CLINICAL PAPERS
Patient Perception of Postoperative Pain After Administration of Liposomal Bupivacaine in Plastic Surgery Nathan Eberle, DDS, MD, and Martin Newman, MD Background: Since obtaining FDA approval for postsurgical pain management in 2011, a number of well-designed studies have reported favorably on the safety and efficacy of liposomal bupivacaine (LB). However, the literature lacks adequate reports of patient perception of postoperative pain and subjective satisfaction. Methods: A telephone survey of patients who received LB injection at time of operation at a single institution was contacted. Included were patients who underwent cosmetic, reconstructive, and/or breast procedures. Patients were asked to report their perception of pain on post-operative day (POD) 1 and 3 using the verbal scale (1–10). Additionally, patients reported on: understanding of medications received, overall satisfaction, perception of economic value, and perception of preference to elastomeric pump. Results: A total of 75 patients met inclusion criteria and could be reached by telephone; 23(31%) cosmetic and 52(69%) reconstructive and/or breast procedures. Mean pain score reported 2.6 (0–9) POD 1 and 3.6 (0–8) POD 3. Thirty-six (48%) patients were aware they had received the medication. Seventythree (98%) reported they would want LB again if they needed surgery in the future and would pay U.S. $230 [$100–$1000] for the medication. All (100%) patients favored LB over a perceived elastomeric pump device. Conclusions: Patient perception of efficacy after the injection of LB correlates with previous clinical findings. Our experience with LB injections for cosmetic and reconstructive breast procedures indicates that patients experienced low postoperative pain scores with high overall patient satisfaction. Additional studies comparing the use of LB to standard narcotic regimens and its use in multimodality pain management are warranted. Key Words: liposomal bupivacaine, breast surgery, abdominoplasty, postoperative pain (Ann Plast Surg 2015;74: S198–S200)
A
n important consideration of any surgical procedure is the strategy for pain management in the postoperative period. Aside from the humanistic factors, it is generally appreciated that by reducing postoperative pain, patients experience earlier mobilization and decreased time to discharge, leading to a reduction in overall hospital costs.1 Traditionally, postoperative pain has been managed by the administration of oral or parental opioids and/or non-narcotic medications. Of these, opioid-based medications have been used for centuries and are still a major component of many postoperative analgesic regimens. However, the negative side effects of opioids, opioid related adverse events, are well established. Among others, these include: nausea, vomiting, ileus, pruritis, urinary retention, drowsiness, respiratory depression, and potential for addiction.2 Over the years, several alternatives or adjuncts to opioid medications have been successfully used. These include, among others, nonsteroidal anti-inflammatory medications, neuromodulators, and local Received November 5, 2014, and accepted for publication, after revision, December 16, 2014. From the Cleveland Clinic Florida Weston, FL. Dr. Newman is a paid speaker and consultant for Pacira Pharmaceuticals, Inc. Dr. Eberle has no conflicts of interest with respect to the research, authorship and publication of this article. Conflicts of interest and sources of funding: none declared. Reprints: Nathan Eberle, DDS, MD, Cleveland Clinic Florida Weston, FL. E-mail: [email protected]. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0148-7043/15/7404–S198 DOI: 10.1097/SAP.0000000000000444
S198
www.annalsplasticsurgery.com
anesthetics (LAs). Local anesthetics have offered the most promise because unlike the other classes of medications discussed, the mechanism by which sodium channel blockers achieve their goal is by blocking the propagation of neural impulses along the neural axon. Although opioids, neuromodulators and non-steroidal anti-inflammatory drugs “potentiate” the perception or intensity of pain signals, sodium channel blockers actually “prevent” transmission of painful stimuli from ever reaching the central nervous system. Historically, the limiting factor prohibiting utilization of LAs for postoperative analgesia was their short duration of action. Even the longest acting formulations did not provide analgesia beyond a number of hours. However, the elastomeric infusion pump which was introduced in the late 1940s seemed to offer a solution to this dilemma. These “pain pumps,” as they were called, offered promise by delivering LAs to the operative site in small doses, continuously for periods that could be measured in days. Nevertheless, results were variable.3 The original devices were fraught with problems with required constant monitoring so as to not overdose a patient with medication.4 In the early 2000s the technology was improved with industry now providing smaller, disposable, more practical, affordable, and precise devices. Studies have demonstrated that modern elastomeric pumps delivering bupivacaine continually and in small doses can safely decrease postoperative pain, encourage earlier ambulation, and decrease