Effect of Dexamethasone Shortly Before Surgery on the Intraoperative Dose of Remifentanil

Effect of Dexamethasone Shortly Before Surgery on the Intraoperative Dose of Remifentanil in Total Knee Arthroplasty Patients Operated Under General Anesthesia: A Post-hoc Sub-study Analysis of the Randomized DEX-2-TKA Trial

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.

Study Overview

• Status: Completed
• Conditions: Perioperative Pain
• Intervention / Treatment: Drug: Dexamethasone; Drug: Isotonic saline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Brøndbyvester, Denmark, 2605
    • Gildhøj Privathospital
  • Copenhagen, Denmark, 2400
    • Bispebjerg Hospital
  • Køge, Denmark, 4600
    • Sjællands Universitetshospital, Køge
  • Næstved, Denmark, 4700
    • Næstsved Sygehus
  • Odense, Denmark, 5000
    • Odense Universitetshospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

• Spinal anestehesia
• Use of sevoflurane

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Treatment A+B; 24 mg dexamethasone i.v. perioperatively	Drug: Dexamethasone; 24 mg intravenous Dexamethasone (6 ml)
PLACEBO_COMPARATOR: Placebo; Placebo (isotonic saline) i.v. perioperatively	Drug: Isotonic saline; 6 ml of isotonic saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative use of remifentanil	mg	During surgery (from surgical incision till last suture)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraoperative use of propofol	mg	During surgery (from surgical incision till last suture)
Anesthesia depth	Measured with bispectral index (BIS) - only for patients at Næstved	During surgery (from surgical incision till last suture)
Time in post-anesthesia care unit (PACU)	Minutes	Time at the PACU (from arrival at the PACU untill transfer to orthopedic ward), approximated 0-4 hours

Collaborators and Investigators

• Sponsor: Naestved Hospital
• Collaborators: Bispebjerg Hospital
• Investigators: Principal Investigator: Kasper S Gasbjerg, MD, Naestved Hospital

Publications and helpful links

General Publications

• Gantzel M, Gasbjerg KS, Hagi-Pedersen D, Meyhoff CS, Olsen MH, Mathiesen O, Jakobsen JC, Lunn TH. Effect of dexamethasone on intraoperative remifentanil dose in total knee arthroplasty surgery under general anaesthesia. Acta Anaesthesiol Scand. 2022 Oct;66(9):1070-1076. doi: 10.1111/aas.14118. Epub 2022 Aug 4.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 14, 2018
• Primary Completion (ACTUAL): March 11, 2020
• Study Completion (ACTUAL): June 7, 2020

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: August 11, 2021
• First Posted (ACTUAL): August 12, 2021

Study Record Updates

• Last Update Posted (ACTUAL): August 12, 2021
• Last Update Submitted That Met QC Criteria: August 11, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: SM1-MG-2021

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No