Opioid-Free Versus Opioid-Based Sedation for Endoscopic Procedures

Safe and comfortable sedation is essential for endoscopic procedures performed outside the operating room. Various sedation strategies have been developed to improve patient safety, procedural conditions, and recovery profiles. Opioids are commonly used as part of sedation regimens; however, opioid administration may be associated with adverse symptoms such as nausea, vomiting, dizziness, drowsiness, difficulty concentrating, fatigue, pruritus, dry mouth, and headache.

This prospective randomized double-blind study will compare dexmedetomidine alone (opioid-free approach) with a combination of dexmedetomidine and remifentanil (opioid-based approach) for sedation during gastroscopy, colonoscopy, and endoscopic retrograde cholangiopancreatography (ERCP). Eighty ASA physical status I-III patients aged 18-80 years will be enrolled at a single center.

Participants will be randomly assigned to one of two study groups using a computer-generated randomization sequence. Study medications will be prepared by an independent anesthesiologist to maintain blinding. In both groups, dexmedetomidine infusion will be administered. The comparison group will additionally receive remifentanil infusion according to the study protocol.

The primary objective is to determine whether the opioid-free approach reduces the incidence of opioid-related adverse symptoms. Secondary objectives include evaluation of postoperative quality of recovery using the QoR-15 questionnaire and assessment of patient, surgeon, and recovery nurse satisfaction. Additional outcomes include hemodynamic parameters, sedation scores, pain scores, rescue analgesic requirements, discharge time, post-anesthesia care unit requirements, and procedure- or anesthesia-related complications.

• Dexmedetomidine (Drug): Dexmedetomidine 200 mcg diluted in 100 mL isotonic saline and administered according to the study protocol.
• Remifentanil (Drug): Remifentanil 5 mg diluted in 100 mL isotonic saline and administered according to the study protocol.

Primary outcomes

• Incidence of Opioid-Related Adverse Symptoms [Perioperative/Periprocedural: from procedure start through recovery room discharge, approximately 2-4 hours]: Incidence of opioid-related adverse symptoms including nausea, vomiting, difficulty concentrating, difficulty staying awake, dizziness, sleepiness, general fatigue or weakness, pruritus, dry mouth, and headache. The occurrence of one or more symptoms will be recorded and compared between the opioid-free and opioid-based sedation groups.

Secondary outcomes

• Quality of Recovery (QoR-15) Score [Baseline (before the procedure) and within 2 hours after the procedure, before discharge from the recovery area]: Postprocedural quality of recovery assessed using the QoR-15 questionnaire. The QoR-15 is a 15-item instrument evaluating five dimensions: physical comfort (5 items), emotional state (4 items), physical independence (2 items), psychological support (2 items), and pain (2 items). Each item is scored 0-10 on a Likert scale; total score ranges from 0 (worst) to 150 (best quality of recovery). Administered to all patients before the procedure (baseline) and after the procedure before discharge.
• Patient Satisfaction Score [Within 1 hour after the procedure, before discharge from the recovery area]: Patient satisfaction assessed using a verbal rating scale from 1 to 10 (1: not satisfied at all, 10: very satisfied). Administered once after the procedure before discharge from the recovery area.
• Surgeon Satisfaction Score [Immediately after the procedure]: Surgeon satisfaction with procedural conditions assessed using a verbal rating scale from 1 to 10 (1: not satisfied at all, 10: very satisfied). Assessed immediately after the procedure.
• Recovery Nurse Satisfaction Score [During the recovery period, before discharge]: Recovery nurse satisfaction assessed using a verbal rating scale from 1 to 10 (1: not satisfied at all, 10: very satisfied). Assessed during the recovery period before discharge.

Other outcomes

• Pain and Analgesic Outcomes [During the recovery period before discharge]: Postprocedural pain assessed using the Visual Analog Scale (VAS; 0-10). Target VAS <4. Rescue analgesia administered as IV paracetamol 1g; tramadol 50 mg IV if insufficient. Total rescue analgesic consumption recorded.
• Post-Anesthesia Care Unit (PACU) Requirement [Immediately after the procedure]: Need for post-anesthesia care unit (PACU) admission following the procedure. Discharge from the recovery unit will be based on the Modified Aldrete Score. The Modified Aldrete Score ranges from 0 to 10, with higher scores indicating better recovery status. Patients with a score of ≥9 will be considered eligible for discharge from the recovery unit.
• Heart Rate [Perioperative/Periprocedural, at 6 predefined time points over approximately 1-3 hours]: Heart rate measured in beats per minute (bpm) at 6 standardized time points: (1) on arrival to the procedure room, (2) immediately after induction, (3) 3 minutes after procedure start, (4) 15 minutes after procedure start, (5) at the end of the procedure, (6) on arrival to the recovery room.
• Mean Arterial Pressure (MAP) [Perioperative/Periprocedural, at 6 predefined time points over approximately 1-3 hours]: Mean arterial pressure measured in millimeters of mercury (mmHg) at 6 standardized time points: (1) on arrival to the procedure room, (2) immediately after induction, (3) 3 minutes after procedure start, (4) 15 minutes after procedure start, (5) at the end of the procedure, (6) on arrival to the recovery room.
• Oxygen Saturation (SpO2) [Perioperative/Periprocedural, at 6 predefined time points over approximately 1-3 hours]: Peripheral oxygen saturation measured as percentage (%) at 6 standardized time points: (1) on arrival to the procedure room, (2) immediately after induction, (3) 3 minutes after procedure start, (4) 15 minutes after procedure start, (5) at the end of the procedure, (6) on arrival to the recovery room.
• Ramsay Sedation Scale Score [Perioperative/Periprocedural, at 6 predefined time points over approximately 1-3 hours]: Sedation depth assessed using the Ramsay Sedation Scale at 6 standardized time points: (1) on arrival to the procedure room, (2) immediately after induction, (3) 3 minutes after procedure start, (4) 15 minutes after procedure start, (5) at the end of the procedure, (6) on arrival to the recovery room. Ramsay Sedation Scale (RSS; ranging from 1 to 6, where 1 = anxious/agitated/restless and 6 = no response to stimulus; higher scores indicate deeper sedation)

Sex: All, ages: 18 Years to 85 Years

Inclusion Criteria:

* Age 18 to 85 years
* ASA physical status I-III
* Scheduled for ERCP, gastroscopy, or colonoscopy

Exclusion Criteria:

* Refusal to participate in the study
* Inability to communicate
* Alcohol or substance abuse
* Neuropsychiatric disease
* Severe respiratory failure
* Severe heart failure
* Pregnancy
* Body mass index (BMI) >30 kg/m²
* Hearing impairment
* History of allergy to study medications
* Requirement for orotracheal intubation or general anesthesia
* Procedures lasting less than 20 minutes

• Yu JM, Tao QY, He Y, Liu D, Niu JY, Zhang Y. Opioid-Free Anesthesia for Pain Relief After Laparoscopic Cholecystectomy: A Prospective Randomized Controlled Trial. J Pain Res. 2023 Oct 30;16:3625-3632. doi: 10.2147/JPR.S432601. eCollection 2023. PMID 37928062
• Hao C, Xu H, Du J, Zhang T, Zhang X, Zhao Z, Luan H. Impact of Opioid-Free Anesthesia on Postoperative Quality of Recovery in Patients After Laparoscopic Cholecystectomy-A Randomized Controlled Trial. Drug Des Devel Ther. 2023 Nov 28;17:3539-3547. doi: 10.2147/DDDT.S439674. eCollection 2023. PMID 38046284