The perioperative administration of dexamethasone and infection (PADDI) trial protocol: rationale and design of a pragmatic multicentre non-inferiority study

Tomás B Corcoran, Paul S Myles, Andrew B Forbes, Ed O'Loughlin, Kate Leslie, David Story, Timothy G Short, Matthew Tv Chan, Pauline Coutts, Jaspreet Sidhu, Allen C Cheng, Leon A Bach, Kwok M Ho, Australian and New Zealand College of Anaesthetists Clinical Trials Network (ANZCA), and the Australian Society for Infectious Diseases (ASID) Clinical Research Network, Chris Frampton, Richard Macisaac, Michael Paech, Bala Venkatesh, Leon Worth, Stephane Heritier, Cathy Martin, Mark Williams, Roger Browning, Emma Hamilton, Paul Ingram, Peter Boan, Tomás B Corcoran, Paul S Myles, Andrew B Forbes, Ed O'Loughlin, Kate Leslie, David Story, Timothy G Short, Matthew Tv Chan, Pauline Coutts, Jaspreet Sidhu, Allen C Cheng, Leon A Bach, Kwok M Ho, Australian and New Zealand College of Anaesthetists Clinical Trials Network (ANZCA), and the Australian Society for Infectious Diseases (ASID) Clinical Research Network, Chris Frampton, Richard Macisaac, Michael Paech, Bala Venkatesh, Leon Worth, Stephane Heritier, Cathy Martin, Mark Williams, Roger Browning, Emma Hamilton, Paul Ingram, Peter Boan

Abstract

Introduction: The intraoperative administration of dexamethasone for prophylaxis against postoperative nausea and vomiting is a common and recommended practice. The safety of the administration of this immunosuppressive agent at a time of significant immunological disruption has not been rigorously evaluated in terms of infective complications.

Methods/analysis: This is a pragmatic, multicentre, randomised, controlled, non-inferiority trial. A total of 8880 patients undergoing elective major surgery will be enrolled. Participants will be randomly allocated to receive either dexamethasone 8 mg or placebo intravenously following the induction of anaesthesia in a 1:1 ratio, stratified by centre and diabetes status. Patient enrolment into the trial is ongoing. The primary outcome is surgical site infection at 30 days following surgery, defined according to the Centre for Disease Control criteria.

Ethics/dissemination: The PADDI trial has been approved by the ethics committees of over 45 participating sites in Australia, New Zealand, Hong Kong, South Africa and the Netherlands. The trial has been endorsed by the Australia and New Zealand College of Anaesthetists Clinical Trials Network and the Australian Society for Infectious Diseases Clinical Research Network. Participant recruitment began in March 2016 and is expected to be complete in mid-2019. Publication of the results of the PADDI trial is anticipated to occur in early 2020.

Trial registration number: ACTRN12614001226695.

Keywords: Dexamethasone; Diabetes; Postoperative Nausea and Vomiting; Surgical Wound Infection; glucocorticoid.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Diagrammatic representation of trial processes.

