Opioid Based Analgesia vs Non-opioid Analgesia for Oocyte Retrieval Procedure
Condition: Women Undergoing Oocyte Retrieval Procedures
Study type: Interventional

Summary: 
      It is unclear whether routine addition of opioids for analgesia during minor gynecological
      procedures is beneficial. In this single-center randomized single-blinded trial, the
      investigators aim to test the primary hypothesis that opioid-sparing anesthesia regimen
      including intravenous acetaminophen is non-inferior to a similar anesthesia regimen
      containing fentanyl in providing postoperative analgesia in women recovering from oocyte
      retrieval procedures for in vitro fertilization. The investigators also aim to assess the
      difference in incidence of patient-reported opioid related adverse-effects between the two
      groups, time to discharge from the post-anesthesia care unit and postoperative rescue
      analgesia requirements. If we demonstrate no clinically important difference between the two
      interventions, clinicians may be able to substantially reduce the amount of opioids
      administered to patients undergoing minor ambulatory procedures, and potentially decrease the
      associated opioid related adverse effects.
    

Detailed description: 
      Study Overview The investigators propose a single-center randomized single-blinded clinical
      trial in which healthy women undergoing oocyte retrieval procedures under general anesthesia
      will be randomized to receive either 1.5mcg/kg fentanyl or IV acetaminophen as part of
      multimodal analgesia. The investigators will evaluate the effects of an opioid-free
      anesthesia on pain scores, analgesic medication consumption during the initial two
      postoperative hours, and time to discharge from PACU, compared to an opioid-containing
      anesthesia.The investigators will also compare the prevalence of opioid-related sedation side
      effect between opioid-free anesthesia and opioid-containing anesthesia.

      Setting and Population Inclusion Criteria

      1. Written informed consent 2. 18-45 years old 3. American Society of Anesthesiologists (ASA)
      physical status 1-2 4. Undergoing oocyte retrieval procedures 5. Planned number of oocytes to
      be retrieved <15 Exclusion Criteria

        1. Known allergy to fentanyl, acetaminophen, dipyrone, lidocaine, propofol or NSAIDs.

        2. Endometriosis

        3. Diagnosis of chronic pain

        4. Opioid dependency, defined by consumption of oral morphine equivalent of greater than or
           equal to 60mg a day for 7 days or longer, for any time period.

        5. Weight < 50 kg

        6. Cannabis use

        7. Major psychiatric disorder - Schizophrenia, bipolar disorder, major depression.

        8. Epilepsy disorder under anti-convulsant therapy.

        9. Renal insufficiency, defined as creatinine clearance <60 ml/hr

       10. Hepatic disease

      Withdrawal Criteria

        1. Patients are free to withdraw from the study at any time, for any reason.

        2. Patients may be withdrawn from the study by a member of the study team or the clinical
           team, if seems appropriate for patient's safety or well-being. Examples of such events
           include (but are not limited) to:

           an allergic reaction, analgesic failure per acute pain service judgement and significant
           patient discomfort.

        3. Reason for exclusion will be documented, and patients will be asked to continue
           follow-up according to the intention-to-treat principle

      Protocol

      The investigators propose a randomized, single-blinded single-center clinical trial. After
      confirming eligibility, patients will be approached before the procedure for possible
      enrollment in the study. After thorough explanation, written informed consent will be
      obtained. Patients will be randomized in a 1:1 ratio by a web-based software to receive
      either:

        1. Opioid-free anesthesia, including

             1. IV propofol 1-1.5 mg/kg

             2. IV acetaminophen 1000mg

             3. IV dipyrone 1000mg

             4. IV lidocaine 1mg/kg

             5. IV dexacort 4mg

             6. PR diclofenac 50 mg

        2. Opioid-supplemented anesthesia, including

             1. IV propofol 1-1.5 mg/kg

             2. IV fentanyl 1.5 mcg/kg

             3. IV dipyrone 1000mg

             4. IV lidocaine 1mg/kg

             5. IV dexacort 4mg

             6. PR diclofenac 50 mg

      The anesthesiologist performing the procedure will not be blinded to group allocation, but
      other research team members and caregivers who evaluate the patients after the procedure will
      be.

      General anesthesia will be induced according to the group allocation as mentioned above.
      Anesthesia maintenance will be achieved with 50% N2O via a face-mask, and additional doses of
      10-20 mg of propofol as needed. Ketamine will not be allowed. Postoperatively, intravenous
      tramadol 100 mg will be ordered for breakthrough pain as well as intravenous ondansetron 4mg
      and metoclopramide 10mg for nausea and vomiting. Patients will be followed until home
      discharge. The rest of postoperative care will be conducted according to standard
      departmental procedures by nurses and physicians.

      Measurements

        -  Patient characteristics and demographic data including age, weight, body mass index
           (BMI), tobacco use, prior IVF treatment, history of pain after previous IVF, chronic
           pain, chronic medication use, and American Society of Anesthesiologists (ASA) physical
           status will be obtained from the medical record and patient interview.

        -  Postoperative pain scores will be documented on an 11-point Numerical Rating Scale (NRS)
           from 0 (no pain) to 10 (worst pain imaginable) at least once every 30 minutes for the
           initial two postoperative hours.

        -  Opioid-induced sedation will be captured through the Passero opioid-induced sedation
           scale (Appendix A) 20 minutes after patient admission to the recovery room.

        -  Patient satisfaction with the anesthesia will be assessed using Likert scale from 1 to 5
           grading "how satisfied are the participant with the pain management they received
           today?"

        -  Time of discharge will be captured from the patient's electronic medical record and/or
           from patient interview.

      Sample Size Considerations To test a unilateral non-inferiority hypothesis, assuming a 2.5%
      significance level, power of 80%, standard deviation of 2 points, a non-inferiority delta of
      no more than 1.5 points in the 11-point NRS pain scale between the two groups, and assumed
      pooled variance of 6, we will need a sample size of 42 patients in each group. Accounting for
      a predicted loss to follow-up of up to 20% of patients, we aim to recruit 100 patients.
    

Intervention name(s): IV acetaminophen; IV fentanyl
Intervention type(s): Drug; Drug
Intervention description(s): Pain management; Pain management
Intervention MeSH terms: Acetaminophen; Fentanyl
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment