MABP (adjusted OR, 1.89; 95% CI, 1.01-3.54) were associated with a shift toward higher 90-day mRS scores, corresponding to a number needed to harm of 10 and 6, respectively. Conclusions and Relevance: Critical MABP thresholds and durations for poor outcome were found to be MABP less than 70 mm Hg for more than 10 minutes and MABP greater than 90 mm Hg for more than 45 minutes, both durations with a number needed to harm of 10 patients. Mean arterial blood pressure may be a modifiable therapeutic target to prevent or reduce poor functional outcome after EVT.

Reduced perioperative blood loss in children undergoing craniosynostosis surgery using prolonged tranexamic acid infusion: a randomised trial.

BACKGROUND: Tranexamic acid (TXA) reduces intraoperative blood loss and transfusion during paediatric craniosynostosis surgery. Additional reduction of postoperative blood loss may further reduce exposure to allogeneic blood products. We studied the effect of combined intra- and postoperative TXA treatment on postoperative blood loss in children. METHODS: Thirty children admitted for craniosynostosis surgery were randomised to combined intra- and postoperative TXA treatment or placebo. The primary endpoint was postoperative blood loss. Secondary endpoints included total blood loss, transfusion requirements, and clot stability evaluated by tissue plasminogen activator-stimulated clot lysis assay. RESULTS: TXA reduced postoperative blood loss by 18 ml kg-1 (95% confidence interval 8.9) and total blood loss from a mean of 52 ml kg-1 (standard deviation [SD]; 20) ml kg-1 to 28 (14) ml kg-1 (P<0.001). Intraoperative red blood cell (RBC) and fresh frozen plasma (FFP) transfusions were reduced in the treatment group from RBC 14.0 (5.2) ml kg-1 to 8.2 (5.1) ml kg-1 (P=0.01) and from FFP 13.0 (6.3) ml kg-1 to 7.8 (5.9) ml kg-1 (P=0.03). Postoperative RBC transfusion median was 5 (inter-quartile range [IQR] 0-6) ml kg-1 in the placebo group and 0 (0-5.7) ml kg-1 in the TXA group. Resistance to lysis was higher in the treatment group (P<0.001). CONCLUSIONS: Combined intra- and postoperative tranexamic acid treatment reduced postoperative and overall blood loss and transfusion requirements. Improved clot stability represents a possible mechanism for blood loss reduction.

Intra- and Postoperative Blood Loss and Transfusion Requirements in Children Undergoing Craniofacial Surgery.

Pediatric craniosynostosis (CS) surgery is frequently associated with extensive blood loss and transfusion requirements. The aim of the study was to evaluate the authors' institutional procedure with 2-surgeon approach and early transfusion strategy on blood loss and blood product transfusions in children undergoing craniofacial surgery. A retrospective analysis of medical records was performed of pediatric CS corrections during a 15-year period. Primary endpoint was blood loss and transfusion requirement during and the following 24 hours postoperatively. Linear regression analyses were performed of associations between intra and- postoperative blood loss and blood loss and weight. A total of 276 children (median 9 months) were included. Intraoperative blood loss was 22 mL/kg (14-33 mL/kg) and postoperatively 27 mL/kg (18-37 mL/kg), with no change during the study period. Intraoperative transfusions of red blood cell and plasma were 16 mL/kg (10-24 mL/kg) and postoperative 14 mL/kg (9-21 mL/kg). Postoperative red blood cell and plasma transfusions were 2 mL/kg (0-6 mL/kg) and of 0 mL/kg, respectively. Craniosynostosis type was related to blood loss (P < 0.001). There was an association between intraoperative and postoperative blood loss (P = 0.012) and intra- and postoperative blood loss and weight (P = 0.002, P = < 0.001). Duration of surgery was 110 minutes (range 60-300 minutes).Pediatric CS surgery is associated with substantial intra- and postoperative blood loss and transfusion requirements, which did not change over a 15-year period. Blood loss was associated with type of CS. Intraoperative blood loss was correlated to postoperative blood loss and body weight.

Effect of General Anesthesia and Conscious Sedation During Endovascular Therapy on Infarct Growth and Clinical Outcomes in Acute Ischemic Stroke: A Randomized Clinical Trial.

