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American Journal of Emergency Medicine 35 (2017) 337–341

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American Journal of Emergency Medicine

journal homepage: www.elsevier.com/locate/ajem

Controversies Something for pain: Responsible use in emergency medicine☆

Reuben J. Strayer, MD a,⁎,SergeyM.Motov,MDb, Lewis S. Nelson, MD c a 79-01 Broadway, Department of Emergency Medicine, Icahn School of Medicine at Mount Sinai, Elmhurst, NY 11373, United States b 4802 Tenth Ave, Department of Emergency Medicine, Maimonides Medical Center, Brooklyn, NY 11219, United States c 185 South Orange Avenue, Department of Emergency Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, United States article info abstract

Article history: The United States is currently experiencing a public health crisis of opioid addiction, which has its genesis in an Received 16 September 2016 industry marketing effort that successfully encouraged clinicians to prescribe liberally, and asserted the Received in revised form 18 October 2016 safety of prescribing opioids for chronic non-cancer pain, despite a preponderance of evidence demonstrating Accepted 20 October 2016 the risks of dependence and misuse. The resulting rise in opioid use has pushed drug overdose deaths in front of motor vehicle collisions to become the leading cause of accidental death in the country. Emergency providers frequently treat patients for complications of opioid abuse, and also manage patients with acute and chronic pain, for which opioids are routinely prescribed. Emergency providers are therefore well positioned to both prevent new cases of opioid misuse and initiate appropriate treatment of existing opioid addicts. In opioid-naive patients, this is accomplished by a careful consideration of the likelihood of benefit and harm of an opioid prescription for acute pain. If opioids are prescribed, the chance of harm is reduced by matching the number of pills prescribed to the expected duration of pain and selecting an opioid preparation with low abuse liability. Patients who present to acute care with exacerbations of chronic pain or painful conditions associated with opioid misuse are best managed by treating symptoms with opioid alternatives and encouraging treatment for opioid addiction. © 2016 Elsevier Inc. All rights reserved.

1. Introduction 1996 around the introduction of Oxycontin. These efforts convinced clinicians–despite thousands of years of contradictory evidence–that We are in the midst of a public health crisis of opioid addiction and opioids could be used chronically without dose escalation, addiction, mortality, largely driven by prescription opioids [1,2,3]. In 2008, drug or overdose [11]. Physician opinion leaders and patient advocacy groups overdose overtook automobile accidents as the leading cause of acci- were enlisted by industry to create the epidemic of untreated pain, from dental death in the United States [4], led by over 28 000 which pain assessment emerged as the “fifth vital sign” along with other deaths in 2014 [5]. This unprecedented surge in opioid mortality was initiatives that greatly expanded the use of opioids for acute and chronic caused by a 700% increase in opioid prescribing over the same period painful conditions. In 2007, Purdue Pharma received a felony conviction [6]. Americans represent 5% of the world's population, yet are and was fined $634 million for misleading doctors, patients, and regula- prescribed more opioids than all other countries combined [7], tors about Oxycontin's abuse liability, but Oxycontin has generated rev- amounting to 259 million prescriptions in 2012–more than the number enues in excess of $30 billion [12]. of American adults. This dramatic expansion of opioid use parallels a Emergency physicians are positioned at the center of the opioid ad- similar rise in chronic pain, which is reported to affect more than 100 diction epidemic. Opioid misusers present for care with illness related million Americans [8]. directly to opioid use (overdose, withdrawal, complications from injec- The overprescription of opioids can be traced to several publications tion) or from downstream harms (addiction, trauma, depression, home- in the 1980s that opened the door to treating non-cancer pain chroni- lessness). Both opioid misusers and chronic pain patients frequent acute cally with opioids [9,10], and then to a marketing effort starting in care facilities with expectations of being treated with an opioid [13]. Least conspicuously, but perhaps most importantly, some patients seen in emergency settings receive a prescription that initiates or con- tributes to an . ☆ All authors contributed substantially to the manuscript's genesis, drafting, and Emergency providers can lessen opioid-associated harms in their revision. All authors report no relevant conflicts of interest and received no external communities by preventing new cases of addiction and promoting funding. treatment in existing misusers. In the following sections we describe ⁎ Corresponding author at: Department of Emergency Medicine, Elmhurst Hospital, 79- fi 01 Broadway, Room B1-27, Elmhurst, NY 11373, United States. how these priorities can be effectively carried out, and include speci c E-mail address: [email protected] (R.J. Strayer). phraseology that can used in these often difficult conversations.

http://dx.doi.org/10.1016/j.ajem.2016.10.043 0735-6757/© 2016 Elsevier Inc. All rights reserved. 338 R.J. Strayer et al. / American Journal of Emergency Medicine 35 (2017) 337–341

2. Prevent New Cases of Addiction: Prescribe Fewer Opioids to Table 1 Fewer Patients Opioid alternatives for outpatient management of acute and chronic pain. 400–800 mg, three times daily (or equivalent NSAID) The relief of pain is a core mission of medicine. Opioids are effective Acetaminophen 1000 mg, four times daily for short term relief of acute pain and are used routinely for this indica- 1500 mg, four times daily (back pain, muscle spasm) tion, to substantial benefit. This benefit, however, must be bal- Topical Gel 3%, apply three times daily (musculoskeletal pain) 100 mg three times daily, increase by 100 mg every 3 days up to fi anced against harms, in the same way that the likelihood of bene tand 900 mg/day (neuropathic pain) harm is assessed before prescribing an anticoagulant, an antibiotic, or patch, apply 12 of 24 h every day (back pain, postherpetic neuralgia) anything else. The balance of benefits and harms for an opioid prescrip- Topical cream 0.025% or patch 8%, apply twice daily (back pain, tion must also be compared to the balance of benefits and harms of al- neuropathic pain) Lidocaine cream or gel 2–3%, apply three times per day (burns, painful rashes) ternate therapies, which vary across patients and painful conditions. Sumatriptan 100 mg once at onset of headache (or equivalent triptan) Furthermore, as with antibiotics and the development of resistant bac- 10 mg at bedtime (neuropathic pain) (or equivalent tricyclic) teria, there are consequential adverse public health effects associated Medical referral (all chronic pain) (indications and availability vary by with the use of opioid that should be considered. jurisdiction) For many current prescribers, the harms of opioids have been under- emphasized and are under-appreciated. In addition to common bother- some adverse effects such as constipation, when taken as prescribed for Most acute pain improves within days [45,46] and if one patient in acute pain opioids may cause dysphoria, confusion, falls, and motor ve- hundred discharged with an opioid prescription is set down the path hicle collisions. Acute physical dependence can develop within several of opioid misuse, the resulting harm to that patient is so immense that days and its attendant withdrawal symptoms may be mistaken for on- it almost certainly exceeds the incremental analgesic benefit opioids going discomfort from the injury or illness, which the patient effectively may offer to everyone else. treats with more opioids [14,15]. The balance of benefit and harm shifts Unfortunately we cannot accurately predict which patients whose dramatically as tolerance develops. Opioid tolerance is a normal physi- acute pain is treated with opioids are likely to develop opioid misuse– ologic response that results in the reduced effectiveness of an opioid at a existing risk assessment tools are unreliable and often not easily applied given dose, requiring a higher dose to obtain the previous degree of pain in the emergency department [47]. Particular caution should be relief. Simultaneously, opioids sensitize patients to pain: opioid-induced exercised when prescribing opioids to groups known to be at high hyperalgesia may occur within a week of opioid therapy and accounts risk: adolescents and young adults, patients with a history of substance for the commonly observed phenomenon in which regular opioid use (including tobacco), social isolation or dysfunction, existing psychi- users experience pain and distress out of proportion to what is expected atric disease, and concomitant use of sedatives [48,49]. for the stimulus (e.g. when starting an IV) [16-20]. Hyperalgesia and tol- When opioids are prescribed for acute pain, the likelihood that mis- erance, which are difficult to distinguish clinically, initiate a cycle of use will arise from that prescription is likely reduced by prescribing pain relief and pain exacerbation, and in predisposed patients catalyze fewer pills, and if severe pain persists beyond several days, the patient the transition from short to long-term opioid use. should be re-evaluated. We therefore recommend that if the patient is The most important change individual emergency providers can thoughttobemorelikelytobenefit than be harmed by outpatient opi- make in their practice to counter the opioid addiction epidemic is to ap- oids, that in addition to optimal non-opioid analgesia, opioids be pre- propriately reduce the number of patients with acute pain discharged scribed for 2–3 days [50]. Because leftover pills are an important with an opioid prescription: to keep opioid-naive patients opioid-naive source of accidental pediatric exposures [51,52] and misused opioids, [21]. Opioid prescribing from the ED doubled between 2000 and 2010 especially in teenagers [53], instruct patients to dispose of unused pills [22], and a recent study estimates that more than 1 in 6 patients is by returning them to the pharmacy, or flushing them down the toilet. discharged from the ED with an opioid prescription [23].Mostofus Although among the most commonly prescribed in America, were taught that abuse could not develop from a short course of opioids and especially are more abuse-prone than used to treat acute pain; [24] we now know this is untrue [25]. Opioid other opioids; [54-56] a simple way to reduce harm caused by opioids is naive patients who receive a prescription for acute pain are more likely therefore to shift prescribing toward alternatives to these agents. Oxyco- to be using opioids long beyond their expected duration of pain [26-31], done and hydrocodone preparations for acute pain are usually combined asignificant proportion of opioid misusers were initially exposed to opi- with acetaminophen, but combination preparations do not offer a clear oids through a doctor's prescription [32-34], and four out of five analgesic benefit over corresponding monotherapies, they prevent opti- users abused prescription opioids before escalating to heroin [35]. mal dosing of acetaminophen, and occasionally cause acetaminophen- Many currently practicing clinicians were trained to liberally pre- induced hepatotoxicity [57-59]. “Weak” opioids such as and scribe opioids for a variety of acute pain syndromes. However, the major- are associated with a host of unique toxicities [60,61].Extended ity of patients discharged from acute care settings with acute pain can be release/long-acting opioid preparations such as OxyContin or effectively managed with opioid alternatives. Ibuprofen 400 mg and acet- patches are more dangerous than immediate release preparations [62] aminophen 1000 mg every six hours will provide effective analgesia for and should not be prescribed in acute care settings. Though data is limit- most adult patients with acute pain–in many cases more effective analge- ed, given the harms associated with alternatives, we recommend sia than opioids [36-43]. There are a variety of pharmacologic and immediate-release , 15 mg tablets, when outpatient opioids nonpharmacologic opioid alternatives effective for most acute pain are thought to be indicated [63]. discharged from emergency settings (Table 1). Some patients with acute pain will have significant pain in the post-discharge period despite treatment with non-opioid modali- 3. Promote Treatment in Misuse: Opioid Addiction and Chronic Pain ties; the harm from this pain must be weighed against the harms of opioids. Managing expectations is a crucial component of treating A much greater challenge is the patient who presents with an exac- patients in pain. The goal is not zero pain, but reducing pain enough erbation of chronic pain or complaints related to what is felt to be opioid to allow the patient to function well for the duration of the painful misuse. Clinicians have powerful incentives to provide these patients condition [44]. with the opioids they request; these include the need to optimize per- formance metrics and customer satisfaction surveys (which may be My job is to manage your pain at the same time that I manage the po- tied to provider incentives), and the desire to avoid a protracted, diffi- tential for some pain medications to harm you. cult patient encounter [64]. Most compelling, however, is that many R.J. Strayer et al. / American Journal of Emergency Medicine 35 (2017) 337–341 339 patients who desire opioids have pain (or withdrawal symptoms) that Opioid misusers and many daily opioid users with chronic pain are is relieved by opioids. harmed by opioids. When these patients present to acute care seeking The most important step in improving the care of these patients is to opioid therapy or an opioid prescription, providers have a chance to in- recognize that despite delivering immediate relief of suffering, opioids tervene in the incapacitating cycle of pain, craving, and withdrawal by are more likely to harm patients with chronic use than help them. Un- encouraging them to treatment. Most will not be receptive, but a single like acute pain, opioids do not benefit most patients with chronic non- misusing patient redirected is a life changed or possibly saved. cancer pain [65,1]. Chronic pain often worsens not despite opioids but because of opioids, through tolerance and hyperalgesia. The relationship Prescription pain medications, even when used as directed, can cause between chronic pain and opioid misuse is complex, overlapping, and patients to become dependent, and I′m concerned that you may now incompletely understood, however emergency clinicians best serve be dependent on the pills we prescribed for you in the past, even though their patients by recognizing that both groups are more likely to be you were using them appropriately. We can help you break free of that harmed than helped by continued opioid use. To treat a patient with dependence. chronic opioid use in the acute care setting with opioids sustains or aug- ments their pain, perpetuates inappropriate expectations about opioid Your pain would improve, and your life would improve, if you stopped efficacy, contributes to misuse, risks addiction and a host of other ad- taking these pain medications. Can I offer you resources that will help verse effects, and delays recovery. The most powerful predictor of pre- you stop taking them, so you can get your life back? scription drug overdose death is three or more visits to an emergency department in the previous year [66]. These are the patients whose Consider dispensing business cards that refer patients to the lives have been ruined by opioids, who are going to be killed by SAMHSA National Helpline–a free, confidential, 24/7 Spanish and En- – opioids their presentation to an emergency department is an opportu- glish treatment referral and information service; similar services exist nity for providers to intervene. in many jurisdictions outside the US. Whether or not opioids are used Emergency providers help chronic opioid users by relieving their to treat chronic opioid users who present in pain, providers can make pain with non-opioid modalities and engaging them to consider addic- a pivotal impact by acknowledging the harm wrought by ongoing opi- tion treatment. Withholding opioids from patients who present seeking oid use and offering paths to recovery. Although outcome data are lim- fl opioids often leads to con ict that can be distressing or even frightening ited, take-home may be a lifesaving intervention in patients at to providers. Rather than dispute what claims are true or how much high risk for overdose; naloxone distribution programs have been suc- fi pain the patient is in, we nd the best approach is to frame an unwilling- cessfully implemented in many jurisdictions [75]. ness to use opioids as coming from a conviction that they are not in the A challenging set of patients present with an acute pain complaint patient's best interests. but raise concern for opioid misuse. Deceptive patients are likely misusing opioids, so it is relevant to identify deception, but rather than I know you are in pain and I want to relieve your pain, but I will not use focusing on deception, these patients are best managed by risk stratifica- medications because I believe those medications are harming tion, using red flags and yellow flags [76,77] (Table 3). The presence of a you. red flag or multiple yellow flags makes opioid misuse likely and should inform clinician judgment as to whether that patient is more likely to Patients who seek opioids for euphoria, or are looking for pills to di- benefit from or be harmed by opioids. Querying a prescription drug mon- vert and sell, are less likely to be interested in opioid alternatives. There- itoring program is useful when it demonstrates high levels of opioid use fore, we feel that the less willing a patient is to discuss opioid or a prescription record discordant with the patient's reported history. alternatives, the less worried the provider should be that they are These recommendations are less applicable to end-of-life scenarios, under-treating pain. such as the palliation of terminal cancer pain, where the overriding pri- For very distressed patients in pain whom are likely to be harmed by ority is immediate relief of pain and suffering. Though care providers opioids and are open to alternatives, there are many options (Table 2). may abuse or divert a dying patient's medications and opioid misuse oc- Severe pain is often effectively managed with analgesic-dose , curs in cancer patients not close to the end of life [78], palliative either as a bolus or infusion. Ketamine is as effective as opioids for se- vere acute pain [67,68]. In addition, ketamine has an evolving role in the management of chronic pain in daily opioid users because it has Table 3 been demonstrated to attenuate opioid-induced hyperalgesia [69].At Opioid misuse flags. low doses, ketamine does not significantly affect cardiorespiratory func- fl tion, and monitoring as for ketamine procedural sedation is not neces- Red ags (demonstrate opioid misuse) sary [70,71]. For severe exacerbations of chronic pain, older literature Patient, relation, or provider reports addiction or diversion supports the use of sedating butyrophenones (droperidol and haloper- Injects or inhales oral opioid preparations Obtains drugs through dubious means (e.g. on the street) idol) [72,73] and others describe its successful use in this context [74]. Uses others' medications, steals Rx pads/syringes, forges Rx, false ID

