Effects of Perioperative Administration of Dexamethasone on Postoperative Complications and Mortality After Non-cardiac Major Surgery

• Status: Completed
• Trial end date: 2019-04-16
• Target enrollment: 0
• Participant gender: All

Summary

Postoperative complications are major healthcare problems and are associated with a reduced short-term and long-term survival after surgery. Major surgery is associated with a predictable and usually transient Systemic Inflammatory Response (SIRS), depending on the magnitude of the surgical trauma. An excessive SIRS syndrome participates to the development of postoperative organ dysfunction, infection and mortality. Corticosteroids may decrease the postsurgical SIRS in cardiac surgery: in a large multicenter randomized trial, a single intravenous administration of high-dose dexamethasone did not reduce the incidence of a composite endpoint of adverse events but was associated with a reduced incidence of postoperative pulmonary complications and infections and with a reduction in hospital stay. However, a similar study, recently published in the Lancet was negative. Evidences from one meta-analysis, including 11 studies of moderate quality (439 patients in total), suggest that intraoperative administration of corticosteroids during major abdominal surgery decreases postoperative complications, including infectious complications, without significant risk of anastomotic leakage. At present, no large randomized controlled trial has been performed in patients undergoing major non-cardiac surgery. In acute medicine, several lines of evidence have shown that low to moderate doses of corticosteroids decrease the excessive inflammatory response, without inducing immuno suppression. However, despite the widespread use of corticosteroids to reduce postoperative nausea and vomiting and to improve analgesia, concerns continue to be raised about their safety, especially regarding an increased risk of postoperative infection.

We hypothesize that the perioperative administration of glucocorticoids would reduce postoperative morbidity after major non-cardiac surgery through dampening of the inflammatory response. Given the number of surgical patients for whom the question applies, the study is of significant clinical importance

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nantes University Hospital
• Treatments: BB 1101; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate

Criteria

Inclusion Criteria:

Major surgery (> 90 minutes and realized under general anesthesia) of the abdomen, pelvis, thorax, face/neck, vascular surgery in a patient older than 65 years Or Major surgery (> 90 minutes and realized under general anesthesia) of the abdomen, pelvis, thorax, face/neck, vascular surgery in a patient older than 50 years and presenting one of the following criteria

• Presence of a defined risk factor for cardiac or respiratory disease (exercise tolerance equivalent to 6 metabolic equivalents or less)

• Medical history of stroke

• Moderate to severe renal impairment (clearance of creatinine ≤ 30 mll/L)

• Active smoking

• Averaged observed blood losses over 500 ml

• Emergency surgery

Exclusion Criteria:

• Pregnant women, Minors, Adults under guardianship or trusteeship

• Treatment with systemic corticosteroids at a dose > 5 mg.day-1 of equivalent prednisolone in the previous 3 months

• Patients with chronic renal failure (clearance of creatinine < 10 ml/min)

• Patients for which death is deemed imminent and inevitable or patients with an underlying disease process with a life expectancy of less than 1 month

• Patient with preoperative shock (defined by the need for vasoactive drugs before surgery)

• Acute Pulmonary edema in the last 7 days

• Active bacterial or viral infection

• Allergy to the intravenous formulation of dexamethasone

• Uncontrolled psychotic disorder (acute or chronical)