Clinical trial NCT04393207: TAP Block Using Liposomal Bupivacaine for Post-cesarean Delivery Analgesia- Walking Towards Recovery
Official title: Transverse Abdominis Plane Block Using Liposomal Bupivacaine for Post-operative Cesarean Delivery Analgesia- Walking Towards Recovery
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Opioid Use
Pain, Acute
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2020-05-19
Enrollment: 147
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The TAP block offers analgesia by blocking the sensory nerves of the anterior abdominal wall. The procedure is performed under ultrasound guidance, after identification of the external oblique, internal oblique and transverse abdominis muscle. Medication is injected in the neurofascial plane between the internal oblique and the tranversus abdominis muscle.

Previous studies have demonstrated limited (\<24 hour) effect of the block when compared to the use of intrathecal morphine (considered to be the "gold standard" for postoperative analgesia). In a study by McMarrow et al., post-caesarian pain control combinations including TAP blocks with local anesthetic (Bupivacaine) or saline after a spinal anesthetic with or without intrathecal morphine were compared.

At 6 hours the Morphine consumption was slightly reduced in the patients that received both intrathecal morphine and TAP blocks with LA when compared to patients that received spinal saline and TAP with saline. At 24 hours the TAP block conferred no benefit in terms of opioid consumption. Similarly, the study by Lee et al. demonstrated better pain scores for the first 2 hours in patients receiving both intrathecal morphine and a TAP block with ropivacaine. At 24 hours there was no difference in the pain scores for patients that received both intrathecal morphine and TAP blocks.

On the contrary, a more recent study utilizing liposomal bupivacaine has been utilized for TAP blocks for post cesarean delivery analgesia, demonstrating opioid reductions for up to 72 hours. Liposomal bupivacaine is a novel, multivesicular formulation designed for rapid absorption, prolonged release of bupivacaine, and analgesia following a single intra-operative administration into the surgical wound or for TAP blocks.

Current anesthesia practices encourage the use of multimodal analgesia that aim at enhanced recovery after surgery (ERAS). The ERAS model aims to decrease immobility, pain and post-operative ileus. Pain and immobility may be closely related, and the latter has rarely been monitored in the post-operative setting. It is planned to use a research validated fit-bit like device (Actigraph GT3-X) to monitor patient steps (mobility).

Detailed description: This is a double blinded, randomized controlled trial. The study will be composed of 3 groups Group 1- Transverse abdominus plain block with liposomal bupivacaine + bupivacaine (LB) Group 2 - Transverse abdominus plain block with bupivacaine (BP) Group 3 - Control group (standard of care with no TAP)

1. Patients will be asked to participate after meeting their anesthesia team and giving verbal consent to receive spinal anesthesia for their cesarean delivery.
2. A computer-generated, single block randomization scheme will be used to allocate patients to one of the three groups (Control group (bupivacaine) Vs TAP LB group or corticosteroid group).
3. In the OR, a spinal using 10-12 mg bupivacaine 0.75%, 10 mcg Fentanyl and 0.1 mg preservative free intrathecal morphine will be performed. Patients will receive IV acetaminophen 1 gram, before skin incision and ketorolac 30 mg after closure of fascia. All patients will receive the same postoperative analgesia orders, which include Tylenol, Ibuprofen and opioids for breakthrough pain. (standard of care)

   After wound closure a TAP block will be performed according to randomization process as described above.
4. The LB TAP block group will receive bilateral ultrasound guided block utilizing 10 ml of liposomal bupivacaine\* and 20 ml of 0.25% bupivacaine. The BP TAP group will receive bilateral ultrasound guided block utilizing 20 ml of 0.25% bupivacaine.(Research procedure)
5. The control group will be approached in the exact same way the TAP block group, that is, the ultrasound would be used to identify the muscle layer, but a covered needle will be used to simulate a TAP block. The randomization and procedure will be handled by a co-investigator not involved in the evaluation or data collection at the stablished time points. Patients will be recruited from 7am-5pm and for elective CD
6. The control group will receive Bupivacaine 25 ml of sensorcaine 0.25% + 5 ml saline flush
7. The corticosteroid group will receive sensorcaince 0.25% -20 ml + 10 mg dexamethasone (0.5 ml) + 40 mg methylprednisolone (1 ml) + 8.5 ml normal saline
8. Patients will be asked to complete the ObsQoR-11 at 24 hours, 48 hours and 72 hours.

All patients in this study will be receiving the standard of care. The current standard of care is spinal anesthesia inclusive of intrathecal morphine.

Eligibility criteria: Inclusion Criteria:

1. Patients between the ages of 18 and 45 presenting for cesarean delivery
2. ASA-1, ASA-2, ASA-3
3. No allergy to morphine
4. No allergy to bupivacaine
5. Patients with BMI \> 45 will be excluded
6. No history of anxiety
7. No recent or chronic opioid use

Exclusion Criteria:

1. Need for Magnesium sulfate therapy
2. Neonatal admission to neonatal intensive care unit
3. Need for additional surgery other than cesarean delivery +/- bilateral tubal ligation (e.g. hysterectomy, cystotomy)

Primary outcomes:
measure: Morphine Milligram Equivalents (MME)
timeFrame: 24 hours
measure: Morphine Milligram Equivalents (MME)
timeFrame: 48 hours
measure: Morphine Milligram Equivalents (MME)
timeFrame: 72 hours
Secondary outcomes:
measure: Self Assessed Recovery Survey Obstetric Quality-of-Recovery Score (ObsQoR-11)
timeFrame: 24 hours, 48 hours, 72 hours
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University
state: Connecticut
Study officials:
affiliation: Yale University
name: Antonio Gonzalez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lee AJ, Palte HD, Chehade JM, Arheart KL, Ranasinghe JS, Penning DH. Ultrasound-guided bilateral transversus abdominis plane blocks in conjunction with intrathecal morphine for postcesarean analgesia. J Clin Anesth. 2013 Sep;25(6):475-82. doi: 10.1016/j.jclinane.2013.05.004. Epub 2013 Sep 3.
citation: McMorrow RC, Ni Mhuircheartaigh RJ, Ahmed KA, Aslani A, Ng SC, Conrick-Martin I, Dowling JJ, Gaffney A, Loughrey JP, McCaul CL. Comparison of transversus abdominis plane block vs spinal morphine for pain relief after Caesarean section. Br J Anaesth. 2011 May;106(5):706-12. doi: 10.1093/bja/aer061.
citation: Baker BW, Villadiego LG, Lake YN, Amin Y, Timmins AE, Swaim LS, Ashton DW. Transversus abdominis plane block with liposomal bupivacaine for pain control after cesarean delivery: a retrospective chart review. J Pain Res. 2018 Dec 10;11:3109-3116. doi: 10.2147/JPR.S184279. eCollection 2018.
citation: Jacques V, Vial F, Lerintiu M, Thilly N, Mc Nelis U, Raft J, Bouaziz H. [Enhanced recovery following uncomplicated elective caesarean section in France: a survey of national practice]. Ann Fr Anesth Reanim. 2013 Mar;32(3):142-8. doi: 10.1016/j.annfar.2013.01.016. Epub 2013 Feb 19. French.
citation: Alharbi M, Bauman A, Neubeck L, Gallagher R. Validation of Fitbit-Flex as a measure of free-living physical activity in a community-based phase III cardiac rehabilitation population. Eur J Prev Cardiol. 2016 Sep;23(14):1476-85. doi: 10.1177/2047487316634883. Epub 2016 Feb 23.