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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

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Peeling the Research Onion Intraoperative dexamethasone and the risk of post-operative infection

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  1. Peeling the Research OnionIntraoperativedexamethasone 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

  2. Layers Rationale Research Studies Results Proposals Research Onion

  3. Dexamethasone for antiemesisSaint or Sinner ?

  4. 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

  5. Biological half life of ~ 3 hours DOA probably up to 24 hours x 20-50 more potent than hydrocortisone Dexamethasone

  6. 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

  7. Increased cortisol with 8 mg 4 Genomic and non-genomic influences hence single doses may produce rapid effects 1 Kunicka. Cellular immunology, 1993. Mice. 2 Durmus. AnesthAnalg 2003. Rats. 3 Czarnetzki et al. JAMA 2008 4.Anaesth Intensive Care 2010; 38: 667-670 Dexamethasone

  8. MOA of Glucocorticoids

  9. 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

  10. 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. AnesthAnalg. Jan 2001;92(1):85-88. Evidence

  11. 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 Our work to date

  12. Cohort Study

  13. Cohort Study

  14. 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 Our work to date

  15. Case Control Study

  16. Our work to date

  17. 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 B cells ] Serum MIF and cytokines measured Current mechanistic studies

  18. Two PRCT 1. Laparoscopic gynae surgery [ ~ Half-way ] 2. Mastectomy patients [ Recruitment complete ] Dex versus granisetron Serum sampled and lymphocyte subsets at baseline, 24 hours, 7 and 42 days Infective complications a secondary endpoint until 90 days Current mechanistic studies

  19. What is the mechanism ? Short term alteration in cell numbers (margination, sequestration in lymphoid tissue) Change in differentiation of myeloid and lymphocyte progenitor cells ?? Altered clonal expansion What are the expected responses in patients undergoing a potent surgical inflammatory response ? Discussion

  20. Preliminary work asking further questions What is the pattern in patients with surgical stress response ? What affect does dexamethasone have on this response and the incidence of infection ? MRCT in the design phase Discussion

  21. Common, cheap and highly effective Cannot assert it’s safety in the absence of evidence (MRCT) Potentially significant long-term implications Pilot data suggests an influence on key immune cells Surgical data will clarify the relevance of this Conclusion

  22. Research Nursing staff Consultant Colleagues in Royal Perth Hospital ANZCA Research Grant 2010 / 2011 ANZCA CTG ASM organising committee Acknowledgements

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