Takeaways
Question : How can we further reduce opioid prescriptions in outpatient abdominoplasty patients?
Findings : We performed a retrospective chart review comparing two different methods for pain control in 80 consecutive outpatient abdominoplasty patients. The multimodal approach to perioperative pain management reduced the morphine milligram equivalents prescribed and led to fewer refills overall while providing better overall pain control.
Meaning : Multimodal perioperative pain control should be considered the standard of care for all outpatient cosmetic surgery cases, including abdominoplasty.
INTRODUCTION
Consistent with national statistics, 6%–9% of opioid naive body-contouring patients develop persistent narcotic use after their surgery.1 2 3 4 5 , 6
Our narcotic prescribing patterns shoulder a significant portion of the blame for the opioid epidemic. Rose et al7 8 9 10
Advancements in patient comfort while accomplishing a reduction in opiate use through use of multimodal methods have been documented for inpatient, reconstructive surgery patients.11–15 16–24
PATIENTS AND METHODS
Institutional review board approval was obtained from the University of Utah Health Science Center (IRB no: 00130783) for a retrospective review of the senior author’s surgical database. From October 2017 to September 2018, 42 patients underwent abdominoplasty by the senior author (R.H.F) at a single clinical location. From October 2018 to September 2019, 38 patients underwent abdominoplasty by the same surgeon at the identical location, using the newly implemented, multimodal approach to managing pain.
The only qualifying criterion for inclusion was that the patient underwent a full abdominoplasty (defined as plication of anterior rectus sheath), and no patients were excluded. We reviewed patient charts and created a database using morphine milligram equivalents (MMEs) to standardize the amount of narcotic each patient received.25
The surgical technique for abdominoplasty remained constant during the retrospective review and was performed under general anesthesia. All abdominoplasties included a multilayered plication of the anterior rectus sheath, progressive tension sutures, and usually included liposuction of the flanks. Most patients underwent additional procedures concomitantly that most frequently included breast procedures. Patients who underwent belt or fleur de lis techniques were also regarded as having undergone additional procedures.
Medical histories were reviewed to determine whether the patient was opioid naive and to record any prescription medications that patients were taking. We collected demographic information and data relating to the surgical and recovery room times and intravenous MMEs, prescribed oral MMEs, number of refills, and whether the patient did not use any oral opiates postoperatively. Because this was a retrospective review, patients did not track their pain or nausea levels.
Control Group
Medical management of the initial group included prescribing 40 Percocet 7.5/325 mg tablets (450 MMEs total). Patients were instructed to take the medication as needed, up to two tablets every 4 hours. Some patients required higher narcotic doses to achieve adequate pain control and, in those cases, either generic oxycodone or hydromorphone was prescribed and cautiously titrated to achieve adequate comfort, and refills of narcotics were given if requested. Promethazine was prescribed as an antiemetic. Nonopioid oral analgesics (cyclobenzaprine, celecoxib, and/or gabapentin) were not given to any of these patients preemptively but were selectively used postoperatively as needed to augment the pain control provided by the narcotic. Patients in this initial group were offered a Marcaine pump or liposomal bupivacaine for an additional fee to help improve their pain control, but only three patients opted to use these resources. All other patients most often cited expense as the reason why they chose not to use these local anesthesia delivery options. Patients in the treatment group were not given the option for a Marcaine pump or liposomal bupivacaine because all patients automatically received the liposomal bupivacaine.
Treatment Group
Initiation of the multimodal pain control protocol included the use of preoperative and postoperative multimodal medications (Table 1 ). All patients were instructed to place the scopolamine patch behind their ear the night before surgery and to take acetaminophen (500 mg), celecoxib 200 mg, and gabapentin 300 mg 2 hours before surgery with a small sip of water. If patients were not compliant with this combination of medications when they arrived at the surgery center, the appropriate medications were administered before surgery. Postoperatively, patients were given instruction how to select and use these medications to optimize their pain control (Fig. 1 ).
