Given the increasing numbers of people who are dependent on and/or addicted to opioids, physicians should have a firm grasp of pain management principles that can avoid adverse side effects. Accordingly, this author explores recent opioid prescription guidelines for managing acute and postoperative pain.
The Centers for Disease Control and Prevention (CDC) reported over 165,000 deaths related to overdoses of prescription opioids from 1999 to 2014.1 In 2011, there were over 400,000 emergency department visits for overdose of prescription opioids.2 The United States Substance Abuse and Mental Health Services Administration reported that in 2014, nearly 2 million people were dependent on or abused prescription opioids.2 In 2014, over 14,000 people died from overdose of prescription opioids, which was a fourfold increase from 1999.1 Boscarino and colleagues found that as many as 25 percent of patients prescribed opioids for non-cancer pain struggled with addiction.3
Opioid prescribing rose significantly from 2000 to 2012 with U.S. healthcare providers issuing 259 million prescriptions for opioid analgesics in 2012.4,5 In 2015, the CDC declared the soaring rate of opioid prescribing, with the use of opioids as the primary treatment of both acute and chronic pain, to be an epidemic.
The increase in opioid prescribing correlates with significant numbers of individuals with chronic pain seeking care. Chronic pain is extremely prevalent among U.S. adults. In 2010, Johannes and coworkers published their results of an Internet-based survey on chronic pain prevalence in the U.S., showing that 30 percent of the population experienced chronic pain.6 Low back pain and osteoarthritis were the most common causes of chronic pain, and the incidence of chronic pain correlated with lower socioeconomic status.
While safety risks have been one of the largest concerns leading to reduction in opioid prescribing, concerns over a lack of efficacy in the management of chronic pain have also contributed to calls for decreased use.7 Physicians frequently treat chronic low back pain with prescription opioids yet data is lacking on the efficacy of opioids in the treatment of chronic low back pain. Chaparro and colleagues found opioid analgesics typically only improved chronic back pain by 8 to 12 points on a 100-point scale.8
What You Should Know About The Effects Of Opioids
Opioids are powerful analgesics that act by binding opioid receptors distributed on neurons throughout the body. There are several types of opioid receptors, which are binding sites for endogenous peptides that modulate body functions including pain, stress, temperature, respiration, endocrine activity, gastrointestinal function and mood.
Subsequently, drugs that bind these receptors have extensive effects on numerous bodily functions. Most opioids are mu receptor full agonists and are associated with pain relief, mood alteration, respiratory depression, decreased gastrointestinal motility, cough suppression and suppression of corticotropin-releasing factor and adrenocorticotropic hormone. Opioids have a high potential for addiction and abuse due to their capacity to affect mood and ability to cause euphoria via mu receptor activation.
There are many adverse effects associated with both short- and long-term opioid use.9 Adverse events reportedly occur at all dose ranges but frequently increase with daily opioid use, higher dosage and long-term therapy.10,11 Common side effects associated with opioids include dry mouth, constipation, sweating, weight gain, somnolence, sleep disturbance, memory loss, anorexia, nausea, vomiting, loss of concentration, fatigue, sexual dysfunction, dizziness, pruritus and urinary retention.12
Lesser known adverse effects of opioids include endocrine disruption and serotonin syndrome. Recently, researchers have found that transdermal and sustained release opioids cause numerous endocrine changes including inhibited release of hypothalamic and pituitary hormones, leading to the suppression of cortisol, testosterone and estrogen.13-15 This inhibition of androgen production results in hypogonadotropic hypogonadism, which presents clinically as decreased libido, erectile dysfunction, fatigue, amenorrhea and infertility.
