Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/27029
Title: A Randomized, Multicenter, Open-Label, Blinded End Point, Phase 2, Feasibility, Efficacy, and Safety Trial of Preoperative Microvascular Protection in Patients Undergoing Major Abdominal Surgery.
Austin Authors: Yanase, Fumitaka ;Tosif, Shervin ;Churilov, Leonid ;Yee, Ken;Bellomo, Rinaldo ;Gunn, Kerry;Kim, Chang;Krizhanovskii, Camilla;Hahn, Robert G;Riedel, Bernhard;Weinberg, Laurence 
Affiliation: Karolinska Institute at Danderyd's Hospital (KIDS), Stockholm, Sweden
Department of Research, Södertälje Hospital, Södertälje, Sweden
Department of Molecular Medicine and Surgery, Karolinska Institute, Solna, Sweden
Intensive Care
Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia
Anaesthesia
Melbourne Brain Centre at Royal Melbourne Hospital, Melbourne Medical School Faculty of Medicine, The University of Melbourne, Melbourne, Australia
Department of Anaesthesia, Auckland City Hospital, Auckland, New Zealand
Department of Anaesthesia, Perioperative and Pain Medicine, Peter MacCallum Cancer Centre; and the Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia
Department of Critical Care, University of Melbourne, Melbourne, Australia
Medicine (University of Melbourne)
Issue Date: 15-Jul-2021
Date: 2021-07-15
Publication information: Anesthesia and Analgesia 2021; 133(4): 1036-1047
Abstract: The endothelial glycocalyx, a carbohydrate-rich layer coating all endothelial surfaces, plays a fundamental role in the function of microcirculation. The primary aim of this study was to evaluate the feasibility of using dexamethasone and albumin to protect the endothelial glycocalyx in patients undergoing abdominal surgery. Secondary and exploratory outcomes included efficacy and safety. We conducted a multicenter, open-label, blinded end point, phase 2, randomized trial. Patients undergoing colorectal, pancreas, or liver surgery were recruited and randomized to receive either intravenous dexamethasone (16 mg) and 20% albumin (100 mL) at induction of anesthesia, then 200 mL of 20% albumin with each subsequent 1000 mL of crystalloid administered (dexamethasone and albumin [Dex-Alb] group), or crystalloid fluid only with no dexamethasone (control group). Feasibility end points included patient recruitment and retention, consent rate, and successful study drug administration. The primary efficacy end point was the measurement of plasma syndecan-1 level on postoperative day (POD) 1, and secondary end points were heparan sulfate levels and inflammatory markers measured at 4 perioperative timepoints. Safety end points included errors in administration of the intervention, hyperglycemia, occurrence of postoperative complications, and patient retention. Seventy-two patients were randomized. All feasibility end points were achievable. There were no statistically significant differences observed in median (interquartile range) syndecan-1 levels on POD 1 (39 ng·mL-1 [20-97] in the Dex-Alb group versus 41 ng·mL-1 [19-84] in the control group; difference in medians -2.1, 95% confidence interval [CI], -13 to 8.6; P = .69). The Dex-Alb group had lower POD 1 heparan sulfate levels (319 ng·mL-1 [161-717] in the Dex-Alb group versus 1422 [670-2430] ng·mL-1 in the control group; difference in medians -1085, 95% CI, -1779 to -391) and C-reactive protein (CRP) levels on POD 1 (48 [29-77] mg·L-1 in the Dex-Alb group versus 85 mg·L-1 [49-133] in the control group; difference in medians -48, 95% CI, -75 to -21). Fewer patients had one or more postoperative complication in the Dex-Alb group than in the control group (6 [17%] vs 18 patients [50%]; odds ratio = 0.2, 95% CI, 0.06-0.6). Intravenous dexamethasone and albumin administration was feasible but did not reduce syndecan-1 on POD 1 in patients undergoing abdominal surgery. Given the clinically important CIs observed between the groups for heparan sulfate, CRP, and postoperative complications, a larger trial assessing the associations between dexamethasone and albumin administration and these outcomes is warranted.
URI: https://ahro.austin.org.au/austinjspui/handle/1/27029
DOI: 10.1213/ANE.0000000000005667
Journal: Anesthesia and Analgesia
PubMed URL: 34269720
Type: Journal Article
Appears in Collections:Journal articles

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