Title: Dexamethasone reduces emesis after major gastro-intestinal surgery: a multicentre randomised controlled trial (DREAMS)
Funder: Department of Health (England)

Abstract: Background: Despite advances in antiemetic, anaesthetic agents and surgical techniques, PONV remains a significant problem. The incidence of PONV is 30% overall and up to 70% in high-risk patients, which are those patients selected into DREAMS(1). The mechanisms underlying PONV include dopamine and 5HT3 receptor stimulation by opiates and anaesthetic agents, and gut chemoreceptor and stretch-receptor stimulation. Risk-factors increasing PONV are female gender, non-smoking status, history of motion sickness, childhood/young adulthood, and increasing length of surgery(1). Both open and laparoscopic gastrointestinal procedures are known to be associated with increased PONV(2), but as yet the value of dexamethasone has been unevaluated in these patients. The antiemetic mechanism of dexamethasone occurs through activation of glucocorticoid receptors(3), inhibition of prostaglandin production and endogenous opioid release(4). It is known to improve appetite(5), aid early recovery and reduce pain by suppression of bradykinin and neuropeptides from nerve-endings(4). Large RCTs(6) have shown a single dose of dexamethasone, given pre-operatively in patients undergoing biliary and gynaecological surgery substantially reduces PONV, supporting its routine use. Similarities between biliary/gynaecological surgery and bowel surgery suggest that dexamethasone would reduce PONV in patients undergoing the latter, however, there is no evidence to support this and resultantly dexamethasone is not routinely given. Aim : To determine the effect of a single intravenous dose of dexamethasone administered preoperatively on PONV in patients undergoing major gastrointestinal surgery. Hypothesis: A single dose of dexamethasone on induction of anaesthesia for bowel surgery reduces PONV. Plan: A double-blind multicentre randomised controlled trial. Patients will be identified, consented and randomised as per the patient pathway. 950 patients will be randomised 1:1 to receive either a single 8mg dose of dexamethasone following induction of anaesthesia or standard care without dexamethasone. DREAMS is double-blind as both the patient and the healthcare professional collecting data are unaware of the patients' randomised allocation. The total number of episodes of vomiting within 24 hours of surgery, measured objectively, is the primary outcome measure. Patient benefits: In a study investigating the ten most undesirable post-operative outcomes, vomiting ranked first, gagging second, pain third, and nausea fourth(3). PONV can cause significant morbidity including dehydration, electrolyte disturbance, delayed return to diet and aspiration pneumonia. Delayed recovery in the hospital setting predisposes to serious and life-threatening complications such as pneumonia and deep venous thrombosis/pulmonary embolism. The delay in resuming an oral diet affects nutrition and subsequent general well-being, predisposing to tissue breakdown, pressure sores, wound infection, fatigue, weakness, delay in mobilisation. If DREAMS demonstrates that dexamethasone reduces PONV in patients undergoing bowel surgery, it will ensure its routine use in this cohort thus helping to reduce the above complications. NHS benefits: 60,000 major colorectal resections are undertaken annually in the UK. PONV can delay recovery, lead to increased hospital stay and, in frail patients, is associated with serious adverse outcomes such as DVT/PE, chest and wound infections at high cost to the NHS. Published evidence from a multicentre RCT highlighting the benefit of dexamethasone will lead to its use becoming routine and allow incorporation into national and international guidelines. Thus improving quality of care, prevent complications and escalation of level of care with the associated costs, reduce patient length-of-stay so reducing financial and logistic burdens on the NHS. 1. Gan P et al: Anaethesia Analgesia, 2006;102; 1884-98. 2. Apfel C et al: Anaesthesiology, 2002;88; 234-40. 3. Wang JJ et al: Anaethesia and Analgesia, 2004;99; 734-9. 4. Holte K et al: J of American College of Surgeons, 2002;195; 694-712. 5. Loprinzi CL et al: J Clin Oncology, 1999;17; 3299-3306. 6. Karanicolas P et al: Annals of Surgery, 2008;248; 751-62.


Research activity codes: 6.4 SURGERY;6.1 PHARMACEUTICALS
Health categories: ORAL AND GASTROINTESTINAL