Opioid-free Anesthesia vs Opioid-based Anesthesia / A Heavyweight Showdown - Randomized Controlled Trial
Phase: NA
Conditions: Morbid Obesity, Postoperative Pain, Opioid Free Anesthesia, Bariatric Surgery
Sponsor: Hospital dos Lusíadas

 
 
Opioid-Free Anesthesia versus Opioid-Based Anesthesia in Laparoscopic Bariatric 
Surgery: A Prospective Randomized Controlled Trial 
NCT Number: NCT07337135  
Registration date: 13 January 2026 (retrospectively registered) 
 
Document Date: 04 February 2026 
Version 2.0 
 
Original protocol date: 01 July 2023 
Last update: 04 February 2026 
 
 

Title 
Opioid-Free Anesthesia versus Opioid-Based Anesthesia in Laparoscopic Bariatric 
Surgery: A Prospective Randomized Controlled Trial 
Version 
2.0 
Principal Investigator 
Emanuel Almeida, MD, Consultant Anesthesiologist 
Institution: Hospital Lusíadas Amadora – Lusíadas Saúde, S.A. 
1. Background and Rationale 
Obesity is a chronic disease with increasing global prevalence and is associated with 
significant morbidity and mortality. Bariatric surgery remains the most effective treatment 
for severe obesity and related comorbidities. Despite advances in perioperative care, 
postoperative pain control and postoperative nausea and vomiting (PONV) remain clinically 
relevant challenges. 
Opioid-based anesthesia (OBA), traditionally used to ensure intraoperative 
antinociception, is associated with several adverse effects, including respiratory depression, 
ileus, hyperalgesia, PONV, and delayed recovery. In contrast, opioid-free anesthesia (OFA) 
combines non-opioid agents (e.g., dexmedetomidine, ketamine, lidocaine) to achieve 
analgesia and hemodynamic stability while minimizing opioid-related complications. 
Emerging evidence suggests that OFA may improve postoperative recovery and 
reduce opioid consumption, particularly in bariatric patients. However, data remain 
heterogeneous, and further prospective studies are required. 
This study aims to compare the efficacy and safety of OFA versus OBA in patients 
undergoing laparoscopic bariatric surgery, with particular focus on postoperative pain, 
rescue analgesia, and intraoperative nociception monitoring using the Nociception Level 
Index (NOL). 
2. Objectives 
• 
Primary: To compare postoperative pain intensity between opioid-free anesthesia 
(OFA) and opioid-based anesthesia (OBA), assessed using the Numerical Rating 
Scale (NRS). 
• 
Secondary: To compare: Intraoperative nociception (NOL index); Need for rescue 
analgesia; Intraoperative nociception (NOL index); Incidence and severity of PONV; 
Patient satisfaction; Perioperative complications. 
3. Study Design 
• 
Interventional, prospective, randomized, parallel-group clinical trial 
• 
Single-center study 
• 
Allocation: Randomized 
• 
Masking: None (open-label) 

• 
Arms: 2 
• 
Primary Purpose: Treatment 
• 
Phase: Not applicable 
4. Study Population 
Inclusion Criteria 
• 
Age ≥ 18 years 
• 
BMI ≥ 35 kg/m² with obesity-related comorbidities or BMI ≥ 40 kg/m² 
• 
Scheduled for elective laparoscopic bariatric surgery 
• 
Written informed consent provided 
Exclusion Criteria 
• 
Pregnancy 
• 
History of substance abuse 
• 
Severe psychiatric disease 
• 
Contraindications to study medications 
5. Interventions 
Arm 1 – Opioid-based anesthesia (OBA): Remifentanil infusion; propofol 
induction; rocuronium neuromuscular blockade; desflurane maintenance; standard 
multimodal postoperative analgesia; rescue analgesia with tramadol and/or morphine. 
Arm 2 – Opioid-free Anesthesia (OFA): Dexmedetomidine bolus followed by 
infusion combined with ketamine and lidocaine; propofol induction; rocuronium 
neuromuscular blockade; desflurane maintenance; postoperative opioid-free multimodal 
analgesia; rescue analgesia with tramadol. 
Both groups received standardized antibiotic prophylaxis, PONV prophylaxis, 
stress-ulcer prophylaxis, and neuromuscular blockade reversal according to institutional 
protocols. 
6. Outcomes 
Primary Outcome 
• 
Postoperative pain (NRS) assessed: 
o Within 30 minutes of arrival at the Post-Anesthesia Care Unit (PACU); 
o At PACU discharge (assessed up to 2 hours after PACU admission); 
o Within the first 24 postoperative hours; 
o 48 hours postoperatively (at hospital discharge). 
 
Secondary Outcomes 
• 
Intraoperative nociception (NOL index at predefined time points) 
• 
Need for rescue analgesia and opioid consumption 
• 
Incidence and severity of PONV (PONV Impact Scale at 6 and 24 hours) 
• 
Patient satisfaction (1–10 scale) 
• 
Perioperative complications 
 

7. Sample Size 
A total of 60 patients (30 per group) were included. No formal a priori sample size 
calculation was performed. The sample size was defined pragmatically based on feasibility 
and the number of eligible patients during the study period. 
8. Randomization 
Randomization was performed using a computer-generated sequence with a 1:1 
allocation ratio. Group assignment was revealed immediately before anesthesia induction. 
9. Blinding 
This was an open-label study. Due to the nature of the interventions, blinding of the 
anesthesia team was not feasible. 
10. Data Collection 
Data collected included: demographic and anthropometric data, comorbidities and 
chronic medication, surgical and anesthetic variables, intraoperative nociception (NOL), 
postoperative pain, PONV and rescue medication, patient satisfaction and perioperative 
complications. 
11. Statistical Analysis 
• 
Distribution assessed using the Shapiro–Wilk test 
• 
Continuous variables: 
o Student’s t-test or Mann–Whitney U test 
• 
Categorical variables: 
o Chi-square test or Fisher’s exact test 
• 
Multivariable analysis: 
o Generalized Linear Models (GLM) with Bonferroni correction 
• 
Significance threshold: p < 0.05 
• 
Statistical software: SPSS version 28.0 
12. Ethical Considerations 
The study was conducted in accordance with the Declaration of Helsinki. 
Approval was obtained from the Ethics Committee of Hospital Lusíadas Amadora. 
Written informed consent was obtained from all participants before enrollment. 
13. Data Management and Confidentiality 
Data were stored in password-protected databases accessible only to the research 
team. Individual participant data will be available from the corresponding author upon 
reasonable request. 
14. Dissemination Plan 
Results will be disseminated through publication in peer-reviewed scientific journals and 
scientific meetings.