Opioid-Free vs Opioid Analgesia for Postoperative Pain

(PAIN-Alt Trial)

Overseen By Karine Roversi, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Must not be taking: Opioids

Disqualifiers: Breast reconstruction, Opioid use disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

Duration: 4 weeks

540 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether pain relief without opioids can match the effectiveness of opioids after breast surgery. The aim is to determine if avoiding opioids can prevent addiction and misuse while still effectively managing pain. Participants will join one of two groups: one will receive opioid analgesia (opioid painkillers), and the other will receive only non-opioid medications. This study suits those undergoing breast surgery, such as mastectomy or lumpectomy, who plan to go home the same day. The findings could guide doctors in deciding when opioids are necessary for post-surgery pain management. As an unphased trial, it offers patients the chance to contribute to research that could lead to safer pain management options.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are taking opioids before the surgery, you cannot participate in the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that opioid-free analgesia (OFA), which manages pain without opioids, is safe for patients after surgery. Research indicates that OFA aids recovery without harmful effects. In several studies, patients using OFA experienced similar pain levels to those using opioids but had fewer side effects like nausea and vomiting.

Opioids are well-known painkillers but carry risks. Common side effects include drowsiness, dizziness, and nausea, along with the risk of misuse or addiction.

Both treatments have undergone safety studies, but OFA may help avoid the risks associated with opioids. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about opioid-free analgesia (OFA) for postoperative pain because it offers a way to manage pain without the risks associated with opioids, like addiction and side effects. Unlike traditional opioid analgesia, OFA uses non-opioid medications and techniques to control pain effectively, potentially reducing the reliance on opioids. This approach could lead to safer postoperative recovery and a significant reduction in opioid-related complications. By exploring OFA, researchers hope to find a safer pain management strategy that doesn't compromise on effectiveness.

What evidence suggests that this trial's treatments could be effective for postoperative pain?

This trial will compare Opioid-Free Analgesia (OFA) with Opioid Analgesia (OA) for managing postoperative pain. Studies have shown that opioid-free pain treatments can be as effective as opioid-based treatments for managing post-surgical pain. Research indicates that individuals using opioid-free pain relief often experience less nausea and vomiting after surgery, aiding faster recovery. One study found that pain levels 24 hours post-surgery were similar between those who received opioid-free treatments and those who received opioids. These findings suggest that opioid-free options might offer effective pain relief without the addiction risk associated with opioids. ^{2 3 6 7 8}

Who Is on the Research Team?

Julio Flavio Fiore, PhD

Principal Investigator

McGill University

Are You a Good Fit for This Trial?

This trial is for patients having outpatient breast surgery (mastectomy or lumpectomy) for cancerous or non-cancerous conditions, with plans to go home the same day. It's not specified who can't join.

Inclusion Criteria

I am having surgery for breast cancer or a non-cancerous breast condition.

I am expected to go home the same day as my surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either opioid or non-opioid analgesia after outpatient breast surgery

4 weeks

Weekly follow-ups for 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Monthly visits for 6 months

Long-term follow-up

Assessment of chronic postsurgical pain and persistent opioid use

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Opioid Analgesia (OA)
• Opioid-Free Analgesia (OFA)

Trial Overview The study compares post-surgery pain management: one group receives opioid drugs and the other gets only non-opioid alternatives. The focus is on pain control effectiveness and side effects of each method.

How Is the Trial Designed?

Group I: Opioid-Free Analgesia (OFA) Experimental Treatment 1 Intervention

Group II: Opioid Analgesia (OA) Active Control 1 Intervention

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Published Research Related to This Trial

Opioid-free anesthesia (OFA) showed lower pain scores and reduced morphine consumption at 2 and 24 hours post-surgery compared to opioid-based anesthesia, but these differences were not clinically significant.

A significant benefit of OFA was observed in reducing postoperative nausea and vomiting (PONV), with a relative risk reduction indicating a much lower incidence of PONV in the OFA group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid-Free Anesthesia Benefit-Risk Balance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Salomé, A., Harkouk, H., Fletcher, D., et al.[2021]

In a study of 10,219 surgical patients across 187 hospitals, opioid-free analgesia (OFA) was found to be underutilized, especially among patients with obesity and depression, who were less likely to receive OFA despite being at higher risk for opioid-related adverse events.

Older patients and those with neurological disorders, diabetes, or psychosis were more likely to receive OFA, indicating that hospital policies and practices significantly influence the adoption of opioid-free pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of predictors of opioid-free analgesia for management of acute post-surgical pain in the United States. Urman, RD., Böing, EA., Khangulov, V., et al.[2019]

In a study of 124 patients undergoing video-assisted lung surgery, opioid-free anesthesia (OFA) resulted in significantly lower pain severity during coughs on the first postoperative day compared to opioid-sparing anesthesia (OSA), with a VAS score of 1.88 versus 2.16.

The OFA group also experienced significantly fewer patient-controlled epidural analgesia (PCEA)-related adverse events, with only 19.6% of patients reporting issues compared to 47.3% in the OSA group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid-free anesthesia reduces the severity of acute postoperative motion-induced pain and patient-controlled epidural analgesia-related adverse events in lung surgery: randomized clinical trial. Wang, S., Li, Y., Liang, C., et al.[2023]

The POFA trial is a large-scale study involving 400 patients to evaluate the effectiveness of opioid-free anaesthesia (OFA) in reducing severe postoperative opioid-related adverse events after major or intermediate non-cardiac surgery.

