Unabridged Version of this White Paper [pdf]

Published 2021

Workgroup Members

Jennifer Robles, MD, MPH (Chair), Nitya E. Abraham, MD, Chad Brummett, MD, Benjamin Davies, MD, Veena Graff, MD, MS, Rajnish Gupta, MD, Vernon M. Pais, Jr., MD, MS, Kevan Sternberg, MD, Ruchika Talwar, MD

Overview

The current United States opioid epidemic originates from pharmaceutical overreach, regulatory oversight, large drops in manufacturing jobs, and a focus on pain scores rather than real clinical outcomes, resulting in a societal shift in physician overprescribing spanning several decades.

One component of this broad opioid use is surgeons relying primarily on opioids to treat post-procedural pain. With the rise of opioid addiction rates, in 2016 the Centers for Disease Control (CDC) released opioid prescribing guidelines for chronic pain. However, due to a lack of data, they only had one general recommendation for acute pain: “to prescribe the lowest effective dose…and no greater quantity than needed.”¹ Though the CDC suggested a duration of three days or less would usually be sufficient, a lack of clear acute pain guidance exacerbated variations in the treatment of post-surgical pain, even within institutions and for the same operations.^1,2,3

Our present, highly variable post-operative pain management strategies have created exposures to opioid medications for many, carrying a risk of dependence and addiction. Furthermore, these practices have created an easily accessible supply of opioids for diversion into the community. A study utilizing a national insurance claims dataset found an approximately 6% rate of persistent use in opioid-naive patients who were prescribed opioids after both major and minor surgery, including urologic surgery.⁴ A concordant rate of persistent use, approximately 6.2%, was found in a similar study of opioid-naive patients post-urologic surgery.⁵

Although surgeons have contributed to the opioid epidemic, the use of multimodal analgesia, prescription drug monitoring programs, and general awareness of increasing rates of opioid addiction have led to opioid prescribing stewardship practices. Furthermore, contemporary evidence-based practice statements may minimize variations in pain management strategies. Multiple studies have shown that opioid prescribing can be greatly reduced without changes in pain, satisfaction or refill requests. The goal of this white paper is to explore evidence and outline strategies for managing post-operative urologic pain with minimal to no opioid prescribing.

What Happens When Opioids Are Prescribed?

Opioid use is commonly associated with problematic side effects for patients. Development of nausea, vomiting, urinary retention, or constipation can be low severity discomforts with opioids.⁶ However, more severe complications such as sedation, respiratory depression, or ileus can become life-threatening. The incidence of respiratory depression after major surgery can be as high as 17% when opioids are prescribed.⁷ These opioid-related adverse effects can result in higher hospital costs, longer length of stay, and significant healthcare utilization.⁸ Patients with gastrointestinal events related to opioids had significantly increased hospitalizations, length of stay, emergency department visits, outpatient office visits, and prescription claims in the three months following opioid prescription resulting in thousands of dollars of additional healthcare costs per patient.^9,10,11

Over-prescription of opioids after surgery has a significant impact to the patient and society as a whole. Multiple studies show that regardless of surgical procedure most patients use significantly fewer opioid pills than were prescribed to them by their surgeons.^12-21 Surgeons often prescribe more pills “just in case” and to “avoid that phone call,” but end up prescribing two to five times more than needed.^13,14 For example, in the Orioles Initiative, 77% of prescribed postoperative opioids went unused after open and robotic radical prostatectomy.²² Many studies have shown that if opioids are prescribed, patients typically only use somewhere between four to ten tablets of opioid pills after surgery, especially when non-opioid pain medications such as acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) are utilized.^16,20,23-27 Additionally, it has been demonstrated that what patients take is directly correlated to how much pain medicine they are given rather than what they truly need, the so-called “portion size effect”. Howard et al. showed that for every additional pill prescribed after general surgery, pill use increased by 0.5.¹²

Ultimately some patients will continue taking opioids far past the recovery period - two studies have found that the rate of new persistent opioid use after urologic surgery in previously naïve patients is 6%.^5,28 A recent large population study found that there was persistent long term use (2%) even after minor urologic procedures where 83% of patients received “weaker” opioids like tramadol.²⁹ Unfortunately, even unused pills can be harmful. Leftover pills become a reservoir to the general population for accidental ingestion as well as opioid sharing, selling, and diversion.^14,30 Allen et al. found that pediatric admissions due to opioid overdose have tripled since 2000.³¹ Purposeful prescribing practices, education on appropriate use, and discussion of pill disposal plans can significantly reduce opioid use and increase the disposal of pills without significant aggravation of post-surgical pain. ³²

The majority (71%) of opioid substance use disorder patients receive their drugs through diversion of a legally prescribed opioid.¹⁸ The current increase in illicit opioid use is directly correlated to high levels of prescription opioids.³³ Eight out of ten heroin users report that they used and abused prescription opioids prior to transitioning to heroin.^19,34-36 Thus, by reducing the number of people initially exposed to opioids and reducing the amount of opioids patients are exposed to when they are needed, it is possible to reduce the number of people turning to long term opioid misuse and illicit opioid substance use.^37,33

Opioid Prescribing

Prescribing Recommendations Vary

Without evidence or guidelines about what to prescribe, historically there has been significant variation and excess prescribing of opioids for postoperative pain control after urologic surgery.^27,38,39 Opioid prescribing practices also vary by setting and provider characteristics. In a statewide analysis, there was 4.7 times more variation in opioid prescribing seen in teaching hospitals compared to non-teaching hospitals, after adjusting for hospital case mix.⁴⁰ Another study noted that the amount of opioids prescribed by advanced practice providers was 18% higher compared to physicians.⁴¹ The opposite was seen in a different study suggesting local culture impacts opioid prescription practices.²⁷

Reducing Opioid Prescribing

Managing Postoperative Pain Expectations Preoperatively

The first step in reducing excess opioid prescriptions is managing patient expectations of postoperative pain. A survey of 951 respondents in a pre-admission testing clinic found that the average acceptable postoperative pain score was 4.1 on a scale of zero to ten.⁴² It is critical to communicate to patients that the goal is to reach a functional pain level for recovery, not zero pain. In one study, preoperative education on the benefits of “natural narcotics” (i.e. endorphins), the side effects of opioids, and the option of non-opioid analgesics led to 90% of patients declining an opioid prescription. Furthermore, pain scores were higher and longer in duration in the control group that did not receive preoperative education.43 Similarly, the provision of preoperative counseling regarding postoperative pain expectations resulted in a reduction in time to opioid cessation.⁴⁴

Intraoperative and Postoperative (Inpatient) Non-Opioid Analgesia Can Reduce Postoperative Pain Needs

Intraoperative measures may decrease postoperative pain and medication requirements. Pre-emptive analgesia is the administration of analgesics prior to noxious stimuli (i.e., surgery), to avoid central sensitization or upregulation of pain centers after tissue injury.⁴⁵ Local blocks like a dorsal penile nerve block prior to penile prosthesis placement can reduce pain in the early postoperative period.⁴⁶ Transversus abdominis plane (TAP) block involves injecting local anesthetic between the internal oblique and transversus abdominis muscles to provide analgesia to the lower anterior abdominal wall.⁴⁷ Several studies including randomized controlled trials showed decreased overall postoperative opioid use after laparoscopic/robotic urologic surgery and radical cystectomy with TAP blocks.^48-50

Opioid Prescription Dose Reduction

Despite previously held beliefs, evidence shows that significant opioid dose reduction can be successfully implemented without increased dissatisfaction, patient calls, or unplanned visits. This has most convincingly been shown on a statewide level via the Michigan Surgical Quality Collaborative⁵¹ but has been replicated by many including Dartmouth, Johns Hopkins, and the Michigan Urological Surgery Improvement Collaborative (MUSIC).^52,53 Similarly, in the general surgery data, large decreases in prescribing opioids did not change patient reported outcomes (PROs) using validated surveys.⁵⁴

Multiple institutions have shown that even completely non-opioid post-ureteroscopy pathways have no significant change in patient reported outcomes.^55,56 In female pelvic medicine and reconstructive surgery, reduction in opioids (or none) prescribed did not affect satisfaction with post-operative pain control.⁵⁷ Two randomized controlled trials have shown that robotic prostatectomy patients need minimal opioids immediately after surgery.^48,58 The University of Pennsylvania demonstrated similar results following robotic urologic oncology procedures. Under their new protocol, 67.7% of patients (including 81% of prostatectomies, 59% of partial nephrectomies, and 44% of radical nephrectomies) were discharged without opioids and the remaining patients had significant reductions in discharge opioids with no increase in PROs or new encounters.⁵⁹ A study at the University of Pittsburgh replicated this, finding that PRO data on robotic prostatectomy patients were the same in every domain.⁶⁰ Mount Sinai reported the same findings for robotic radical cystectomies.^60,61

Thus, there is increasing evidence – particularly after endourologic and prostatectomy procedures – that the use of opioids postoperatively in minimally invasive surgery patients is often unnecessary. If needed, opioids can easily be prescribed electronically. Urologic surgery is not the first discipline to substantially decrease or stop opioids after surgery. Non-opioid multi-modal pain management has been shown to be effective in many other specialties including dentistry, general surgery, gynecology, and orthopedics.^62-64

Technology to Reduce Opioid Prescribing & Abuse

Electronic prescribing (e-prescribing) of opioids is now nationally available and Congress passed the SUPPORT act in 2018 which requires all opioid prescriptions paid by Medicare part D to be prescribed electronically by 2021. E-prescribing eliminates the potential for paper prescription fraud and removes a major barrier to prescribing fewer opioids. Previously if a patient needed more pain medication after discharge, they had to travel to pick up a written prescription in person which could be a substantial inconvenience. Now an opioid prescription can be sent to their local pharmacy instantly. Danovich et al. (2019) showed that opioid prescribing in their institution decreased by 53% after electronic prescribing was mandated by New York state.⁶⁵

One of the easiest interventions to reduce opioid prescribing is to utilize an electronic medical record (EMR) system. Behavioral science suggests a role for reframing default choices to influence decisions without formal mandates or prohibitions, the so-called “nudge.” These have been championed as an inexpensive and effective means to affect change without impinging upon provider autonomy.⁶⁶ Multiple centers have shown that just reducing the default EMR opioid prescription pill quantities (ex: from 30 to 12 pills) significantly decreases opioid prescribing without consequence.^67,68

Safe Opioid Disposal to Further Reduce Community Diversion

The opioid epidemic began with over-prescribing but continues to diffuse through communities due to large amounts of unused opioids in homes. Encouraging safe disposal of unused opioids helps combat this issue. One option, used by some institutions and commercial pharmacies, is to provide activated charcoal drug disposal devices to patients who are prescribed opioids. The University of Michigan recently reported that providing activated charcoal bags to surgery patients nearly doubled the rate of safe medication disposal.⁶⁹

If bags are not an option, patients can be educated about the location(s) of nearby safe drug disposal boxes which are in most major pharmacies and hospitals. Finally, as a last resort, opioids are on the Food and Drug Administrations “Flush List” which recommends flushing the medication if a drug disposal site is not easily available. The Environmental Protection Agency has raised concerns about this practice, as it may expose the waterways to large quantities of opioids, though the FDA has ruled this “negligible.”⁷⁰

Multimodal Therapy and Non-Opioid Options for Reducing Postoperative Opioid Prescribing

Multimodal analgesia involves the use of two or more analgesics with different mechanisms of action that have synergistic effects. The goal is to improve pain relief while minimizing the use of perioperative opioids and decreasing opioid-related adverse effects (e.g., nausea, vomiting, sedation, ileus, pruritus, respiratory depression).

Pharmacologic Interventions

Acetaminophen

Acetaminophen is one of the world’s most widely used analgesics; however, its mechanism of action has still not been fully elucidated. Acetaminophen has been used in multi modal pathways and shown to reduce postoperative pain, nausea, and vomiting when administered as a single systemic dose.^71,72 When used in combination with opioids, it reduces opioid consumption.⁷³ Importantly, acetaminophen used in combination with NSAIDS has been found to have a synergistic effect and be more effective in terms of pain intensity and analgesic supplementation when compared to acetaminophen or NSAID alone.⁷⁴

Nonsteroidal Anti-inflammatory Drugs (NSAIDS)

NSAIDS act both peripherally and centrally to reduce pain predominantly by blocking cyclooxygenase (COX) enzyme mediated prostaglandin production. Numerous studies have found that NSAIDS reduce perioperative pain and opioid use.^74,75,76 In urology, NSAIDS have been shown to be efficacious following a variety of procedures: endourologic, minimally invasive, and open.^77-80 A 2018 meta-analysis of treatment for acute renal colic found that NSAIDS were equivalent to opioids with fewer side effects.⁸¹

NSAID side effects are dose and time dependent. Hence, most patients can tolerate a short course of around-the-clock NSAIDs after surgery. The majority of studies on adverse events of NSAIDS are based on chronic use of months, not acute use of less than 1 week.

Choosing an NSAID: Different prescription NSAIDS provide equivalent analgesia, but differ in their pharmacodynamic and side effect profiles (Table 2).⁸⁶ Though they require more frequent dosing, NSAIDS with a shorter half-life (e.g. diclofenac, ketorolac) have a faster onset and provide windows for COX recovery between doses which may reduce adverse effects.⁸⁷ NSAIDS with COX-1 selectivity have greater GI and platelet effects, while some studies suggest that COX-2 selective NSAIDS have higher rates of adverse CV events.

Tramadol

Tramadol is a mu-opioid agonist and carries risk for dependence and addiction. Tramadol is a prodrug, which means it requires metabolism to have effect, thereby leading to highly variable activity. Up to 30% of some racial/ethnic populations are “ultra-rapid” metabolizers of tramadol with an increased risk of side effects including respiratory depression, while up to 30% of others are poor or intermediate metabolizers who get decreased effect.⁸⁸ Tramadol also inhibits the synaptic uptake of serotonin and can cause seizures or serotonin syndrome, especially if the patient has a history of seizure or is on other serotonergic medications. In general, unless the patient has tolerated it previously, tramadol is not a good alternative and should be used sparingly if at all.

Gabapentinoids

Gabapentin (Neurontin) and pregabalin (Lyrica) are anticonvulsant agents commonly used as perioperative analgesics. These medications were initially used for treatment of chronic neuropathic pain, but recent evidence suggests that they may reduce acute and chronic post-operative pain as part of multi-modal analgesia protocols.^89,90 Use in an inpatient monitored setting may be safe, however in 2019 the FDA issued a warning about co-administration of gabapentinoids with other nervous system depressants (such as opioids), citing multiple studies showing an increase in respiratory depression and death when these drugs are given together.⁹¹

Muscle Relaxants

Muscle relaxants such as cyclobenzaprine (Flexeril), baclofen, tizanidine, and methocarbamol are common components of multi-modal anesthesia pathways, especially after musculoskeletal procedures.⁹² Many muscle relaxants have centrally acting sedative effects , and though evidence for their inclusion is mixed, they are increasingly being prescribed post-operatively as part of opioid-reduction protocols. Their addictive potential is considered low, but they are recommended for short term use only. Sedative effects can increase dangerously when combined with other central depressants such as gabapentinoids or opioids.

Some clinicians use benzodiazepines for muscle relaxation; however, they have been shown to significantly increase post-operative mortality when taken in conjunction with opioids.⁹³ In 2016 the FDA released a black box warning about the dangers of combining opioids and benzodiazepines. Furthermore, benzodiazepines have strong addictive potential. Benzodiazepine use is not recommended as there are safer, alternative medications.

Adjuncts for Stent-Related Pain

Pain after endourologic procedures represents a unique situation primarily due to the use of ureteral stents. Stent related symptoms impact daily activities and reduce quality of life in up to 80% of patients.⁹⁴ Current evidence suggests that a multimodal approach to stent-related symptoms and pain with alpha-blockers, anticholinergic medications, anti-inflammatory and opioid pain medications is likely the most effective.⁹⁵ Alpha-blockers when given alone have been shown to decrease stent-related symptoms in terms of lower urinary symptom scores and body pain scores.^96,95,97 Improvements can persist for more than four weeks, and both tamsulosin and alfuzosin have proven to be efficacious in this setting.⁹⁸

Anticholinergic medications have also shown to be well-tolerated for the treatment of lower urinary tract symptoms (LUTS), stent-related body pain and hematuria.⁹⁹ The beneficial effects of combined alpha-blockers and antimuscarinics have been demonstrated to be potentially superior to either alpha-blockers or antimuscarinics alone.^100,101 Phenazopyridine, an oral local anesthetic, has not been shown to improve stent-related symptoms over placebo although this mediation has not been studied extensively.¹⁰²

Non-pharmacologic Interventions

Non-pharmacologic interventions have been shown to be effective in improving pain control and can be used as part of the multimodal approach to postoperative pain. By targeting the emotional and psychological aspects of the pain experience, these adjunct techniques not only improve the perception of pain but also show changes in the central nervous system and neurotransmitter activity known to be involved in pain. Moreover, these techniques could offer a precision health approach to treating anxiety, which has been consistently associated with increased opioid consumption, new chronic opioid use and increased postoperative pain.^4,103 While behavioral interventions have promise for the management of perioperative pain and anxiety, the data supporting their use in acute pain are still limited and future studies are needed.

Mindfulness Meditation and Alternative Medicine

Mindfulness meditation, generally defined as “non-elaborative, non-judgmental awareness” of the present moment experience, has been shown to mediate the subjective experience of pain. Studies have also shown that mindfulness meditation is superior to placebo in controlling pain and is independent of endogenous opioid mechanisms.^83,84

Alternative medicine practices (including hypnosis, acupuncture and acupressure) may present another venue to impact postoperative pain. Acupuncture analgesia involves insertion of needles into specific “acupoints.” Its mechanism of analgesia is not fully understood but involves multiple levels of the central nervous system and many signal molecules and receptors including the opioid peptides.¹⁰⁴ Similar pain reduction, although less sustained, has been shown in patients receiving acupuncture for renal colic when compared to acetaminophen and diclofenac.¹⁰⁵ While the data for acupressure are more limited, the low-cost, self-guided nature of acupressure offers many advantages.

Summary and Recommendations

Post-operative prescribing of large amounts of opioids has become routine practice in the United States, though there is no evidence or guideline indicating its necessity and despite clear documentation of its harms. Post-operative opioid use has significant potential morbidity, including nausea, vomiting, constipation, ileus, and resultant increased emergency department visits and readmissions. Additionally, post-operative new persistent opioid use is one of the most common surgical complications of many urologic procedures, with potentially devastating lifelong effects for our patients and their families. Even if the opioids we prescribe go unused by our patients, there is a high rate of diversion into the community, furthering the opioid epidemic.

Studies within endourologic, minimally invasive, reconstructive and oncologic urology populations have shown that the majority of opioid-naïve patients may not require a post-operative opioid prescription. With use of non-opioid multi-modal medications, equivalent patient reported outcomes and substantially reduced morbidity can be achieved. If an opioid prescription is later desired it can be sent electronically, supporting a paradigm shift away from default opioid prescriptions for all post-operative patients.

If a post-operative opioid prescription is deemed necessary prior to discharge, it should be for the lowest effective dose and duration. There are multiple methods to achieve this transition in practice. For those who have protocolized what they prescribe based on procedure, we recommend a tapered approach: start by prescribing non-opioid multi-modal medications and reducing default opioid prescribing amount by 50% (i.e. decrease from 30 pills to 15 pills). If no significant impact on patient outcomes/satisfaction is observed, decrease default opioid prescribing by 50% again. Repeat until the minimum necessary dose for the patient population is reached. Alternatively, some institutions have successfully reduced prescribing by quantifying the opioids each patient uses the day before discharge and using this to determine what to prescribe. Those who used no opioids in the 24hrs prior to discharge required none afterwards.⁵²

While there is substantial evidence on best practices for the opioid-naïve surgical population, there is a paucity of data on patients with chronic pain or those undergoing large open procedures. These patients are historically complex to treat and are commonly excluded from studies of post-operative pain management. Strategies for these patients are developing, but we recommend: 1) Incorporation of advanced multi-modal therapies as non-opioid naive patients may already be on high doses of opioids and patients with large incisions may have multiple etiologies for their pain (muscular, neuropathic, etc.). Many large centers have acute/transitional pain services to help manage chronic pain medications and/or advanced therapies; 2) Consult the patient’s usual prescriber (chronic pain specialist or primary care physician) to create a plan before surgery, including post-discharge management.

The management of acute post-operative pain is evolving away from relying exclusively on opioids, but many questions remain. For example, cannabinoids are being actively evaluated for acute pain, but the data is not yet mature. Multiple organizations are now working on guidance for managing post-operative pain – the Canadian "Consensus Statement for the Prescription of Pain Medication at Discharge after Elective Adult Surgery” was published in March 2020 and the American Society of Anesthesiologists is actively working on consolidating recommendations from varied surgical societies into a consensus document. This paper will be updated periodically as new evidence and guidance emerges.

Conclusion

During the era of "Pain as the 5th vital sign," surgeons were encouraged to routinely prescribe large quantities of opioids and unwittingly played a perilous role in creating our current crisis. Mounting data confirms that post-operative opioid prescriptions for urologic patients can be dramatically reduced without harm, and many have demonstrated the feasibility of eliminating default opioid prescribing. With multi-modal therapies, urologists have the ability to help curtail this crisis by enacting measures to dramatically reduce opioid exposure to our patients and communities.

References

1. Dowell D, Haegerich TM and Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. MMWR Recomm Rep 2016; 65: 1.
2. Paulozzi LJ, Mack KA, Hockenberry JM, et al. Vital signs: variation among States in prescribing of opioid pain relievers and benzodiazepines - United States, 2012. MMWR Morb Mortal Wkly Rep 2014; 63: 563.
3. Hill MV, McMahon ML, Stucke RS, et al. Wide Variation and Excessive Dosage of Opioid Prescriptions for Common General Surgical Procedures. Ann Surg 2017; 265: 709.
4. Brummett CM, Waljee JF, Goesling J, et al. New Persistent Opioid Use After Minor and Major Surgical Procedures in US Adults. JAMA Surg 2017; 152: e170504.
5. Berger I, Strother M, Talwar R, et al. National Variation in Opioid Prescription Fills and Long-Term Use in Opioid Naive Patients after Urological Surgery. J Urol 2019; 202: 1036.
6. Benyamin R, Trescot AM, Datta S, et al. Opioid complications and side effects. Pain Physician 2008; 11: S105.
7. Kharasch ED and Brunt LM. Perioperative Opioids and Public Health. Anesthesiology 2016; 124: 960.
8. Kane-Gill SL, Rubin EC, Smithburger PL, et al. The cost of opioid-related adverse drug events. J Pain Palliat Care Pharmacother 2014; 28: 282.
9. Kwong WJ, Diels J and Kavanagh S. Costs of gastrointestinal events after outpatient opioid treatment for non-cancer pain. Ann Pharmacother 2010; 44: 630.
10. Kessler ER, Shah M, Gruschkus SK, et al. Cost and quality implications of opioid-based postsurgical pain control using administrative claims data from a large health system: opioid-related adverse events and their impact on clinical and economic outcomes. Pharmacotherapy 2013; 33: 383.
11. Oderda GM, Gan TJ, Johnson BH, et al. Effect of opioid-related adverse events on outcomes in selected surgical patients. J Pain Palliat Care Pharmacother 2013; 27: 62.
12. Howard R, Fry B, Gunaseelan V, et al. Association of Opioid Prescribing With Opioid Consumption After Surgery in Michigan. JAMA Surg 2019; 154: e184234.
13. Theisen KM, Myrga JM, Hale N, et al. Excessive Opioid Prescribing After Major Urologic Procedures. Urology 2019; 123: 101.
14. Kaafarani HMA. Surgeons as Part of the Solution: Changing the Culture of Opioid Prescribing. Ann Surg 2018; 267: e48.
15. Schwartz MA, Naples JG, Kuo CL, et al. Opioid Prescribing Patterns among Otolaryngologists. Otolaryngol Head Neck Surg 2018; 158: 854.
16. Tan WH, Yu J, Feaman S, et al. Opioid Medication Use in the Surgical Patient: An Assessment of Prescribing Patterns and Use. J Am Coll Surg 2018; 227: 203.
17. Sabatino MJ, Kunkel ST, Ramkumar DB, et al. Excess Opioid Medication and Variation in Prescribing Patterns Following Common Orthopaedic Procedures. J Bone Joint Surg Am 2018; 100: 180.
18. Thiels CA, Anderson SS, Ubl DS, et al. Wide Variation and Overprescription of Opioids After Elective Surgery. Ann Surg 2017; 266: 564.
19. Becker SD and Becker DG. Review and update on postoperative opioid use after nasal and sinus surgery. Curr Opin Otolaryngol Head Neck Surg 2018; 26: 41.
20. Chen EY, Marcantonio A and Tornetta P, 3rd. Correlation Between 24-Hour Predischarge Opioid Use and Amount of Opioids Prescribed at Hospital Discharge. JAMA Surg 2018; 153: e174859.
21. Feinberg AE, Chesney TR, Srikandarajah S, et al. Opioid Use After Discharge in Postoperative Patients: A Systematic Review. Ann Surg 2018; 267: 1056.
22. Patel HD, Srivastava A, Patel ND, et al. A Prospective Cohort Study of Postdischarge Opioid Practices After Radical Prostatectomy: The ORIOLES Initiative. Eur Urol 2019; 75: 215.
23. Stepan JG, London DA, Osei DA, et al. Perioperative Celecoxib and Postoperative Opioid Use in Hand Surgery: A Prospective Cohort Study. J Hand Surg Am 2018; 43: 346.
24. As-Sanie S, Till SR, Mowers EL, et al. Opioid Prescribing Patterns, Patient Use, and Postoperative Pain After Hysterectomy for Benign Indications. Obstet Gynecol 2017; 130: 1261.
25. 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.
26. Gawande AA. It's Time to Adopt Electronic Prescriptions for Opioids. Ann Surg 2017; 265: 693.
27. Bates C, Laciak R, Southwick A, et al. Overprescription of postoperative narcotics: a look at postoperative pain medication delivery, consumption and disposal in urological practice. J Urol 2011; 185: 551.
28. Tam CA, Ghani KR, Gunaseelan V, et al: New Persistent Opioid Use After Outpatient Ureteroscopy for Upper Tract Stone Treatment. Urology. 2019.
29. Welk B, McClure J, Clarke Collin, et al. An Opioid Prescription for Men Undergoing Minor Urologic Surgery Is Associated with an Increased Risk of New Persistent Opioid Use. Eur Urol. 2020; 77: 68-75.
30. Yaster M, Benzon HT and Anderson TA. "Houston, We Have a Problem!": The Role of the Anesthesiologist in the Current Opioid Epidemic. Anesth Analg 2017; 125: 1429.
31. Allen JD, Casavant MJ, Spiller HA, et al. Prescription Opioid Exposures Among Children and Adolescents in the United States: 2000-2015. Pediatrics, 2017.
32. Patel, H., Faisal, F., Patel, N., Pavlovich, C., Allaf, M., Han, M., Herati, A. (2019). Effect of a prospective opioid reduction intervention on opioid prescribing and use after radical prostatectomy: results of the Opioid Reduction Intervention for Open, Laparoscopic, and Endoscopic Surgery (ORIOLES) Initiative BJU International 125(3), 426-432.
33. Schuchat A, Houry D and Guy GP, Jr. New Data on Opioid Use and Prescribing in the United States. JAMA 2017; 318: 425.
34. Monico LB and Mitchell SG. Patient perspectives of transitioning from prescription opioids to heroin and the role of route of administration. Subst Abuse Treat Prev Policy 2018; 13: 4.
35. Nalamachu SR and Shah B. Abuse of immediate-release opioids and current approaches to reduce misuse, abuse, and diversion. Postgrad Med 2018; 1.
36. Mital S, Windle M, Cooper HLF, et al. Trends in non-medical prescription opioids and heroin co-use among adults, 2003-2014. Addict Behav 2018; 86: 17.
37. Waljee JF, Li L, Brummett CM, et al. Iatrogenic Opioid Dependence in the United States: Are Surgeons the Gatekeepers? Ann Surg 2017; 265: 728.
38. Solouki S, Plummer M, Agalliu I, et al. Opioid prescribing practices and medication use following urogynecological surgery. Neurourol Urodyn 2019; 38: 363.
39. Ziegelmann MJ, Joseph JP, Glasgow AE, et al. Wide Variation in Opioid Prescribing After Urological Surgery in Tertiary Care Centers. Mayo Clin Proc 2019; 94: 262.
40. Cron DC, Hwang C, Hu HM, et al. A statewide comparison of opioid prescribing in teaching versus nonteaching hospitals. Surgery 2019; 165: 825.
41. Cron DC, Lee JS, Dupree JM, et al. Provider Characteristics Associated With Outpatient Opioid Prescribing After Surgery. Ann Surg 2018.
42. Oliver JB, Kashef K, Bader AM, et al. A survey of patients' understanding and expectations of persistent postsurgical pain in a preoperative testing center. J Clin Anesth 2016; 34: 494.
43. Sugai DY, Deptula PL, Parsa AA, et al. The importance of communication in the management of postoperative pain. Hawaii J Med Public Health 2013; 72: 180.
44. Holman JE, Stoddard GJ, Horwitz DS, et al. The effect of preoperative counseling on duration of postoperative opiate use in orthopaedic trauma surgery: a surgeon-based comparative cohort study. J Orthop Trauma 2014; 28: 502.
45. Vadivelu N, Mitra S, Schermer E, et al. Preventive analgesia for postoperative pain control: a broader concept. Local Reg Anesth 2014; 7: 17.
46. Raynor MC, Smith A, Vyas SN, et al. Dorsal penile nerve block prior to inflatable penile prosthesis placement: a randomized, placebo-controlled trial. J Sex Med 2012; 9: 2975.
47. Shahait M and Lee DI. Application of TAP Block in Laparoscopic Urological Surgery: Current Status and Future Directions. Curr Urol Rep 2019; 20: 20.
48. Cacciamani GE, Menestrina N, Pirozzi M, et al. Impact of combination of local anaesthetic wounds infiltration and ultrasound transversus abdominal plane block in patients undergoing robot-assisted radical prostatectomy: perioperative results of a double-blind randomized controlled trial. J Endourol. 2019.
49. Covotta M, Claroni C, Costantini M, et al. The Effects of Ultrasound-Guided Transversus Abdominis Plane Block on Acute and Chronic Postsurgical Pain After Robotic Partial Nephrectomy: A Prospective Randomized Clinical Trial. Pain Med 2019.
50. Matulewicz RS, Patel M, Jordan BJ, et al. Transversus Abdominis Plane Blockade as Part of a Multimodal Postoperative Analgesia Plan in Patients Undergoing Radical Cystectomy. Bladder Cancer 2018; 4: 161.
51. Vu JV, Howard RA, Gunaseelan V, et al. Statewide Implementation of Postoperative Opioid Prescribing Guidelines. N Engl J Med 2019; 381: 680.
52. Hill MV, Stucke RS, Billmeier SE, et al. Guideline for Discharge Opioid Prescriptions after Inpatient General Surgical Procedures. J Am Coll Surg 2018; 226: 996.
53. Koo K, Faisal F, Gupta N, et al. Recommendations for Opioid Prescribing after Endourological and Minimally Invasive Urological Surgery. J Urology, 2020.
54. Louie CE, Kelly JL and Barth RJ, Jr. Association of Decreased Postsurgical Opioid Prescribing With Patients' Satisfaction With Surgeons. JAMA Surg 2019.
55. Large T, Heiman J, Ross A, et al. Initial Experience with Narcotic-Free Ureteroscopy: A Feasibility Analysis. J Endourol 2018; 32: 907.
56. Sobel DW, Cisu T, Barclay T, et al. A Retrospective Review Demonstrating the Feasibility of Discharging Patients Without Opioids After Ureteroscopy and Ureteral Stent Placement. J Endourol 2018; 32: 1044.
57. Moskowitz D, Amin K, Lucioni A, Kobashi K, Lee U. Opioid Prescription and Use in Sacral Neuromodulation, Mid Urethral Sling and Pelvic Organ Prolapse Surgery: An Educational Intervention to Avoid Over Prescribing. J Urol. 2019;201(5):979-986.
58. Wang V.C., Preston M.A., Kibel A.S., et al: A prospective, randomized, double-blind, placebo-controlled trial to evaluate intravenous acetaminophen versus placebo in patients undergoing robotic-assisted laparoscopic prostatectomy. J Pain Palliat Care Pharmacother 2018; 32: pp. 82-89.
59. Talwar R, Xia L, Serna J. Preventing Excess Narcotic Prescriptions in New Robotic Surgery Discharges. J Endourology, 2019.
60. Davies B and Brummett CM. Anchoring to Zero Exposure: Opioid-free Minimally Invasive Surgery. Ann Surg 2020; 271: 37.
61. Audenet F, Attalla K, Giordano M, et al. Prospective implementation of a nonopioid protocol for patients undergoing robot-assisted radical cystectomy with extracorporeal urinary diversion. Urol Oncol 2019; 37: 300 e17.
62. Barden J, Edwards JE, McQuay HJ, et al. Relative efficacy of oral analgesics after third molar extraction. Br Dent J 2004; 197: 407.
63. Moore PA and Hersh EV. Combining ibuprofen and acetaminophen for acute pain management after third-molar extractions: translating clinical research to dental practice. J Am Dent Assoc 2013; 144: 898.
64. Gimbel JS, Brugger A, Zhao W, et al. Efficacy and tolerability of celecoxib versus hydrocodone/acetaminophen in the treatment of pain after ambulatory orthopedic surgery in adults. Clin Ther 2001; 23: 228.
65. Danovich D, Greenstein J, Chacko J, et al: Effect of New York State Electronic Prescribing Mandate on Opioid Prescribing Patterns. J. Emerg. Med. 2019; 57: 156–161.
66. Zhang DDQ, Dossa F and Baxter NN. How to Combat the Opioid Epidemic, 1 Nudge at a Time. JAMA Surg 2018; 153: 1020.
67. Montoy JCC, Coralic Z, Herring AA, et al: Association of Default Electronic Medical Record Settings With Health Care Professional Patterns of Opioid Prescribing in Emergency Departments: A Randomized Quality Improvement Study. JAMA Intern. Med. 2020. Available at: http://dx.doi.org/10.1001/jamainternmed.2019.6544.
68. Delgado MK, Shofer FS, Patel MS, et al: Association between Electronic Medical Record Implementation of Default Opioid Prescription Quantities and Prescribing Behavior in Two Emergency Departments. J. Gen. Intern. Med. 2018; 33: 409–411.
69. Brummett CM, Steiger R, Englesbe M, et al: Effect of an Activated Charcoal Bag on Disposal of Unused Opioids After an Outpatient Surgical Procedure: A Randomized Clinical Trial. JAMA Surg. 2019. Available at: http://dx.doi.org/10.1001/jamasurg.2019.0155.
70. Center for Drug Evaluation and Research: Drug Disposal: Flush Potentially Dangerous Medicine. U.S. Food and Drug Administration 2019. Available at: http://www.fda.gov/drugs/disposal-unused-medicines-what-you-should-know/drug-disposal-flush-potentially-dangerous-medicine, accessed February 2, 2020.
71. Toms L, McQuay HJ, Derry S, et al. Single dose oral paracetamol (acetaminophen) for postoperative pain in adults. Cochrane Database Syst Rev 2008; CD004602.
72. De Oliveira GS, Jr., Castro-Alves LJ and McCarthy RJ. Single-dose systemic acetaminophen to prevent postoperative pain: a meta-analysis of randomized controlled trials. Clin J Pain 2015; 31: 86.
73. McNicol ED, Ferguson MC, Haroutounian S, et al. Single dose intravenous paracetamol or intravenous propacetamol for postoperative pain. Cochrane Database Syst Rev 2016; CD007126.
74. Ong CK, Seymour RA, Lirk P, et al. Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg 2010; 110: 1170.
75. Chou R, Gordon DB, de Leon-Casasola OA, et al. Management of Postoperative Pain: A Clinical Practice Guideline From the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. J Pain 2016; 17: 131.
76. Graff V and Grosh T. Multimodal Analgesia and Alternatives to Opioids for Postoperative Analgesia. 2018. Anesthesia Patient Safety Foundation Newsletter. https://www.apsf.org/article/multimodal-analgesia-and-alternatives-to-opioids-for-postoperative-analgesia/. January 20, 2020.
77. Kara C, Resorlu B, Cicekbilek I, et al. Analgesic efficacy and safety of nonsteroidal anti-inflammatory drugs after transurethral resection of prostate. Int Braz J Urol 2010; 36: 49.
78. Yu YD, Hwang JH, Seo YE, et al. Effects of Nonsteroidal Anti-Inflammatory Drugs as Patient Controlled Analgesia on Early Bowel Function Recovery after Radical Cystectomy. Sci Rep 2018; 8: 4658.
79. Grimsby GM, Conley SP, Trentman TL, et al. A double-blind randomized controlled trial of continuous intravenous Ketorolac vs placebo for adjuvant pain control after renal surgery. Mayo Clin Proc 2012; 87: 1089.
80. Heid F and Jage J. The treatment of pain in urology. BJU Int 2002; 90: 481.
81. Pathan SA, Mitra B, Cameron PA. A Systematic Review and Meta-analysis Comparing the Efficacy of Nonsteroidal Anti-inflammatory Drugs, Opioids, and Paracetamol in the Treatment of Acute Renal Colic. Eur Urol. 2018 Apr;73(4):583-595.
82. Wu MS, Chen KH, Chen IF, et al. The Efficacy of Acupuncture in Post-Operative Pain Management: A Systematic Review and Meta-Analysis. PLoS One 2016; 11: e0150367.
83. Zeidan F, Emerson NM, Farris SR, et al. Mindfulness Meditation-Based Pain Relief Employs Different Neural Mechanisms Than Placebo and Sham Mindfulness Meditation-Induced Analgesia. J Neurosci 2015; 35: 15307.
84. Zeidan F, Adler-Neal AL, Wells RE, et al. Mindfulness-Meditation-Based Pain Relief Is Not Mediated by Endogenous Opioids. J Neurosci 2016; 36: 3391.
85. Chai PR, Carreiro S, Ranney ML, et al. Music as an Adjunct to Opioid-Based Analgesia. J Med Toxicol 2017; 13: 249.
86. Varrassi G, Pergolizzi JV, Dowling P, et al. Ibuprofen Safety at the Golden Anniversary: Are all NSAIDs the Same? Adv Ther. 2020 Jan;37(1):61-82. doi: 10.1007/s12325-019-01144-9. Epub 2019 Nov 8.
87. Hunter TS, Robison C, Gerbino PP. Emerging evidence in NSAID pharmacology: important considerations for product selection. Am J Manag Care. 2015 Apr;21(7 Suppl):S139-47.
88. Dean L: Tramadol Therapy and CYP2D6 Genotype. In: Medical Genetics Summaries. Edited by V Pratt, H McLeod, W Rubinstein, et al. Bethesda (MD): National Center for Biotechnology Information (US) 2015.
89. Clarke H, Bonin RP, Orser BA, et al. The prevention of chronic postsurgical pain using gabapentin and pregabalin: a combined systematic review and meta-analysis. Anesth Analg 2012; 115: 428.
90. Gilron I. Review article: the role of anticonvulsant drugs in postoperative pain management: a bench-to-bedside perspective. Can J Anaesth 2006; 53: 562.
91. U.S. Food and Drug Administration. FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin and pregabalin. FDA Drug Safety Communication, 2019.
92. Devin CJ, McGirt MJ. Best evidence in multimodal pain management in spine surgery and means of assessing postoperative pain and functional outcomes. J Clin Neurosci. 2015 Jun;22(6):930-8. doi: 10.1016/j.jocn.2015.01.003. Epub 2015 Mar 9.
93. Sigurdsson MI, Helgadottir S, Long TE, et al. Association Between Preoperative Opioid and Benzodiazepine Prescription Patterns and Mortality After Noncardiac Surgery. JAMA Surg. 2019 Jun 19.
94. Joshi HB, Stainthorpe A, MacDonagh RP, et al. Indwelling ureteral stents: evaluation of symptoms, quality of life and utility. J Urol 2003; 169: 1065.
95. Fischer KM, Louie M and Mucksavage P. Ureteral Stent Discomfort and Its Management. Curr Urol Rep 2018; 19: 64.
96. Chen YB, Gao L, Jiang Q, et al. Tamsulosin Monotherapy Is Effective in Reducing Ureteral Stent-related Symptoms: A Meta-analysis of Randomized Controlled Studies. Curr Med Sci 2019; 39: 707.
97. Lamb AD, Vowler SL, Johnston R, et al. Meta-analysis showing the beneficial effect of alpha-blockers on ureteric stent discomfort. BJU Int 2011; 108: 1894.
98. Zhou L, Cai X, Li H, et al. Effects of alpha-Blockers, Antimuscarinics, or Combination Therapy in Relieving Ureteral Stent-Related Symptoms: A Meta-Analysis. J Endourol 2015; 29: 650.
99. Lee YJ, Huang KH, Yang HJ, et al. Solifenacin improves double-J stent-related symptoms in both genders following uncomplicated ureteroscopic lithotripsy. Urolithiasis 2013; 41: 247.
100. Zhang YM, Chu P and Wang WJ. PRISMA-combined alpha-blockers and antimuscarinics for ureteral stent-related symptoms: A meta-analysis. Medicine (Baltimore) 2017; 96: e6098.
101. Yan H, Wang Y, Sun R, et al. The Efficacy of Antimuscarinics Alone or in Combination with Alpha-Blockers for the Treatment of Ureteral Stent-Related Symptoms: A Systematic Review and Meta-Analysis. Urol Int 2017; 99: 6.
102. Norris RD, Sur RL, Springhart WP, et al. A prospective, randomized, double-blinded placebo-controlled comparison of extended release oxybutynin versus phenazopyridine for the management of postoperative ureteral stent discomfort. Urology 2008; 71: 792.
103. Larach DB, Sahara MJ, As-Sanie S, et al. Patient Factors Associated with Opioid Consumption in the Month Following Major Surgery. Ann Surg. 2019.
104. Lin JG and Chen WL. Acupuncture analgesia: a review of its mechanisms of actions. Am J Chin Med 2008; 36: 635.
105. NIH Consensus Conference. Acupuncture. JAMA 1998; 280: 1518.