Table 1. -
Medications Used by Each Cohort
Control
Multimodal Analgesia
Percocet 7.5/325 #40 (450 MMEs); 1–2 orally q 6 h prn
Oxycodone 5 mg #42 (315 MMEs); 0.5–2 tablets orally q 6 h prn
Cefadroxil 500 mg #28; 1 orally twice daily
Cefadroxil 500 mg #28; 1 orally twice daily
Promethazine 25 mg #30; 1 orally q 6 h prn
Ondansetron ODT 4 mg #15; 1 sublingually q 6 h prn
* Enoxaparin 40 mg #7; 1 subcutaneously daily
* Enoxaparin 40 mg #7; 1 subcutaneously daily
* Celecoxib 200 mg #20; 1 orally twice daily
* Gabapentin 300 mg #30; 1 orally three times daily prn
* Scopolamine 1 mg patch: one behind ear before surgery
* Acetaminophen 500 mg; 1 orally q 4 h
Over the counter omeprazole or famotidine; follow package instructions
* Administered before surgery.
Fig. 1.: Multimodal analgesia patient instructions.
All patients in the multimodal group received subfascial field blocks with liposomal bupivacaine (20 ml) mixed with 0.25% Marcaine (up to a maximum of 50 ml) and diluted in 200 ml of normal saline. If liposuction was performed to the flanks in addition to the abdominoplasty, then 0.25% Marcaine (up to a maximum of 50 ml) was used in the tumescent fluid (instead of the typical lidocaine tumescent) and 200 ml of this Marcaine tumescence was saved to dilute the liposomal bupivacaine. In this situation, the total amount of Marcaine used for the field block of the anterior abdominal wall constituted 20% of the total free Marcaine dose that the patient received during the surgery. The maximum dose of free Marcaine (2.5 mg/kg) was not exceeded in any patient. Narcotic refills were given if requested.
A single patient in the control group had a minor wound healing complication at the inverted-T junction of the abdominoplasty incision (fleur de lis technique) that was treated for several weeks with Iodoform packing until completely healed. One patient in the multimodal group required reoperation for evacuation of a stable, supraumbilical hematoma 1 week after her initial surgery. We believe the hematoma was a random occurrence of a well-recognized complication of abdominoplasty and was not related to the subfascial field block or any component of the multimodal analgesia regimen. No other complications were identified in the two groups during the minimum 3-month follow-up. All patients in both groups were discharged from the recovery room and none were admitted to short stay or other recovery centers. All patients were treated on a purely outpatient basis.
We analyzed the outcomes of total MMEs given intravenously, and MMEs prescribed. We did not estimate partial prescription use, but rather assumed 100% usage of each prescription unless the patient stated specifically that they took none, in which case the MMEs were recorded as zero. Additional outcomes evaluated were the number of patients getting narcotic refills and patients who took no oral opiates during their recovery.
STATISTICAL ANALYSIS
Demographic data were summarized and compared between the two treatment cohorts using independent samples t tests. Levene’s test for equality of variance was used to check for equal variances between the two treatment cohorts for intravenous MMEs received in the operating room, intravenous MMEs received in recovery room, and MMEs prescribed postoperatively. Appropriate independent samples t tests were used to test for differences in the mean MMEs between the two treatment cohorts based on the results of Levene’s tests. Fisher exact tests were used to test for differences between the two treatment cohorts in the number of refills written and the number of patients who received no oral narcotics. We used a Bonferroni corrected alpha value of α = 0.01 to adjust for the multiple hypothesis tests conducted on all our outcome variables to decrease the possibility of a type I error. Analyses were done using Microsoft Excel and PSPP statistical analysis software.
RESULTS
Eighty consecutive abdominoplasty patients were identified through retrospective review of the senior author’s surgical database; 42 were evaluated as controls and 38 as the multimodal analgesia cohort. The cohorts were very similar in almost all categories (Table 2 ). Age was the only statistically significant demographic data that was different with mean age of the control 37 years versus 42 for treatment (P = 0.002). Although age heterogeneity was different between the two groups, age was not used as an inclusion criterion, and age was not used to guide subsequent treatment of the patients’ perception of pain. Gender, BMI, naivete to narcotics, use of selective norepinephrine reuptake inhibitor (SNRI) or selective serotonin reuptake inhibitor (SSRIs), the number of additional surgical procedures performed simultaneously, operative time, and time to discharge from recovery room were insignificant in our analysis (P > 0.01).
Table 2. -
Cohort Comparison
Control
Multimodal Analgesia
P
Sex
Female
41
97.6%
38
97.4%
0.958
Male
1
2.4%
1
2.6%
—
Age, y
Mean age
37.3
42.6
0.002
≤25
1
2.4%
0
0.0%
—
26–35
18
42.9%
5
12.8%
0.002
36–45
20
47.6%
23
59.0%
0.312
46–55
2
4.8%
7
17.9%
0.060
>55
1
2.4%
4
10.3%
0.145
Body mass index
≤20
4
9.5%
2
5.1%
0.457
21–25
25
59.5%
20
51.3%
0.462
26–30
13
31.0%
16
41.0%
0.351
>30
0
0.0%
1
2.6%
—
Opiate naive
Yes
42
100.0%
38
97.4%
0.302
No
0
0.0%
1
2.6%
—
SSRI/antidepressant
Yes
8
19.0%
9
23.1%
0.661
No
34
81.0%
30
76.9%
0.661
Procedure
Abdominoplasty ± flank liposuction
13
30.2%
14
35.9%
0.642
Abdominoplasty plus breast procedure
24
55.8%
22
56.4%
0.948
Belt abdominoplasty
4*
9.3%
0
0.0%
0.488
Fleur de lis abdominoplasty
2*
4.7%
2
5.1%
0.940
Abdominoplasty plus rhinoplasty
0
0.0%
1
2.6%
0.302
Average time (h:min)
Operating room
5:41
6:24
0.082
Recovery room
1:27
1:21
0.442
* One case included both fleur de lis and belt abdominoplasties
SSRI, selective serotonin reuptake inhibitor.
Intravenous MMEs received in the operating room and in the recovery room were evaluated independently. Although the amount of intravenous narcotic received in the operating room (25.15 versus 22.78 mean MMEs; P = 0.365) and recovery room (2.83 versus 1.64 mean MMEs; P = 0.104) decreased in the multimodal analgesia group, neither achieved statistical significance (Table 3 ). After discharge to home, the mean oral MMEs decreased by two-thirds from 787.08 to 251.45 (p < 0.001). Likewise, the number of patients receiving refills declined dramatically (p < 0.001). Thirty of the 42 patients in the control group received a total of 36 refills while four of the 38 multimodal patients each received one refill. Our analysis of this outcome did not consider that the control group received 450 MMEs with their initial prescription compared to 315 for the multimodal arm, already a 30% reduction in baseline narcotic equivalents. Inclusion of this information could only increase the significance of our findings. The number of patients who did not use oral narcotics during their recovery increased from one (2%) to 10 (26%; P = 0.002). The three patients in the control group who elected for either Marcaine pumps or liposomal bupivacaine (but did not receive the other multimodal medications) showed no decrease in narcotic use; all three received a refill of their opiate prescription.
Table 3. -
Multimodal Analgesia Effect on Narcotic Usage
Control
Multimodal Analgesia
P
Operating room intravenous narcotics
Mean MME
25.2
22.1
0.365
Recovery room intravenous narcotics
Mean MME
2.6
1.4
0.104
Outpatient oral narcotics
Mean MME
787.1
265.3
<0.001
Total number of narcotic refills
36
4
<0.001
No narcotic consumed
1
2.4%
10
26.3%
0.002
DISCUSSION
Despite encouragement in the literature to adopt multimodal approaches for postoperative pain control in ambulatory aesthetic surgery, there are few reports of successful transition away from opiates.19 , 24 , 26
Although we did not track pain scores in this retrospective study, we analyzed the number of refill requests and the number of people not consuming any oral narcotics as indirect measures of patient comfort. These indirect measurements both indicated statistically meaningful improvement in pain control. Despite using significantly less narcotics, the patients appeared to be considerably more comfortable.