the amount of oral narcotics consumed.5 Nevertheless, despite their advantages over other options designed to reduce postoperative pain, elastomeric pumps are not without their disadvantages including cost, potential as a source of infection, and the presence of an “additional” indwelling catheter. In October 2011, liposomal bupivacaine (LB) (Exparel; Pacira Pharmaceuticals, Inc., San Diego, CA) received FDA approval for local infiltration into wounds to control postsurgical pain.6 Since that time, there have been several well-designed trials showing not only its efficacy but also its safety.6,7 Liposomal bupivacaine is a formulation of bupivacaine encapsulated in multiple spheres. It is indicated for single-dose infiltration into surgical site to produce analgesia.8 The medication has been studied in patients undergoing soft tissue surgery (augmentation mammoplasty9 and abdominoplasty10) and orthopedic surgery (total knee arthoplasty11 and bunionectomy12) in addition to other surgical procedures, such as hemmorhoidectomy,13 abdominal wall reconstruction,14 and ostomy reversal.1 Although LB has been demonstrated to be effective in clinical practice by commonly studied parameters (e.g., length of stay, opioid consumption, dollars spent, etc.), absent from the literature are studies, which examine the patient's perception of the medication. Considering the increasing role of patient feedback in the ever-evolving health care landscape, patient perception has become a critical factor in the overall effectiveness of any medication or operating room adjunct. Thus, our objective in this investigation was to investigate the use of LB in patients undergoing surgery in our specialty, common plastic surgery procedures. We hypothesized that intraoperative administration of this long-acting LA would render low postoperative pain scores leading to high patient satisfaction.
METHODS Institutional review board approval was granted as a patient quality improvement project. A retrospective chart review was performed to identify patients who received LB at the time of operation at a single Annals of Plastic Surgery • Volume 74, Supplement 4, June 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Annals of Plastic Surgery • Volume 74, Supplement 4, June 2015
institution. A telephone survey of patients undergoing common plastic surgery procedures was then carried out. Procedures performed included: augmentation mammaplasty, abdominoplasty with rectus plication and immediate or delayed breast reconstruction with tissue expanders. The study period was arbitrarily set at 6 months. From July 2013 to January 2014, we performed a total of 106 operations that met inclusion criteria. All procedures were performed by 2 plastic surgeons and, when procedures involved mastectomy, 2 breast surgeons. All procedures were performed at the same surgical facility. All surgeries were conducted under general anesthesia. Patients undergoing abdominoplasty received LB in an abdominal field block fashion as has been previously described.10 Patients undergoing breast surgery underwent administration as described by Newman.15 Patients undergoing cosmetic surgery of the breast were treated on an ambulatory surgery basis and patients undergoing mastectomy with reconstruction or abdominoplasty were admitted for overnight observation. At the time of survey, patients were asked to report their “perception of pain” on post-operative day (POD) 1 and again on POD 3 using the verbal analog scale (1–10). Additionally, patients reported on their understanding of medications received, overall satisfaction, perception of LB's economic value, and perception of preference (LB vs elastomeric pump).
SURGICAL TECHNIQUE At the appropriate time, under a surgeon's direction, 266 mg of LB in 20 cc of solution was expanded with various amounts of normal saline to cover the appropriate surgical field. Our routine expansion for a bilateral breast reconstruction is to add 80 mL of saline to 20 mL (266 mg) of LB. The manufacturer recommends not expanding beyond 0.89 mg/mL (1:14). In our practice, we use a 25-gauge needle to inject the medication, although the medication can be injected through needles as small as 30 gauge without impact on depofoam integrity or drug encapsulation.8,16 The medication should be used within 4 hours once diluted.8 If the surgeon chooses to use a shorter-acting LA for immediate analgesia, the LB was not injected for at least 20 minutes as per the manufacturer's recommendations.8 In our practice, we inject 45 to 60 minutes before the end of the procedure. When we inject the breast, we like to think of injecting the medication in 2 separate planes. Initially, the medication is deposited in all 4 quadrants of the chest muscles (pectoralis and serratus) followed by injecting around the edges of the skin incision and drain site. When injecting the abdominal wall, we prefer to think of the abdomen as diamond shape. We begin by injecting laterally under the fascia so as to block the ilioinginaul, iliohypogastric, lateral and anterior intercostal branches followed by injection of the midline fascial plication., just under the rectus sheath. We complete our abdominal administration with injections to both the superior and inferior skin incision margins.
