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Transdermal Scopolamine as an Adjunct to Multimodal Pain Management in Patients Undergoing Total Joint Arthroplasty
The Journal of Arthroplasty 34 (2019) S159eS163
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Primary Arthroplasty
Transdermal Scopolamine as an Adjunct to Multimodal Pain Management in Patients Undergoing Total Joint Arthroplasty Ari R. Berg, Akshay Lakra, MD, Emma L. Jennings, BS, H. John Cooper, MD, Roshan P. Shah, MD, JD, Jeffrey A. Geller, MD * Center for Hip and Knee Replacement, Department of Orthopedic Surgery, Columbia University Medical Center, New York, NY
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 December 2018 Received in revised form 8 March 2019 Accepted 11 March 2019 Available online 19 March 2019
Background: Postoperative nausea and vomiting (PONV) after surgery degrades patient experience, tolerance of pain medication, rehabilitation progress, and functional outcomes. Given the importance of early rehabilitation following total joint arthroplasty (TJA), we asked whether transdermal scopolamine is effective in reducing rates of PONV and improving functional outcomes following TJA. Methods: We retrospectively reviewed the charts of 1580 consecutive patients who underwent TJA between 2014 and 2017 and compared patients before the addition of the scopolamine patch (control group) to those after the addition (study group). Patients were given the scopolamine patch in the holding area unless contraindicated. A total of 495 patients were excluded. Charts were reviewed for PONV, demographic information, surgical time, length of stay, distance walked with physical therapy, and Visual Analog Scale pain scores. Student t-test was used to compare continuous data and chi-square was used for categorical variables. Results: The incidence of PONV was significantly lower in the study group compared to the control group (14.4% vs 29.3%, P < .0001). Patients who were given scopolamine had lower Visual Analog Scale pain scores on postoperative days (POD) 0 through 2 (P < .01), were able to walk further distances on POD 0 through 3 (P < .001), and received fewer morphine equivalents on POD 1 and 2 (P < .001). Greater morphine equivalents were received by the study group on POD 0. Conclusion: Use of a scopolamine patch was associated with significant reduction in PONV and improvement in functional outcomes following TJA. These data support the use of transdermal scopolamine as part of a multimodal, perioperative pain protocol in patients undergoing TJA. © 2019 Elsevier Inc. All rights reserved.
Keywords: total hip arthroplasty transdermal scopolamine postoperative nausea and vomiting multimodal pain management total joint arthroplasty
Postoperative nausea and vomiting (PONV) is a common and distressing complaint following surgery, with an incidence of 20%30% among all patients and as high as 70% to 80% in high-risk patients undergoing surgery [1,2]. PONV is of particular concern in patients undergoing total joint arthroplasty (TJA) because of the importance of early mobilization and recovery. Postoperative analgesia using opioids is associated with a high incidence of PONV, despite multimodal preventive approaches [3e5]. Whereas adequate pain control allows faster rehabilitation and reduces the risk of postoperative 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 https://doi.org/10.1016/j.arth.2019.03.028. * Reprint requests: Jeffrey A. Geller, MD, Center for Hip and Knee Replacement, Columbia University Medical Center, 622 West 168th Street, PH 11, New York, NY 10032. https://doi.org/10.1016/j.arth.2019.03.028 0883-5403/© 2019 Elsevier Inc. All rights reserved.
complications, the physical and psychological complications of PONV may interfere with rehabilitation therapy after surgery and thereby affect functional outcomes, prolong hospitalization, increase the cost of treatment, and lead to other systemic complications [6,7]. Furthermore, PONV has been shown to be associated with increased patient dissatisfaction, which can further impact the patient’s postoperative rehabilitation [8e11]. There is currently no standard approach for the management of PONV and it remains a challenge for both the patients and the treating doctors. The Society for Ambulatory Anesthesia Consensus Guidelines for the Management of PONV include providing prophylactic treatment and rescue medication with an antiemetic drug if needed [1]. Scopolamine, an antimuscarinic agent that acts on the central nervous system and blocks transmissions to the vomiting center, is one such antiemetic initially developed to prevent motion sickness and approved in 2001 by the US Food and Drug Administration for the prevention of PONV [12,13]. Scopolamine has been
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reported to decrease PONV induced by intrathecal and epidural analgesia in cesarean delivery and outpatient laparoscopy [14e16]. The prophylactic use of a transdermal scopolamine patch in conjunction with dexamethasone was also found to be effective in the prevention of PONV compared to dexamethasone alone or dexamethasone plus ramosetron in patients who received epidural PCA after major orthopedic surgery [17]. To our knowledge, the efficacy of scopolamine in preventing PONV in patients undergoing TJA has not yet been studied. The purpose of this study is to determine whether transdermal scopolamine patch is effective in reducing rates of PONV in patients undergoing TJA. Secondary outcome measures were length of stay (LOS) and discharge disposition, as well as functional outcomes such as Visual Analog Scale (VAS) pain scores, morphine equivalents (ME) consumed, and the number of feet walked with physical therapy. Materials and Methods Institutional review board approval was obtained before start of this study. We retrospectively reviewed the charts of 1580 consecutive patients who underwent TJA between January 2014 and December 2017. Starting in September 2014, surgeons at our institution sequentially adopted scopolamine for patients undergoing primary total hip (THA) and knee arthroplasty (TKA) unless contraindicated in our protocol. Thus, these are consecutive cohorts with the inflection date overlapping between surgeons. All patients were divided into 2 cohorts: those who underwent TJA before the implementation of the scopolamine patch in our perioperative regimen (control group) and those who underwent TJA after implementation (study group). A scopolamine patch was not given to any patient greater than 75 years old and those with acute angle glaucoma, a history of urinary retention, or a history of adverse side effects with intake of scopolamine in any form. Exclusion from the study group occurred for patients who did not receive scopolamine patch due to older age, history of adverse effects, or other labeled contraindication. Based upon these criteria, 495 patients were excluded leaving 1085 patients. Furthermore, after reviewing each individual chart, a number of patients who underwent TJA after scopolamine was implemented did not receive the patch and were therefore included in the control group. Finally, 369 patients were in the study group and 716 patients were in the control group. Scopolamine 1.5-mg transdermal patch was placed behind the ear approximately 2 hours before surgery and left undisturbed for 72 hours. Regardless of whether they received a scopolamine patch or not, patients received a standard set of preoperative medications (Table 1). Over the study period, patients preferably received spinal anesthesia, or occasionally received general anesthesia if spinal was unobtainable. There was no material change in surgical technique, patient education, or rehab protocols over the study period. A multimodal pain protocol was followed for all patients in the postoperative period (Table 2). Patients who had PONV were treated with ndansetron 4 mg as needed. Table 1 Preoperative Cocktail of Medications Given to Patients. (1) 400 mg Celebrex if creatinine <1.2 or 200 mg if creatinine between 1.2 and 1.5 or no NSAIDs if creatinine >1.5. (2) Scopolamine patch 1.5-mg transdermal patch (leave for 72 h). Hold if >75 y old. (3) Gabapentin 300 mg. Hold if >75 y old (or altered mental status). (4) Tylenol 975 mg. Hold if elevated AST or ALT. (5) Extended-release oxycodone HCl 10 mg (PO), hold for age 80 y. (6) Ultrasound-guided adductor canal block, 0.5% bupivacaine (TKAs only). AST, aspartate aminotransferase; ALT, alanine aminotransferase; NSAIDs, nonsteroidal anti-inflammatory drugs; TKAs, total knee arthroplasties.