Serotonin syndrome is another potential adverse event that can result from chronic opioid therapy. The Food and Drug Administration (FDA) recently required changes in opioid labeling to include the risk of serotonin syndrome.16 With antidepressants currently the third most commonly prescribed class of prescription medications and opioids frequently prescribed for acute and chronic pain, the risk of this potentially harmful interaction is high.17
The Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5) identifies opioid use disorder as continued opioid use despite adverse consequences. The disorder is characterized by at least two of the following criteria occurring in a 12-month period.18
• Taking an increased dose or prolonged course of opioids.
• Experiencing a persistent desire for opioids and unsuccessfully decreasing or controlling opioid use.
• Spending extensive time obtaining, using or recovering from use of opioids.
• Craving or having a strong desire to use opioids.
• Using opioids in a way that interferes with major life obligations.
• Continuing to use opioids despite negative social and interpersonal consequences caused by opioid use.
• Avoiding social, occupational or recreational activities because of opioid use.
• Using opioids in physically hazardous situations.
• Continuing opioid use despite physical or psychological problems resulting from or exacerbated by opioid use.
• Developing tolerance, defined by a significantly decreased effect with continued use of the same amount of an opioid, often requiring markedly increased amounts of opioids to achieve the same effect.
• Opioid withdrawal syndrome or taking opioids to avoid withdrawal.
The leading cause of opioid-related mortality is respiratory depression. Less common effects of opioid overdose are acute lung injury, status epilepticus and cardiotoxicity. Both hepatic and renal disease can inhibit opioid metabolism and increase the risk of opioid overdose. Opioid-related deaths increased significantly from 2002 to 2010 and again from 2013 to 2014.19,20 From 2013 to 2014, the overdose death rates related to opioids rose 14 percent, reaching 9.0 per 100,000-person population.20
A Closer Look At The CDC Guideline On The Opioid Epidemic
In response to the opioid crisis, the CDC published its “Guideline for Prescribing Opioids for Chronic Pain” in March 2016.21 This guideline offers recommendations about appropriate prescribing of opioid pain relievers and alternative treatment modalities for chronic pain. While the guideline is intended for primary care physicians managing chronic opioid therapy, it is important for foot and ankle surgeons to be aware of the CDC guideline, both to understand chronic opioid management for their patients as well as considering the potential impact of their prescribing of opioids for acute lower extremity injuries and postoperative pain management.
The guideline provides 12 recommendations and intends to improve communication regarding the risks and benefits of opioid therapy, improve effectiveness of chronic pain treatment and decrease risks associated with chronic opioid therapy.21,22
1. Use non-pharmacological and non-opioid pharmacologic therapy. The primary CDC recommendation is the use of non-pharmacologic and non-opioid therapies for the management of chronic pain.21 In patients who do require long-term opioid therapy, one should combine non-opioid therapies with opioids whenever possible. Non-pharmacologic therapies that have been effective in the management of chronic pain include exercise, cognitive behavioral therapy, physical therapy and acupuncture.23-27
2. Establish treatment goals for long-term opioid therapy. The CDC recommends establishing goals prior to starting long-term opioid therapy and assessing improvements in both pain and function.21 The CDC generally recommends that opioid treatment only continue if there is 30 percent improvement in pain and function scores.28 However, there are some clinical disorders, including degenerative diseases and severe traumatic injuries, for which providers may expect opioid therapy to improve pain but provide no functional benefit.
3. Prior to starting and periodically during treatment, clinicians should discuss risks and benefits of opioid therapy. One should inform patients that the goals of opioid therapy are to improve pain and function, and that function may improve without complete resolution of pain. Educate patients that there are no long-term studies showing the successful treatment of chronic pain with opioid medications. Review with all patients the risks of opioid therapy, including constipation, nausea, vomiting, drowsiness, inability to operate a vehicle safely, respiratory depression, physical dependence, withdrawal, opioid use disorder, overdose and death.
4. Prescribe immediate-release opioids whenever possible, especially when starting opioid therapy. Given the unpredictable pharmacodynamics of many extended-release/long-acting (ER/LA) opioids, the CDC encourages use of immediate release opioids whenever possible. The new guidelines state that one should not use ER/LA opioids for initial treatment or for intermittent use in the management of chronic pain.21 The CDC additionally cautions against combining ER/LA opioids with immediate release opioids.