We did not track the actual MMEs consumed but rather assumed 100% consumption of each prescription unless the patient indicated that no pills were used. Many patients in the multimodal arm indicated they only used “a few” of the narcotic pills; despite these statements, we considered their consumption as 100%. Interestingly, the control group was prescribed 40 pills, and the treatment group received 42. Since the total number of pills prescribed has the strongest association with the number of pills patients reported using according to Howard et al, the treatment group should have been inclined to use more narcotics, but they were not.8
These results indicating a decrease in the opiates necessary to maintain comfort simply underscore the necessity for changes in our prescribing patterns because surgeons in the United States overprescribe.27 , 28 29
A major tenet of the multimodal approach is using medications from several different classes to minimize exposure to harmful side effects. One can assume that if our treatment group consumed less narcotics, then they experienced fewer complications related to opiate-induced nausea, constipation, pruritis, and others. The safety and efficacy of combining these elements of this multimodal strategy have, however, been well documented in other reports.15 , 22 , 23 , 30–38
Some may refer to this multimodal strategy with the historically pejorative term “polypharmacy” or claim that it is too confusing for patients to follow accurately. Perhaps, we should reconsider our bias against polypharmacy in specific situations—especially those where it is not intended for long-term management of a condition, but rather short-term treatment of acute pain. We also need to give our patients and their caregivers some credit for being able to follow written instructions. If the instructions are not followed, then perchance it may be our inability to describe our intentions accurately and simply enough.
Cost must also be considered when analyzing any treatment recommendations to ensure the benefits outweigh the cost. One may argue on face value that preventing a single patient from developing opioid use disorder or avoiding a single narcotic overdose is worth the increased cost. One must also weigh the economic burden to society of $1 trillion/year that is a direct result of our failure to curb or resolve this epidemic.39 , 40 41
The timing of pharmacological intervention continues to generate some controversy with mixed reports regarding efficacy of preoperative dosing.26 , 42–45 14 , 18 , 19 , 24 , 26 , 31 , 32 , 35 , 44 , 46–49
While the mean intravenous MMEs in the operating room and recovery room both decreased in the multimodal group, and the recovery room time was shortened by 7%, none of them achieved significance (P = 0.365, P = 0.104, and P = 0.442, respectively). Failure to achieve significance in our review could be caused in part by the healthcare providers’ usual methods and procedures in dosing narcotics. Another potential confounding factor for the insignificant shortening of recovery time in our review is that the criteria for discharge to home are different than those for admission to the hospital. The documented decrease in operating room and recovery room opiates and the shortening of recovery time are hard to dispute in many inpatient, reconstructive procedures.11–15
It is important to note that all patients in our retrospective review received narcotics intravenously in the operating room even if they chose not to use any oral opiates postoperatively. This may seem insignificant, but there is a chance that by routinely administering narcotics as an essential component of general anesthesia in the absence of objective evidence that the patient is aware of painful stimulus, we could be increasing our patients’ perception of pain once they become conscious. This is known as opioid-induced hyperalgesia and, although a potentially controversial subject, warrants further investigation.50–56
We are gaining a better understanding of the physiology, and pathophysiology, of pain and recognize that the better and earlier that we intervene in managing acute pain decreases the incidence of chronic pain.57 , 58
CONCLUSIONS
This study evaluated the effectiveness of transitioning away from largely opiate-dependent postoperative recovery regimens toward a multimodal perioperative approach in outpatient abdominoplasty patients. Significantly less opioids are necessary when optimizing nonnarcotic medications, and some of our outcomes point toward even higher patient comfort levels. When patients have only one narcotic pain pill to manage their pain, they are likely to take that pill when their subjective pain score is a two or a nine. When patients have multiple different pills to treat their pain, a multimodal analgesia regimen allows sufficient relief of pain using different medications, and narcotics are used only for breakthrough pain. Future prospective evaluations of different multimodal combinations are necessary to further optimize narcotic-sparing protocols in outpatient plastic surgery.
