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

Background :

Postoperative complications are major healthcare problems and are associated with a reduced short-term and long-term survival after surgery. Corticosteroids may decrease the postsurgical SIRS in cardiac surgery, but this treatment is not recommended yet. The aim of the current study is to assess the efficiency and the safety of dexamethasone to prevent on postoperative complications.

Methods :

The PACMAN trial is a multicenter, randomized, controlled, double-blind, two-arms study. 1222 patients undergoing major surgery (duration >90 minutes and one or more risk factor of postoperative complication) are randomized to dexamethasone (0.2mg/kg at the end of the surgery and at day1) or to placebo. The primary outcome is a composite outcome of major postoperative complication during 14 days after the surgery.

Analyzes will be conducted, first, on data from the intention-to-treat (ITT) population, second, in the modified intention-to-treat (mITT) population as well as in the per-protocol population. All statistical analyzes will take into account stratified randomization (cancer and type of surgery) and will be adjusted on the center as random effect as.

Discussion :

The PACMAN trial is the first randomized controlled trial powered to investigate whether perioperative administration of dexamethasone in high risk patients improve outcomes.

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)