Opioid Prescribing for Acute Pain Management in Children and Adolescents in Outpatient Settings: Clinical Practice Guideline Part 1
Myron Yaster MD, Elliot J. Krane MD, and Lynne G. Maxwell MD
The use of opioids in the treatment of moderate to severe acute pain has over the decades been a widely swinging pendulum: from liberal use in the 2000s (the multifactorial result of the JCAHO’s emphasis on “pain is the fifth vital sign,” pain society treatment guidelines and pernicious marketing by you-know-who) to the current conservative to the point of paranoid prescription refusal/avoidance/dose limitations due to CDC pronouncements, draconian VA rules, fear of opioid abuse, and opioid overdose deaths and DEA surveillance and prosecution of prescribers.
In today’s PAAD, Hadland et al.1 provide the American Academy of Pediatrics’ well balanced and very thoughtful clinical practice guideline on the management of acute pain in children and adolescents. Written primarily for pediatricians, many of the concepts like multimodal analgesia are familiar and essential components of your daily practice. However, for those of you who are actively involved in pediatric pain management and teaching, this article is a must for your teaching files and for your students/trainees.
We’ve discussed many of the issues in this clinical practice guideline in many previous PAADs, perhaps most importantly the article by Kharasch et al.2 entitled Opioids and Public Health: The Prescription Opioid Ecosystem and Need for Improved Management (PAAD 01/06/2022 Prescription Opioid Ecosystem https://ronlitman.substack.com/p/readers-comments ). If you haven’t read that PAAD, I’d urge you to download it and read it today as well.
There is a lot to unpack in this clinical practice guideline and in keeping with our 5-6 minute reading time rule I’ve decided to split it into 2 parts. Almost all of the recommendations (key action statements) in this guideline make sense and align with current practice. For us, one of the strengths of the guideline is that the committee writing it ensured inclusion and perspectives of patients and their families, the potential repercussions of prescribing fewer opioids, namely, the undertreatment of pain. Additionally, the authors underscored the immediate need for equity in this guideline. It is well established that minority groups, nonverbal patients and patients with physical, developmental, or intellectual disabilities are frequently under-treated with opioids for pain.3-5 Their needs are appropriately highlighted in this guideline.
One question that often isn’t discussed and is mentioned in the guideline is “why do some patients develop opioid (or other substance) use disorder and others do not?” The answer: “individuals with unaddressed mental health concerns (eg, depression, anxiety, trauma and PTSD), genetic vulnerability (estimated to account for as much as 70% of the risk of OUD) or prior substance use (eg, nicotine, alcohol, cannabis, psychostimulants) are at elevated risk for OUD, poisoning, or overdose.”6 We will dive deeper into this question and the implications of ACEs, trauma and depression in an upcoming PAAD (from this month’s issue of Scientific American). So, stay tuned! Myron Yaster MD
PS: The PAAD’s primary reviewer of pain articles, Dr. Rita Agarwal, was one of the authors of this paper. Congratulations to Rita!
Original article
Hadland SE, Agarwal R, Raman SR, Smith MJ, Bryl A, Michel J, Kelley-Quon LI, Raval MV, Renny MH, Larson-Steckler B, Wexelblatt S, Wilder RT, Flinn SK. Opioid Prescribing for Acute Pain Management in Children and Adolescents in Outpatient Settings: Clinical Practice Guideline. Pediatrics. 2024 Sep 30:e2024068752. doi: 10.1542/peds.2024-068752. Epub ahead of print. PMID: 39344439.
The clinical guideline has 9 key action items. The stated goals of this clinical practice guidelines are to maximize analgesia, limit the use of opioids, and reduce the risk of patients developing opioid use disorder (OUD).
To be honest, we disagree with this foundational orientation. Opioids have been used in the treatment of pain for over 5,000 years, because they work and no better strong analgesic has been found in these millenia! There is no question that they are associated with common (constipation, nausea/vomiting, pruritus, development of tolerance and dependance) and uncommon (respiratory depression/death) side effects and risks.
