To evaluate the effects of early combination therapy with intravenous vitamin C and thiamine on recovery from organ failure in patients with septic shock. Methods: The ascorbic acid and thiamine effect in septic shock (ATESS) trial was a multi-centre, double-blind, randomized, controlled trial conducted in four academic emergency departments, enrolling adult patients with septic shock from December 2018 through January 2020. Patients were randomly assigned in a 1:1 ratio to either the treatment group [intravenous vitamin C (50 mg/kg, maximum single dose 3 g) and thiamine (200 mg) administration every 12 h for a total of 48 h] or the placebo group (identical volume of 0.9% saline with the same protocol). The primary outcome was Δ Sequential Organ Failure Assessment (SOFA) score (SOFA score at enrolment-SOFA score after 72 h). Eighteen secondary outcomes were predefined, including shock reversal and 28-day mortality. Results: A total of 111 patients were enrolled, of which 53 were assigned to the treatment group and 58 were assigned to the placebo group. There was no significant difference in ΔSOFA scores between the treatment group and the placebo group [3, interquartile range (IQR) − 1 to 5 vs. 3, IQR 0-4, respectively, p = 0.96]. Predefined secondary outcomes were also not significantly different between the groups. Conclusion: In this study, vitamin C and thiamine administration in the early phase of septic shock did not improve organ function compared with placebo, despite improvements in vitamin C and thiamine levels.

Campbell, B. C. V. et al. (2018) Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data. Lancet Neurology, 17(1), pp. 47-53. (doi:10.1016/S1474-4422(17)30407-6) This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/149670/ variables. An alternative approach using propensity-score stratification was also used. To account for between-trial variance we used mixed-effects modeling with a random effect for trial incorporated in all models. Bias was assessed using the Cochrane tool.Findings: Of 1764 patients in 7 trials, 871 were allocated to endovascular thrombectomy. After exclusion of 74 patients (72 who did not undergo the procedure and 2 with missing data on anaesthetic strategy), 236/797 (30%) of endovascular patients were treated under GA. At baseline, GA patients were younger and had shorter time to randomisation but similar pre-treatment clinical severity compared to non-GA. Endovascular thrombectomy improved functional outcome at 3 months versus standard care in both GA (adjusted common odds ratio (cOR) 1·52, 95%CI 1·09-2·11, p=0·014) and non-GA (adjusted cOR 2·33, 95%CI 1·75-3·10, p<0·001) patients. However, outcomes were significantly better for those treated under non-GA versus GA (covariate-adjusted cOR 1·53, 95%CI 1·14-2·04, p=0·004; propensitystratified cOR 1·44 95%CI 1·08-1·92, p=0·012). The risk of bias and variability among studies was assessed to be low.Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons. Funding:The HERMES collaboration was funded by an unrestricted grant from Medtronic to the University of Calgary. Research in contextEvidence before this study between abolition of the thrombectomy treatment effect in MR CLEAN and no effect in THRACE. Three single-centre randomised trials of general anaesthesia versus conscious sedation found either no difference in functional outcome between groups or a slight benefit of general anaesthesia. Added value of this studyThese data from contemporary, high quality randomised trials form the largest study to date of the association between general anesthesia and the benefit of endovascular thrombectomy versus standard care. We used two different approaches to adjust for baseline imbalances (multivariable logistic regression and propensity-score stratification). We found that GA for endovascular thrombectomy, as practiced in contemporary clinical care across a wide range of expert centres during the rand...

Our findings indicate lactate and lactate clearance are both useful targets in patients with septic shock defined by Sepsis-3. Serum lactate level at 6-hour can be an easier and more effective tool for prognosis of septic shock patients who were treated with protocol-driven resuscitation bundle therapy.