ACKNOWLEDGMENT
The authors thank Lacey Gunter, MS, PhD (Gunter Statistical Consulting) for her assistance with statistical analysis.
REFERENCES
1. Bennett KG, Kelley BP, Vick AD, et al. Persistent opioid use and high-risk prescribing in body contouring patients. Plast Reconstr Surg. 2019;143:87–96.
2. Crystal DT, Blankensteijn LL, Ibrahim AMS, et al. Quantifying the crisis: opioid-related adverse events in outpatient ambulatory plastic surgery. Plast Reconstr Surg. 2020;145:687–695.
3. Gan TJ, Habib AS, Miller TE, et al. Incidence, patient satisfaction, and perceptions of post-surgical pain: results from a US national survey. Curr Med Res Opin. 2014;30:149–160.
4. Apfelbaum JL, Chen C, Mehta SS, et al. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003;97:534–540.
5. O’Brien AL, Krasniak PJ, Schroeder MJ, et al. Impact of opioid restriction legislation on prescribing practices for outpatient plastic and reconstructive surgery. Plast Reconstr Surg. 2022;150:213–221.
6. Slater RR, Beverley L. The opioid epidemic in America: pandemic impacts. J Am Acad Orthop Surg. 2022;30:e1302–e1310.
7. Rose KR, Christie BM, Block LM, et al. Opioid prescribing and consumption patterns following outpatient plastic surgery procedures. Plast Reconstr Surg. 2019;143:929–938.
8. Howard R, Fry B, Gunaseelan V, et al. Association of opioid prescribing with opioid consumption after surgery in Michigan. JAMA Surg. 2019;154:e184234.
9. Bucknor A, Egeler SA, Chen AD, et al. National mortality rates after outpatient cosmetic surgery and low rates of perioperative deep vein thrombosis screening and prophylaxis. Plast Reconstr Surg. 2018;142:90–98.
10. Battista NA, Pearcy LB, Strickland WC. Modeling the prescription opioid epidemic. Bull Math Biol. 2019;81:2258–2289.
11. Ochoa O, Rajan M, Garza R, et al. Enhanced recovery pathway reduces hospital stay and opioid use in microsurgical breast reconstruction: a single center, private practice experience. Plast Reconstr Surg. 2022;150:13–21e.
12. Colvin J, Rosen M, Prabhu A, et al. Enhanced recovery after surgery pathway for patients undergoing abdominal wall reconstruction. Surgery. 2019;166:849–853.
13. Orenstein SB, Martindale RG. Enhanced recovery pathway for complex abdominal wall reconstruction. Plast Reconstr Surg. 2018;142(3 suppl):133S–141S.
14. Khansa I, Koogler A, Richards J, et al. Pain management in abdominal wall reconstruction. Plast Reconstr Surg Glob Open. 2017;5:e1400–e1400.
15. Temple-Oberle C, Shea-Budgell MA, Tan M, et al.; ERAS Society. Consensus review of optimal perioperative care in breast reconstruction: Enhanced Recovery after Surgery (ERAS) Society recommendations. Plast Reconstr Surg. 2017;139:1056e–1071e.
16. Shestak KC, Rios L, Pollock TA, et al. Evidenced-based approach to abdominoplasty update. Aesthet Surg J. 2019;39:628–642.
17. Harrison B, Khansa I, Janis JE. Evidence-based strategies to reduce postoperative complications in plastic surgery. Plast Reconstr Surg. 2016;137:351–360.
18. Murphy AM, Haykal S, Lalonde DH, et al. Contemporary approaches to postoperative pain management. Plast Reconstr Surg. 2019;144:1080e–1094e.
19. Bartlett EL, Zavlin D, Friedman JD, et al. Enhanced recovery after surgery: the plastic surgery paradigm shift. Aesthet Surg J. 2018;38:676–685.