RESULTS A total of 75 patients met inclusion criteria and could be reached by telephone; 23(31%) cosmetic breast and abdomen and 52(69%) reconstructive breast procedures, all were women. Ten patients were discharged home on the day of surgery, and the remaining 65 were discharged home the next day after overnight observation. Mean pain score reported on POD 1 was 2.6 (0–9) and POD 3 was 3.6 (0–8). Thirty-six (48%) patients reported they could recall having had a conversation regarding the medication usage before their surgery, although all had been counseled by the treating physician preoperatively. Seventy-three (97%) reported they would want LB again if they needed surgery. Further that if in the future they required addition surgery, they would value the cost of the medication at U.S. $230 ($100–$1000) if not covered by their insurance. All (100%) patients favored LB over a perceived elastomeric pump device. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Pain After Administration of Liposomal Bupivacaine
DISCUSSION Liposomal bupivacaine (Exparel) represents a newer option for long-acting local anesthesia. The novel design of a multivesicular liposomal delivery system allows molecules of medication (bupivacaine in this case) to be encapsulated without altering structure. Each sphere in the multivesicular design contains multiple molecules of medication. Over a prolonged period of time, the patient's body resorbs the lipid walls slowly releasing the bupivacaine. Systemic plasma levels of bupivacaine can persist up to 96 hours after injection.8 The medication is currently available in a 20-mL single-use vial, 1.3% (266 mg, 13.3 mg/mL). This 20-mL vial represents the maximum recommended dose of LB (266 mg), which is equivalent to 300 mg of nonencapsulated bupivacaine.17 However, even this dose is far below the maximum safe dose of bupivacaine (400 mg) in 24 hours in a 70-kg patient.2 Nausea, constipation, and vomiting are the most common adverse reactions associated with the use of LB.12,13 The overall incidence of serious adverse events in clinical trials has been less for LB than bupivacaine alone (1.9% vs 3.9%).18 The most common cardiac events are tachycardia and bradycardia.18 This long-acting form of bupivacaine can last up to 72 hours, far longer than previous longest-acting LA lasting approximately 7 hours. In our experience, our patient's perception correlates with the currently available literature with using LB suspension injections for treating both cosmetic and reconstructive patients having low postoperative pain scores. There have been previous studies on plastic surgery patients undergoing combined abdominoplasty plus multiple other procedures.10 This study showed that by using abdominal field block injections, surgeons could decrease narcotic use and patients ambulated earlier and returned to normal activity quicker. In an older study prior to the advent of LB or elastomeric pumps, Feng et al3 performed their own version of an abdominal field block using bupivacaine with epinephrine, pontocaine, and Depo-medrol. Their patients also experienced a significant reduction in pain; however this was only in the immediate recovery period. It has been our experience that by expanding the LB, we can easily and effectively perform an abdominal or breast field block without impairing efficacy for a prolonged duration. In past years, a bupivacaine elastomeric pump was the only option for delivering LA in a prolonged fashion, which did improve the postoperative recovery experience for patients. As stated previously, there are multiple disadvantages of these pumps including: additional catheter attached to cumbersome elastomeric pumps which can lead to kinking and malfunction, not to mention exposure of the surgeons dissection pocket and hence implantable device, such as a tissue expander possibly leading to a higher rate of infection. Beyond this, the design of the pumps is in such a way that the bupivacaine is suppose to “bathe” the wound bed with LA, but in most cases, our patients have closed suction drains in similar areas likely evacuating out a portion of the anesthetic which is supposed to be delivered. Over the past 3 years, our institution has converted to injecting LB for all invasive cosmetic surgery procedures of the breast and trunk along with oncologic surgery of the breast. There are several large limitations in our study that should be addressed. We did not include a control group, but this study was undertaken to better understand patient perception of their postoperative pain control with use of LB. A second limitation is that not all patients underwent the exact same procedure. Theoretically speaking, an abdominoplasty procedure should be far more painful than an oncologic breast procedure. With our patient population, we had more reconstructive breast patients than cosmetic plastic surgery patients, which could have skewed our data. A third limitation is the questionnaire was completed when the patients were remote to the actual surgical event so despite proper questioning, the patient's recall of the events might be better or worse than reported. An additional limitation of our study is the lack of any complications associated with the medication www.annalsplasticsurgery.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
S199
Annals of Plastic Surgery • Volume 74, Supplement 4, June 2015
Eberle and Newman
administered. As stated previously, nausea, vomiting, and constipation are the most commonly reported side effects of the medication, which also happen to be symptoms commonly associated with the postgeneral anesthesia period and narcotic administration. Further, the study is limited by not looking into the consumption of narcotic based pain medication in the immediate postoperative period to see if it was confounding our reported low postoperative pain scores. Further, when we initially were using the medication, we were expanding it in a 1:1 fashion and over time began to expand it with more normal saline so at to better distribute the medication. Lastly, we recognize this study is not a double-blinded, randomized, controlled trial. This study was set up to primarily focus on patient satisfaction and perception of pain. We are currently in the process of setting up a controlled trial comparing this medication against a control.
