The Ugly Truth: Opioids and the History of the Opioid Epidemic

Throughout my training and experience as a student, resident, and attending, I have observed a pervasive idea that opioids should be the cornerstone of postoperative and acute pain management. There is no standard or protocol for the exact amount or morphine milliequivalents (MME) that should be dispensed after surgery, so it seems many prescribe an arbitrary number that either they learned in training, or “have always done it that way.” Many physicians will prescribe 20–60 doses of oxycodone or hydrocodone 5mg (150–450 MME) after foot or ankle surgery.¹ The cornerstone of medicine is practicing in an evidence-based manner, and I believe prescribing more than 100 MME for most foot surgery is harmful and should be frowned upon.

To determine what postoperative analgesic medications should be prescribed for acute postsurgical foot and ankle pain, the efficacy, safety profile, and cost should all be considered. Oftentimes the default prescription for postoperative pain relief is generally an opioid, due to the persistent but flawed thought that opioids are the optimal pain relief drugs.² The World Health Organization (WHO) has come out with a pain relief ladder that emphasizes that the foundation should be rooted in non-opioid medicines with adjuvants; however, American physicians do not typically follow this.³ Orthopedic surgeons (including podiatrists) are among the highest prescribers of opioids per capita.⁴ The liberal use of opioid medication by physicians in general is possibly at least in part due to a lack of comprehensive education on postoperative pain management. Also, the addiction, respiratory depression, and other sinister side effects are rarely discussed or mentioned with patients.

The History of Opioid Overconsumption and Marketing

The current epidemic in the United States is taking the lives of over 80,000 people every year.⁵ While part of the responsibility is on physicians, the history of the current opioid epidemic has its roots in disingenuous marketing tactics and outside pressure from hospitals and patients alike. There has been a history of overprescribing opioids, especially in the late 1990s and early 2000s.⁵ However, there are various extraneous pressures that have led to overprescribing. Large pharmaceutical companies willingly misled physicians with their “opioids are non-addictive” claims based on falsified data.⁶ This gave the appearance that opioid drugs were near-perfect for pain control: effective, non-addictive, and few negative side effects. These claims have all been proven time and again to have been misrepresentation of data that was lobbied for by various organizations.

This “data” initially stemmed from a letter to the editor in the New England Journal of Medicine in 1980 by Porter and Jick.⁶ This letter (which was not a peer-reviewed study) had analyzed hospital inpatients who were suffering from cancer or chronic pain with a tightly controlled opioid dosing regimen and claimed that the development of addiction was incredibly rare in this subset of patients. This study was then misrepresented many times, by influential magazines Scientific American and Time, as well as Purdue Pharma, claiming this was a “landmark” or “extensive” study, despite the fact that this was merely a letter to the editor without passing the rigor of peer review.^7,8

The very aggressive marketing of opioids directly to patients and doctors has led to patients expecting opioids when they are in pain, which was further pushed due to the Joint Commission’s “pain is the fifth vital sign” campaign.⁹ While well intentioned, the campaign tied physician and hospital compensation to the patient's subjective pain scores after leaving the hospital, which may have incentivized overtreatment for pain.¹⁰ The Joint Commission has since changed its pain standards after nearly 20 years, with an emphasis on patient safety and multimodal analgesia.¹¹

Physicians also faced pressure from patients expecting opioids who could threaten the physician and hospital with negative reviews and lower Press-Ganey scores, which lowers compensation for both the hospital and the physician in question.^10,12,13 This could lead to a downward cycle of increased opioid prescriptions, often inappropriately. There are also patients who inappropriately use prescriptions and turn to other dangerous illicit substances (such as heroin or fentanyl).

This pattern of overconsumption is clearly demonstrated by this startling fact: Americans, despite only being 4.6% of the world's population, consume 99% of the world’s hydrocodone and 80% of the oxycodone.¹⁴ American patients do not experience pain any more or less than other populations. However, opioids have leeched their way into our medical system and I find many patients now expect them for their acute or chronic pain (surgical or not), causing further and greater use. An interesting study done in the Netherlands compared Dutch and American patients after bimalleolar ankle fracture surgery, finding American patients took significantly more opioids and pain medicine in every metric recorded. The authors concluded that this implies a large psychological component is involved and managing expectations preoperatively can likely reduce postoperative pain.^15,16

Weighing Opioid Benefits Against Risks

The commonly known negative side effects of opioids—like nausea, constipation, respiratory depression, and confusion—are often largely downplayed by physicians due to the thought that opioids’ benefits of significant pain reduction outweigh the potential risks. However, when comparing opioids to other pain-relieving medicines, opioids have been shown to be inferior to nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen in the postoperative setting, which have a much safer side effect profile.^17,18

Helmerhorst demonstrated in a randomized controlled trial (RCT) that after an extremity fracture, there was no difference in relief between acetaminophen versus acetaminophen plus an opioid.¹⁹ Saini and colleagues found that in a RCT, there was no difference in pain relief of acetaminophen vs. acetaminophen with tramadol for breakthrough pain after orthopedic surgery.²⁰ A study in Prescrire International found that tramadol and acetaminophen was no more effective at pain control than ibuprofen and similarly, Edwards and colleagues reviewed five RCTs and found that for postoperative pain, tramadol with acetaminophen was similar to 400mg of ibuprofen.^21,22 Brattwall and colleagues demonstrated that etoricoxib was more effective at postoperative analgesia after hallux valgus surgery than tramadol.²³ Treating acute, perioperative, or chronic pain for many foot and ankle pathologies does not need to be anchored with copious amounts of opioids.

