TAP infiltration can be performed preoperatively with minimal sedation. Intravenous midazolam 1–2 mg, with or without intravenous ketamine 10 mg, can be administered for sedation and/or anxiolysis. Alternatively, TAP infiltration can be performed intraoperatively under direct vision, before abdominal closure during DIEP flap surgery. With direct visualization (e.g., during field block or infiltration of the breast or pectoralis), the entire operative field is wide open and directly accessible. Although administering TAP infiltration before beginning a case may be beneficial during surgery, the surgeon can perform the block 45–60 minutes before final closure to ensure adequate analgesia in the postanesthesia care unit. Combining this technique with the use of bupivacaine HCl may provide similar early postoperative pain relief. Intravenous acetaminophen can also be initiated approximately 30 minutes before the end of the case but no earlier than 4 hours after an oral dose of preoperative acetaminophen to ensure onset of analgesia.
In the past, longer-acting local anesthetics, such as bupivacaine HCl or ropivacaine, were commonly used in field block infiltrations.38,39 More recently, a novel, prolonged-release local anesthetic, liposomal bupivacaine, marketed in the United States by Pacira Pharmaceuticals, Inc., Parsippany, N.J., as Exparel (bupivacaine liposome injectable suspension), has become available.40 Liposomal bupivacaine is indicated for surgical-site infiltration and field block infiltrations where the anesthetic is placed in the fascial plane between muscles.32,40 This includes TAP block for DIEP and muscle-sparing transverse rectus abdominis myocutaneous flap procedures, to produce postsurgical analgesia, and is consistent with Pecs I and II infiltration.19 Liposomal bupivacaine is an encapsulated formulation of bupivacaine released over time by multivesicular liposomes.40,41 Liposomes are deposited throughout the surgical site upon administration; as they are metabolized through normal biologic processes, bupivacaine is continually released over a period of several days.42
Clinical Evidence Supporting the Use of Liposomal Bupivacaine in Breast Reconstruction
Liposomal bupivacaine has been used in a wide range of surgical sites, and improved analgesia with reduced postsurgical opioid usage has been demonstrated in clinical trials.43 Liposomal bupivacaine has been evaluated for use in breast surgical procedures, including oncologic, reconstructive, and cosmetic procedures.3,27,44–48
A retrospective chart review27 evaluated postsurgical analgesia and LOS for 90 patients undergoing mastectomy and immediate implant-based breast reconstruction; all were transitioned to oral opioids.27 Patients receiving field block with liposomal bupivacaine had a numerically shorter mean LOS compared with patients receiving intravenous/oral opioids (1.5 versus 2.0 days; P = 0.062), a higher rate of hospital discharge within 1 day after surgery (P = 0.016),27 and significantly lower pain scores at 4, 8, 12, 16, and 24 hours (P < 0.01).27 It should be noted that intercostal field block infiltration and regional (e.g., intercostal) nerve block are different techniques27,33 and that liposomal bupivacaine is indicated for infiltration into the surgical site but not for regional nerve block.40
Another retrospective review of patients undergoing mastectomy with immediate tissue expander reconstruction44 compared 53 patients who received intraoperative local infiltration with liposomal bupivacaine with 44 patients who were administered preoperative ultrasound-guided paravertebral block. Liposomal bupivacaine was administered into the base of the mastectomy skin flaps, the pectoralis major muscle and serratus fascia, periaxillary tissues, and drain sites following the mastectomy and before tissue expander placement. In the liposomal bupivacaine group, opioid use in the recovery room was significantly lower versus the paravertebral block group [mean (SD) = 9.4 (16.4) versus 24.8 (23.9) oral morphine equivalents, respectively; P < 0.001]. LOS in the recovery unit was comparable between groups. Pain scores on the day of surgery were lower in the liposomal bupivacaine group than in the paravertebral block group [mean (SD) = 3.2 (1.8) versus 4.2 (1.5), respectively; P = 0.008]. Time to first postsurgical opioid dose was significantly longer for patients in the liposomal bupivacaine group versus patients in the paravertebral block cohort [mean (SD) = 210 (212) versus 125 (171) minutes, respectively; P = 0.04). Further, those who received liposomal bupivacaine were less likely to require opioids during the recovery period (44% versus 74%, respectively; P = 0.006).44
In another study of 100 women undergoing abdominally based microsurgical free-flap breast reconstruction,3 an ERAS pathway that included intraoperative use of liposomal bupivacaine was compared with traditional care after surgery. In the ERAS cohort, mean hospital LOS was significantly decreased compared with the traditional care after surgery cohort (3.9 versus 5.5 days, respectively; P < 0.001). For the first 3 PODs, total inpatient opioid usage (oral morphine equivalents) was 71% less for the ERAS group versus the traditional care after surgery group (167.3 versus 574.3 mg, respectively; P < 0.001), with similar pain scores for both groups at most time points.3
Use of liposomal bupivacaine in cosmetic breast procedures has also been studied. In a phase 3, randomized, multicenter, double-blind study, 136 patients undergoing bilateral submuscular breast augmentation under general anesthesia were administered either the 266-mg maximum dose of liposomal bupivacaine40 (n = 66) or 100 mg of bupivacaine HCl/epinephrine 1:200,000 (n = 70) into each implant pocket.48 Pain intensity with activity was significantly lower at 8 hours and 12 hours after study drug administration in the liposomal bupivacaine group versus the bupivacaine HCl/epinephrine group [4.9 (0.41) versus 6.7 (0.40) at 8 hours; P = 0.0016 and 5.6 (0.40) versus 6.9 (0.37) at 12 hours; P = 0.0143). Mean total postsurgical rescue opioid consumption was lower in the liposomal bupivacaine group through 72 hours.48