CONCLUSIONS In conclusion, patient perception of efficacy after the injection of LB correlates with previous clinical findings. Our experience with LB injections for cosmetic and reconstructive plastic surgery procedures indicates that patients experienced low postoperative pain scores with high overall patient satisfaction. Additional studies comparing the use of LB to standard narcotic regimens or elastomeric pumps and its use in multimodality pain management are warranted. REFERENCES 1. Marcet JE, Nfonsam VN, Larach S. An extended pain relief trial utilizing the infiltration of a long-acting Multivesicular liposome formulation of bupivacaine, EXPAREL(IMPROVE):a phase IV health economic trial in adult patients undergoing ileostomy reversal. J Pain Res. 2013;6:549–555. 2. Miller RD. Millers Anesthesia. Philadelphia, PA: Churchill Livingstone Elsevier; 2010. 3. Feng L. Painless abdominoplasty: the efficacy of combined intercostal and pararectus blocks in reducing post- operative pain and recovery time. Plast Reconstr Surg. 2010;126:1723–1732. 4. Ansbro PA. A method of continuous brachial plexus block. Am J Surg. 1946;121: 716–722.
S200
www.annalsplasticsurgery.com
5. Mentz HA, Ruiz-Razura A, Newall G, et al. Use of a regional infusion pump to control postoperative pain after an abdominoplasty. Aesthetic Plast Surg. 2005; 29:415–422. 6. Naseem A, Harada T, Wang D, et al. Bupivacaine extended release liposome injection does not prolong QTc interval in a thorough QT/QTc study in healthy volunteers. J Clin Pharmacol. 2011;4. doi:10.1177/0091270011419853. 7. Ilfeld BM, Malhotra N, Furnish TJ, et al. Liposomal bupivacaine as a single injection peripheral nerve block: a dose-response study. Anesth Analg. 2013;117: 1248–1256. 8. Exparel (bupivacaine liposome extended release injectable suspension [prescribing information]. San Diego, CA: Pacira Pharmaceuticals Inc; 2011. 9. Minkowitz H, Smoot J. Long-term safety of Exparel (bupivacaine extended release liposome injection) reveals no impact on silicone breast implants at up to two years followup. Presented at: American Society of Plastic Surgeons Annual Meeting; September 24, 2011; Denver, CO. 10. Morales R Jr, Mentz H 3rd, Newall G, et al. Use of abdominal field block injections with liposomal bupivicaine to control postoperative pain after abdominoplasty. Aesthet Surg J. 2013;33:1148–1153. 11. Bramlett K, Onel E, Viscusi ER, et al. A randomized, double-blind, dose-ranging study comparing wound infiltration of DepoFoam bupivacaine, an extendedrelease liposomal bupivacaine, to bupivacaine HCl for postsurgical analgesia in total knee arthroplasty. Knee. 2012;19:530–536. doi: 10.1016/j.knee.2011.12.004. 12. Golf M, Daniels SE, Onel E. A phase 3, randomized, placebo-controlled trial of DepoFoam bupivacaine (extended release bupivacaine local analgesic) in bunionectomy. Adv Ther. 2011;28:776–788. 13. Gorfine SR, Onel E, Patou G, et al. Bupivacaine extended release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, doubleblind, placebo controlled trial. Dis Colon Rectum. 2011;54:1552–1559. 14. Fayezizadeh M, Petro CC, Rosen MJ, et al. Enhanced recovery after surgery pathway for abdominal wall reconstruction: pilot study and preliminary outcomes. Plast Reconstr Surg. 2014;134(4 suppl 2):151S–159S. 15. Newman MI, Eberle NA. The use of liposomal bupivacane (LB) for analgesia after breast surgery: a paradigm shift in postoperative pain control. Plast Surg Pulse News. 2014;2. 16. Schrier JA, Los K, Zhu L. Syringeability assessment of depofoam multivesicular liposomes with narrow gauge needles. Presented at: Annual Meeting of the Parenteral Drug Association; April 1418 2008; Colorado Springs, CO. 17. Exparel (bupivicaine liposomal injectable suspension) [monograph]. San Diego, CA: Pacira Pharmaceuticals, Inc; 2012. 18. Viscusi ER, Sinatra AS. The safety of Exparel, a multivesicular liposomal extended release bupivacaine [abstract + poster]. Anesth Analg. 2011;112:S305.