References

    1. Cruickshank MFJ, Reducing harm to patients from health care associated infection: the role of surveillance. Australian Commission on Safety and Quality in Health Care, 2008.
    1. Magill SS, Edwards JR, Bamberg W, et al. . Multistate point-prevalence survey of health care-associated infections. N Engl J Med 2014;370:1198–208. 10.1056/NEJMoa1306801
    1. Khuri SF, Henderson WG, DePalma RG, et al. . Determinants of long-term survival after major surgery and the adverse effect of postoperative complications. Ann Surg 2005;242:326–41. discussion 41-3 10.1097/01.sla.0000179621.33268.83
    1. Klevens RM, Edwards JR, Richards CL, et al. . Estimating health care-associated infections and deaths in U.S. hospitals, 2002. Public Health Rep 2007;122:160–6. 10.1177/003335490712200205
    1. Myles PS, Leslie K, Chan MTV, et al. . The safety of addition of nitrous oxide to general anaesthesia in at-risk patients having major non-cardiac surgery (ENIGMA-II): a randomised, single-blind trial. Lancet 2014;384:1446–54. 10.1016/S0140-6736(14)60893-X
    1. Neumayer L, Hosokawa P, Itani K, et al. . Multivariable predictors of postoperative surgical site infection after general and vascular surgery: results from the patient safety in surgery study. J Am Coll Surg 2007;204:1178–87. 10.1016/j.jamcollsurg.2007.03.022
    1. Clement S, Braithwaite SS, Magee MF, et al. . Management of diabetes and hyperglycemia in hospitals. Diabetes Care 2004;27:553–91. 10.2337/diacare.27.2.553
    1. Smiley DD, Umpierrez GE. Perioperative glucose control in the diabetic or nondiabetic patient. South Med J 2006;99:580–9. quiz 90-1 10.1097/01.smj.0000209366.91803.99
    1. Bach LA, Ekinci EI, Engler D, et al. . The high burden of inpatient diabetes mellitus: the Melbourne public hospitals diabetes inpatient audit. Med J Aust 2014;201:334–8. 10.5694/mja13.00104
    1. Kotagal M, Symons RG, Hirsch IB, et al. . Perioperative hyperglycemia and risk of adverse events among patients with and without diabetes. Ann Surg 2015;261:97–103. 10.1097/SLA.0000000000000688
    1. Holman N, Hillson R, Young RJ. Excess mortality during Hospital stays among patients with recorded diabetes compared with those without diabetes. Diabet Med 2013;30:1393–402. 10.1111/dme.12282
    1. De Oliveira GS, Castro-Alves LJS, Ahmad S, et al. . Dexamethasone to prevent postoperative nausea and vomiting: an updated meta-analysis of randomized controlled trials. Anesth Analg 2013;116:58–74. 10.1213/ANE.0b013e31826f0a0a
    1. Kovac AL. Update on the management of postoperative nausea and vomiting. Drugs 2013;73:1525–47. 10.1007/s40265-013-0110-7
    1. Gan TJ, Diemunsch P, Habib AS, et al. . Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg 2014;118:85–113. 10.1213/ANE.0000000000000002
    1. Myles PS, Williams DL, Hendrata M, et al. . Patient satisfaction after anaesthesia and surgery: results of a prospective survey of 10,811 patients. Br J Anaesth 2000;84:6–10. 10.1093/oxfordjournals.bja.a013383
    1. Henzi I, Walder B, Tramèr MR. Dexamethasone for the prevention of postoperative nausea and vomiting: a quantitative systematic review. Anesth Analg 2000;90:186–94. 10.1097/00000539-200001000-00038
    1. Apfel CC, Korttila K, Abdalla M, et al. . A factorial trial of six interventions for the prevention of postoperative nausea and vomiting. N Engl J Med 2004;350:2441–51. 10.1056/NEJMoa032196
    1. Allen TK, Jones CA, Habib AS. Dexamethasone for the prophylaxis of postoperative nausea and vomiting associated with neuraxial morphine administration: a systematic review and meta-analysis. Anesth Analg 2012;114:813–22. 10.1213/ANE.0b013e318247f628