Charts were reviewed for incidence of PONV, as well as for demographic information, operative and postoperative criteria. The primary outcome measure was PONV, which was defined as any incidence of nausea and/or vomiting that occurred in the postoperative period. Presence of either nausea or vomiting for each postoperative day (POD) was given “yes” and absence was given “no” for statistical calculations. Secondary outcome measures were LOS, discharge disposition, VAS pain scores during the hospital stay, total ME consumed during the hospital stay, ME consumed per LOS (ME/LOS), and the number of feet walked with physical therapy on POD 0, POD 1, POD 2, and POD 3. We also recorded any possible adverse effects of scopolamine use. Narcotic conversion factors were used to convert administered narcotics to ME. Outcomes were evaluated for the combined cohort of all total joint patients, as well as for subgroups of THA and TKA. Demographic parameters between the 2 groups, including patients’ age, body mass index (BMI), and American Society of Anesthesiologists (ASA) scores, were compared by a 2-sided t-test for continuous variables. Categorical variables such as gender, surgery type, diagnosis, and anesthesia type were compared between the 2 groups by using chi-square test. All the primary and secondary outcome continuous variables were compared using a 2-sided Student t-test and categorical variables were compared using chi-square test or Mann-Whitney U test. Multivariate analysis was performed to assess the effect of PONV on functional outcomes. Univariate analysis was completed for age, gender, BMI, ASA, operating room time, LOS, ME consumed, and number of feet walked with physical therapy on POD 1, POD 2, and POD 3. Variables with a P value of less than .05, such as age, BMI, ASA, and ME consumed, were excluded from the multivariate analysis. All the statistical analyses were performed using SPSS (version 24.0, IBM Corp, Armonk, NY). A P value <.05 was considered as statistically significant. Results There was no significant difference between the 2 groups with regard to age, gender, BMI, ASA scores, diagnosis, and anesthesia type (all P > .05, Table 3). Mean age for the scopolamine group and control group was 63.9 ± 10.1 years and 65.1 ± 10.2 years, respectively. The scopolamine group was 61.8% female and the control group 66.1% female (P ¼ .16). Mean BMI was 30.3 kg/m2 and 29.1 kg/ m2 for the scopolamine and control groups, respectively (P ¼ .15). Combined Cohort (THA þ TKA) The incidence of PONV was significantly lower in the scopolamine (study) group compared to the control group (14.4% vs 29.3%, P < .0001), for the entire hospital stay and for each POD other than Table 2 Perioperative Multimodular Pain Management Protocol. Intraoperative Multimodal Analgesia (Operating Room) (1) Spinal anesthesia (when not contraindicated). (2) Periarticular injection 60 cc 0.5% bupivacaine. Postoperative Multimodal Analgesia (Recovery Room/Orthopedic Floor) (1) Ketorolac 30 mg every 6 h 4 doses (IV), if normal renal function ketorolac 15 mg every 6 h 4 doses (IV), if creatinine 1.1-1.3 mg/dL hold ketorolac if renal insufficiency (creatinine 1.4 mg/dL). (2) Celecoxib 200 mg every 12 h (PO), starting 24 h postoperatively old celecoxib if renal insufficiency (creatinine 1.4 mg/dL). (3) Acetaminophen 975 mg every 8 h (PO). (4) Oxycodone HCl extended release 10 mg every 12 h 3 doses (PO), hold for age 80 y. (5) Oxycodone 5 mg every 3 h (PO), as needed for moderate pain. (6) Oxycodone 10 mg every 3 h (PO), as needed for severe pain. (7) Hydromorphone 0.4 mg every 3 h (IV), as needed for breakthrough. IV, intravenous; PO, oral.
A.R. Berg et al. / The Journal of Arthroplasty 34 (2019) S159eS163 Table 3 Demographic Variables Between the 2 Cohorts.
Table 5 Combined Cohort Primary and Secondary Outcomes.
Variable
Scopolamine Arm (N ¼ 369)
Control Arm (N ¼ 716)
Age (y) Gender (%) F M BMI (kg/m2) ASA Procedure TKA THA Diagnosis OA Other Anesthesia type Spinal GA
63.9 ± 10.1
65.1 ± 10.22
228 (61.8%) 141 (38.2%) 30.3 ± 14.4 2.2 ± 0.52
473 (66.1%) 243 (35.9%) 29.1 ± 8.6 2.23 ± 0.6
164 (44.4%) 205 (55.6%)
504 (70.4%) 212 (29.6%)
<.0001
339 (91.9%) 30 (8.1%)
664 (92.7%) 52 (7.3%)
.61
315 (85.4%) 54 (14.6%)
618 (86.3%) 98 (13.7%)
.67
P Value .066
.16 .15 .075
ASA, American Society of Anesthesiologists; BMI, body mass index; F, female; GA, general anesthesia; M, male; OA, osteoarthritis; TKA, total knee arthroplasty; THA, total hip arthroplasty.
POD 0 (Table 4). Of the patients who experienced PONV, the majority had only 1 episode of PONV throughout the entire hospital stay. The percentage of patients who experienced more than 1 episode of PONV was significantly lower in the scopolamine group compared to the control group (7.5% vs 17.1%, P < .0001). In addition, patients who were given scopolamine had a significantly shorter LOS (2.3 days vs 2.8 days, P < .0001), were more likely to be discharged home (84% vs 64%, P < .0001), had lower VAS pain scores on POD 0 through 2 (P < .0034), and were able to walk further distances on POD 0 through 3 (P < .0006; Table 5). The scopolamine group received greater ME on POD 0, but fewer ME when compared to the control group on POD 1 and POD 2 (P < .00072; Table 5). TKA Cohort The incidence of PONV was significantly lower in the scopolamine (study) group compared to the control group (12.8% vs 29.8%, P < .0001), throughout the hospital stay (Table 6). In addition, patients who were given scopolamine also had a significantly shorter LOS (2.5 days vs 2.9 days, P ¼ .0024), were more likely to be discharged home (86.6% vs 57.03%, P < .0001), had lower VAS pain scores on POD 1 through 3 (P < .035), were able to walk further distances on POD 1 through 3 (P < .0075), and received fewer ME when compared to the control group on POD 1 and POD 2 (P < .036; Table 4 Combined Cohort Postoperative Nausea and Vomiting. Variable PONV Yes No PONV Yes No PONV Yes No PONV Yes No PONV Yes No
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Scopolamine THA (N ¼ 369)
Control THA (N ¼ 716)
P Value
26 (7.0%) 343 (93.0%)
51 (7.1%) 665 (92.9%)
17 (4.6%) 352 (95.4%)
98 (13.7%) 618 (86.3%)
<.0001
3 (0.8%) 366 (99.2%)
41 (5.7%) 675 (94.3%)
.0001
2 (0.5%) 367 (99.5%)
22 (3.1%) 694 (96.9%)
.0073
53 (14.4%) 316 (83.6%)
210 (29.3%) 506 (70.7%)
<.0001
(POD 0)
Variable PONV Yes No LOS (d) Discharge disposition Home Outside institution VAS pain scores POD 0 POD 1 POD 2 POD 3 Feet walked on PT POD 0 POD 1 POD 2 POD 3 ME (mg) POD 0 POD 1 POD 2 POD 3 ME/LOS
Scopolamine Arm (N ¼ 369)
Control Arm (N ¼ 716)
53 (14.4%) 316 (83.6%) 2.3 ± 1.2
210 (29.3%) 506 (70.7%) 2.81 ± 1.3
<.0001 <.0001
310 (84.01%) 59 (15.99%)
458 (63.9%) 258 (36.1%)
<.0001
3.1 3.1 3.3 3.0
± ± ± ±
2.8 2.5 2.7 2.7
117.3 384.3 332.6 216.4
± ± ± ±
118.6 321.7 253.8 201.6
58.8 66.6 30.1 47.4 69.8
± ± ± ± ±
28.3 43.5 39.8 48.6 54.1
P Value
3.73 3.61 3.83 3.7
± ± ± ±
2.6 2.4 2.3 2.4
80.54 254.54 256.0 131.0
± ± ± ±
92.2 263.4 241.2 117.2
.00065 <.0001 <.0001 <.0001
45.4 75.4 49.7 42.1 64.3
± ± ± ± ±
28.9 53.5 40.2 32.5 41.5
<.0001 .00072 <.0001 .26 .0651
.0022 .00335 .00344 .06
LOS, length of stay; ME, morphine equivalents; PONV, postoperative nausea and vomiting; POD, postoperative day; PT, physical therapy; VAS, Visual Analog Scale.
