Abstract
The purpose of this study was to determine whether the use of a periarticular injection using liposomal bupivacaine could decrease pain and improve outcomes after total knee arthroplasty. Fifty consecutive patients received no periarticular injections (group A). Another 50 consecutive patients received a periarticular injection of liposomal bupivacaine (group B). There were no differences in the groups with respect to gender, age, body mass index (BMI), or comorbidities. There was a significant reduction in the amount of narcotics used in the liposomal bupivacaine group (60.97-mg oral morphine equivalent vs 89.74 mg, P = 0.009). Patients in group B with a BMI <40 and a Charlson comorbidity index of 0-3 had decreased length of stay (2.64 vs 3.06 days, P = .004), narcotic use over 24-48 hours (110.66 vs 182.47 mg, P = .013), and narcotic use over 48-72 hours (49.61 vs. 112.65 mg, P = .004). In patients with a BMI <40 and comorbidity index of ≤3, periarticular injection using liposomal bupivacaine leads to earlier discharge along with decreased use of narcotics.
Keywords: Liposomal bupivacaine, Pain, Postoperative, Total knee arthroplasty
Introduction
The number of patients undergoing total knee arthroplasty (TKA) has increased substantially in the last two decades, and currently, TKA is one of the most common orthopaedic procedures performed in the United States [1]. For many patients, pain after TKA can be severe and can compromise postoperative management leading to poor outcomes. Using a multimodal pain management protocol has been shown to improve pain scores, increase patient satisfaction, and enhance early recovery [2]. Currently, there are many postoperative pain management protocols used by orthopaedic surgeons. Regional nerve blocks and local infiltrative analgesia are two techniques that have been shown to provide postoperative pain relief, lower narcotic usage, and improve patient satisfaction in the early postoperative period [3]. Liposomal bupivacaine, Exparel (Pacira Pharmaceuticals, Parsippany, NJ), is an extended-release local anesthetic that uses multivesicular liposomes to diffuse bupivacaine over a period of 72 hours after single injection at the operative site [4]. Postoperative pain reduction extended for a period of up to 72 hours would benefit the patient by allowing for a more accelerated rehabilitation protocol, which ultimately will lead to shorter length of hospital stay and improved outcomes. In other surgical procedures, liposomal bupivacaine has been shown to offer multiple clinical advantages over short-acting bupivacaine HCl. After hemorrhoidectomy, it demonstrated a longer duration of action, decreased opioid requirement, and fewer opioid-related adverse effects [5]. Extended-release bupivacaine has also been shown to provide extended pain relief and decreased opioid use after bunionectomy compared to a placebo-controlled group [6].
The purpose of this retrospective study was to understand the contribution to pain control and recovery after primary TKA that liposomal bupivacaine adds in the setting of a comprehensive pain protocol. Narcotic usage, length of hospital stay, and walking distance were the primary outcomes investigated. In addition, we aimed to stratify this patient cohort based on comorbidities and body mass index (BMI) to provide insight into which patient populations will benefit most from periarticular injection (PAI) using liposomal bupivacaine.
Material and methods
Fifty consecutive patients who underwent primary TKA and received an intraoperative PAI using liposomal bupivacaine between April 2013 and August 2013 were retrospectively reviewed. A separate cohort of fifty consecutive patients who underwent primary TKA without PAI between June 2012 and August 2012 were retrospectively included as a control group. All procedures were performed by a single surgeon. This study was approved by our institutional review board and was Health Insurance Portability and Accountability Act compliant.
All patients received a single-shot femoral and sciatic nerve block performed by the anesthesia staff, and all patients received intravenous sedation unless general anesthesia was required for better airway control. A subvastus approach was the primary mode of exposure in both groups unless there was a contraindication. All cases were performed using a Stryker Triathlon TKA implant (Stryker, Mahwah, NJ). In the study group, the intraoperative PAI was performed after all components were implanted; the wound was irrigated with a dilute Betadine (Purdue Products LT, Stanford, CT 06901) irrigation and was then washed with normal saline from a pulse irrigator. The PAI was administered according to the liposomal bupivacaine manufacturer’s instructions. The PAI consisted of 20 mL of 1.3% liposomal bupivacaine (1 vial; 266 mg) diluted with 40-mL normal saline to create a total injection volume of 60 mL. The control group did not receive any type of intraoperative PAI.
The postoperative pain control regimen was the same for both groups and included the use of oral acetaminophen, celecoxib, tramadol, patient-controlled analgesia, and oral narcotics. Patient-controlled analgesia was administered using morphine, unless contraindicated, at which point hydromorphone was substituted. All postoperative pain medications administered were tabulated and converted to a total oral morphine equivalent (mg) for use in the comparison of the two groups (Table 1) [7].
Table 1.
Equianalgesic conversion.
| Drug | Administration | Dose (mg) | Conversion factor | PO morphine equivalent dose (mg) |
|---|---|---|---|---|
| Morphine | PO | 10 | 1 | 10 |
| IV | 10 | 3 | 30 | |
| Hydromorphone | PO | 10 | 4 | 40 |
| IV | 10 | 20 | 200 | |
| Hydrocodone | PO | 10 | 1 | 10 |
| Oxycodone | PO | 10 | 1.5 | 15 |
| Tramadol | PO | 10 | 0.25 | 2.5 |
PO, oral; IV, intravenous.
A standardized physical therapy protocol was initiated for each group on postoperative day 1. The physical therapy regimen consisted of 2 hours of continuous passive motion machine twice daily, assisted standing, and assisted walking. All patients were discharged when deemed medically stable, their pain was under control, and the physical therapy goals were met.
Standard statistical Student’s t tests were used to evaluate the mean outcome of continuous variables between groups, and chi-square tests were used to evaluate categorical variables. Dedicated statistical software (SPSS 22; SPSS Inc., Chicago, IL) was used to perform the data analysis. The two groups were compared on the basis of length of hospital stay; amount of narcotic pain medication used over the first 24, 48, and 72 hours; and the distance walked on postoperative days 1, 2, and 3. Statistically significant difference was considered at P ≤ .05 between groups.
Results
Fifty consecutive patients were identified in the study group, consisting of 34 female and 16 male patients, with an average age of 64 (range: 46-88) years and an average BMI of 35 (range: 21-58). This was compared to the control group of 50 consecutive patients, consisting of 32 female and 18 male patients, with an average age of 64 (range: 38-85) years and an average BMI of 35 (range: 20-63). The average Charlson comorbidity index (CCI) for the study group was 3.34 (range: 2-6), and for the control group, it was 3.58 (range: 0-8). There were no statistically significant differences between the groups with respect to gender, age, BMI, comorbidities, or surgical approach. The cohort characteristics are outlined in Table 2.
Table 2.
Cohort characteristics.
| Demographics | Liposomal bupivacaine PAI | No PAI | Chi square | df | P value |
|---|---|---|---|---|---|
| Male | 16 | 18 | 0.18 | 1 | 0.67 |
| Female | 34 | 32 | |||
|
P value |
|||||
| Age | 64 (46-88) | 64 (38-85) | 0.837 | ||
| BMI | 35 (21-58) | 35 (20-63) | 0.93 | ||
| CCI | 3.34 (2-6) | 3.58 (0-8) | 0.366 | ||
| Chi square |
df |
P value |
|||
| Subvastus | 33 | 39 | 1.79 | 1 | 0.18 |
| Parapatellar | 17 | 11 |
df, degrees of freedom; PAI, periarticular injection.
There was a statistically significant reduction in the amount of narcotics used over the 48-72-hour postoperative period in the liposomal bupivacaine group (60.97-mg oral morphine equivalent vs 89.74 mg, P = .009). There was no statistical difference between the two groups with respect to length of hospital stay, amount of narcotics used from 0-24 hours and 24-48 hours, or the postoperative walking distance (Table 3).
Table 3.
