The Perioperative ADministration of Dexamethasone and Infection (PADDI) trial recruited 8880 patients from March 2016 to July 2019 from 55 sites across Australia, New Zealand, Hong Kong and South Africa. The manuscript detailing the trial results is now published in the New England Journal of Medicine.
We thank all our PADDI trial committee members, site investigators, fellows, trainees, research coordinators and the thousands of patients who were involved in the trial. Their efforts ultimately improve safety and care in the perioperative setting. The PADDI trial was the brainchild of Professor Tomás Corcoran and brings to fruition more than 10 years of concept development and preliminary research in the lead up to the major funding announcement in 2014, when it was awarded the highest valued National Health and Medical Research Council (NHMRC) project grant at that point of time in the history of the scheme.
For all the latest updates on PADDI, follow @PADDI_Trial on Twitter
Patients were enrolled between March 2016 and July 2019 at 55 centres in Australia, New Zealand, Hong Kong and South Africa.
Every year millions of patients undergo surgery worldwide. Surgical site infections (SSI) occur in up to 12 per cent of these patients. Complications resulting from SSI lead to increased morbidity and mortality, extended hospital stays, and carry an associated cost of up to US$10 billion per annum.
Dexamethasone is widely used by anaesthetists in the perioperative period, principally as an effective antiemetic to prevent postoperative nausea and vomiting (PONV). The molecular mechanisms underlying dexamethasone’s antiemetic action are not fully understood. However, because it is a potent glucocorticosteroid, it has immunosuppressive and hyperglycaemia effects. It is hypothesised that these actions may increase the risk of perioperative infections, particularly in patients with diabetes mellitus, who are already at increased risk of complications. Whether the use of dexamethasone in the perioperative period increases the risk of surgical site and other infections, has not been definitively established. This is an important health priority as in Australia alone up to one million patients will receive dexamethasone as part of their anaesthesia care annually.
This study aims to definitively address the impact of dexamethasone on surgical site infection and will be stratified according to diabetes status.
Study size
8880 adult patients
Study design
Multi-centre prospective, double blind, active control, parallel assessment, stratified, pragmatic non-inferiority safety and efficacy study.
Primary outcome
Surgical site infection within 30 days of surgery.
Secondary outcomes
Secondary outcomes include nausea and vomiting parameters, quality of perioperative analgesia, the incidence of chronic postsurgical pain, length of hospital stay, quality of recovery on days 1 and 30, inflammatory responses, glucose-related outcomes, infections at site other than the surgical site (pneumonia, bloodstream infection, urinary tract infection) up to 30 days, the incidence of sepsis and the incidence of wound dehiscence.
Study population
Adult patients, ASA physical status 1-4, undergoing elective or expedited (non-cardiac) surgery of at least two hours duration, using general anaesthesia with or without regional block, with a single (or multiple) surgical skin incision(s) of >5 cm in length, and a minimum anticipated hospital stay of at least one night.
The Australian National Health and Medical Research Council, Monash University and the Research Grant Council of Hong Kong.
Australian New Zealand Clinical Trials Registry registration number: ACTRN12614001226695
Corcoran TB, Myles PS, Forbes AB, Cheng AC, Bach LA, O'Loughlin E, Leslie K, Chan MTV, Story D, Short TG, Martin C, Coutts P, Ho KM; PADDI Investigators; Australian and New Zealand College of Anaesthetists Clinical Trials Network; Australasian Society for Infectious Diseases Clinical Research Network. Dexamethasone and Surgical-Site Infection. N Engl J Med. 2021 May 6;384(18):1731-1741. doi: 10.1056/NEJMoa2028982. PMID: 33951362.
Barden A, Phillips M, Shinde S, Corcoran T, Mori TA. The effects of perioperative dexamethasone on eicosanoids and mediators of inflammation resolution: A sub-study of the PADDAG trial. Prostaglandins Leukot Essent Fatty Acids. 2021 Aug 17;173:102334. doi: 10.1016/j.plefa.2021.102334. Epub ahead of print. PMID: 34455200.
Corcoran TB, O'Loughlin E, Chan MTV, Ho KM. Perioperative ADministration of Dexamethasone And blood Glucose concentrations in patients undergoing elective non-cardiac surgery - the randomised controlled PADDAG trial. Eur J Anaesthesiol. 2020 Aug 21.
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.
Corcoran TB, Myles PS, Forbes AB, et al. The perioperative administration of dexamethasone and infection (PADDI) trial protocol: rationale and design of a pragmatic multicentre non-inferiority study. BMJ Open 2019;9:e030402.
Myles PS, Corcoran T. Benefits and Risks of Dexamethasone in Noncardiac Surgery. Anesthesiology. 2021 Aug 9. Epub ahead of print. PMID: 34370818.
Professor Tomás Corcoran presented the results on 6 May 2021 with panelists Professor Paul Myles, A/Professor Trisha Peel, Professor Allen Cheng and Ms Karen Goulding. The recording of the webinar is now available on YouTube.
Professor Tomás Corcoran and Professor Paul Myles feature in a podcast explaining the PADDI trial and results. Listen here.
Australia
Alfred Hospital
Austin Hospital
Ballarat Health Services
Barwon Health
Blacktown Hospital
Box Hill Hospital
Cabrini Health
Canterbury Hospital
Concord Repatriation General Hospital
Dandenong Hospital
Epworth HealthCare Richmond
Fiona Stanley Hospital
Flinders Medical Centre
Gosford Hospital
Gold Coast University Hospital
John Hunter Hospital
King Edward Memorial Hospital
Mackay Base Hospital
Macquarie University Hospital
Maroondah Hospital
Monash Medical Centre
Peter MacCallum Cancer Centre
Prince of Wales Hospital NSW
Princess Alexandra Hospital
Redcliffe Hospital
Rockingham Hospital
Royal Adelaide Hospital
Royal Brisbane and Women’s Hospital
Royal Darwin Hospital
Royal Hobart Hospital
Royal Melbourne Hospital
Royal North Shore Hospital
Royal Perth Hospital
Royal Prince Alfred Hospital
Sir Charles Gairdner Hospital
St John of God Hospital Ballarat
St John of God Hospital Subiaco
St Vincent’s Hospital Melbourne
Sunshine Coast University Hospital
The Canberra Hospital
The Northern Hospital
The Tweed Hospital
Wagga Wagga Rural Referral Centre
Western Health
Westmead Hospital
Wollongong Hospital
Hong Kong, China
Prince of Wales Hospital, The Chinese University of Hong Kong Tuen Mun Hospital
New Zealand
Auckland City Hospital
Auckland City Hospital CVICU
Christchurch Hospital
Hauora Tairawhiti Gisborne Hospital
Middlemore Hospital and Manukau Surgical Centre, Counties Manukau Health
South Africa
Groote Schuur Hospital