This explorative post hoc analysis included patients randomized in the DEX-2-TKA trial (NCT03506789) who were operated under general anesthesia with remifentanil and propofol. Patients having general anesthesia with sevoflurane were excluded. As the two groups receiving preoperative dexamethasone were identical at the time of outcome assessment, they were merged to one and were compared with placebo.

The DEX-2-TKA was a randomized, blinded, placebo-controlled, multicenter trial in participants undergoing primary TKA conducted to investigate the effects of dexamethasone on morphine consumption, levels of postoperative pain, and harm. The methodology has been described in detail in the primary publication (ref), the protocol article and in the statistical analysis plan. In short, the trial was conducted at one private and four public Danish hospitals. Patients were randomized into one of three groups receiving either: Dexamethasone + placebo, dexamethasone + dexamethasone or placebo + placebo in a 1:1:1 ratio. The first dose of trial medication (intravenous dexamethasone 24 mg or placebo) was administered immediately after onset of anesthesia. Twenty-four hours after end of surgery, the second dose (dexamethasone 24 mg or placebo) was administered.

As the two groups receiving preoperative dexamethasone were identical at the time of outcome assessment for thi post-hoc analysis, they were merged to one and were compared with placebo yielding a ratio of 2:1 between the groups recieving dexamethsone and the placebo group.

Patients received either spinal anesthesia or general anesthesia (remifentanil and propofol were preferred). Before end of surgery all patients received ondansetron iv 4 mg. For patients in general anesthesia, sufentanil (0.3 μg/kg) was administered. All participants were provided with a patient-controlled analgesia pump (morphine 1 mg/mL, bolus 2 mg, lock-out 6 minutes, no background infusion) for 24 hours postoperatively. Additional boluses of 2 mg morphine on participant request were allowed the first hour after cessation of anesthesia. All participants received a protocolled non-opioid analgesic pain alleviation regime comprised of oral paracetamol 1 g and ibuprofen 400 mg given 1 hour before and every 6 hours after surgery and the surgeon administered local infiltration analgesia intraoperatively according to a standardized regimen.

The present explorative post hoc analysis included patients randomized in the DEX-2-TKA trial who were operated under general anesthesia with remifentanil and propofol. Patients having general anesthesia with sevoflurane were excluded.

Inclusion Criteria:

• Participation in DEX-2-TKA (NCT03506789)
• General anesthesia

Exclusion Criteria:

• Spinal anestehesia
• Use of sevoflurane