The primary outcome will assess the occurrence of adverse events like hypoxaemia, ileus, or cognitive dysfunction within 48 hours post-surgery, aiming to demonstrate that OFA leads to fewer complications compared to standard anaesthesia protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

POFA trial study protocol: a multicentre, double-blind, randomised, controlled clinical trial comparing opioid-free versus opioid anaesthesia on postoperative opioid-related adverse events after major or intermediate non-cardiac surgery. Beloeil, H., Laviolle, B., Menard, C., et al.[2019]

In a study of 60 patients undergoing elective laparoscopic cholecystectomy, opioid-free anesthesia (OFA) resulted in significantly lower pain scores and reduced opioid requirements compared to traditional anesthesia with fentanyl, particularly noted at 1 and 24 hours post-surgery.

The OFA group reported no severe pain (scores of 7-10 on the Visual Analogue Scale) at 24 hours after surgery, demonstrating that OFA is a safe and effective alternative that minimizes opioid-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is Opioid-Free General Anesthesia More Superior for Postoperative Pain Versus Opioid General Anesthesia in Laparoscopic Cholecystectomy? Toleska, M., Dimitrovski, A.[2022]

Opioid-free analgesia (OFA) multimodal analgesia (MMA) strategies have shown promise in reducing opioid use during perioperative care, leading to improved pain control and higher patient satisfaction.

Implementing OFA strategies can enhance patient recovery and lower healthcare costs, but widespread adoption is still in the early stages and requires tailored approaches to meet individual patient needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving the management of acute perioperative pain towards opioid free protocols: a narrative review. Nassif, GJ., Miller, TE.[2020]

This pilot randomized clinical trial successfully demonstrated the feasibility of comparing opioid analgesia (OA) and opioid-free analgesia (OFA) in 76 patients after outpatient surgery, fulfilling all pre-defined feasibility criteria.

The study found that 99% of participants adhered to their assigned treatment, indicating strong compliance, which supports the potential for a larger trial to evaluate the effectiveness of these pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Prospectively Comparing Opioid Analgesia With Opioid-Free Analgesia After Outpatient General Surgery: A Pilot Randomized Clinical Trial. Do, U., El-Kefraoui, C., Pook, M., et al.[2022]

In a study of 521 patients undergoing laparoscopic hysterectomy, Opioid-Free Anaesthesia (OFA) was found to be feasible and did not result in higher pain scores compared to traditional opioid-based anaesthesia, indicating its effectiveness in managing postoperative pain.

Patients receiving OFA used significantly less morphine equivalent during the procedure, suggesting that OFA can effectively reduce opioid consumption without compromising pain management or increasing complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is Intraoperative Opioids Avoidance A Utopia? A Matched Study in Laparoscopic Hysterectomy. Forget, P., De Kock, M., Lovqvist, L., et al.[2022]

In a study of 311 patients undergoing major surgeries, a total intravenous opioid-free anesthesia (OFA) protocol was successfully implemented, resulting in minimal use of IV morphine (only 2 mg on average) during recovery, indicating effective pain management without opioids.

The findings suggest that OFA is a safe and feasible approach, as it effectively managed the physiological stress responses during surgery and required very low opioid consumption in the postoperative period, supporting a shift away from traditional opioid-based anesthesia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons from the Analysis of a Retrospective Cohort of Patients Who Underwent Large Open Abdominal Surgery Under Total Intravenous Opioid-Free Anesthesia. Estebe, JP., Morel, M., Daouphars, T., et al.[2021]

Opioid-free anaesthesia (OFA) is a technique that avoids the use of opioids during surgery, which has shown benefits, particularly for patients who are morbidly obese or have sleep apnoea, as supported by various studies and case reports.

OFA employs alternative methods such as non-opioid adjuvants (like NSAIDs and local anaesthetics) and techniques like dexmedetomidine and low-dose ketamine to manage pain, potentially reducing the risk of postoperative complications like hyperalgesia and chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Special indications for Opioid Free Anaesthesia and Analgesia, patient and procedure related: Including obesity, sleep apnoea, chronic obstructive pulmonary disease, complex regional pain syndromes, opioid addiction and cancer surgery. Sultana, A., Torres, D., Schumann, R.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12532408/

Opioid-free anesthesia: comparable analgesia with ... Tripodi et al.'s findings confirm that while postoperative pain at 24 h did not differ significantly, OFA, especially combinations including ...

2. frontiersin.org frontiersin.org/article/1714040

Opioid-free anesthesia: a scoping review of efficacy, safety ... The most consistent and immediate benefit reported is a significant reduction in PONV. While short-term pain control and recovery outcomes ...

3. janesthanalgcritcare.biomedcentral.com janesthanalgcritcare.biomedcentral.com/articles/10.1186/s44158-025-00272-9

Effectiveness and safety of opioid-free anesthesia compared ... Clinical studies suggest that patients receiving OFA experience faster recovery times, less postoperative nausea and vomiting (PONV) and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0952818025003198

Opioid-free versus opioid-based anaesthesia and ... Opioid-free anaesthesia, including esketamine, dexmedetomidine and lidocaine did not improve postoperative recovery, postoperative nausea and vomiting or ...

5. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00365-6/fulltext

Analgesic efficacy of an opioid-free postoperative pain ... The primary outcome was postoperative analgesic efficacy, which was indicated by the cumulative area under the curve (AUC) of the pain visual ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12351777/

Effectiveness and safety of opioid-free anesthesia compared ... No OFA regimens showed a statistically significant effect over OBA in reducing postoperative pain within the first 24 h following surgery.

7. bmjopen.bmj.com bmjopen.bmj.com/content/15/3/e085988

a systematic review and meta-analysis Total opioid-free general anaesthesia can improve postoperative outcomes after surgery, without evidence of adverse effects on patient safety and pain ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38553433/

Opioid-Free Analgesia is Safe and Effective in Anterior ... The primary outcome variable was subjective pain level at 24 hours postoperative. The final study cohort consisted of 50 patients (22 OF, 28 ...