Opioid-free Anesthesia as an Alternative to General Anesthesia in Abdominal Surgery

August 24, 2026 updated by: Tomasz Skladzien, Jagiellonian University

Opioid-free anesthesia (OFA) is a multimodal technique that eliminates intraoperative opioids by combining dexmedetomidine, ketamine, lidocaine, NSAIDs, and regional analgesia. Growing evidence suggests OFA reduces postoperative opioid consumption, opioid-related adverse effects, and may have favorable oncological implications in cancer surgery.

This randomized controlled trial compares OFA with opioid-based anesthesia (remifentanil) in patients undergoing elective urological surgery: laparoscopic nephrectomy, robotic nephrectomy, laparoscopic prostatectomy, robotic prostatectomy, laparoscopic cystectomy, and robotic cystectomy.

The PRIMARY OBJECTIVE is to compare the total postoperative oxycodone dose (mg) administered via patient-controlled analgesia (PCA) during the first 24 hours after surgery between the OFA and remifentanil groups.

SECONDARY OBJECTIVES include: postoperative pain intensity (NRS) at 1, 2, 6, 12, and 24 hours; incidence of postoperative nausea and vomiting (PONV); change in serum creatinine from baseline to postoperative day 1; change in white blood cell (WBC) count from baseline to postoperative day 1; and the ratio of demanded to delivered PCA boluses.

PRE-SPECIFIED SUBGROUP ANALYSES will compare outcomes by surgical procedure type: laparoscopic nephrectomy, robotic nephrectomy, laparoscopic prostatectomy, robotic prostatectomy, laparoscopic cystectomy, and robotic cystectomy. Subgroup-by-treatment interaction tests will be performed and reported as forest plots.

Planned enrollment: approximately 600 patients (300 per arm). Follow-up: 24 hours postoperatively.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

All consecutive patients undergoing elective urological surgery (laparoscopic or robotic nephrectomy, prostatectomy, or cystectomy) will be randomly divided into two groups: one under completely opioid-free anesthesia (infusion of ketamine, lidocaine and dexmedetomidine, with inhalation of sevoflurane) and the other under combined general anesthesia (using an infusion of remifentanil intraoperatively). In the postoperative period, all patients will receive oxycodone in a PCA pump or in the form of oral tablets [oxycodone hydrochloride + naloxone hydrochloride] and co-analgesics in the form of paracetamol and metamizole.

Opioid-free general anesthesia is a recognized method used during anesthesia. It allows participants to effectively control pain, reducing the number of complications associated with taking large doses of opioid drugs. It should be emphasized that it is approved for use in routine anesthetic practice, and whether such a technique is used in a given patient depends on the experience, knowledge and preferences of the anesthesiologist. It is used in everyday anesthetic practice, but there is no conclusive scientific data confirming its advantage in patients undergoing major urological surgery.

Mulier et al. proposed an OFA scheme including dexmedetomidine, ketamine and lidocaine for the induction of anesthesia, ensuring sedation, analgesia and sympatholytic therapy, followed by a maintenance infusion of lidocaine and dexmedetomidine. The protocol proposed by Mulier et al. is widely used and accepted worldwide. Initially used in patients undergoing bariatric procedures, it was subsequently extended to other types of surgical procedures.

In the postoperative period, pain will be assessed using the NRS scale at 1, 2, 6, 12, and 24 hours after the procedure. Serum creatinine and white blood cell (WBC) count will be measured preoperatively (baseline) and on postoperative day 1.

Study Type

Interventional

Enrollment (Estimated)

600

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Poland
    • Lesser Poland Voivodeship
      • Krakow, Lesser Poland Voivodeship, Poland, 31501
        • Recruiting
        • Jagiellonian University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults aged 18-75 years scheduled for elective urological surgery under general anesthesia: laparoscopic or robotic nephrectomy, laparoscopic or robotic prostatectomy, or laparoscopic or robotic cystectomy.
  • Ability to operate a patient-controlled analgesia (PCA) pump postoperatively.
  • Ability to understand and use the Numeric Rating Scale (NRS) for pain assessment.
  • Written informed consent.

