In 2017 the White House declared the opioid epidemic a public health emergency and mobilized resources to combat it. Prior to this, increased awareness in the medical community caused many surgeons to begin to question their use of opioids and experiment with low/no opioid pain protocols. The national focus on opioid prescribing appeared to have an impact as overdose deaths due to prescription opioids decreased from 2017–2019. Unfortunately, the pandemic’s negative effects on mental health and access to health and addiction resources appear to have reversed prior progress. The Centers for Disease Control (CDC) recently reported more than 81,000 overdose deaths from May 2019 to 2020, the largest number ever recorded within a 1-year period.¹ The majority of these were opioid related, with many tied to prescription opioid use whether directly or indirectly (given that most patients with opioid use disorder begin with prescription medications).

In 2016 the CDC released opioid prescribing guidelines for chronic pain in response to the growing opioid epidemic, but their recommendation for treatment of acute pain was nonspecific: “prescribe the lowest effective dose…and no greater quantity than needed.” This recommendation was open to liberal interpretation as the lowest effective dose of opioids for acute, surgical pain was (and remains) unknown. Thus, substantial variation exists in the amount of opioids prescribed for surgical pain, even as evidence accumulates about the morbidity of even short-term opioid use.

Surgical opioid prescribing has been linked to increased lengths of stay, emergency department visits, hospitalizations, encounter costs, and new persistent opioid use. Two studies have found that the rate of new persistent opioid use after urological surgery is 6%,^2,3 establishing persistent opioid use as one of the most prevalent iatrogenic complications of surgery. Given the now well-established harms of opioids, and the lack of evidence regarding their ideal use, there has been vigorous interest in opioid dose reduction and multi-modal treatment pathways for surgical pain which incorporate nonopioid medications to reduce opioid use. Increasingly there is evidence that the lowest effective dose of opioids may often be zero, as nonopioid based protocols have been shown to achieve equivalent pain outcomes across a wide spectrum of surgical procedures.

Setting realistic pain expectations preoperatively is a crucial first step to reducing postoperative opioid use. Establishing that the goal after surgery is not zero pain but, rather, pain that is managed well enough to allow for functional movement and recovery has been shown to reduce the amount of postoperative opioid consumption. The impact is largest when also educating patients about the harms of opioids and the rationale for limiting their use.⁴

Many institutions have now shown that significantly reducing the amount of opioids prescribed after surgery is safe and effective, without any impact to patient satisfaction, number of phone calls to the office, or increased emergency department visits. A recent study from a large statewide collaborative, the Michigan Opioid Prescribing and Engagement Network, found that patients who were counseled preoperatively about nonopioid pain options and given low-dose or no opioids postoperatively had, in fact, improved pain scores compared to patients given usual care.⁵ Patients prescribed more tend to use more, without an improvement in outcomes. Regardless of what was prescribed, most patients did not use all of their pills, a consistent finding across studies with significant implications for the community as diversion of unused opioids for illicit use is a common issue. From this vantage, opioid stewardship can serve the purposes of both primary and secondary prevention, as the excess supply of opioids from historical prescribing patterns puts not only the intended recipient at risk, but also other members of their household and community

Successful urological opioid dose reduction protocols for minimally invasive and open surgery have been published from the University of Pennsylvania, the University of Pittsburgh, Johns Hopkins University and our own institutions, amongst others.^6–8 These studies consistently show equivalent outcomes from low/no opioid protocols across a wide variety of urological procedures: pediatrics, ureteroscopy with stent placement, reconstructive pelvic surgery, penile implantation, and oncologic procedures such as radical prostatectomy, partial and radical nephrectomy, and open cystectomy. For example, while prescriptions of 30 or more oxycodone pills following laparoscopic/robotic surgery were previously standard, several of these protocols have shown that 0–7 pills often work just as well. In addition to reducing the number of pills prescribed, the opioid strength can be adjusted–hydrocodone is half the morphine equivalent of oxycodone.

Tramadol is a weak partial opioid agonist but has highly variable metabolism based on variants of the CYP2D6 gene–in the United States an estimated 40% of people are either poor metabolizers who will have poor pain control with tramadol, or ultra-rapid metabolizers who are at risk for potentially lethal respiratory depression. Along with its potentially morbid serotonergic interactions, prescribing tramadol requires caution but can be considered in patients with a prior good response. Of note, benzodiazepines are never recommended for pain control and patients on benzodiazepines require nonopioid alternatives given U.S. Food and Drug Administration “black box” warnings of a 10× higher risk of overdose in patients taking both medications.

Nonopioid multi-modal analgesia is thus an important adjunct to opioid dose reduction protocols, especially if the goal is to get to zero opioid use. Multi-modal analgesia involves using multiple agents which target pain via different pathways with potentially synergistic effects. The best studied is the combination of acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), which has been shown to have synergistic effects which are equally effective to opioids for a variety of acute pain conditions.

Specifically, NSAIDs have been shown to be safe and efficacious following endourological, minimally invasive prostate and kidney, and open oncologic surgeries. Many surgeon concerns about NSAIDs are addressed in the literature. Notably, NSAIDs have not been shown to increase postoperative bleeding in multiple meta-analyses and large studies, even after high risk procedures like partial nephrectomy. Cardiovascular risk is not increased with short-term use. NSAIDs are safe for patients with healthy kidneys but do have a risk of acute kidney injury in patients with chronic kidney disease, significant dehydration, or those on angiotensin-converting enzyme (ACE) inhibitors.

Other common medications used in multi-modal analgesia pathways are gabapentinoids and muscle relaxants (such as Flexeril®). Neither has been shown, thus far, to have significant addictive potential but both carry risks of respiratory depression when mixed with other potentially sedating drugs such as opioids so they may be best suited for nonopioid protocols. Of note, there are several nonopioid adjuncts which have been shown to be quite effective for stent-related pain specifically. These include tamsulosin and anticholinergic medications, such as Ditropan or belladonna/opium suppositories. In combination with acetaminophen/NSAIDs, several large institutions have been able to prescribe zero opioids for the majority of their patients after stent placement.

In summary, despite some initial progress in reducing opioid-related morbidity and mortality in the past 5 years, the past year unfortunately saw record-breaking levels of these devastating complications. It is increasingly recognized that long-held assumptions about post-operative opioid pain requirements may be inaccurate and that there are costs to overprescribing for both patients and their communities. Urologists have led a number of efforts to address these challenges and there is mounting evidence across urological sub-specialties supporting the use of low/no opioid protocols for postoperative pain. Additional resources to support practice improvements are available online from the AUA’s (American Urological Association’s) Quality Improvement Summit on Opioid Stewardship, as well as a forthcoming AUA document summarizing, in greater detail, the topics discussed in this article.