Table 6). In the TKA cohort, patients in the scopolamine group received greater ME than the control group on POD 0. THA Cohort The incidence of PONV was significantly lower in the scopolamine (study) group compared to the control group (15.6% vs 28.0%, P ¼ .0029), throughout the hospital stay (Table 7). In addition, patients who were given scopolamine also had a significantly shorter LOS (2.1 days vs 3.6 days, P ¼ .0028), were more likely to be discharged home (91.2% vs 80.6%, P ¼ .0012), had lower VAS pain scores on POD 0, P ¼ .045), were able to walk further distances on POD 1 through 2 (P < .047), and received fewer ME when compared to the control group on POD 2, P ¼ .0022; Table 7). In the THA cohort, patients in the scopolamine group received greater ME than the control group on POD 0. There were no statistically significant differences between the 2 groups with regard to adverse events such as urinary retention, dizziness, syncope, or itchiness. The scopolamine (study) group had a significantly lower rate of constipation compared to the control group (0.8% vs 3.1%, P ¼ .02). There were no readmissions due to narrow-angle glaucoma for either group. On multivariate analysis, there was a statistically significant difference in physical therapy performance based on PONV, F (5, 289) ¼ 4.295, P ¼ .001; Wilk's L ¼ 0.931, partial h2 ¼ .069.
.96
(POD 1)
Discussion
(POD 2)
(POD 3)
(total)
THA, total hip arthroplasty; PONV, postoperative nausea and vomiting; POD, postoperative day.
Management of pain following TJA is an important component of the procedure, as adequate pain control allows faster rehabilitation and reduces the risk of complications [6,7]. Pain control is often managed via a multimodal approach, which includes the use of opioids. Although very effective as analgesics, opioids are associated with a high incidence of PONV [3e5]. PONV is a challenging and frequent condition with an overall incidence of 20%-30% [1], with more than 1 million total joint arthroplasties performed each year, which amounts to more than 200,000-300,000 cases of inhospital PONV attributable to TJA annually [18]. PONV can complicate recovery from surgery. It
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Table 6 TKA Cohort Primary and Secondary Outcome Measures. Variable PONV Yes No LOS (d) Discharge disposition Home Outside institution VAS pain scores POD 0 POD 1 POD 2 POD 3 Feet walked on PT POD 0 POD 1 POD 2 POD 3 ME (mg) POD 0 POD 1 POD 2 POD 3 ME/LOS
Scopolamine TKA (N ¼ 164)
Control TKA (N ¼ 507)
21 (12.8%) 143 (87.2%) 2.5 ± 1.2
151 (29.8%) 356 (70.2%) 2.9 ± 1.3
<.0001 .0024
142 (86.6%) 22 (13.4%)
288 (57.03%) 217 (42.97%)
<.0001
3.3 3.1 3.4 2.8
± ± ± ±
3.0 2.5 2.8 2.6
3.8 3.7 4.04 3.7
± ± ± ±
2.4 2.3 2.1 2.3
79.5 340.9 310.7 244.5
± ± ± ±
84.2 344.5 233.6 209.9
72.5 226.1 244.4 131.8
± ± ± ±
76.6 252.9 236.7 118.8
55.8 69.9 36.7 42.3 69.5
± ± ± ± ±
27.05 35.3 35.8 30.6 31.1
46.6 80.1 50.8 39.8 64.0
± ± ± ± ±
30.3 58.3 41.7 32.8 39.5
P Value
.086 .0028 .024 .035 .64 <.0001 .0075 <.0001 .00043 .036 .00023 .75 .105
TKA, total knee arthroplasty; PONV, postoperative nausea and vomiting; LOS, length of stay; VAS, Visual Analog Scale; POD, postoperative day; PT, physical therapy; ME, morphine equivalents.
can prevent early mobilization, delaying rehabilitation and discharge and increasing the risk of venous thromboembolism and other serious complications [6,7]. We therefore sought to determine whether scopolamine, an antimuscarinic agent that acts on the central nervous system and blocks transmissions to the vomiting center, is effective in reducing the number of episodes of PONV after TJA. We found that patients undergoing THA and TKA who received transdermal scopolamine had a lower incidence of PONV compared to those who did not receive scopolamine. They also had a shorter LOS, were more likely to be discharged home, had better functional outcomes, such as
Table 7 THA Cohort Primary and Secondary Outcome Measures. Variable PONV Yes No LOS (d) Discharge disposition Home Outside institution VAS pain scores POD 0 POD 1 POD 2 POD 3 Feet walked on PT POD 0 POD 1 POD 2 POD 3 ME (mg) POD 0 POD 1 POD 2 POD 3 ME/LOS
Scopolamine THA (N ¼ 205)
Control THA (N ¼ 211)
32 (15.6%) 173 (84.4%) 2.1 ± 1.1
59 (28.0%) 152 (72.0%) 3.6 ± 1.3
.0029 .0028
187 (91.2%) 18 (8.8%)
170 (80.6%) 41 (19.4)
.0012
3.0 3.1 3.0 3.2
± ± ± ±
2.6 2.5 2.6 2.8
135.4 421.3 357.6 179.7
± ± ± ±
128.4 296.9 274.02 186.6
57.8 59.3 32.8 44.1 71.8
± ± ± ± ±
31.04 40.13 35.8 33.5 66.2
P Value
3.6 3.2 3.2 3.0
± ± ± ±
2.8 2.5 2.7 2.9
.045 .82 .61 .8
92.0 325.4 290.02 171.5
± ± ± ±
110.2 276.1 254.2 104.0
.011 .0011 .047 .79
45.2 63.7 46.3 52.3 65.1
± ± ± ± ±
29.0 37.4 35.3 28.9 48.0
.000032 .26 .0022 .26 .25
LOS, length of stay; ME, morphine equivalents; THA, total hip arthroplasty; PONV, postoperative nausea and vomiting; POD, postoperative day; PT, physical therapy; VAS, Visual Analog Scale.
lower VAS pain scores, were able to walk further distances with physical therapy, and received fewer ME compared to the control group after POD 0. There were no statistically significant differences in adverse events, other than a higher rate of constipation in the control group. This result is likely due to the increased narcotic consumption in this cohort. Importantly, there were no readmissions for narrowangle glaucoma, which has been reported in the literature as a possible side effect of transdermal scopolamine [19]. This study reports close to a 50% reduction in the incidence of PONV with the use of transdermal scopolamine. In addition to the functional and psychological toll PONV can have on a patient, there are also associated costs of additional supplies and hospital services [20]. Our study also suggests a decrease in LOS for those patients who received transdermal scopolamine, which secondarily reflects meeting discharge requirements earlier, including pain control and functional milestones. The reduction in ME after POD 0 highlights the role PONV plays in postoperative pain control. With less PONV, patients can tolerate effective narcotic pain medication on the day of surgery, achieving better pain control and gaining early confidence in their new joint. In other words, the increased ME consumed by scopolamine group patients on POD 0 may be due to the ability to consume more narcotics that accompanies decreased nausea/vomiting. Thereafter, with less PONV, patients may be better able to tolerate multimodal per os medications, requiring less frequent usage of stronger parenteral narcotic medications. Transdermal scopolamine is effective for the first 48-72 hours, which correlates with our finding of significantly fewer ME consumed on POD 1 and 2 in the scopolamine group. There was no statistically significant difference between the 2 groups with regard to ME consumed on POD 3. Nevertheless, there were statistically fewer incidents of PONV in the scopolamine group, leading us to believe that ME consumed is not the main contributor to PONV. There have been a number of studies that assessed the efficacy of transdermal scopolamine in reducing PONV in certain patient populations. Kotelko et al studied 203 healthy patients undergoing elective cesarean section and receiving epidural morphine for postoperative analgesia plus either transdermal scopolamine or placebo. They reported a significant reduction in nausea, vomiting, and retching and a decreased requirement of antiemetic rescue medications in those patients who received scopolamine in the study period of 2-10 h after surgery [15]. Harnett et al carried out a similar study comparing the efficacy of transdermal scopolamine, intravenous ondansetron, and placebo during the first 24 h postoperatively in women undergoing cesarean section. They showed that scopolamine was significantly superior to ondansetron or placebo in preventing PONV [16]. Similar studies have been performed in other surgical areas and in combination with other antiemetics. Einarsson et al showed a significant reduction in the incidence and severity of PONV in the first 24 h after gynecologic laparoscopic surgery in patients who received transdermal scopolamine, and Sah et al revealed similar efficacy of transdermal scopolamine plus ondansetron versus placebo patch plus ondansetron on the incidence of PONV in 126 patients undergoing plastic surgery [21,22]. Studies showing the efficacy of transdermal scopolamine in preventing PONV in orthopedic surgery procedures are limited. A prospective blinded study by Lee et al [23] concluded that combined use of transdermal scopolamine and dexamethasone in patients undergoing major orthopedic surgery using patient-controlled analgesia was more effective in preventing PONV compared with dexamethasone alone or dexamethasone plus ramosetron. However, there were several limitations with this study, including the lack of a control group that did not receive any prophylaxis and a 24-h limit on patient evaluation postoperatively. To our knowledge, this is the
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first study to determine the efficacy of transdermal scopolamine in preventing PONV in patients undergoing TJA. The primary limitation of this study is that it is a retrospective review of prospectively collected data. Along with this are all the inherent biases of a retrospective cohort study, including lack of randomization and blinding. The retrospective design allowed us to analyze a large number of patients. Additionally, this study reviewed data from operations performed over the span of 3 years. Although there was no material change in surgical technique, patient education, or rehab protocols over the study period, it is possible that global evolution of TJA management in the era of bundles affected LOS results and discharge to home. However, these macro changes would not be expected to alter PONV, VAS pain scores, or narcotic requirements. Conclusions As the annual number of TJA procedures continues to rise, with rapid recovery, outpatient procedures, and transition from hospital environments to home, PONV will be a major bottleneck to optimizing the postoperative experience. Reducing rates of PONV in these patients can lead to significant postoperative functional benefits, as well as patient satisfaction. In this study, we report a significant reduction in PONV with the use of transdermal scopolamine in patients undergoing TJA. These data support the use of transdermal scopolamine as part of a multimodal, perioperative pain protocol in patients undergoing TJA. References [1] Gan TJ, Diemusch P, Habib AS, Kovac A, Kranke P, Meyer TA, et al. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg 2014;118:85e113. [2] Gan TJ. Postoperative nausea and vomiting: can it be eliminated? JAMA 2002;287:1233e6. [3] Song JW, Park EY, Lee JG, Park YS, Kang BC, Shim YH. The effect of combining dexamethasone with ondansetron for nausea and vomiting associated with fentanylbased intravenous patient-controlled analgesia. Anaesthesia 2011;66:263e7. [4] Ishikawa Y, Imashuku Y, Kitagawa H, Kawamoto S, Yuasa M, Nosaka S. [Evaluation of the side effects of intravenous patient controlled analgesia after spine surgery]. Masui 2011;60:920e3. r MR, Walder B. Efficacy and adverse effects of prophylactic antiemetics [5] Trame during patient-controlled analgesia therapy: a quantitative systematic review. Anesth Analg 1999;88:1354e61.