    1. Dungan KM, Braithwaite SS, Preiser JC. Stress hyperglycaemia. Lancet 2009;373:1798–807. 10.1016/S0140-6736(09)60553-5
    1. Kiran RP, Turina M, Hammel J, et al. . The clinical significance of an elevated postoperative glucose value in nondiabetic patients after colorectal surgery: evidence for the need for tight glucose control? Ann Surg 2013;258:599–604. discussion -5 10.1097/SLA.0b013e3182a501e3
    1. Kwon S, Thompson R, Dellinger P, et al. . Importance of perioperative glycemic control in general surgery: a report from the surgical care and outcomes assessment program. Ann Surg 2013;257:8–14. 10.1097/SLA.0b013e31827b6bbc
    1. Frisch A, Chandra P, Smiley D, et al. . Prevalence and clinical outcome of hyperglycemia in the perioperative period in noncardiac surgery. Diabetes Care 2010;33:1783–8. 10.2337/dc10-0304
    1. Abdelmalak BB, Knittel J, Abdelmalak JB, et al. . Preoperative blood glucose concentrations and postoperative outcomes after elective non-cardiac surgery: an observational study. Br J Anaesth 2014;112:79–88. 10.1093/bja/aet297
    1. Corcoran TB, Edwards T. A survey of antiemetic dexamethasone administration-frequency of use and perceptions of benefits and risks. Anaesth Intensive Care 2015;43:167–74. 10.1177/0310057X1504300205
    1. Cowie BS, Allen KJ, Said SA, et al. . Anti-Emetic doses of dexamethasone suppress cortisol response in laparoscopic cholecystectomy. Anaesth Intensive Care 2010;38:667–70. 10.1177/0310057X1003800408
    1. Hans P, Vanthuyne A, Dewandre PY, et al. . Blood glucose concentration profile after 10 Mg dexamethasone in non-diabetic and type 2 diabetic patients undergoing abdominal surgery. Br J Anaesth 2006;97:164–70. 10.1093/bja/ael111
    1. Abdelmalak BB, Bonilla AM, Yang D, et al. . The hyperglycemic response to major noncardiac surgery and the added effect of steroid administration in patients with and without diabetes. Anesth Analg 2013;116:1116–22. 10.1213/ANE.0b013e318288416d
    1. Murphy GS, Szokol JW, Avram MJ, et al. . The effect of single low-dose dexamethasone on blood glucose concentrations in the perioperative period: a randomized, placebo-controlled investigation in gynecologic surgical patients. Anesth Analg 2014;118:1204–12. 10.1213/ANE.0b013e3182a53981
    1. Tien M, Gan TJ, Dhakal I, et al. . The effect of anti-emetic doses of dexamethasone on postoperative blood glucose levels in non-diabetic and diabetic patients: a prospective randomised controlled study. Anaesthesia 2016;71:1037–43. 10.1111/anae.13544
    1. Madan R, Bhatia A, Chakithandy S, et al. . Prophylactic dexamethasone for postoperative nausea and vomiting in pediatric strabismus surgery: a dose ranging and safety evaluation study. Anesth Analg 2005;100:1622–6. 10.1213/01.ANE.0000150977.14607.E1
    1. Bolac CS, Wallace AH, Broadwater G, et al. . The impact of postoperative nausea and vomiting prophylaxis with dexamethasone on postoperative wound complications in patients undergoing laparotomy for endometrial cancer. Anesth Analg 2013;116:1041–7. 10.1213/ANE.0b013e318276cf58
    1. Dieleman JM, Nierich AP, Rosseel PM, et al. . Intraoperative high-dose dexamethasone for cardiac surgery: a randomized controlled trial. JAMA 2012;308:1761–7. 10.1001/jama.2012.14144
    1. Percival VG, Riddell J, Corcoran TB. Single dose dexamethasone for postoperative nausea and vomiting – a matched case-control study of postoperative infection risk. Anaesth Intensive Care 2010;38:661–6. 10.1177/0310057X1003800407
    1. Corcoran TB, Truyens EB, Ng A, et al. . Anti-Emetic dexamethasone and postoperative infection risk: a retrospective cohort study. Anaesth Intensive Care 2010;38:654–60. 10.1177/0310057X1003800406