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Patient Perception of Postoperative Pain After Administration of Liposomal Bupivacaine in Plastic Surgery Nathan Eberle, DDS, MD, and Martin Newman, MD Background: Since obtaining FDA approval for postsurgical pain management in 2011, a number of well-designed studies have reported favorably on the safety and efficacy of liposomal bupivacaine (LB). However, the literature lacks adequate reports of patient perception of postoperative pain and subjective satisfaction. Methods: A telephone survey of patients who received LB injection at time of operation at a single institution was contacted. Included were patients who underwent cosmetic, reconstructive, and/or breast procedures. Patients were asked to report their perception of pain on post-operative day (POD) 1 and 3 using the verbal scale (1–10). Additionally, patients reported on: understanding of medications received, overall satisfaction, perception of economic value, and perception of preference to elastomeric pump. Results: A total of 75 patients met inclusion criteria and could be reached by telephone; 23(31%) cosmetic and 52(69%) reconstructive and/or breast procedures. Mean pain score reported 2.6 (0–9) POD 1 and 3.6 (0–8) POD 3. Thirty-six (48%) patients were aware they had received the medication. Seventythree (98%) reported they would want LB again if they needed surgery in the future and would pay U.S. $230 [$100–$1000] for the medication. All (100%) patients favored LB over a perceived elastomeric pump device. Conclusions: Patient perception of efficacy after the injection of LB correlates with previous clinical findings. Our experience with LB injections for cosmetic and reconstructive breast procedures indicates that patients experienced low postoperative pain scores with high overall patient satisfaction. Additional studies comparing the use of LB to standard narcotic regimens and its use in multimodality pain management are warranted. Key Words: liposomal bupivacaine, breast surgery, abdominoplasty, postoperative pain (Ann Plast Surg 2015;74: S198–S200)
A
n important consideration of any surgical procedure is the strategy for pain management in the postoperative period. Aside from the humanistic factors, it is generally appreciated that by reducing postoperative pain, patients experience earlier mobilization and decreased time to discharge, leading to a reduction in overall hospital costs.1 Traditionally, postoperative pain has been managed by the administration of oral or parental opioids and/or non-narcotic medications. Of these, opioid-based medications have been used for centuries and are still a major component of many postoperative analgesic regimens. However, the negative side effects of opioids, opioid related adverse events, are well established. Among others, these include: nausea, vomiting, ileus, pruritis, urinary retention, drowsiness, respiratory depression, and potential for addiction.2 Over the years, several alternatives or adjuncts to opioid medications have been successfully used. These include, among others, nonsteroidal anti-inflammatory medications, neuromodulators, and local Received November 5, 2014, and accepted for publication, after revision, December 16, 2014. From the Cleveland Clinic Florida Weston, FL. Dr. Newman is a paid speaker and consultant for Pacira Pharmaceuticals, Inc. Dr. Eberle has no conflicts of interest with respect to the research, authorship and publication of this article. Conflicts of interest and sources of funding: none declared. Reprints: Nathan Eberle, DDS, MD, Cleveland Clinic Florida Weston, FL. E-mail: [email protected]. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0148-7043/15/7404–S198 DOI: 10.1097/SAP.0000000000000444
S198
www.annalsplasticsurgery.com
anesthetics (LAs). Local anesthetics have offered the most promise because unlike the other classes of medications discussed, the mechanism by which sodium channel blockers achieve their goal is by blocking the propagation of neural impulses along the neural axon. Although opioids, neuromodulators and non-steroidal anti-inflammatory drugs “potentiate” the perception or intensity of pain signals, sodium channel blockers actually “prevent” transmission of painful stimuli from ever reaching the central nervous system. Historically, the limiting factor prohibiting utilization of LAs for postoperative analgesia was their short duration of action. Even the longest acting formulations did not provide analgesia beyond a number of hours. However, the elastomeric infusion pump which was introduced in the late 1940s seemed to offer a solution to this dilemma. These “pain pumps,” as they were called, offered promise by delivering LAs to the operative site in small doses, continuously for periods that could be measured in days. Nevertheless, results were variable.3 The original devices were fraught with problems with required constant monitoring so as to not overdose a patient with medication.4 In the early 2000s the technology was improved with industry now providing smaller, disposable, more practical, affordable, and precise devices. Studies have demonstrated that modern elastomeric pumps delivering bupivacaine continually and in small doses can safely decrease postoperative pain, encourage earlier