Importance: Endovascular therapy (EVT) is the standard of care for select patients who had a stroke caused by a large vessel occlusion in the anterior circulation, but there is uncertainty regarding the optimal anesthetic approach during EVT. Observational studies suggest that general anesthesia (GA) is associated with worse outcomes compared with conscious sedation (CS). Objective: To examine the effect of type of anesthesia during EVT on infarct growth and clinical outcome. Design, Setting, and Participants: The General or Local Anesthesia in Intra Arterial Therapy (GOLIATH) trial was a single-center prospective, randomized, open-label, blinded end-point evaluation that enrolled patients from March 12, 2015, to February 2, 2017. Although the trial screened 1501 patients, it included 128 consecutive patients with acute ischemic stroke caused by large vessel occlusions in the anterior circulation within 6 hours of onset; 1372 patients who did not fulfill inclusion criteria and 1 who did not provide consent were excluded. Primary analysis was unadjusted and according to the intention-to-treat principle. Interventions: Patients were randomized to either the GA group or the CS group (1:1 allocation) before EVT. Main Outcomes and Measures: The primary end point was infarct growth between magnetic resonance imaging scans performed before EVT and 48 to 72 hours after EVT. The hypothesis formulated before data collection was that patients who were under CS would have less infarct growth. Results: Of 128 patients included in the trial, 65 were randomized to GA, and 63 were randomized to CS. For the entire cohort, the mean (SD) age was 71.4 (11.4) years, and 62 (48.4%) were women. Baseline demographic and clinical variables were balanced between the GA and CS treatment arms. The median National Institutes of Health Stroke Scale score was 18 (interquartile range [IQR], 14-21). Four patients (6.3%) in the CS group were converted to the GA group. Successful reperfusion was significantly higher in the GA arm than in the CS arm (76.9% vs 60.3%; P = .04). The difference in the volume of infarct growth among patients treated under GA or CS did not reach statistical significance (median [IQR] growth, 8.2 [2.2-38.6] mL vs 19.4 [2.4-79.0] mL; P = .10). There were better clinical outcomes in the GA group, with an odds ratio for a shift to a lower modified Rankin Scale score of 1.91 (95% CI, 1.03-3.56). Conclusions and Relevance: For patients who underwent thrombectomy for acute ischemic stroke caused by large vessel occlusions in the anterior circulation, GA did not result in worse tissue or clinical outcomes compared with CS. Trial Registration: clinicaltrials.gov Identifier: NCT02317237.

Effect of ephedrine and phenylephrine on brain oxygenation and microcirculation in anaesthetised patients with cerebral tumours: study protocol for a randomised controlled trial.

INTRODUCTION: During brain tumour surgery, vasopressor drugs are commonly administered to increase mean arterial blood pressure with the aim of maintaining sufficient cerebral perfusion pressure. Studies of the commonly used vasopressors show that brain oxygen saturation is reduced after phenylephrine administration, but unaltered by ephedrine administration. These findings may be explained by different effects of phenylephrine and ephedrine on the cerebral microcirculation, in particular the capillary transit-time heterogeneity, which determines oxygen extraction efficacy. We hypothesised that phenylephrine is associated with an increase in capillary transit-time heterogeneity and a reduction in cerebral metabolic rate of oxygen compared with ephedrine. Using MRI and positron emission tomography (PET) as measurements in anaesthetised patients with brain tumours, this study will examine whether phenylephrine administration elevates capillary transit-time heterogeneity more than ephedrine, thereby reducing brain oxygenation. METHODS AND ANALYSIS: This is a double-blind, randomised clinical trial including 48 patients scheduled for surgical brain tumour removal. Prior to imaging and surgery, anaesthetised patients will be randomised to receive either phenylephrine or ephedrine infusion until mean arterial blood pressure increases to above 60 mm Hg or 20% above baseline. Twenty-four patients were allocated to MRI and another 24 patients to PET examination. MRI measurements include cerebral blood flow, capillary transit-time heterogeneity, cerebral blood volume, blood mean transit time, and calculated oxygen extraction fraction and cerebral metabolic rate of oxygen for negligible tissue oxygen extraction. PET measurements include cerebral metabolic rate of oxygen, cerebral blood flow and oxygen extraction fraction. Surgery is initiated after MRI/PET measurements and subdural intracranial pressure is measured. ETHICS AND DISSEMINATION: This study was approved by the Central Denmark Region Committee on Health Research Ethics (12 June 2015; 1-10-72-116-15). Results will be disseminated via peer-reviewed publication and presentation at international conferences. TRIAL REGISTRATION NUMBER: NCT02713087; Pre-results. 2015-001359-60; Pre-results.

Probabilistic versus deterministic tractography for delineation of the cortico-subthalamic hyperdirect pathway in patients with Parkinson disease selected for deep brain stimulation.