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[6] Tali M, Maaroos J. Lower limbs function and pain relationships after unilateral total knee arthroplasty. Int J Rehabil Res 2010;33:264e7. [7] Hollmann MW, Wieczorek KS, Smart M, Durieux ME. Epidural anesthesia prevents hypercoagulation in patients undergoing major orthopedic surgery. Reg Anesth Pain Med 2001;26:215e22. [8] Dorr LD, Chao L. The emotional state of the patient after total hip and knee arthroplasty. Clin Orthop Relat Res 2007;463:7e12. [9] Koivuranta M, Laara E, Snare L, Alahuhta S. A survey of post-operative nausea and vomiting. Anesthesia 1997;52:443e9. [10] Macario A, Weinger M, Carney S, Kim A. Which clinical anesthesia outcomes are important to avoid? The perspective of patient. Anesth Analg 1999;89: 652e8. [11] Myles PS, Williams DL, Hendrata M, Anderson H, Weeks AM. Patient satisfaction after anesthesia and surgery: results of prospective survey of 10811 patients. Br J Anaesth 2000;84:6e10. [12] Renner UD, Oretel R, Kirch W. Pharmacokinetics and pharmacodynamics in clinical use of scopolamine. Ther Drug Monit 2005;27:655e65. [13] Clissold SP, Heel RC. Transdermal hyoscine (scopolamine). A preliminary review of its pharmacodynamic properties and therapeutic efficacy. Drugs 1985;29:189e207. [14] Bailey PL, Streisand JB, Pace NL, Bubbers SJ, East KA, Mulder S, et al. Transdermal scopolamine reduces nausea and vomiting after outpatient laparoscopy. Anesthesiology 1990;72:977e80. [15] Kotelko DM, Rottman RL, Wright WC, Stone JJ, Yamashiro AY, Rosenblatt RM. Transdermal scopolamine decreases nausea and vomiting following cesarean section in patients receiving epidural morphine. Anesthesiology 1989;71: 675e8. [16] Harnett MJ, O'Rourke N, Walsh M, Carabuena JM, Segal S. Transdermal scopolamine for prevention of intrathecal morphine-induced nausea and vomiting after cesarean delivery. Anesth Analg 2007;105:764e9. [17] Lee HK, Lee JH, Chon SS, Ahn EK, Kim JH, Jang YH. The effect of transdermal scopolamine plus intravenous dexamethasone for prevention of postoperative nausea and vomiting in patients with epidural PCA after major orthopedic surgery. Korean K Anesthesiol 2010;58:50e5. [18] Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am 2007;89:780e5. [19] Fraunfelder FF. Transdermal scopolamine precipitating narrow-angle glaucoma. N Engl J Med 1982;307:1079. [20] Dzwonczyk R, Weaver TE, Puente EG, Bergese SD. Postoperative nausea and vomiting prophylaxis from an economic point of view. Am J Ther 2012;19: 11e5. [21] Einarsson JI, Audbergsson BO, Thorsteinsson A. Scopolamine for prevention of postoperative nausea in gynecologic laparoscopy, a randomized trial. J Minim Invasive Gynecol 2008;15:26e31. [22] Sah N, Ramesh V, Kaul B, Dalby P, Shestak K, Vallejo MC. Transdermal scopolamine patch in addition to ondansetron for postoperative nausea and vomiting prophylaxis in patients undergoing ambulatory cosmetic surgery. J Clin Anesth 2009;21:249e52. [23] Lee HK, Lee JH, Chon SS, Ahn EK, Kim JH, Jang YH. The effect of transdermal scopolamine plus intravenous dexamethasone for the prevention of postoperative nausea and vomiting in patients with epidural PCA after major orthopedic surgery. Korean J Anesthesiol 2010;58:50e5.
Contents lists available at ScienceDirect
The Journal of Arthroplasty journal homepage: www.arthroplastyjournal.org
Primary Arthroplasty
Transdermal Scopolamine as an Adjunct to Multimodal Pain Management in Patients Undergoing Total Joint Arthroplasty Ari R. Berg, Akshay Lakra, MD, Emma L. Jennings, BS, H. John Cooper, MD, Roshan P. Shah, MD, JD, Jeffrey A. Geller, MD * Center for Hip and Knee Replacement, Department of Orthopedic Surgery, Columbia University Medical Center, New York, NY
a r t i c l e i n f o
a b s t r a c t
Article history: Received 7 December 2018 Received in revised form 8 March 2019 Accepted 11 March 2019 Available online 19 March 2019
Background: Postoperative nausea and vomiting (PONV) after surgery degrades patient experience, tolerance of pain medication, rehabilitation progress, and functional outcomes. Given the importance of early rehabilitation following total joint arthroplasty (TJA), we asked whether transdermal scopolamine is effective in reducing rates of PONV and improving functional outcomes following TJA. Methods: We retrospectively reviewed the charts of 1580 consecutive patients who underwent TJA between 2014 and 2017 and compared patients before the addition of the scopolamine patch (control group) to those after the addition (study group). Patients were given the scopolamine patch in the holding area unless contraindicated. A total of 495 patients were excluded. Charts were reviewed for PONV, demographic information, surgical time, length of stay, distance walked with physical therapy, and Visual Analog Scale pain scores. Student t-test was used to compare continuous data and chi-square was used for categorical variables. Results: The incidence of PONV was significantly lower in the study group compared to the control group (14.4% vs 29.3%, P < .0001). Patients who were given scopolamine had lower Visual Analog Scale pain scores on postoperative days (POD) 0 through 2 (P < .01), were able to walk further distances on POD 0 through 3 (P < .001), and received fewer morphine equivalents on POD 1 and 2 (P < .001). Greater morphine equivalents were received by the study group on POD 0. Conclusion: Use of a scopolamine patch was associated with significant reduction in PONV and improvement in functional outcomes following TJA. These data support the use of transdermal scopolamine as part of a multimodal, perioperative pain protocol in patients undergoing TJA. © 2019 Elsevier Inc. All rights reserved.
Keywords: total hip arthroplasty transdermal scopolamine postoperative nausea and vomiting multimodal pain management total joint arthroplasty
Postoperative nausea and vomiting (PONV) is a common and distressing complaint following surgery, with an incidence of 20%30% among all patients and as high as 70% to 80% in high-risk patients undergoing surgery [1,2]. PONV is of particular concern in patients undergoing total joint arthroplasty (TJA) because of the importance of early mobilization and recovery. Postoperative analgesia using opioids is associated with a high incidence of PONV, despite multimodal preventive approaches [3e5]. Whereas adequate pain control allows faster rehabilitation and reduces the risk of postoperative 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 https://doi.org/10.1016/j.arth.2019.03.028. * Reprint requests: Jeffrey A. Geller, MD, Center for Hip and Knee Replacement, Columbia University Medical Center, 622 West 168th Street, PH 11, New York, NY 10032. https://doi.org/10.1016/j.arth.2019.03.028 0883-5403/© 2019 Elsevier Inc. All rights reserved.
complications, the physical and psychological complications of PONV may interfere with rehabilitation therapy after surgery and thereby affect functional outcomes, prolong hospitalization, increase the cost of treatment, and lead to other systemic complications [6,7]. Furthermore, PONV has been shown to be associated with increased patient dissatisfaction, which can further impact the patient’s postoperative rehabilitation [8e11]. There is currently no standard approach for the management of PONV and it remains a challenge for both the patients and the treating doctors. The Society for Ambulatory Anesthesia Consensus Guidelines for the Management of PONV include providing prophylactic treatment and rescue medication with an antiemetic drug if needed [1]. Scopolamine, an antimuscarinic agent that acts on the central nervous system and blocks transmissions to the vomiting center, is one such antiemetic initially developed to prevent motion sickness and approved in 2001 by the US Food and Drug Administration for the prevention of PONV [12,13]. Scopolamine has been
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reported to decrease PONV induced by intrathecal and epidural analgesia in cesarean delivery and outpatient laparoscopy [14e16]. The prophylactic use of a transdermal scopolamine patch in conjunction with dexamethasone was also found to be effective in the prevention of PONV compared to dexamethasone alone or dexamethasone plus ramosetron in patients who received epidural PCA after major orthopedic surgery [17]. To our knowledge, the efficacy of scopolamine in preventing PONV in patients undergoing TJA has not yet been studied. The purpose of this study is to determine whether transdermal scopolamine patch is effective in reducing rates of PONV in patients undergoing TJA. Secondary outcome measures were length of stay (LOS) and discharge disposition, as well as functional outcomes such as Visual Analog Scale (VAS) pain scores, morphine equivalents (ME) consumed, and the number of feet walked with physical therapy. Materials and Methods Institutional review board approval was obtained before start of this study. We retrospectively reviewed the charts of 1580 consecutive patients who underwent TJA between January 2014 and December 2017. Starting in September 2014, surgeons at our institution sequentially adopted scopolamine for patients undergoing primary total hip (THA) and knee arthroplasty (TKA) unless contraindicated in our protocol. Thus, these are consecutive cohorts with the inflection date overlapping between surgeons. All patients were divided into 2 cohorts: those who underwent TJA before the implementation of the scopolamine patch in our perioperative regimen (control group) and those who underwent TJA after implementation (study group). A scopolamine patch was not given to any patient greater than 75 years old and those with acute angle glaucoma, a history of urinary retention, or a history of adverse side effects with intake of scopolamine in any form. Exclusion from the study group occurred for patients who did not receive scopolamine patch due to older age, history of adverse effects, or other labeled contraindication. Based upon these criteria, 495 patients were excluded leaving 1085 patients. Furthermore, after reviewing each individual chart, a number of patients who underwent TJA after scopolamine was implemented did not receive the patch and were therefore included in the control group. Finally, 369 patients were in the study group and 716 patients were in the control group. Scopolamine 1.5-mg transdermal patch was placed behind the ear approximately 2 hours before surgery and left undisturbed for 72 hours. Regardless of whether they received a scopolamine patch or not, patients received a standard set of preoperative medications (Table 1). Over the study period, patients preferably received spinal anesthesia, or occasionally received general anesthesia if spinal was unobtainable. There was no material change in surgical technique, patient education, or rehab protocols over the study period. A multimodal pain protocol was followed for all patients in the postoperative period (Table 2). Patients who had PONV were treated with ndansetron 4 mg as needed. Table 1 Preoperative Cocktail of Medications Given to Patients. (1) 400 mg Celebrex if creatinine <1.2 or 200 mg if creatinine between 1.2 and 1.5 or no NSAIDs if creatinine >1.5. (2) Scopolamine patch 1.5-mg transdermal patch (leave for 72 h). Hold if >75 y old. (3) Gabapentin 300 mg. Hold if >75 y old (or altered mental status). (4) Tylenol 975 mg. Hold if elevated AST or ALT. (5) Extended-release oxycodone HCl 10 mg (PO), hold for age 80 y. (6) Ultrasound-guided adductor canal block, 0.5% bupivacaine (TKAs only). AST, aspartate aminotransferase; ALT, alanine aminotransferase; NSAIDs, nonsteroidal anti-inflammatory drugs; TKAs, total knee arthroplasties.
Charts were reviewed for incidence of PONV, as well as for demographic information, operative and postoperative criteria. The primary outcome measure was PONV, which was defined as any incidence of nausea and/or vomiting that occurred in the postoperative period. Presence of either nausea or vomiting for each postoperative day (POD) was given “yes” and absence was given “no” for statistical calculations. Secondary outcome measures were LOS, discharge disposition, VAS pain scores during the hospital stay, total ME consumed during the hospital stay, ME consumed per LOS (ME/LOS), and the number of feet walked with physical therapy on POD 0, POD 1, POD 2, and POD 3. We also recorded any possible adverse effects of scopolamine use. Narcotic conversion factors were used to convert administered narcotics to ME. Outcomes were evaluated for the combined cohort of all total joint patients, as well as for subgroups of THA and TKA. Demographic parameters between the 2 groups, including patients’ age, body mass index (BMI), and American Society of Anesthesiologists (ASA) scores, were compared by a 2-sided t-test for continuous variables. Categorical variables such as gender, surgery type, diagnosis, and anesthesia type were compared between the 2 groups by using chi-square test. All the primary and secondary outcome continuous variables were compared using a 2-sided Student t-test and categorical variables were compared using chi-square test or Mann-Whitney U test. Multivariate analysis was performed to assess the effect of PONV on functional outcomes. Univariate analysis was completed for age, gender, BMI, ASA, operating room time, LOS, ME consumed, and number of feet walked with physical therapy on POD 1, POD 2, and POD 3. Variables with a P value of less than .05, such as age, BMI, ASA, and ME consumed, were excluded from the multivariate analysis. All the statistical analyses were performed using SPSS (version 24.0, IBM Corp, Armonk, NY). A P value <.05 was considered as statistically significant. Results There was no significant difference between the 2 groups with regard to age, gender, BMI, ASA scores, diagnosis, and anesthesia type (all P > .05, Table 3). Mean age for the scopolamine group and control group was 63.9 ± 10.1 years and 65.1 ± 10.2 years, respectively. The scopolamine group was 61.8% female and the control group 66.1% female (P ¼ .16). Mean BMI was 30.3 kg/m2 and 29.1 kg/ m2 for the scopolamine and control groups, respectively (P ¼ .15). Combined Cohort (THA þ TKA) The incidence of PONV was significantly lower in the scopolamine (study) group compared to the control group (14.4% vs 29.3%, P < .0001), for the entire hospital stay and for each POD other than Table 2 Perioperative Multimodular Pain Management Protocol. Intraoperative Multimodal Analgesia (Operating Room) (1) Spinal anesthesia (when not contraindicated). (2) Periarticular injection 60 cc 0.5% bupivacaine. Postoperative Multimodal Analgesia (Recovery Room/Orthopedic Floor) (1) Ketorolac 30 mg every 6 h 4 doses (IV), if normal renal function ketorolac 15 mg every 6 h 4 doses (IV), if creatinine 1.1-1.3 mg/dL hold ketorolac if renal insufficiency (creatinine 1.4 mg/dL). (2) Celecoxib 200 mg every 12 h (PO), starting 24 h postoperatively old celecoxib if renal insufficiency (creatinine 1.4 mg/dL). (3) Acetaminophen 975 mg every 8 h (PO). (4) Oxycodone HCl extended release 10 mg every 12 h 3 doses (PO), hold for age 80 y. (5) Oxycodone 5 mg every 3 h (PO), as needed for moderate pain. (6) Oxycodone 10 mg every 3 h (PO), as needed for severe pain. (7) Hydromorphone 0.4 mg every 3 h (IV), as needed for breakthrough. IV, intravenous; PO, oral.
A.R. Berg et al. / The Journal of Arthroplasty 34 (2019) S159eS163 Table 3 Demographic Variables Between the 2 Cohorts.
Table 5 Combined Cohort Primary and Secondary Outcomes.
Variable
Scopolamine Arm (N ¼ 369)
Control Arm (N ¼ 716)
Age (y) Gender (%) F M BMI (kg/m2) ASA Procedure TKA THA Diagnosis OA Other Anesthesia type Spinal GA
63.9 ± 10.1
65.1 ± 10.22
228 (61.8%) 141 (38.2%) 30.3 ± 14.4 2.2 ± 0.52
473 (66.1%) 243 (35.9%) 29.1 ± 8.6 2.23 ± 0.6
164 (44.4%) 205 (55.6%)
504 (70.4%) 212 (29.6%)
<.0001
339 (91.9%) 30 (8.1%)
664 (92.7%) 52 (7.3%)
.61
315 (85.4%) 54 (14.6%)
618 (86.3%) 98 (13.7%)
.67
P Value .066
.16 .15 .075
ASA, American Society of Anesthesiologists; BMI, body mass index; F, female; GA, general anesthesia; M, male; OA, osteoarthritis; TKA, total knee arthroplasty; THA, total hip arthroplasty.
POD 0 (Table 4). Of the patients who experienced PONV, the majority had only 1 episode of PONV throughout the entire hospital stay. The percentage of patients who experienced more than 1 episode of PONV was significantly lower in the scopolamine group compared to the control group (7.5% vs 17.1%, P < .0001). In addition, patients who were given scopolamine had a significantly shorter LOS (2.3 days vs 2.8 days, P < .0001), were more likely to be discharged home (84% vs 64%, P < .0001), had lower VAS pain scores on POD 0 through 2 (P < .0034), and were able to walk further distances on POD 0 through 3 (P < .0006; Table 5). The scopolamine group received greater ME on POD 0, but fewer ME when compared to the control group on POD 1 and POD 2 (P < .00072; Table 5). TKA Cohort The incidence of PONV was significantly lower in the scopolamine (study) group compared to the control group (12.8% vs 29.8%, P < .0001), throughout the hospital stay (Table 6). In addition, patients who were given scopolamine also had a significantly shorter LOS (2.5 days vs 2.9 days, P ¼ .0024), were more likely to be discharged home (86.6% vs 57.03%, P < .0001), had lower VAS pain scores on POD 1 through 3 (P < .035), were able to walk further distances on POD 1 through 3 (P < .0075), and received fewer ME when compared to the control group on POD 1 and POD 2 (P < .036; Table 4 Combined Cohort Postoperative Nausea and Vomiting. Variable PONV Yes No PONV Yes No PONV Yes No PONV Yes No PONV Yes No
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Scopolamine THA (N ¼ 369)
Control THA (N ¼ 716)
P Value
26 (7.0%) 343 (93.0%)
51 (7.1%) 665 (92.9%)
17 (4.6%) 352 (95.4%)
98 (13.7%) 618 (86.3%)
<.0001
3 (0.8%) 366 (99.2%)
41 (5.7%) 675 (94.3%)
.0001
2 (0.5%) 367 (99.5%)
22 (3.1%) 694 (96.9%)
.0073
53 (14.4%) 316 (83.6%)
210 (29.3%) 506 (70.7%)
<.0001
(POD 0)
Variable PONV Yes No LOS (d) Discharge disposition Home Outside institution VAS pain scores POD 0 POD 1 POD 2 POD 3 Feet walked on PT POD 0 POD 1 POD 2 POD 3 ME (mg) POD 0 POD 1 POD 2 POD 3 ME/LOS
Scopolamine Arm (N ¼ 369)
Control Arm (N ¼ 716)
53 (14.4%) 316 (83.6%) 2.3 ± 1.2
210 (29.3%) 506 (70.7%) 2.81 ± 1.3
<.0001 <.0001
310 (84.01%) 59 (15.99%)
458 (63.9%) 258 (36.1%)
<.0001
3.1 3.1 3.3 3.0
± ± ± ±
2.8 2.5 2.7 2.7
117.3 384.3 332.6 216.4
± ± ± ±
118.6 321.7 253.8 201.6
58.8 66.6 30.1 47.4 69.8
± ± ± ± ±
28.3 43.5 39.8 48.6 54.1
P Value
3.73 3.61 3.83 3.7
± ± ± ±
2.6 2.4 2.3 2.4
80.54 254.54 256.0 131.0
± ± ± ±
92.2 263.4 241.2 117.2
.00065 <.0001 <.0001 <.0001
45.4 75.4 49.7 42.1 64.3
± ± ± ± ±
28.9 53.5 40.2 32.5 41.5
<.0001 .00072 <.0001 .26 .0651
.0022 .00335 .00344 .06
LOS, length of stay; ME, morphine equivalents; PONV, postoperative nausea and vomiting; POD, postoperative day; PT, physical therapy; VAS, Visual Analog Scale.
Table 6). In the TKA cohort, patients in the scopolamine group received greater ME than the control group on POD 0. THA Cohort The incidence of PONV was significantly lower in the scopolamine (study) group compared to the control group (15.6% vs 28.0%, P ¼ .0029), throughout the hospital stay (Table 7). In addition, patients who were given scopolamine also had a significantly shorter LOS (2.1 days vs 3.6 days, P ¼ .0028), were more likely to be discharged home (91.2% vs 80.6%, P ¼ .0012), had lower VAS pain scores on POD 0, P ¼ .045), were able to walk further distances on POD 1 through 2 (P < .047), and received fewer ME when compared to the control group on POD 2, P ¼ .0022; Table 7). In the THA cohort, patients in the scopolamine group received greater ME than the control group on POD 0. There were no statistically significant differences between the 2 groups with regard to adverse events such as urinary retention, dizziness, syncope, or itchiness. The scopolamine (study) group had a significantly lower rate of constipation compared to the control group (0.8% vs 3.1%, P ¼ .02). There were no readmissions due to narrow-angle glaucoma for either group. On multivariate analysis, there was a statistically significant difference in physical therapy performance based on PONV, F (5, 289) ¼ 4.295, P ¼ .001; Wilk's L ¼ 0.931, partial h2 ¼ .069.
.96
(POD 1)
Discussion
(POD 2)
(POD 3)
(total)
THA, total hip arthroplasty; PONV, postoperative nausea and vomiting; POD, postoperative day.
Management of pain following TJA is an important component of the procedure, as adequate pain control allows faster rehabilitation and reduces the risk of complications [6,7]. Pain control is often managed via a multimodal approach, which includes the use of opioids. Although very effective as analgesics, opioids are associated with a high incidence of PONV [3e5]. PONV is a challenging and frequent condition with an overall incidence of 20%-30% [1], with more than 1 million total joint arthroplasties performed each year, which amounts to more than 200,000-300,000 cases of inhospital PONV attributable to TJA annually [18]. PONV can complicate recovery from surgery. It
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Table 6 TKA Cohort Primary and Secondary Outcome Measures. Variable PONV Yes No LOS (d) Discharge disposition Home Outside institution VAS pain scores POD 0 POD 1 POD 2 POD 3 Feet walked on PT POD 0 POD 1 POD 2 POD 3 ME (mg) POD 0 POD 1 POD 2 POD 3 ME/LOS
Scopolamine TKA (N ¼ 164)
Control TKA (N ¼ 507)
21 (12.8%) 143 (87.2%) 2.5 ± 1.2
151 (29.8%) 356 (70.2%) 2.9 ± 1.3
<.0001 .0024
142 (86.6%) 22 (13.4%)
288 (57.03%) 217 (42.97%)
<.0001
3.3 3.1 3.4 2.8
± ± ± ±
3.0 2.5 2.8 2.6
3.8 3.7 4.04 3.7
± ± ± ±
2.4 2.3 2.1 2.3
79.5 340.9 310.7 244.5
± ± ± ±
84.2 344.5 233.6 209.9
72.5 226.1 244.4 131.8
± ± ± ±
76.6 252.9 236.7 118.8
55.8 69.9 36.7 42.3 69.5
± ± ± ± ±
27.05 35.3 35.8 30.6 31.1
46.6 80.1 50.8 39.8 64.0
± ± ± ± ±
30.3 58.3 41.7 32.8 39.5
P Value
.086 .0028 .024 .035 .64 <.0001 .0075 <.0001 .00043 .036 .00023 .75 .105
TKA, total knee arthroplasty; PONV, postoperative nausea and vomiting; LOS, length of stay; VAS, Visual Analog Scale; POD, postoperative day; PT, physical therapy; ME, morphine equivalents.