    1. Abdelmalak BB, Bonilla A, Mascha EJ, et al. . Dexamethasone, light anaesthesia, and tight glucose control (DeLiT) randomized controlled trial. Br J Anaesth 2013;111:209–21. 10.1093/bja/aet050
    1. Kurz A, Fleischmann E, Sessler DI, et al. . Effects of supplemental oxygen and dexamethasone on surgical site infection: a factorial randomized trial ‡. Br J Anaesth 2015;115:434–43. 10.1093/bja/aev062
    1. Myles PS. Stopping trials early. Br J Anaesth 2013;111:133–5. 10.1093/bja/aet079
    1. DREAMS Trial Collaborators and West Midlands Research Collaborative Dexamethasone versus standard treatment for postoperative nausea and vomiting in gastrointestinal surgery: randomised controlled trial (dreams trial). BMJ 2017;357:j1455 10.1136/bmj.j1455
    1. Dhatariya K. Ii. does dexamethasone-induced hyperglycaemia contribute to postoperative morbidity and mortality? Br J Anaesth 2013;110:674–5. 10.1093/bja/aet010
    1. Ali Khan S, McDonagh DL, Gan TJ. Wound complications with dexamethasone for postoperative nausea and vomiting prophylaxis: a moot point? Anesth Analg 2013;116:966–8. 10.1213/ANE.0b013e31828a73de
    1. Bartlett R, Hartle AJ. Routine use of dexamethasone for postoperative nausea and vomiting: the case against. Anaesthesia 2013;68:892–6. 10.1111/anae.12309
    1. De Oliveira GS, Almeida MD, Benzon HT, et al. . Perioperative single dose systemic dexamethasone for postoperative pain: a meta-analysis of randomized controlled trials. Anesthesiology 2011;115:575–88. 10.1097/ALN.0b013e31822a24c2
    1. Waldron NH, Jones CA, Gan TJ, et al. . Impact of perioperative dexamethasone on postoperative analgesia and side-effects: systematic review and meta-analysis. Br J Anaesth 2013;110:191–200. 10.1093/bja/aes431
    1. Toner AJ, Ganeshanathan V, Chan MT, et al. . Safety of perioperative glucocorticoids in elective noncardiac surgery: a systematic review and meta-analysis. Anesthesiology 2017;126:234–48. 10.1097/ALN.0000000000001466
    1. Polderman JA, Farhang-Razi V, Van Dieren S, et al. . Adverse side effects of dexamethasone in surgical patients. Cochrane Database Syst Rev 2018;11:CD011940 10.1002/14651858.CD011940.pub3
    1. Mauri L, D’Agostino RB. Challenges in the design and interpretation of Noninferiority trials. N Engl J Med 2017;377:1357–67. 10.1056/NEJMra1510063
    1. Kaul S, Diamond GA. Good enough: a primer on the analysis and interpretation of Noninferiority trials. Ann Intern Med 2006;145:62–9. 10.7326/0003-4819-145-1-200607040-00011
    1. Chan AW, Tetzlaff JM, Altman DG, et al. . Spirit 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med 2013;158:200–7. 10.7326/0003-4819-158-3-201302050-00583
    1. Stark PA, Myles PS, Burke JA. Development and psychometric evaluation of a postoperative quality of recovery score. Anesthesiology 2013;118:1332–40. 10.1097/ALN.0b013e318289b84b
    1. Horan TC, Andrus M, Dudeck MA. CDC/NHSN surveillance definition of health care–associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 2008;36:309–32. 10.1016/j.ajic.2008.03.002
    1. Pinkney TD, Calvert M, Bartlett DC, et al. . Impact of wound edge protection devices on surgical site infection after laparotomy: multicentre randomised controlled trial (ROSSINI trial). BMJ 2013;347:f4305 10.1136/bmj.f4305
    1. Piaggio G, Elbourne DR, Pocock SJ, et al. . Reporting of noninferiority and equivalence randomized trials: extension of the CONSORT 2010 statement. JAMA 2012;308:2594–604. 10.1001/jama.2012.87802
    1. Holm S. A simple sequentially rejective multiple test procedure. Scand J Statist 1979;6:65–70.

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