Outcomes in all patients.
| Outcome & Narcotic Usage | Liposomal bupivacaine PAI | No PAI | P value |
|---|---|---|---|
| Length of stay (d) | 2.94 | 3.26 | 0.092 |
| Narcotic use 0-24 h (mg) | 119.04 | 111.58 | 0.608 |
| Narcotic use 24-48 h (mg) | 114.74 | 132.18 | 0.217 |
| Narcotic use 48-72 h (mg) | 60.97 | 89.74 | 0.009 |
| Walking distance POD 1 (ft) | 61.32 | 44.5 | 0.067 |
| Walking distance POD 2 (ft) | 97.15 | 81.42 | 0.229 |
| Walking distance POD 3 (ft) | 101.93 | 123.07 | 0.246 |
POD, postoperative day; PAI, periarticular injection.
When a subset analysis was performed, the patients from the study group with a BMI <40 and a CCI of 0-3 were found to have a statistically significant difference with respect to length of stay (2.64 vs 3.06 days, P = .004), narcotic use over 24-48 hours (110.66 vs 182.47 mg, P = .013), and narcotic use over 48-72 hours (49.61 vs 112.65 mg, P = .004). There was a trend toward increased walking distance on postoperative day 2 (114.77 vs 84.82 ft, P = .193), but this was not statistically significant with the numbers available for study (Table 4). All other subsets reviewed did not show any statistically significant differences between the two groups with the numbers available for review (Table 5, Table 6, Table 7).
Table 4.
Outcomes in patients with BMI <40, CCI 0-3.
| Outcome & narcotic usage | Liposomal bupivacaine PAI | No PAI | P value |
|---|---|---|---|
| Length of stay (d) | 2.64 | 3.06 | 0.004 |
| Narcotic use 0-24 h (mg) | 117.61 | 145.53 | 0.298 |
| Narcotic use 24-48 h (mg) | 110.66 | 182.47 | 0.013 |
| Narcotic use 48-72 h (mg) | 49.61 | 112.65 | 0.004 |
| Walking distance POD 1 (ft) | 73.29 | 59.07 | 0.456 |
| Walking distance POD 2 (ft) | 114.77 | 84.82 | 0.193 |
| Walking distance POD 3 (ft) | 137.27 | 119.38 | 0.545 |
POD, postoperative day; PAI, periarticular injection; BMI, body mass index; CCI, Charlson comorbidity index.
Table 5.
Outcomes in patients with BMI <40, CCI >3.
| Outcome & narcotic usage | Liposomal bupivacaine PAI | No PAI | P value |
|---|---|---|---|
| Length of stay (d) | 3.07 | 3.55 | 0.252 |
| Narcotic use 0-24 h (mg) | 109.8 | 87.5 | 0.283 |
| Narcotic use 24-48 h (mg) | 108.93 | 92.23 | 0.228 |
| Narcotic use 48-72 h (mg) | 75.38 | 68.57 | 0.716 |
| Walking distance POD 1 (ft) | 61.43 | 40.95 | 0.08 |
| Walking distance POD 2 (ft) | 81.64 | 78.23 | 0.828 |
| Walking distance POD 3 (ft) | 82 | 122.1 | 0.176 |
POD, postoperative day; PAI, periarticular injection; BMI, body mass index; CCI, Charlson comorbidity index.
Table 6.
Outcomes in patients with BMI >40, CCI 0-3.
| Outcome & narcotic usage | Liposomal bupivacaine PAI | No PAI | P value |
|---|---|---|---|
| Length of stay (d) | 3 | 3 | 1 |
| Narcotic use 0-24 h (mg) | 156.5 | 99.63 | 0.106 |
| Narcotic use 24-48 h (mg) | 155.39 | 126.75 | 0.38 |
| Narcotic use 48-72 h (mg) | 80 | 83.43 | 0.867 |
| Walking distance POD 1 (ft) | 45.56 | 31.43 | 0.482 |
| Walking distance POD 2 (ft) | 94.38 | 109.38 | 0.738 |
| Walking distance POD 3 (ft) | 96.67 | 156.67 | 0.214 |
POD, postoperative day; PAI, periarticular injection; BMI, body mass index; CCI, Charlson comorbidity index.
Table 7.