5. Start opioid therapy at the lowest effective dose and gradually increase the dose with caution if needed. The new CDC guidelines recommend that opioid therapy for chronic pain start at the lowest effective dose.21 While the CDC does not specify an exact time course for dose increments, it recommends caution with dose increases and by the smallest amount possible. The CDC recommends considering additional precautions such as more frequent follow up and prescribing naloxone (Evzio, Kaleo) when patients reach a daily opioid dose of 50 morphine milligram equivalents (MMEs).
6. For acute pain, prescribe the lowest effective dose of immediate-release opioids for only the expected duration of severe pain (three to seven days). This CDC recommendation is one of the most relevant to foot and ankle surgeons.21 Given that long-term opioid use frequently starts with the treatment of acute pain, the CDC recommends limiting opioid treatment of acute pain to the shortest duration possible, often three days or less, and rarely more than seven days. Additionally, the CDC recommends that clinicians only use immediate-release opioids for the treatment of acute pain. While the CDC guideline refers clinicians to the Washington State Agency Medical Directors’ Group Interagency Guideline on Prescribing Opioids for Pain for recommendations regarding the use of opioids for post-surgical pain management, it is important to consider this recommendation for the management of acute pain.29
7. One should frequently monitor the benefits and harms of opioid therapy. The CDC recommends evaluating the benefits and harms of opioid therapy one to four weeks after starting or changing the dose of opioid therapy for chronic pain.21 The CDC also recommends evaluating continued opioid therapy at least every three months. At follow-up, determine if patients are meeting their treatment goals with continued improvement in pain and function, and whether there have been any adverse events. Signs such as difficulty controlling opioid use can indicate opioid use disorder. Episodes of sedation or slurred speech can indicate possible overdose. If the benefits of opioid therapy do not outweigh the risks, patients should reduce or discontinue their use. The CDC recommends a decrease of 10 percent of the original dose per week to minimize opioid withdrawal symptoms.
8. Evaluate risk factors for opioid-related harm and incorporate strategies to decrease these risks. Several risk factors including respiratory disorders, sleep-disordered breathing, pregnancy, renal disease, hepatic disease, age > 65 years, depression, anxiety, and drug or alcohol use disorders increase the chances of opioid-related adverse events. Other factors that increase the risk of opioid overdose include a history of substance abuse disorder, higher opioid dose (> 50 MME/day) and benzodiazepine use. Consider these risk factors when starting opioid therapy and periodically reevaluate these factors throughout continued opioid treatment. For patients with risk factors who do require opioid therapy, one can incorporate adjunct modalities, including naloxone, to lower the risk of adverse events.
9. Review state prescription drug monitoring program (PDMP) data. The PDMP data can provide valuable information regarding opioid and other controlled substance prescriptions from other prescribers. The CDC recommends reviewing PDMP data before every opioid prescription in order to help avoid overdose or dangerous medication combinations.21 This practice can be limited, however, in states with poorly functioning or difficult to access PDMPs.
10. Use urine drug testing prior to starting and at least annually when prescribing opioids for chronic pain. The CDC recommends that primary care physicians perform urine drug testing to screen for prescribed opioids as well as other controlled substances and illicit drugs that can increase overdose risk.21
11. Avoid concurrent prescribing of opioids and benzodiazepines. Given the risk of respiratory depression, physicians should avoid prescribing opioids concurrently with benzodiazepines. An exception to this is the use of opioids for acute pain in patients taking long-term low dose benzodiazepines. Additionally, physicians should try to avoid prescribing opioids with other central nervous system depressants such as muscle relaxants and sleep aids.
12. Offer evidence-based treatment for patients with opioid use disorder. If one suspects opioid use disorder (this can be based on patient behavior or PDMP data), discuss this with the patient and make a referral for evidence-based treatment. There are numerous evidence-based treatment modalities including methadone, buprenorphine and naloxone.30-32
The CDC guideline and subsequent similar state regulatory agency recommendations on opioid prescribing have led to considerable amounts of debate from both physicians concerned about limitation of their prescribing practices and inability to manage patients’ pain adequately, as well as patients with chronic pain who are concerned about discontinuation of their opioid therapy.21,29
The CDC is careful to remind providers and patients that the goal of this guideline is to improve communication between clinicians and patients about the risks and benefits of opioid therapy, and improve the safety of chronic opioid therapy. The guidelines highlight that there is insufficient evidence for every clinical decision regarding the use of opioids and that clinicians must use discretion in light of these recommendations and individual patient situations to determine the best pain management strategy.33
While the CDC guidelines for the management of chronic pain have received the greatest attention in the nation’s attempt to address the opioid crisis, the CDC recommends the Washington State Agency Medical Directors’ Group Interagency Guideline on Prescribing Opioids for Pain for recommendations on the use of opioids for post-surgical pain management.29 Similar to the CDC guidelines, the recommendations from the Washington State Agency Medical Directors’ Group highlight the use of non-opioid treatment modalities for pain management.
They recommend multimodal therapy incorporating an array of non-pharmacological therapies including cognitive behavioral therapy, spiritual care, mindfulness-based stress reduction, yoga, meditation, graded exercises, group exercise, sleep hygiene and physical therapy. Additionally, the Washington State Agency Medical Directors’ Group recommends non-opioid analgesics including acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors and anticonvulsants for neuropathic and centralized pain syndromes.29 The Washington State Agency Medical Directors’ Group defines the acute phase as pain that occurs between zero to six weeks following severe injury or surgery. It recommends only using opioids during this period if non-opioid options are insufficient or contraindicated. If opioids are required, the guidelines recommend using the lowest necessary dose and the shortest duration (typically 14 days).29
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 have also recently issued guidelines on the management of postoperative pain.35 The 2016 “Guidelines for the Management of Postoperative Pain” emerged to address high levels of inadequate pain relief with evidence showing that less than half of surgical patients reported adequate pain relief.35 These guidelines additionally recommend the following modalities to reduce postoperative opioid analgesic requirements.35
1. Preoperative education and perioperative pain management planning
• Patient- and family-centered education regarding treatment options, the plan for and goals of postoperative pain management can lower preoperative anxiety, decrease opioid requirements and shorten hospital stays.36
• Conduct a preoperative evaluation, including assessment of medical and psychiatric comorbidities, history of chronic pain and substance abuse, and previous postoperative treatment regimens to guide the perioperative pain management plan. Encourage patients to be engaged in collaborative care and share in decision-making regarding their pain management plan.
• Use validated pain assessment tools to track the response of postoperative pain to treatment (e.g. Visual Analogue Scale, numeric rating scales or Faces Pain Rating Scale).
• Adjust pain management plan based on outcomes and adverse events.
2. Multimodal therapy for the management of postoperative pain
• One should use multimodal analgesia, combining a variety of analgesic medications and non-pharmacological interventions. Researchers have shown that this model decreases opioid consumption and provides superior pain relief.37,38
3. Use of physical modalities
• Consider physical modalities including transcutaneous electrical nerve stimulation (TENS), acupuncture, massage and cold therapy as adjuncts to other postoperative pain treatments. Research has shown that TENS activates opioid receptors and reduces postoperative analgesic requirements.39
4. Use of systemic pharmacological therapies
• Use oral rather than intravenous opioids whenever possible.
• Avoid intramuscular administration of analgesics due to unreliable absorption.
• If parental medications are required, use patient-controlled analgesia (PCA) for postoperative pain.
• Avoid basal infusion of opioids with intravenous PCA.