20. Demsey D, Carr NJ, Clarke H, et al. Managing opioid addiction risk in plastic surgery during the perioperative period. Plast Reconstr Surg. 2017;140:613e–619e.
21. Nahai F. The opioid crisis: what must aesthetic surgeons do about it? Aesthet Surg J. 2019;39:924–926.
22. Constantine FC, Matarasso A. Putting it all together: recommendations for improving pain management in body contouring. Plast Reconstr Surg. 2014;134(4S-2 Current Concepts in Pain Management in Plastic Surgery):113S–119S.
23. Joshi GP. Putting it all together: recommendations for improving pain management in plastic surgical procedures. Plast Reconstr Surg. 2014;134(4S-2 Current Concepts in Pain Management in Plastic Surgery):94S–100S.
24. Nguyen T-HC, Lombana NF, Zavlin D, et al. Transition to nonopioid analgesia does not impair pain control after major aesthetic plastic surgery. Aesthet Surg J. 2018;38:1139–1144.
25. CMS CfMMS. Opioid oral morphine milligram equivalent (MME) conversion factors | guidance portal. Available at
https://www.hhs.gov/guidance/sites/default/files/hhs-guidance-documents/Opioid%20Morphine%20EQ%20Conversion%20Factors%20%28vFeb%202018%29.pdf . Accessed August 31, 2020.
26. Barker JC, DiBartola K, Wee C, et al. Preoperative multimodal analgesia decreases postanesthesia care unit narcotic use and pain scores in outpatient breast surgery. Plast Reconstr Surg. 2018;142:443e–450e.
27. Kaafarani HMA, Han K, El Moheb M, et al. Opioids after surgery in the United States versus the rest of the world: the International Patterns of Opioid Prescribing (iPOP) multicenter study. Ann Surg. 2020;272:879–886.
28. Chu JJ, Janis JE, Skoracki R, et al. Opioid overprescribing and procedure-specific opioid consumption patterns for plastic and reconstructive surgery patients. Plast Reconstr Surg. 2021;147:669e–679e.
29. Bell L. The global diversion of pharmaceutical drugs: opiate treatment and the diversion of pharmaceutical opiates: a clinician’s perspective. Addiction. 2010;105:1531–1537.
30. Sarac BA, Schoenbrunner AR, Brower KI, et al. Analysis of adverse effects of multimodal gabapentin in abdominal wall reconstruction. Plast Reconstr Surg. 2022;149:733–739.
31. Kaye A, Urman R, Rappaport Y, et al. Multimodal analgesia as an essential part of enhanced recovery protocols in the ambulatory settings. J Anaesthesiol Clin Pharmacol. 2019;35:40–45.
32. Barker JC, Joshi GP, Janis JE. Basics and best practices of multimodal pain management for the plastic surgeon. Plast Reconstr Surg Glob Open. 2020;8:e2833.
33. Gupta A, Jakobsson J. Acetaminophen, nonsteroidal anti-inflammatory drugs, and cyclooxygenase-2 selective inhibitors: an update. Plast Reconstr Surg. 2014;134(4S-2 Current Concepts in Pain Management in Plastic Surgery):24S–31S.
34. Parsa AA, Sprouse-Blum AS, Jackowe DJ, et al. Combined preoperative use of celecoxib and gabapentin in the management of postoperative pain. Aesthetic Plast Surg. 2009;33:98–103.
35. Dunkman WJMD, Manning MWMDP. Enhanced recovery after surgery and multimodal strategies for analgesia. Surg Clin North Am. 2018;98:1171–1184.
36. Lin SJ. Discussion: consensus review of optimal perioperative care in breast reconstruction: Enhanced Recovery after Surgery (ERAS) Society recommendations. Plast Reconstr Surg. 2017;139:1072e–1073e.
37. Services USDoHaH. Pain management best practices inter-agency task force report: updates, gaps, inconsistencies, and recommendations. 2022. Available at
https://www.hhs.gov/sites/default/files/pmtf-final-report-2019-05-23.pdf . Accessed August 24, 2022.
