The Transversus Abdominis Plane (TAP) Block has been used to decrease postoperative pain since 2001 [1] . Multiple studies have demonstrated that TAP blocks provide effective postoperative analgesia for incisions on the mid and lower abdominal wall [2] [3] [4] . TAP blocks with non-liposomal ropivacaine and bupivacaine provide post-Cesarean section analgesia for up to 12 - 24 hours [5] [6] . The post-partum minimization of intravenous opiate administration is especially important for nursing mothers who are concerned about opiate side effects on themselves and opiate levels in their breast milk [7] . There is limited data on the efficacy of liposomal bupivacaine in TAP blocks for control of post- Cesarean section pain. Exparel®, a liposomal bupivacaine, was approved in 2011 by the Food and Drug Administration. Exparel® formulations combine bupivacaine with DepoFoam®, a technology which delivers medication over an extended period of time. A single dose of liposomal bupivacaine in the transversus abdominis plane releases bupivacaine for up to 72 hours, thereby minimizing pain and the need for opiates throughout this time period. This objective of this study was to investigate the ability of liposomal bupivacaine, administered in bilateral TAP blocks, for lengthened post-operative analgesia after Cesarean sections and if the data demonstrated significant it would be used as the basis for future controlled, double blinded, and randomized study.

This is a prospective case series of women who underwent an elective Cesarean delivery under spinal anesthesia. After institutional review board (IRB) approval, 12 participants at Maimonides Medical Center in Brooklyn, New York were consented to receive bilateral TAP blocks with liposomal bupivacaine for post Cesarean section analgesia and record their pain scores, usage of post-operative narcotics and overall satisfaction with their pain management. Each participant received an intraoperative spinal dose of hyperbaric bupivacaine 0.75%, fentanyl 15mcg, and preservative free morphine 0.2 mg, as per standard anesthetic practice for providing anesthesia for C-Section. Within minutes of incision closure, each participant received an ultrasound guided bilateral TAP block as previously described [8] with 20 milliliters of liposomal bupivacaine (266 mg/20ml; 13.3 mg/ml); however, instead of diluting the liposomal bupivacaine with normal saline we diluted it with 20 ml of 0.25% bupivacaine. The TAP plane was confirmed and created by separation of the transverses abdominis and internal oblique muscles with 5 ml of 0.25% bupivacaine [8] . Subsequently, 20 ml of the 0.25%/bupivacaine/ liposomal bupivacaine mixture was injected into this plane using real time ultrasound visualization. All subjects were ordered intravenous (IV) Tylenol and ketorolac as needed for mild pain and 1 - 2 tables of oxycodone (5 mg)/acetaminophen (325 mg) per os (p.o.) as needed for moderate to severe pain.

• The primary outcome was self-reported pain (using an 11-point (0 - 10) numeric rating scale (NRS) scale). From an earlier study [8] and from our increased use [9] [10] and application of liposomal bupivacaine [11] , enrollment of 12 patients would allow us to investigate the ability of liposomal bupivacaine, administered in bilateral TAP blocks, for lengthened post-operative analgesia after Cesarean sections and give use the ability to plan a future double blinded randomized study.

• Secondary outcomes were reduction in the opiate use postoperatively and patient satisfaction.

• The incidence of post anesthesia adverse effects was also being noted.

Patients demographic are listed in Table 1. Patients had an average age 31 years old. Their average weight was 82.5 kgs with and average body mass index of 30.5. An average parity of 1.3 reflected a cohort of 3 primigravidas and 8 multigravidas. Only one patient lacked a high school diploma; whereas half of the patients had college degrees or graduate level education (Table 1).

Subjects who received bilateral TAP blocks with liposomal bupivacaine had resting pains scores, (mean ± standard deviation (SD)) of 1.0 ± 1.4, 1.4 ± 2.1, 1.7 ± 1.9, 1.9 ± 3.3 and 1.9 ± 2.3 at 6, 12, 24, 48 and 72 hours respectively (Table 2). The mean pain score, when first requesting pain medication, was 1.3 ± 2.3 on a scale of 0 - 10. The mean pain score noted at all requests for pain medication was 0.8 ± 1.8. There were no reported adverse events.

Overall, patients in the TAP block group used little narcotics. Within 24 hours, only 1 patient used tables of oxycodone (5 mg)/acetaminophen (325 mg). On postoperative day 3, 72 hour after the TAP block, an additional patient requested and received 5 mgs of oxycodone with 325 mgs of acetaminophen 3 times. Additional, a third patient was transferred to the cardiac ICU for continuous monitoring since she had postpartum cardiomyopathy after her last pregnancy. She received tables of oxycodone (5 mg)/acetaminophen (325 mg) every day for anticipated pain (even through her report pains were 0).