On top of this, a number of studies have also demonstrated overprescription of opioid pain relievers after surgical intervention. Finney and colleagues showed that almost 13% of hallux valgus surgery patients did not fill their opioid prescription at all.²⁴ Kvarda and colleagues showed that patients routinely took 50% or fewer than the opioids prescribed to them.²⁵ Merrill and colleagues demonstrated rampant overprescription specifically in foot and ankle surgery (as well as oral, general, and urological surgery specialties), though the authors did not offer a protocol to help curb this.¹ Zhu and colleagues studied lower extremity trauma (fracture and dislocations) and 60% of the patients used less than their prescription and 10% didn’t fill it at all.26 Finney and colleagues showed around 6.2% of patients who were given opioid prescriptions after hallux valgus surgery were persistent users 1 year later.²⁴ This suggests a significant need to address appropriate non-opioid pain management in hallux valgus surgery. Saini, Basilico and their respective colleagues revealed similar trends in the literature—surgeons are giving their patients too many opioids and there can be dire consequences from this.^20,27 Another reason this is concerning is that this leaves a large reservoir of unused pills, and 80% of modern heroin users reported nonmedical use of legal prescription opioid use prior to heroin initiation.^28-31 Similarly shocking, 66% of opioids used for nonmedical purposes are obtained from a friend or relative.^29,30

Opioids also have many lesser-appreciated negative effects on the outcomes of surgery. There have been associations with decreases in bone and wound healing. Buchheit and colleagues recently found a significant increase in nonunion risk in patients who use opioids, with the highest risk in patients who are chronic opioid users.³² Patients who are chronic opioid users also have decreased bone mass density compared to non-opioid using controls.³³ Opioids effect may be related to their central nervous system side effects, their endocrine effects, or direct action on bone cells. Opioid pain medicine leads to weaker bone callus as well as impeding callus maturation when compared to controls.^33,34 There have also been animal models showing a negative effect on bone remodeling and healing after use of fentanyl.³⁵ Something that lends credence to this idea is that opioid antagonists are being utilized for treatment of osteoporosis and this accelerates bone healing in those patients.³⁵

One of their most potent effects is a decrease in testosterone production, which is absolutely critical for anabolic pathways, including bone and wound healing. Bawor and colleagues completed a systematic review and demonstrated that up to 50% of endogenous testosterone is lost in opioid-using patients.³⁶ A similar result was found by Colluzi and colleagues, who found that in non–cancer patients, testosterone production dropped significantly as well.³⁷ Fimmel, Demling and their respective colleagues have demonstrated that testosterone is absolutely critical in order to have patients recover properly in the postoperative period.^38,39 On top of the decrease in testosterone, opioids modulate and weaken the immune system due to specialized mu receptors, and the immune system is necessary to respond to inflammation, which is a vital step in the process to heal bone and soft tissue. These effects on surgical wound healing in orthopedic procedures have not been fully elucidated, but it is not an unreasonable hypothesis that opioids are potentially delaying healing and recovery in surgical patients, possibly synergizing with patient comorbidities that already modulate the immune response.^40-43 Opioid tolerance and induced hyperalgesia are also large drawbacks that aren’t commonly discussed.⁴⁴ Sleep is also interrupted as opioids are sedatives, not sleep-enhancing agents. Opioids create a worse sleep quality and less-restful sleep, which can lead to an increased perception of pain, an increase in sleep-disordered breathing, as well as a significant decrease in quality of life.^45-49

There are problems with specific opioids as well. For example, hydromorphone, which is sometimes given for large reconstructive surgery, was found to be indistinguishable from diacetylmorphine (heroin) in a blinded trial in active heroin users.^50,51 Tramadol is an incredibly toxic drug that is made even more dangerous by the common misnomer that “it’s not a real opioid.”^21,52 Tramadol has many drug-drug interactions, induces the CYP2D6, lowers the seizure threshold, its effects are all not fully reversed by naloxone, tramadol use can lead to hypoglycemia, and tramadol been shown to increase the risk of serotonin syndrome.^53,54,55

In Conclusion

Further research into decreasing opioid prescribing by an even greater amount will require collaboration with the preoperative staff, anesthesia, the surgeon, and post-anesthesia care unit (PACU) staff. There is promising data to suggest that a preoperative cocktail of acetaminophen, celecoxib, and gabapentin can significantly reduce opioid consumption.⁵⁶ During the procedure, there is data to suggest that ketorolac, dexamethasone, ketamine, magnesium, or dexmedetomidine can decrease pain and opioid consumption as well.^57-65 Future data may bring to light an optimal opioid-sparing protocol following foot and ankle surgery.

Dr. Ehlers is in private practice in Arvada, CO, and is an attending at the Highlands-Presbyterian/St. Luke’s Podiatric Residency Program. He finds interest in debunking medical myths and dogma.

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