Outcomes in patients with BMI >40, CCI > 3.
| Outcome & narcotic usage | Liposomal bupivacaine PAI | No PAI | P value |
|---|---|---|---|
| Length of stay (d) | 4 | 3 | 0.391 |
| Narcotic use 0-24 h (mg) | 77.25 | 119.67 | 0.618 |
| Narcotic use 24-48 h (mg) | 67.5 | 154.67 | 0.254 |
| Narcotic use 48-72 h (mg) | 30 | 125 | 0.237 |
| Walking distance POD 1 (ft) | 24.33 | 3 | 0.472 |
| Walking distance POD 2 (ft) | 47.67 | 11 | 0.28 |
POD, postoperative day; PAI, periarticular injection; BMI, body mass index; CCI, Charlson comorbidity index.
Discussion
Periarticular injections after TKA have been widely used to alleviate postoperative pain to improve patient satisfaction and outcomes 8, 9. Many groups have used these injections as part of their multimodal pain control management plan after TKA. The use of liposomal bupivacaine as a PAI is a novel technique that can provide long-acting postoperative pain relief 10, 11.
This retrospective study was undertaken to determine whether the addition of a PAI using liposomal bupivacaine compared to no PAI would enhance the postoperative pain relief of patients undergoing TKA. Based on our study, the use of a liposomal bupivacaine PAI led to a decrease in narcotic use in the immediate postoperative period in patients undergoing primary TKA. Patients receiving liposomal bupivacaine were able to be discharged from the hospital sooner and had a trend toward increased walking distance earlier in their postoperative course. The greatest benefit was seen for the healthier (CCI, ≤3) and nonmorbidly obese patients (BMI, <40). No statistically significant difference in length of stay, narcotic use, or walking distance was noted when comparing morbidly obese (BMI, >40) patients and those with multiple comorbidities (CCI, >3). Patients most likely to benefit from the addition of a PAI using liposomal bupivacaine in this study were those with a BMI <40 and a CCI ≤3.
There are limitations to this study, but despite being a retrospective review, this study was performed at a single institution using consecutive patients, without variation in surgical technique, anesthesia, or the postoperative protocol. The study cohort and control groups both consisted of a consecutive series of patients that underwent primary TKA during a similar time period of the year to best eliminate selection bias. There are several questions that arise from the results of this study, which need further exploration. There is an added cost to each case using liposomal bupivacaine as a PAI. In a study by Bagsby et al [12], they concluded that liposomal bupivacaine PAIs provided inferior pain control compared to the less-expensive traditional PAI using short-acting bupivacaine. However, this was also a retrospective study with two different surgeons, and the authors acknowledge that the results may be technique dependent. It is also important to note that this study compared PAI using liposomal bupivacaine versus short-acting bupivacaine, in comparison to our study, which compared liposomal bupivacaine to no PAI in the control group. A prospective, randomized study by Schroer et al [13] that comparing liposomal bupivacaine to standard bupivacaine did not show any significant benefit between the two periarticular injections in patients undergoing primary TKA. Long-acting pain relief with the use of PAIs appears to be an important part of a multimodal pain regimen that allows for earlier discharge and improved outcomes. There is increasing evidence that short-stay and outpatient TKA is feasible in the near future [14]. Long-acting pain relief through the use of PAI may allow for this to become a possibility. We demonstrated that healthier patients and those with a BMI <40 had a shorter hospital stay and used fewer narcotics with the use of liposomal bupivacaine. Patients who are morbidly obese and with multiple medical problems may have difficulty in earlier return to function because of their inherent comorbid conditions despite the use of PAIs. In addition, it is not clear whether there are any differences in absorption and release of these PAIs in the morbidly obese patients because of the excess adipose tissue. Additional studies are required to demonstrate the true benefits of liposomal bupivacaine with respect to cost effectiveness compared to a hospital pharmacy–prepared PAI, actual duration of pain relief, and its role in outpatient or short-stay hospitalization after TKA.
Conclusions
Periarticular TKA injection using liposomal bupivacaine in patients with a BMI of less than 40 kg/m2 and a comorbidity index of less than or equal to 3 leads to earlier hospital discharge and decreased narcotic usage.