Yellow flags (raise concern for opioid misuse) Table 2 fi Parenteral opioid alternatives for management of acute and chronic pain in acute care. Many visits, re ll requests, dose escalation Requesting specific medications, requesting IV route, declines non- 15 mg IV or 30 mg IM opioids Acetaminophen 1000 mg IV over 15 min (when oral route unavailable) From out of town, primary provider unavailable, passed by closer Lidocaine 2% 1.5 mg/kg IV over 15 min (renal colic, back pain, neuropathic pain) institutions Bupivicaine 0.25% 10–15 mL infiltrated at point of maximal pain (back pain, Allergies to opioid alternatives or less potent opioids musculoskeletal pain) Opioid or prescription is lost or stolen, no picture ID Metoclopramide 10 mg (headache, abdominal pain) (may substitute prochlorperazine) Uninterested in diagnosis or alternative treatments, refuses tests Propofol 10 mg IV every five minutes until relief (headache) Repeatedly misses follow-up appointments, has been terminated by Ketamine 0.25 mg/kg IV over 10 min, then 0.25 mg/kg/h, titrated (all acute and providers chronic pain) History of substance abuse or incarceration Droperidol 2.5 mg IV or IM (chronic pain) (may substitute haloperidol 5 mg) Absence of objective findings of acute pain Dexmedetomidine IV 0.5 mcg/kg bolus then by 0.3 mcg/kg/h infusion (all acute and Symptom magnification, inconsistency, distractibility chronic pain) Rehearsed, textbook presentations 50–70% inhaled (acute pain) Deterioration of work/social function, disability 340 R.J. 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