Exclusion Criteria:

  • Patient's refusal to participate.
  • Inability to operate the PCA pump.
  • Inability to understand the NRS pain scale.
  • Known hypersensitivity to any of the study drugs (anesthetics, ketamine, dexmedetomidine, ropivacaine, oxycodone, metamizole, paracetamol, ibuprofen).
  • Second- or third-degree atrioventricular block, or symptomatic bradycardia.
  • Chronic opioid use.
  • Contraindication to the planned regional anesthesia technique (e.g. coagulopathy or therapeutic anticoagulation, infection at the puncture site).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Opioid-based anesthesia (remifentanil)
Opioid-based general anesthesia. Premedication includes dexamethasone, paracetamol, metamizole, magnesium sulfate, and ibuprofen. Induction with propofol and rocuronium under TOF monitoring. Maintenance with sevoflurane titrated to MAC; intraoperative analgesia provided by remifentanil infusion (total intraoperative dose recorded). Regional analgesia by procedure: bilateral ESP block (nephrectomy), bilateral QL block (prostatectomy), and continuous epidural ropivacaine infusion (cystectomy). Postoperative analgesia: oxycodone PCA (2 mg bolus, 10-min lockout, no background infusion) with paracetamol and metamizole.
Experimental: Opioid-free anesthesia (OFA)
Opioid-free general anesthesia. Premedication includes dexamethasone, paracetamol, metamizole, magnesium sulfate, ibuprofen, and dexmedetomidine (OFA group only). Induction with propofol, ketamine (OFA group only), and rocuronium under TOF monitoring. Maintenance with sevoflurane titrated to MAC; intraoperative analgesia provided by a continuous dexmedetomidine/ketamine infusion with rescue boluses for tachycardia or hypertension. Regional analgesia by procedure: bilateral ESP block (nephrectomy), bilateral QL block (prostatectomy), and continuous epidural ropivacaine infusion (cystectomy). Postoperative analgesia: oxycodone PCA (2 mg bolus, 10-min lockout, no background infusion) with paracetamol and metamizole.
Other: anesthesia without opioids
Opioid free general anesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total postoperative oxycodone dose administered via PCA (mg)
Time Frame: 0-24 hours after surgery
Total postoperative oxycodone dose administered via PCA (mg) - Cumulative dose of oxycodone (mg) self-administered via PCA pump during the first 24 hours after surgery, compared between the OFA and remifentanil groups.
0-24 hours after surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Postoperative pain (NRS)
Time Frame: 1, 2, 6, 12, and 24 hours after surgery
Postoperative pain intensity as assessed by the Numeric Rating Scale (NRS) - NRS (0 = no pain, 10 = worst imaginable pain) at rest, compared between groups; score reported at each time point.
1, 2, 6, 12, and 24 hours after surgery

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Postoperative nausea and vomiting (PONV)
Time Frame: 0-24 hours after surgery
Number of participants with postoperative nausea and/or vomiting (PONV) - Number (and proportion) of participants with any nausea and/or vomiting within 24 h after surgery (binary: yes/no), compared between groups.
0-24 hours after surgery
Postoperative renal function (serum creatinine)
Time Frame: Baseline and postoperative day 1
Change in serum creatinine from baseline to postoperative day 1 (µmol/L) - Serum creatinine (µmol/L) at baseline (preoperative) and on POD1; change from baseline compared between groups.
Baseline and postoperative day 1
Patient-controlled analgesia (PCA) demand/administered ratio
Time Frame: 0-24 hours after surgery
Ratio of demanded to delivered PCA boluses - Ratio of demanded to delivered PCA bolus attempts within 24 h after surgery, compared between groups.
0-24 hours after surgery
Change in white blood cell (WBC) count from baseline to postoperative day 1 (×10⁹/L)
Time Frame: Baseline and postoperative day 1
White blood cell (WBC) count (×10⁹/L) measured preoperatively (baseline) and on postoperative day 1; change from baseline compared between the OFA and remifentanil groups.
Baseline and postoperative day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jagiellonian University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 29, 2024

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

April 16, 2024

First Submitted That Met QC Criteria

April 18, 2024

First Posted (Actual)

April 23, 2024

Study Record Updates

Last Update Posted (Actual)

August 26, 2026

Last Update Submitted That Met QC Criteria

August 24, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1072.6120.136.2023

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

We plan to share demografic data, type of surgery, score in NRS and opioid consumption dosage.

IPD Sharing Time Frame

The data will be available in 2026 for 1 year

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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