ambulation, and decrease the amount of oral narcotics consumed.5 Nevertheless, despite their advantages over other options designed to reduce postoperative pain, elastomeric pumps are not without their disadvantages including cost, potential as a source of infection, and the presence of an “additional” indwelling catheter. In October 2011, liposomal bupivacaine (LB) (Exparel; Pacira Pharmaceuticals, Inc., San Diego, CA) received FDA approval for local infiltration into wounds to control postsurgical pain.6 Since that time, there have been several well-designed trials showing not only its efficacy but also its safety.6,7 Liposomal bupivacaine is a formulation of bupivacaine encapsulated in multiple spheres. It is indicated for single-dose infiltration into surgical site to produce analgesia.8 The medication has been studied in patients undergoing soft tissue surgery (augmentation mammoplasty9 and abdominoplasty10) and orthopedic surgery (total knee arthoplasty11 and bunionectomy12) in addition to other surgical procedures, such as hemmorhoidectomy,13 abdominal wall reconstruction,14 and ostomy reversal.1 Although LB has been demonstrated to be effective in clinical practice by commonly studied parameters (e.g., length of stay, opioid consumption, dollars spent, etc.), absent from the literature are studies, which examine the patient's perception of the medication. Considering the increasing role of patient feedback in the ever-evolving health care landscape, patient perception has become a critical factor in the overall effectiveness of any medication or operating room adjunct. Thus, our objective in this investigation was to investigate the use of LB in patients undergoing surgery in our specialty, common plastic surgery procedures. We hypothesized that intraoperative administration of this long-acting LA would render low postoperative pain scores leading to high patient satisfaction.
METHODS Institutional review board approval was granted as a patient quality improvement project. A retrospective chart review was performed to identify patients who received LB at the time of operation at a single Annals of Plastic Surgery • Volume 74, Supplement 4, June 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Annals of Plastic Surgery • Volume 74, Supplement 4, June 2015
institution. A telephone survey of patients undergoing common plastic surgery procedures was then carried out. Procedures performed included: augmentation mammaplasty, abdominoplasty with rectus plication and immediate or delayed breast reconstruction with tissue expanders. The study period was arbitrarily set at 6 months. From July 2013 to January 2014, we performed a total of 106 operations that met inclusion criteria. All procedures were performed by 2 plastic surgeons and, when procedures involved mastectomy, 2 breast surgeons. All procedures were performed at the same surgical facility. All surgeries were conducted under general anesthesia. Patients undergoing abdominoplasty received LB in an abdominal field block fashion as has been previously described.10 Patients undergoing breast surgery underwent administration as described by Newman.15 Patients undergoing cosmetic surgery of the breast were treated on an ambulatory surgery basis and patients undergoing mastectomy with reconstruction or abdominoplasty were admitted for overnight observation. At the time of survey, patients were asked to report their “perception of pain” on post-operative day (POD) 1 and again on POD 3 using the verbal analog scale (1–10). Additionally, patients reported on their understanding of medications received, overall satisfaction, perception of LB's economic value, and perception of preference (LB vs elastomeric pump).
SURGICAL TECHNIQUE At the appropriate time, under a surgeon's direction, 266 mg of LB in 20 cc of solution was expanded with various amounts of normal saline to cover the appropriate surgical field. Our routine expansion for a bilateral breast reconstruction is to add 80 mL of saline to 20 mL (266 mg) of LB. The manufacturer recommends not expanding beyond 0.89 mg/mL (1:14). In our practice, we use a 25-gauge needle to inject the medication, although the medication can be injected through needles as small as 30 gauge without impact on depofoam integrity or drug encapsulation.8,16 The medication should be used within 4 hours once diluted.8 If the surgeon chooses to use a shorter-acting LA for immediate analgesia, the LB was not injected for at least 20 minutes as per the manufacturer's recommendations.8 In our practice, we inject 45 to 60 minutes before the end of the procedure. When we inject the breast, we like to think of injecting the medication in 2 separate planes. Initially, the medication is deposited in all 4 quadrants of the chest muscles (pectoralis and serratus) followed by injecting around the edges of the skin incision and drain site. When injecting the abdominal wall, we prefer to think of the abdomen as diamond shape. We begin by injecting laterally under the fascia so as to block the ilioinginaul, iliohypogastric, lateral and anterior intercostal branches followed by injection of the midline fascial plication., just under the rectus sheath. We complete our abdominal administration with injections to both the superior and inferior skin incision margins.