These results demonstrate that post Cesarean section patients receiving the TAP blocks with liposomal bupivacaine had significant postoperative pain relief (Table 2) and used little postoperative narcotic. Patient satisfaction scores were 9.3 ± 1.1 (mean ± SD) (Table 3) on an 11 point scale.

Intravenous and oral opiates have historically been the most commonly administered analgesics for post-Cesarean section pain. Osmundson et al. found in a prospective study that 83% of women used opiates for pain control for a median of 8 days post operatively after Cesarean delivery [12] . Bateman et al.’s analysis of Clinformatics Data Mart database found that 0.36% of opiate naïve women

Patient characteristics: (Mean ± Standard deviation, N = 12). Level of education was recorded: 1 = Did not graduate High School; 2 = High School Diploma; 3 = College Diploma; 4 = Graduate level education.

Patient pain scores from all 12 patients were recorded at every visit. There were asked on a scale of 0 - 10, where 0 was no pain and 10 was the worst pain you can imagine: how do you rate you pain?

Patient satisfaction were recorded from all 12 patients at either last visit or they were called at home. There were asked on a scale of 0 - 10, where 0 was the worst and 10 was the best, how do you rate you pain management?

became persistent opiate users following Cesarean delivery [13] . Komatsu et al. analyzed opiate free functional recovery in normal vaginal delivery and Cesarean section and found that as many as 91% of women required opiates for postoperative pain with a median time for stopping opiates of 9 days (range of 0 - 39 days) [14] . Post-Cesarean section TAP blocks with liposomal bupivacaine likely decrease postoperative lengths of stay and opiate usage, thereby enabling decreases mothers to avoid opiate side effects such as sedation, hypoventilation, constipation, nausea, and vomiting as well as the potential for opiate addiction [15] [16] [17] [18] . Opiate sparing postoperative pain control allays the fear of mothers concerned with opiate delivered in breast milk.

TAP blocks with administration of non-liposomal local anesthetics offer minimal analgesic advantages, if any, over intrathecal or epidural opiates [19] . One randomized, double-blinded study by McMorrow et al. demonstrated that pain scores and IV opiate consumption were lowest in patients receiving intrathecal morphine with minimal improvement by the addition of TAP blocks with non-liposomal bupivacaine [20] . Similar findings have been observed in another meta-analysis but with additional opiate side effects in intrathecal morphine group [19] . Epidural morphine generally offers fewer risks as compared to parenteral opiate, but parenteral opiates are frequently required once the epidural catheter is removed [21] .

The use of liposomal bupivacaine in TAP blocks decreases the potential for local anesthetic systemic toxicity in comparison with the non-liposomal form. The sustained DepoFoam lipid based delivery system in liposomal bupivacaine minimizes the likelihood of elevated local anesthetic plasm levels [22] . Griffiths et al. studied local anesthetic toxicity associated with TAP block using ropivacaine (2.5 mg per kilogram dose) and found that the total plasma concentration was elevated above the potential toxic threshold of 2.2 microgram per milliliters in the first hour post TAP blocks in 12 patients out of 30. Three of these 12 patients (25%) reported symptoms of neuro toxicity (paresthesia, metallic taste and slurred speech) that resolved after 10 - 70 minutes [23] . Miranda et al. studied plasma absorption of levobupivacaine in TAP blocks and concluded that epinephrine should be added when levobupivacaine was used in doses >1.5 mg per kilogram in order to decrease toxicity symptoms by 0.1% [24] .

This case series provides the only available prospective data on post-Cesarean section patients who received postoperative TAP blocks with liposomal bupivacaine. The primary weakness of this study lies in the small patient population and lack of randomization and blinding and lack of a controlled group. It also does not address both the variability in the dermatomal level of the administration of local anesthetics and the expertise of the anesthesiologist performing the injection. Further studies of liposomal bupivacaine in post cesarean section TAP blocks using a control group that will receive only regular bupivacaine in their bilateral TAP blocks is needed. This case series endorses the need for a larger double blinded randomized study with a control group, which could result in more powerful conclusions that would answer the question does liposomal bupivacaine significantly prolong the duration of bilateral TAP block after Caesarian section compared to regular bupivacaine, as well as, recovery room throughput, patient satisfaction/comfort, and record any adverse anesthesia effects.

The use of liposomal bupivacaine in TAP block provides long acting, post-Cesa- rean section analgesia. It enables patients to avoid or minimize opiate usage and addiction potential as well as their adverse side effects on both mother and newborn.

Feierman, D., Bronstein, A., Flaum, M., Dany, M., Garg, M., Gupta, P. and Tyagaraj, K. (2017) A Case Series of 12 Patients Receiving Bilateral Transverse Abdominis Plane Blocks after Cesarean Section. Open Journal of Anesthesiology, 7, 407-414. https://doi.org/10.4236/ojanes.2017.712042