The 21-aminosteroids are a series of compounds designed to inhibit lipid peroxidation in the cell, and, as such, may have cerebral protective effects. The current study was performed to evaluate the effect of a 21-aminosteroid, tirilazad mesylate (U74006F), on cerebral blood flow, metabolism, and carbon dioxide reactivity.Using a double-blind study design, eight volunteers received tirilazad mesylate, and eight others received only vehicle. The cerebral blood flow was measured by single photon emission computerized tomography using 133Xe inhalation in the resting condition at the beginning of the study and after infusion of tirilazad mesylate (1.5 mg/kg) or vehicle. Cerebral oxygen metabolism was calculated from the cerebral blood flow and the measured cerebral arteriovenous oxygen content difference. After both of the above cerebral blood flow measurements, arterial carbon dioxide tension was decreased by voluntary hyperventilation, and, later, increased by breathing an air/carbon dioxide mixture. The relative changes in cerebral blood flow induced by the PaCO2 variations were estimated from the changes in the arteriovenous oxygen content difference.Blood pressure, pulse rate, and PaCO2 were similar before and after the infusion of tirilazad mesylate in both groups, and there was no difference between the groups. The cerebral blood flow and oxygen metabolism did not change after the tirilazad mesylate infusion. The slope of the regression line of relative change of estimated cerebral blood flow and PaCO2 (regression coefficients in both groups, > 0.90) was unchanged after infusion.Tirilazad mesylate has no effect on cerebral blood flow, cerebral oxygen metabolism, or reactivity of cerebral blood flow to carbon dioxide in healthy volunteers.
Background: The purpose of the present study was to measure the incidence and type of incidents that occurred in relation to anaesthesia and surgery during a 1‐year period in six Danish hospitals. Furthermore, we wanted to identify risk factors for incidents, as well as risk factors for incidents being deemed critical. Methods: A four‐page questionnaire describing patient data, type of anaesthesia and surgery, and occurrence of incidents was filled in for all anaesthesias in the period, and subsequently processed. The incident reporting form incorporated 59 predefined adverse events. The occurrence of one or more of these events described the incident. When the reporting anaesthetist deemed that an incident had harmed the patient, that incident was defined as critical. Results: A total of 64,312 anaesthesias were reported, and in 7754 of them one or more incidents occurred. A total of 8510 incidents occurred, 4077 of them were solely related to the anaesthetic procedure, 3702 described events related to physiological alterations in the patient (physiological incidents). Three hundred and twenty‐three of the incidents were deemed critical. High ASA score, high age, abdominal surgery, urgent surgery, and complex anaesthetic procedure were significant risk factors for physiological incidents and critical incidents. We could not identify a simple subset of adverse events that could adequately be used to describe the critical incidents. However, complex incidents, i.e. incidents involving more than one adverse event, were more likely to be deemed critical than simple incidents. Conclusion: The incidence of incidents was 12.1%, and the incidence of critical incidents was 0.5%. Incidents were more likely to be deemed critical in patients with an ASA score of III and above undergoing urgent surgery.
Abstract Introduction Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease with great heterogeneity. Biological prognostic markers are needed for the patients to plan future supportive treatment, palliative treatment, and end-of-life decisions. In addition, prognostic markers are greatly needed for the randomization in clinical trials. Objective This study aimed to test the ALS Functional Rating Scale-Revised (ALSFRS-R) progression rate (ΔFS) as a prognostic marker of survival in a Danish ALS cohort. Methods The ALSFRS-R score at test date in association with duration of symptoms, from the onset of symptoms until test date, (defined as ΔFS’) was calculated for 90 Danish patients diagnosed with either probable or definite sporadic ALS. Median survival time was then estimated from the onset of symptoms until primary endpoint (either death or tracheostomy). ΔFS’ was subjected to survival analysis using Cox proportional hazards modelling, log-rank test, and Kaplan-Meier survival analysis. Results and conclusions Both ΔFS’ and age was found to be strong predictors of survival of the Danish ALS cohort. Both variables are easily obtained at the time of diagnosis and could be used by clinicians and ALS patients to plan future supportive and palliative treatment. Furthermore, ΔFS’, is a simple, prognostic marker that predicts survival in the early phase of disease as well as at later stages of the disease.