OBJECTIVE Diffusion-weighted MRI (DWI) and tractography allows noninvasive mapping of the structural connections of the brain, and may provide important information for neurosurgical planning. The hyperdirect pathway, connecting the subthalamic nucleus (STN) with the motor cortex, is assumed to play a key role in mediating the effects of deep brain stimulation (DBS), which is an effective but poorly understood treatment for Parkinson disease. This study aimed to apply recent methodological advances in DWI acquisition and analysis to the delineation of the hyperdirect pathway in patients with Parkinson disease selected for surgery. METHODS High spatial and angular resolution DWI data were acquired preoperatively from 5 patients with Parkinson disease undergoing DBS. The authors compared the delineated hyperdirect pathways and associated STN target maps generated by 2 different tractography methods: a tensor-based deterministic method, typically available in clinical settings, and an advanced probabilistic method based on constrained spherical deconvolution. In addition, 10 high-resolution data sets with the same scanning parameters were acquired from a healthy control participant to assess the robustness of the tractography results. RESULTS Both tractography approaches identified connections between the ipsilateral motor cortex and the STN. However, the 2 methods provided substantially different target regions in the STN, with the target center of gravity differing by > 1.4 mm on average. The probabilistic method (based on constrained spherical deconvolution) plausibly reconstructed a continuous set of connections from the motor cortex, terminating in the dorsolateral region of the STN. In contrast, the tensor-based method reconstructed a comparatively sparser and more variable subset of connections. Furthermore, across the control scans, the probabilistic method identified considerably more consistent targeting regions within the STN compared with the deterministic tensor-based method, which demonstrated a 1.9-2.4 times higher variation. CONCLUSIONS These data provide a strong impetus for the use of a robust probabilistic tractography framework based on constrained spherical deconvolution, or similar advanced DWI models, in clinical settings. The inherent limitations and demonstrated inaccuracy of the tensor-based method leave it questionable for use in high-precision stereotactic DBS surgery. The authors have also described a straightforward method for importing tractography-derived information into any clinical neuronavigation system, based on the generation of track-density images.

[Head injuries in Duckburg in 1959 and 2009].

Comic books have been a part of popular culture through generations. Debates concerning their graphic depictions of violence have been ongoing for nearly as long. Our aim was to examine if the violence in "Donald Duck & Co." (a weekly published Danish comic book), illustrated through the number of head injuries, increased in the period from 1959 to 2009. The comic book vintages from the years 1959 and 2009 were read, and the number of head injuries noted. The head injuries were characterized by severity, in part by a modified Glasgow Coma Scale and in part by a newly developed Comic Book Coma Scale. The number of head injuries were equal in the examined years, however, the number of head injuries per page decreased from 1/10 pages to 1/20 pages. Donald Duck sustained a better part of the injuries increasing from 17% in 1959 to 33% in 2009. The study indicates that we, with peace of mind, can read a comic book while the rest of the family takes care of the dishes at Christmas.

Anesthetic strategy during endovascular therapy: General anesthesia or conscious sedation? (GOLIATH - General or Local Anesthesia in Intra Arterial Therapy) A single-center randomized trial.

RATIONALE: Endovascular therapy after acute ischemic stroke due to large vessel occlusion is now standard of care. There is equipoise as to what kind of anesthesia patients should receive during the procedure. Observational studies suggest that general anesthesia is associated with worse outcomes compared to conscious sedation. However, the findings may have been biased. Randomized clinical trials are needed to determine whether the choice of anesthesia may influence outcome. AIM AND HYPOTHESIS: The objective of GOLIATH (General or Local Anestesia in Intra Arterial Therapy) is to examine whether the choice of anesthetic regime during endovascular therapy for acute ischemic stroke influence patient outcome. Our hypothesis is that that conscious sedation is associated with less infarct growth and better functional outcome. METHODS: GOLIATH is an investigator-initiated, single-center, randomized study. Patients with acute ischemic stroke, scheduled for endovascular therapy, are randomized to receive either general anesthesia or conscious sedation. STUDY OUTCOMES: The primary outcome measure is infarct growth after 48-72 h (determined by serial diffusion-weighted magnetic resonance imaging). Secondary outcomes include 90-day modified Rankin Scale score, time parameters, blood pressure variables, use of vasopressors, procedural and anesthetic complications, success of revascularization, radiation dose, and amount of contrast media. DISCUSSION: Choice of anesthesia may influence outcome in acute ischemic stroke patients undergoing endovascular therapy. The results from this study may guide future decisions regarding the optimal anesthetic regime for endovascular therapy. In addition, this study may provide preliminary data for a multicenter randomized trial.

Capillary transit time heterogeneity and flow-metabolism coupling after traumatic brain injury.

Most patients who die after traumatic brain injury (TBI) show evidence of ischemic brain damage. Nevertheless, it has proven difficult to demonstrate cerebral ischemia in TBI patients. After TBI, both global and localized changes in cerebral blood flow (CBF) are observed, depending on the extent of diffuse brain swelling and the size and location of contusions and hematoma. These changes vary considerably over time, with most TBI patients showing reduced CBF during the first 12 hours after injury, then hyperperfusion, and in some patients vasospasms before CBF eventually normalizes. This apparent neurovascular uncoupling has been ascribed to mitochondrial dysfunction, hindered oxygen diffusion into tissue, or microthrombosis. Capillary compression by astrocytic endfeet swelling is observed in biopsies acquired from TBI patients. In animal models, elevated intracranial pressure compresses capillaries, causing redistribution of capillary flows into patterns argued to cause functional shunting of oxygenated blood through the capillary bed. We used a biophysical model of oxygen transport in tissue to examine how capillary flow disturbances may contribute to the profound changes in CBF after TBI. The analysis suggests that elevated capillary transit time heterogeneity can cause critical reductions in oxygen availability in the absence of 'classic' ischemia. We discuss diagnostic and therapeutic consequences of these predictions.