A phase 4, multicenter, prospective, observational study34 evaluated the effect of a single intraoperative administration of liposomal bupivacaine 266 mg into the surgical site on postsurgical pain, opioid use, and opioid-related adverse events in 49 subjects undergoing breast surgery and/or abdominoplasty. Low pain intensity scores and reduced opioid consumption were observed compared with investigators’ previous experiences with patients not receiving liposomal bupivacaine. Mean numeric rating scale pain scores were ≤ 4.3 from discharge through POD 3. Median daily oral opioid consumption was approximately 1 tablet postsurgically on the day of surgery and approximately 2 tablets by POD 3. Subjects’ satisfaction with postsurgical analgesia was high, with a low rate of opioid-related adverse events.34
In a telephone survey of 75 women who had received liposomal bupivacaine at the time of either a cosmetic breast/abdominal procedure (n = 23) or breast reconstruction (n = 52), mean pain scores using a 1–10 verbal scale were 2.6 (0–9) on POD 1 and 3.6 (0–8) on POD 3. All patients preferred liposomal bupivacaine over their perceptions of an elastomeric pump device, and 97% reported they would want to receive liposomal bupivacaine should they need surgery again.38
In a recently published case report37 describing ultrasound-guided lateral and medial pectoral nerve block using liposomal bupivacaine before surgical incision for submuscular breast augmentation, the authors reported complete relaxation of the pectoralis major muscle, facilitating surgical dissection and markedly diminishing postsurgical pain and muscle spasms. The patient required no opioids from discharge through POD 10.37
Technical Considerations for Administration of Liposomal Bupivacaine
The recommended dose of liposomal bupivacaine is based on various factors including volume required to cover the site, allowed maximum dose of 266 mg (20 mL), and patient risk factors.40 Liposomal bupivacaine is intended for single-dose administration only; a single 20-mL vial may be expanded with ≤ 280 mL of normal sterile saline or lactated Ringer’s solution to ensure sufficient coverage of larger surgical sites. Administration technique can greatly affect the efficacy of analgesia in wound infiltration; liposomal bupivacaine should be injected slowly into soft tissue using a 25-gauge or larger bore needle. Also, liposomal bupivacaine does not spread as extensively as bupivacaine HCl, so the “moving needle” technique is crucial to ensure adequate spread of the anesthetic. For larger areas (e.g., during lower abdominal incision for DIEP flap reconstruction or abdominoplasty), it may be easier to use a blunt tip infiltration cannula rather than a 25-gauge needle. Accurate infiltration of all relevant tissue layers of the surgical site is recommended for efficacy, with frequent aspirations to check for blood, to reduce the chance of an inadvertent intravascular injection.22,40
There are precautions to consider when using liposomal bupivacaine in conjunction with other local anesthetics. Nonbupivacaine local anesthetics, such as lidocaine, can be administered before administration of liposomal bupivacaine, into the same site, but a separation of ≥ 20 minutes is required. Rapid release of bupivacaine from liposomes may occur when lidocaine or similar nonbupivacaine local anesthetics are locally coadministered.40 This rapid release of bupivacaine from liposomes could potentially affect properties of liposomal bupivacaine and alter its efficacy and safety.40 Other formulations of bupivacaine HCl may be admixed with liposomal bupivacaine in the same syringe, as long as the ratio of milligram dose of bupivacaine HCl:liposomal bupivacaine does not exceed 1:2. For example, there are 266 mg of bupivacaine in a 20-mL vial of liposomal bupivacaine, which is equivalent to 300 mg bupivacaine HCl40; therefore, up to 150 mg of bupivacaine HCl can be coadministered with a 20-mL vial of liposomal bupivacaine.
Postoperative pain management is a key component of ERAS pathways for breast surgical procedures. Perioperative multimodal analgesia and opioid-sparing analgesic regimens utilizing a combination of oral and intravenous nonopioids, as well as regional and local infiltration techniques, are optimal for providing pain relief following surgery. However, the proposed analgesic options should supplement, not replace, clinical judgment when making treatment decisions. Evidence supports the use of liposomal bupivacaine infiltration to produce postsurgical analgesia for a broad range of surgical procedures utilizing a wide range of injection techniques. Studies evaluating liposomal bupivacaine in breast surgical procedures have shown reduced postoperative opioid usage coupled with a low burden of opioid-related adverse events, reduced hospital LOS, lower postsurgical pain scores, and high patient satisfaction. Liposomal bupivacaine can be used in a variety of local and field infiltration techniques, including Pecs I and II, serratus plane infiltration, TAP infiltration for DIEP flaps, chest wall infiltration, and incisional or drain site infiltration. Meticulous administration to all tissue layers is essential for optimal results.
Under author direction, editorial and medical writing assistance was provided by Michael D. Morren, RPh, MBA, of Peloton Advantage, LLC, supported by Pacira Pharmaceuticals, Inc., the manufacturer of liposomal bupivacaine. The authors were fully responsible for the content, editorial decisions, and opinions expressed in the current article. All authors were involved in the critical revision and review of the article text and figures, as well as approval of the final draft for submission. The authors did not receive an honorarium related to the development of this article.
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