38. Argoff CE. Recent management advances in acute postoperative pain. Pain Pract. 2014;14:477–487.
39. Florence C, Luo F, Rice K. The economic burden of opioid use disorder and fatal opioid overdose in the United States, 2017. Drug Alcohol Depend. 2021;218:108350–108350.
40. Luo F, Li M, Florence C. State-level economic costs of opioid use disorder and fatal opioid overdose—United States, 2017. MMWR Morb Mortal Wkly Rep. 2021;70:541–546.
41. Pacira Pharmaceuticals I. Exparel healthcare professional website. Updated 2022. Available at
https://www.exparel.com/hcp/value/total-hip-arthroplasty . Accessed August 29, 2022.
42. Sun T, Sacan O, White PF, et al. Perioperative versus postoperative celecoxib on patient outcomes after major plastic surgery procedures. Anesth Analg. 2008;106:950–958.
43. Task-Force ASoA. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology. 2012;116:248–273.
44. Rosero EB, Joshi GP. Preemptive, preventive, multimodal analgesia: what do they really mean? Plast Reconstr Surg. 2014;134(4S-2 Current Concepts in Pain Management in Plastic Surgery):85S–93S.
45. Penprase BPRNCNEA, Brunetto EMSNC, Dahmani EMSNC, et al. The efficacy of preemptive analgesia for postoperative pain control: a systematic review of the literature. AORN J. 2015;101:94–105.e8.
46. Allen BFS, Jablonski PM, McEvoy MD, et al. Implementation of an Enhanced Recovery Protocol (ERP) is associated with an increase in the perioperative use of non-opioid multimodal analgesia for non-ERP patients. J Clin Anesth. 2020;62:109694–109694.
47. Beverly A, Kaye AD, Ljungqvist O, et al. Essential elements of multimodal analgesia in Enhanced Recovery After Surgery (ERAS) guidelines. Anesthesiol Clin. 2017;35:e115–e143.
48. Kehlet H. Multimodal approach to control postoperative pathophysiology and rehabilitation. Br J Anaesth. 1997;78:606–617.
49. Kehlet H, Wilmore DW. Multimodal strategies to improve surgical outcome. Am J Surg. 2002;183:630–641.
50. Chu LF, Angst MS, Clark D. Opioid-induced hyperalgesia in humans: molecular mechanisms and clinical considerations. Clin J Pain. 2008;24:479–496.
51. Weber L, Yeomans DC, Tzabazis A. Opioid-induced hyperalgesia in clinical anesthesia practice: what has remained from theoretical concepts and experimental studies? Curr Opin Anaesthesiol. 2017;30:458–465.
52. Colvin LA, Bull F, Hales TG. Perioperative opioid analgesia—when is enough too much? A review of opioid-induced tolerance and hyperalgesia. Lancet. 2019;393:1558–1568.
53. Edwards RR, Dolman AJ, Michna E, et al. Changes in pain sensitivity and pain modulation during oral opioid treatment: the impact of negative affect. Pain Med. 2016;17:1882–1891.
54. Kim SH, Stoicea N, Soghomonyan S, et al. Intraoperative use of remifentanil and opioid induced hyperalgesia/acute opioid tolerance: systematic review. Front Pharmacol. 2014;5:108–108.
55. Chia YY, Liu K, Wang JJ, et al. Intraoperative high dose fentanyl induces postoperative fentanyl tolerance. Can J Anaesth. 1999;46:872–877.
56. Angst MS, Clark JD. Opioid-induced hyperalgesia: a qualitative systematic review. Anesthesiology. 2006;104:570–587.
57. Lee GI, Neumeister MW. Pain: pathways and physiology. Clin Plast Surg. 2020;47:173–180.
58. Glare P, Aubrey KR, Myles PS. Transition from acute to chronic pain after surgery. Lancet. 2019;393:1537–1546.