RESULTS A total of 75 patients met inclusion criteria and could be reached by telephone; 23(31%) cosmetic breast and abdomen and 52(69%) reconstructive breast procedures, all were women. Ten patients were discharged home on the day of surgery, and the remaining 65 were discharged home the next day after overnight observation. Mean pain score reported on POD 1 was 2.6 (0–9) and POD 3 was 3.6 (0–8). Thirty-six (48%) patients reported they could recall having had a conversation regarding the medication usage before their surgery, although all had been counseled by the treating physician preoperatively. Seventy-three (97%) reported they would want LB again if they needed surgery. Further that if in the future they required addition surgery, they would value the cost of the medication at U.S. $230 ($100–$1000) if not covered by their insurance. All (100%) patients favored LB over a perceived elastomeric pump device. © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Pain After Administration of Liposomal Bupivacaine
DISCUSSION Liposomal bupivacaine (Exparel) represents a newer option for long-acting local anesthesia. The novel design of a multivesicular liposomal delivery system allows molecules of medication (bupivacaine in this case) to be encapsulated without altering structure. Each sphere in the multivesicular design contains multiple molecules of medication. Over a prolonged period of time, the patient's body resorbs the lipid walls slowly releasing the bupivacaine. Systemic plasma levels of bupivacaine can persist up to 96 hours after injection.8 The medication is currently available in a 20-mL single-use vial, 1.3% (266 mg, 13.3 mg/mL). This 20-mL vial represents the maximum recommended dose of LB (266 mg), which is equivalent to 300 mg of nonencapsulated bupivacaine.17 However, even this dose is far below the maximum safe dose of bupivacaine (400 mg) in 24 hours in a 70-kg patient.2 Nausea, constipation, and vomiting are the most common adverse reactions associated with the use of LB.12,13 The overall incidence of serious adverse events in clinical trials has been less for LB than bupivacaine alone (1.9% vs 3.9%).18 The most common cardiac events are tachycardia and bradycardia.18 This long-acting form of bupivacaine can last up to 72 hours, far longer than previous longest-acting LA lasting approximately 7 hours. In our experience, our patient's perception correlates with the currently available literature with using LB suspension injections for treating both cosmetic and reconstructive patients having low postoperative pain scores. There have been previous studies on plastic surgery patients undergoing combined abdominoplasty plus multiple other procedures.10 This study showed that by using abdominal field block injections, surgeons could decrease narcotic use and patients ambulated earlier and returned to normal activity quicker. In an older study prior to the advent of LB or elastomeric pumps, Feng et al3 performed their own version of an abdominal field block using bupivacaine with epinephrine, pontocaine, and Depo-medrol. Their patients also experienced a significant reduction in pain; however this was only in the immediate recovery period. It has been our experience that by expanding the LB, we can easily and effectively perform an abdominal or breast field block without impairing efficacy for a prolonged duration. In past years, a bupivacaine elastomeric pump was the only option for delivering LA in a prolonged fashion, which did improve the postoperative recovery experience for patients. As stated previously, there are multiple disadvantages of these pumps including: additional catheter attached to cumbersome elastomeric pumps which can lead to kinking and malfunction, not to mention exposure of the surgeons dissection pocket and hence implantable device, such as a tissue expander possibly leading to a higher rate of infection. Beyond this, the design of the pumps is in such a way that the bupivacaine is suppose to “bathe” the wound bed with LA, but in most cases, our patients have closed suction drains in similar areas likely evacuating out a portion of the anesthetic which is supposed to be delivered. Over the past 3 years, our institution has converted to injecting LB for all invasive cosmetic surgery procedures of the breast and trunk along with oncologic surgery of the breast. There are several large limitations in our study that should be addressed. We did not include a control group, but this study was undertaken to better understand patient perception of their postoperative pain control with use of LB. A second limitation is that not all patients underwent the exact same procedure. Theoretically speaking, an abdominoplasty procedure should be far more painful than an oncologic breast procedure. With our patient population, we had more reconstructive breast patients than cosmetic plastic surgery patients, which could have skewed our data. A third limitation is the questionnaire was completed when the patients were remote to the actual surgical event so despite proper questioning, the patient's recall of the events might be better or worse than reported. An additional limitation of our study is the lack of any complications associated with the medication www.annalsplasticsurgery.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
S199
Annals of Plastic Surgery • Volume 74, Supplement 4, June 2015
Eberle and Newman
administered. As stated previously, nausea, vomiting, and constipation are the most commonly reported side effects of the medication, which also happen to be symptoms commonly associated with the postgeneral anesthesia period and narcotic administration. Further, the study is limited by not looking into the consumption of narcotic based pain medication in the immediate postoperative period to see if it was confounding our reported low postoperative pain scores. Further, when we initially were using the medication, we were expanding it in a 1:1 fashion and over time began to expand it with more normal saline so at to better distribute the medication. Lastly, we recognize this study is not a double-blinded, randomized, controlled trial. This study was set up to primarily focus on patient satisfaction and perception of pain. We are currently in the process of setting up a controlled trial comparing this medication against a control.
CONCLUSIONS In conclusion, patient perception of efficacy after the injection of LB correlates with previous clinical findings. Our experience with LB injections for cosmetic and reconstructive plastic surgery procedures indicates that patients experienced low postoperative pain scores with high overall patient satisfaction. Additional studies comparing the use of LB to standard narcotic regimens or elastomeric pumps and its use in multimodality pain management are warranted. REFERENCES 1. Marcet JE, Nfonsam VN, Larach S. An extended pain relief trial utilizing the infiltration of a long-acting Multivesicular liposome formulation of bupivacaine, EXPAREL(IMPROVE):a phase IV health economic trial in adult patients undergoing ileostomy reversal. J Pain Res. 2013;6:549–555. 2. Miller RD. Millers Anesthesia. Philadelphia, PA: Churchill Livingstone Elsevier; 2010. 3. Feng L. Painless abdominoplasty: the efficacy of combined intercostal and pararectus blocks in reducing post- operative pain and recovery time. Plast Reconstr Surg. 2010;126:1723–1732. 4. Ansbro PA. A method of continuous brachial plexus block. Am J Surg. 1946;121: 716–722.
S200
www.annalsplasticsurgery.com
5. Mentz HA, Ruiz-Razura A, Newall G, et al. Use of a regional infusion pump to control postoperative pain after an abdominoplasty. Aesthetic Plast Surg. 2005; 29:415–422. 6. Naseem A, Harada T, Wang D, et al. Bupivacaine extended release liposome injection does not prolong QTc interval in a thorough QT/QTc study in healthy volunteers. J Clin Pharmacol. 2011;4. doi:10.1177/0091270011419853. 7. Ilfeld BM, Malhotra N, Furnish TJ, et al. Liposomal bupivacaine as a single injection peripheral nerve block: a dose-response study. Anesth Analg. 2013;117: 1248–1256. 8. Exparel (bupivacaine liposome extended release injectable suspension [prescribing information]. San Diego, CA: Pacira Pharmaceuticals Inc; 2011. 9. Minkowitz H, Smoot J. Long-term safety of Exparel (bupivacaine extended release liposome injection) reveals no impact on silicone breast implants at up to two years followup. Presented at: American Society of Plastic Surgeons Annual Meeting; September 24, 2011; Denver, CO. 10. Morales R Jr, Mentz H 3rd, Newall G, et al. Use of abdominal field block injections with liposomal bupivicaine to control postoperative pain after abdominoplasty. Aesthet Surg J. 2013;33:1148–1153. 11. Bramlett K, Onel E, Viscusi ER, et al. A randomized, double-blind, dose-ranging study comparing wound infiltration of DepoFoam bupivacaine, an extendedrelease liposomal bupivacaine, to bupivacaine HCl for postsurgical analgesia in total knee arthroplasty. Knee. 2012;19:530–536. doi: 10.1016/j.knee.2011.12.004. 12. Golf M, Daniels SE, Onel E. A phase 3, randomized, placebo-controlled trial of DepoFoam bupivacaine (extended release bupivacaine local analgesic) in bunionectomy. Adv Ther. 2011;28:776–788. 13. Gorfine SR, Onel E, Patou G, et al. Bupivacaine extended release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, doubleblind, placebo controlled trial. Dis Colon Rectum. 2011;54:1552–1559. 14. Fayezizadeh M, Petro CC, Rosen MJ, et al. Enhanced recovery after surgery pathway for abdominal wall reconstruction: pilot study and preliminary outcomes. Plast Reconstr Surg. 2014;134(4 suppl 2):151S–159S. 15. Newman MI, Eberle NA. The use of liposomal bupivacane (LB) for analgesia after breast surgery: a paradigm shift in postoperative pain control. Plast Surg Pulse News. 2014;2. 16. Schrier JA, Los K, Zhu L. Syringeability assessment of depofoam multivesicular liposomes with narrow gauge needles. Presented at: Annual Meeting of the Parenteral Drug Association; April 1418 2008; Colorado Springs, CO. 17. Exparel (bupivicaine liposomal injectable suspension) [monograph]. San Diego, CA: Pacira Pharmaceuticals, Inc; 2012. 18. Viscusi ER, Sinatra AS. The safety of Exparel, a multivesicular liposomal extended release bupivacaine [abstract + poster]. Anesth Analg. 2011;112:S305.
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