can prevent early mobilization, delaying rehabilitation and discharge and increasing the risk of venous thromboembolism and other serious complications [6,7]. We therefore sought to determine whether scopolamine, an antimuscarinic agent that acts on the central nervous system and blocks transmissions to the vomiting center, is effective in reducing the number of episodes of PONV after TJA. We found that patients undergoing THA and TKA who received transdermal scopolamine had a lower incidence of PONV compared to those who did not receive scopolamine. They also had a shorter LOS, were more likely to be discharged home, had better functional outcomes, such as
Table 7 THA Cohort Primary and Secondary Outcome Measures. Variable PONV Yes No LOS (d) Discharge disposition Home Outside institution VAS pain scores POD 0 POD 1 POD 2 POD 3 Feet walked on PT POD 0 POD 1 POD 2 POD 3 ME (mg) POD 0 POD 1 POD 2 POD 3 ME/LOS
Scopolamine THA (N ¼ 205)
Control THA (N ¼ 211)
32 (15.6%) 173 (84.4%) 2.1 ± 1.1
59 (28.0%) 152 (72.0%) 3.6 ± 1.3
.0029 .0028
187 (91.2%) 18 (8.8%)
170 (80.6%) 41 (19.4)
.0012
3.0 3.1 3.0 3.2
± ± ± ±
2.6 2.5 2.6 2.8
135.4 421.3 357.6 179.7
± ± ± ±
128.4 296.9 274.02 186.6
57.8 59.3 32.8 44.1 71.8
± ± ± ± ±
31.04 40.13 35.8 33.5 66.2
P Value
3.6 3.2 3.2 3.0
± ± ± ±
2.8 2.5 2.7 2.9
.045 .82 .61 .8
92.0 325.4 290.02 171.5
± ± ± ±
110.2 276.1 254.2 104.0
.011 .0011 .047 .79
45.2 63.7 46.3 52.3 65.1
± ± ± ± ±
29.0 37.4 35.3 28.9 48.0
.000032 .26 .0022 .26 .25
LOS, length of stay; ME, morphine equivalents; THA, total hip arthroplasty; PONV, postoperative nausea and vomiting; POD, postoperative day; PT, physical therapy; VAS, Visual Analog Scale.
lower VAS pain scores, were able to walk further distances with physical therapy, and received fewer ME compared to the control group after POD 0. There were no statistically significant differences in adverse events, other than a higher rate of constipation in the control group. This result is likely due to the increased narcotic consumption in this cohort. Importantly, there were no readmissions for narrowangle glaucoma, which has been reported in the literature as a possible side effect of transdermal scopolamine [19]. This study reports close to a 50% reduction in the incidence of PONV with the use of transdermal scopolamine. In addition to the functional and psychological toll PONV can have on a patient, there are also associated costs of additional supplies and hospital services [20]. Our study also suggests a decrease in LOS for those patients who received transdermal scopolamine, which secondarily reflects meeting discharge requirements earlier, including pain control and functional milestones. The reduction in ME after POD 0 highlights the role PONV plays in postoperative pain control. With less PONV, patients can tolerate effective narcotic pain medication on the day of surgery, achieving better pain control and gaining early confidence in their new joint. In other words, the increased ME consumed by scopolamine group patients on POD 0 may be due to the ability to consume more narcotics that accompanies decreased nausea/vomiting. Thereafter, with less PONV, patients may be better able to tolerate multimodal per os medications, requiring less frequent usage of stronger parenteral narcotic medications. Transdermal scopolamine is effective for the first 48-72 hours, which correlates with our finding of significantly fewer ME consumed on POD 1 and 2 in the scopolamine group. There was no statistically significant difference between the 2 groups with regard to ME consumed on POD 3. Nevertheless, there were statistically fewer incidents of PONV in the scopolamine group, leading us to believe that ME consumed is not the main contributor to PONV. There have been a number of studies that assessed the efficacy of transdermal scopolamine in reducing PONV in certain patient populations. Kotelko et al studied 203 healthy patients undergoing elective cesarean section and receiving epidural morphine for postoperative analgesia plus either transdermal scopolamine or placebo. They reported a significant reduction in nausea, vomiting, and retching and a decreased requirement of antiemetic rescue medications in those patients who received scopolamine in the study period of 2-10 h after surgery [15]. Harnett et al carried out a similar study comparing the efficacy of transdermal scopolamine, intravenous ondansetron, and placebo during the first 24 h postoperatively in women undergoing cesarean section. They showed that scopolamine was significantly superior to ondansetron or placebo in preventing PONV [16]. Similar studies have been performed in other surgical areas and in combination with other antiemetics. Einarsson et al showed a significant reduction in the incidence and severity of PONV in the first 24 h after gynecologic laparoscopic surgery in patients who received transdermal scopolamine, and Sah et al revealed similar efficacy of transdermal scopolamine plus ondansetron versus placebo patch plus ondansetron on the incidence of PONV in 126 patients undergoing plastic surgery [21,22]. Studies showing the efficacy of transdermal scopolamine in preventing PONV in orthopedic surgery procedures are limited. A prospective blinded study by Lee et al [23] concluded that combined use of transdermal scopolamine and dexamethasone in patients undergoing major orthopedic surgery using patient-controlled analgesia was more effective in preventing PONV compared with dexamethasone alone or dexamethasone plus ramosetron. However, there were several limitations with this study, including the lack of a control group that did not receive any prophylaxis and a 24-h limit on patient evaluation postoperatively. To our knowledge, this is the
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first study to determine the efficacy of transdermal scopolamine in preventing PONV in patients undergoing TJA. The primary limitation of this study is that it is a retrospective review of prospectively collected data. Along with this are all the inherent biases of a retrospective cohort study, including lack of randomization and blinding. The retrospective design allowed us to analyze a large number of patients. Additionally, this study reviewed data from operations performed over the span of 3 years. Although there was no material change in surgical technique, patient education, or rehab protocols over the study period, it is possible that global evolution of TJA management in the era of bundles affected LOS results and discharge to home. However, these macro changes would not be expected to alter PONV, VAS pain scores, or narcotic requirements. Conclusions As the annual number of TJA procedures continues to rise, with rapid recovery, outpatient procedures, and transition from hospital environments to home, PONV will be a major bottleneck to optimizing the postoperative experience. Reducing rates of PONV in these patients can lead to significant postoperative functional benefits, as well as patient satisfaction. In this study, we report a significant reduction in PONV with the use of transdermal scopolamine in patients undergoing TJA. These data support the use of transdermal scopolamine as part of a multimodal, perioperative pain protocol in patients undergoing TJA. References [1] Gan TJ, Diemusch P, Habib AS, Kovac A, Kranke P, Meyer TA, et al. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg 2014;118:85e113. [2] Gan TJ. Postoperative nausea and vomiting: can it be eliminated? JAMA 2002;287:1233e6. [3] Song JW, Park EY, Lee JG, Park YS, Kang BC, Shim YH. The effect of combining dexamethasone with ondansetron for nausea and vomiting associated with fentanylbased intravenous patient-controlled analgesia. Anaesthesia 2011;66:263e7. [4] Ishikawa Y, Imashuku Y, Kitagawa H, Kawamoto S, Yuasa M, Nosaka S. [Evaluation of the side effects of intravenous patient controlled analgesia after spine surgery]. Masui 2011;60:920e3. r MR, Walder B. Efficacy and adverse effects of prophylactic antiemetics [5] Trame during patient-controlled analgesia therapy: a quantitative systematic review. Anesth Analg 1999;88:1354e61.
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