Clinical trial NCT04933058: Opioid Based Analgesia vs Non-opioid Analgesia for Oocyte Retrieval Procedure
Official title: Opioid Based Analgesia vs Non-opioid Analgesia for Oocyte Retrieval Procedure - a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Women Undergoing Oocyte Retrieval Procedures
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
First posted: 2021-06-21
Enrollment: 100
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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

Primary outcomes:
measure: the difference in average pain scores
timeFrame: 1 year
measure: the dependent categorical variable of time-to-discharge readiness
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
measure: comparison of the average sedation scores 20 minutes after admission to the recovery room
timeFrame: 1 year
Locations:
city: Tel Aviv
country: Israel
facility: tel aviv SMO
Study officials:
affiliation: senior doctor
name: Elena Farladansky, MD
role: PRINCIPAL_INVESTIGATOR
References: