Peeling the Research Onion Intraoperative dexamethasone and the risk of post-operative infection Tomás Corcoran School of Medicine and Pharmacology University of Western Australia Department of Anaesthesia and Pain Medicine Royal Perth Hospital Western Australia
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Peeling the Research Onion Intraoperative dexamethasone and the risk of post-operative infection
Peeling the Research Onion Intraoperative dexamethasone and the risk of post-operative infection. Tomás Corcoran School of Medicine and Pharmacology University of Western Australia Department of Anaesthesia and Pain Medicine Royal Perth Hospital Western Australia. Layers Rationale - PowerPoint PPT Presentation
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Peeling the Research OnionIntraoperative dexamethasone and the risk of
post-operative infection
Tomás CorcoranSchool of Medicine and Pharmacology
University of Western Australia
Department of Anaesthesia and Pain MedicineRoyal Perth Hospital
Western Australia
Layers
− Rationale
− Research Studies
− Results
− Proposals
Research Onion
Dexamethasone for antiemesis
Saint or Sinner ?
Dexamethasone• Dexamethasone commonly used as a component
of multimodal therapy for PONV
• Doses of 2-12mg used
• Recommendation of 0.15mg/kg• Gan et al
Dexamethasone• Biological half life of ~ 3 hours
• DOA probably up to 24 hours
• x 20-50 more potent than hydrocortisone
Dexamethasone• Glucocorticoids influence B / T-cell development
• Single dose of dexamethasone in vivo inhibits cell proliferation and reduces.1
• Dexamethasone reduces collagenisation, epithelialisation and fibroblast content in wounds.2
• When given as PONV prophylaxis in tonsillectomies, 0.5mg/kg increased the risk of bleeding (RR=6.9, p=0.003).3
Dexamethasone
• Increased cortisol with 8 mg 4
• Genomic and non-genomic influences– hence single doses may produce rapid effects
Evidence• No RCT with infection as a primary outcome• One PRCT
– 80 ASA I-III patients undergoing anorectal day surgery under sedation
– Dex 4mg versus placebo– Primary outcome was home readiness– Follow up for wound infections at 24 hours and
10 days– No differences in infection rates [ 8% vs 12% ]
Evidence– BUT
• 27 / 80 patients had HIV, 15 / 80 had systemic cancer
• Follow-up limited to 10 days• Short procedures with little systemic
inflammatory activation• Underpowered to detect differences in
infection• Other infective complications were not
identified– Coloma M, et al. Dexamethasone facilitates discharge after outpatient
anorectal surgery. Anesth Analg. Jan 2001;92(1):85-88.
Our work to date• One retrospective observational cohort study
– 439 patients undergoing single procedure, non-emergency surgery in a university trauma centre
– Follow up for infections up to 90 days– 98 episodes of infection ( 22% )– No differences between those who did and did not
receive dex
Cohort Study
Cohort Study
Our work to date• One matched Case-Control study
– 63 cases who developed postoperative infection– Operational definitions– 127 Age, Gender and procedure matched controls– 4:1 optimal power in CCS– Hypothesis generating study– Build upon the cohort study
Case Control Study
Our work to date
Current mechanistic studies• One pilot study
– 32 volunteers receive saline / dex 2mg, 4mg or 8mg – Serum sampled at baseline / 4 / 24 hours and 7 days– Lymphocyte subsets [ T, B, NK, Memory B and naieve