Experimentally induced hypoxia triggers migraine and aura attacks in patients suffering from migraine with aura (MA). We investigated the blood oxygenation level-dependent (BOLD) signal response to visual stimulation during hypoxia in MA patients and healthy volunteers. In a randomized double-blind crossover study design, 15 MA patients were allocated to 180 min of normobaric poikilocapnic hypoxia (capillary oxygen saturation 70-75%) or sham (normoxia) on two separate days and 14 healthy volunteers were exposed to hypoxia. The BOLD functional MRI (fMRI) signal response to visual stimulation was measured in the visual cortex ROIs V1-V5. Total cerebral blood flow (CBF) was calculated by measuring the blood velocity in the internal carotid arteries and the basilar artery using phase-contrast mapping (PCM) MRI. Hypoxia induced a greater decrease in BOLD response to visual stimulation in V1-V4 in MA patients compared to controls. There was no group difference in hypoxia-induced total CBF increase. In conclusion, the study demonstrated a greater hypoxia-induced decrease in BOLD response to visual stimulation in MA patients. We suggest this may represent a hypoxia-induced change in neuronal excitability or abnormal vascular response to visual stimulation, which may explain the increased sensibility to hypoxia in these patients leading to migraine attacks.
Background In this systematic review, we evaluated double‐blind, randomized and controlled trials on the effect of wound infiltration with local anesthetics compared with the effect of placebo on post‐operative pain after lumbar spine surgery. Methods M edline, the C ochrane L ibrary and G oogle S cholar were searched for appropriate trials. Qualitative analysis of post‐operative effectiveness was evaluated by assessment of significant difference ( P < 0.05) between study groups regarding pain relief using pain scores, supplemental analgesic consumption and time to first analgesic request as outcome measures. Data on adverse effects were extracted and evaluated. Results Nine trials including 12 comparisons and 529 patients met the inclusion criteria. Ten comparisons presented data on pain scores. In only three of these 10 comparisons (30%), a reduction in pain score using local anesthetic infiltration was observed averaging between 8 and 40 mm on a 100 mm visual analog scale. In six out of 12 comparisons, the local anesthetic infiltration significantly reduced the supplemental opioid consumption after surgery. Observed reductions in analgesic consumption over the first 24 h averaged between 2.5 mg and approximately 15 mg of morphine. Data on opioid‐related adverse effects were incomplete and difficult to interpret. Conclusion Interpretation of the results was difficult because of diversity of the studies. However, clinical significance was in general questionable, with only a few trials showing a small or a modest reduction in pain intensity, which was observed mainly immediately after the operation. Similarly, although more frequently observed, only a minor and probably not clinically relevant reduction in opioid consumption was shown.
Summary We compared a small and transportable Capnometer (EMMA™) with a reference capnometer, the Siesta i TS Anaesthesia. During air‐breathing through a facemask, both the EMMA (nine modules) and reference capnometer sampled expired gas simultaneously. A wide range of end‐tidal carbon dioxide values were obtained during inhalation of carbon dioxide and voluntary hyperventilation. The median IQR [range] difference between all sets of carbon dioxide values (EMMA – reference) was −0.3 (−0.6 to 0.0 [−1.7 to 1.6] kPa; n = 297) using new batteries, which was statistically significant (p = 0.04) and located to two of the nine EMMAs tested. Using batteries with reduced voltage did not influence the measurements. The 95% CI of the medians of the differences were −0.4 to −0.2. We conclude that the EMMA can slightly under‐read the end‐tidal carbon dioxide but is generally comparable with a free‐standing monitor. The precision of the EMMAs was similar whether new batteries or batteries with reduced voltage were used.
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