Footnotes
One or more of the authors of this paper have disclosed potential or pertinent conflicts of interest, which may include receipt of payment, either direct or indirect, institutional support, or association with an entity in the biomedical field which may be perceived to have potential conflict of interest with this work. For full disclosure statements refer to http://dx.doi.org/10.1016/j.artd.2015.09.001
Appendix. Supplementary data
References
- 1.Cram P., Lu X., Kates S.L. Total knee arthroplasty volume, utilization, and outcomes among Medicare beneficiaries, 1991-2010. JAMA. 2012;308:1227. doi: 10.1001/2012.jama.11153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Lamplot J.D., Wagner E.R., Manning D.W. Multimodal pain management in total knee arthroplasty. J Arthroplasty. 2014;29(2):329. doi: 10.1016/j.arth.2013.06.005. [DOI] [PubMed] [Google Scholar]
- 3.Moghtadaei M., Farahini H., Faiz S.H. Pain management for total knee arthroplasty: single-injection femoral nerve block versus local infiltration analgesia. Iran Red Crescent Med J. 2014;16(1):e13247. doi: 10.5812/ircmj.13247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Pacira Pharmaceuticals, Inc. www.pacira.com; [accessed 4.11.2011].
- 5.Gorfine S.R., Onel E., Patou G. Bupivacaine extended-release liposome injection for prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, randomized, double-blind, placebo-controlled trial. Dis Colon Rectum. 2011;54(12):1552. doi: 10.1097/DCR.0b013e318232d4c1. [DOI] [PubMed] [Google Scholar]
- 6.Golf M., Daniels S.E., Onel E. A phase 3, randomized, placebo-controlled trial of DepoFoam bupivacaine (extended-release bupivacaine local analgesic) in bunionectomy. Adv Ther. 2011;28(9):776. doi: 10.1007/s12325-011-0052-y. [DOI] [PubMed] [Google Scholar]
- 7.McPherson M.L. American Society of Health-System Pharmacists, Inc.; Bethesda, MD: 2009. Demystifying opioid conversion calculations: a guide for effective dosing. [Google Scholar]
- 8.Essving P., Axelsson K., Kjellberg J. Reduced morphine consumption and pain intensity with local infiltration analgesia (LIA) following total knee arthroplasty. Acta Orthop. 2010;81(3):354. doi: 10.3109/17453674.2010.487241. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Busch C.A., Shore B.J., Bhandari R. Efficacy of periarticular multimodal drug injection in total knee arthroplasty: a randomized trial. J Bone Joint Surg Am. 2006;88:959. doi: 10.2106/JBJS.E.00344. [DOI] [PubMed] [Google Scholar]
- 10.Richard B.M., Newton P., Ott L.R. The safety of EXPAREL® (bupivacaine liposome injectable suspension) administered by peripheral nerve block in rabbits and dogs. J Drug Deliv. 2012;2012:962101. doi: 10.1155/2012/962101. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Dasta J., Ramamoorthy S., Patou G., Sinatra R. Bupivacaine liposome injectable suspension compared with bupivacaine HCl for the reduction of opioid burden in the postsurgical setting. Curr Med Res Opin. 2012;28(10):1609. doi: 10.1185/03007995.2012.721760. [DOI] [PubMed] [Google Scholar]
- 12.Bagsby D.T., Ireland P.H., Meneghini R.M. Liposomal bupivacaine versus traditional periarticular injection for pain control after total knee arthroplasty. J Arthroplasty. 2014;29(8):1687. doi: 10.1016/j.arth.2014.03.034. [DOI] [PubMed] [Google Scholar]
- 13.Schroer W.C., Diesfeld P.G., LeMarr A.R., Morton D.J., Reedy M.E. Does extended-release liposomal bupivacaine better control pain than bupivacaine after TKA? A prospective, randomized clinical trial. J Arthroplasty. 2015;30(9):64. doi: 10.1016/j.arth.2015.01.059. [DOI] [PubMed] [Google Scholar]
- 14.Kolisek F.R., McGrath M.S., Jessup N.M. Comparison of outpatient versus inpatient total knee arthroplasty. Clin Orthop Relat Res. 2009;467(6):1438. doi: 10.1007/s11999-009-0730-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.