• Monitor patients receiving systemic opioids for adverse events including sedation and respiratory depression.
• Unless the medications are contraindicated, patients should receive acetaminophen and/or NSAIDs as part of a multimodal analgesia regimen. The use of acetaminophen and/or NSAIDs may reduce pain and opioid consumption.40-43
• Clinicians should consider giving a preoperative dose of oral celecoxib in patients without contraindications. Celecoxib (Celebrex, Pfizer) may reduce opioid requirements after major surgery.44-46
• Clinicians should consider gabapentin or pregabalin (Lyrica, Pfizer) as a component of multimodal analgesia. Both medications may reduce postoperative opioid requirements.47-49
• Clinicians should consider intravenous ketamine as a component of multimodal analgesia. Ketamine may decrease postoperative pain scores and also reduce the risk of prolonged postoperative pain.50,51
5. Use of local pharmacological therapies and peripheral regional anesthesia
• Clinicians should consider site-specific local anesthetic injections. The use of long-acting local anesthetics at the surgical site may be effective in decreasing postoperative pain in several surgical procedures, including total knee replacement and arthroscopic knee surgery.52-54
• Consider a site-specific regional anesthetic block and, if possible, use continuous, local anesthetic-based peripheral anesthetic analgesic techniques.
• Consider adding clonidine as an adjunct to prolong peripheral nerve blocks.
This aforementioned guideline focuses on developing a multimodal plan tailored to the individual patient. Monitoring of the results and adverse effects of the treatment is key. Patient involvement and education are also important components of these guidelines. Adequate pain management, especially chronic pain, remains a challenge. Opioids are powerful medications and their safe use requires careful analysis of risk and benefits. The CDC, Washington State Agency Medical Directors’ Group and American Pain Society guidelines are useful tools for determining appropriate plans for pain management and opioid use.
Chronic pain as well as opioid misuse and abuse are significant public health problems. Although currently underway, further efforts are needed to change our approach to pain management. New non-opioid and non-pharmacological treatment modalities for pain need to be developed, and incorporated into multimodal analgesic treatment plans. Additionally, access to alternative therapy needs to improve and disparities in care need to be reduced.
Dr. Hoffman is an attending physician in the Department of Orthopedics at Denver Health Medical Center. She is an Assistant Professor in the Department of Vascular Surgery/Podiatry at the University of Colorado School of Medicine.
- Wide-ranging online data for epidemiologic research (WONDER). CDC, National Center for Health Statistics; 2016. http://wonder.cdc.gov .
- Prescription opioid overdose data. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/drugoverdose/data/overdose.html . Published June 21, 2016. Accessed October 3, 2016.
- Boscarino JA, Rukstalis M, Hoffman SN, et al. Risk factors for drug dependence among out-patients on opioid therapy in a large US health-care system. Addiction. 2010;105(10):1776-1782.
- Daubresse M, Chang HY, Yu Y, et al. Ambulatory diagnosis and treatment of nonmalignant pain in the United States, 2000-2010. Med Care. 2013;51(10):870-878.
- Centers for Disease Control and Prevention. Opioid Painkiller Prescribing, Where You Live Makes a Difference. Centers for Disease Control and Prevention, Atlanta, 2014. Available at http://www.cdc.gov/vitalsigns/opioid-prescribing/ .
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- Manchikanti L, Manchikanti KN, Pampati V, Cash KA. Prevalence of side effects of prolonged low or moderate dose opioid therapy with concomitant benzodiazepine and/or antidepressant therapy in chronic non-cancer pain. Pain Physician. 2009;12(1):259-267.
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- Brown RT, Zuelsdorff M, Fleming M. Adverse effects and cognitive function among primary care patients taking opioids for chronic nonmalignant pain. J Opioid Manag. 2006;2(3):137-146.
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- Daniell HW. Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of nonmalignant pain. J Pain. 2008;9(1):28-36.
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