However, the link between the legitimate use of opioids and the development of opioid use disorder and death is not as clear as this guideline and some of our professional societies suggest. Indeed, in 2024 there still isn’t a well established causative connection between legitimate prescription opioids in the management of pain and the development of opioid abuse and/or OUD, especially in youth. (Here it is important to distinguish misuse of opioids – something we would wager the majority of you readers have committed – from OUD/opioid abuse, wherein misuse is the use of opioids without the prescriber’s approval, such as taking a dose larger or more often than prescribed, or an old leftover prescription for a subsequent pain event, while abuse is their use for nonmedical purposes.) And, this is one of the paradoxes of current treatment strategies and these guidelines. Despite all of our successful efforts to reduce the quantities and duration of dispensed opioids, the prevalence of death from opioids has actually increased. Indeed, between 2000 and 2010 illicitly obtained prescription opioids were responsible for the majority of opioid deaths, but since 2010, opioid deaths are primarily the result of heroin and most recently illicit fentanyl, and not the non-medical use of prescription opioids.7,8
1. Optimizing Nonpharmacologic Approaches and Nonopioid Medications for Pain Management: “Pediatricians and other PHCPs should treat acute pain using a multimodal approach that includes the appropriate use of nonpharmacologic therapies, nonopioid medications, and, when needed, opioid medications.”1 As anesthesiologists we are all familiar with and use multimodal approaches to analgesia on a daily basis. This includes acetaminophen, NSAIDs, local anesthetics/regional anesthetic techniques AND opioids. Thus, these guidelines recognize that opioids are an essential part of pain management. Further, the guidelines recognize that “Chronic medical conditions, such as sickle cell disease or cancer—which come with frequent or recurrent episodes of acute pain—should, ideally, be managed by the pediatrician in consultation with a pain management specialist.”
2. Pediatricians and other PHCPs should NOT prescribe opioids as monotherapy for children and adolescents who have acute pain. This is a return to the old WHO pain treatment ladder.
3. When prescribing opioids for acute pain in children and adolescents, PHCPs should provide immediate-release opioid formulations, start with the lowest age- and weight-appropriate doses, and provide an initial supply of 5 days or fewer, unless the pain is related to trauma or surgery with an expected duration of pain of more than 5 days. For many reasons, prescribers often prescribe more opioid than patients actually use.9 The leftover opioid may contribute to a pool of drug that can result in later non-medical use of prescription opioids. One of the key reasons for prescribing too much? To limit the need for refills and call back from families. For many surgical patients in which pain is expected and more than a 5 day supply is warranted (posterior spine fusion, limb salvage, major trauma, pectus excavatum repair) a better solution that would require changes in American law would be to allow pharmacies to dispense less than the full amount written in the prescription. For example, the doctor could write to dispense a 10 or even 30 day supply but to dispense only 5 days of meds. If the patient needed more they can go to pharmacy for more without the need for a new prescription. In most of the United States this is currently illegal. The guidelines also state that “Opioid doses are typically weight based for children and adolescents <50 kg (eg, for oxycodone, 0.1 to 0.2 mg/kg per dose every 4 to 6 hours) and given in fixed doses for those ≥50 kg (eg, for oxycodone, 5 to 10 mg every 4 to 6 hours). For children and adolescents who are obese, PHCPs may consider consulting with a pharmacist to determine the appropriate dose because hydrophilic opioids (eg, oxycodone, morphine) should initially be dosed based on ideal body weight, whereas lipophilic opioids (eg, methadone) should initially be dosed based on total body weight.” Finally, there may be a place for long acting, sustained release opioid preparations in the treatment of some chronic pain conditions, but not in the initial treatment of ACUTE pain.
4. When treating acute pain in children and adolescents younger than 12 years, pediatricians and other PHCPs should NOT prescribe codeine or tramadol. Ah, the answer to the test question in all training examinations! The metabolism of codeine into morphine by the CYP 2D6 can result in too much morphine (fast or ultra-rapid metabolizers) or no morphine in slow (poor) metabolizers. Tramadol is also metabolized in the 2D6 pathway into the active metabolite O-desmethyltramadol (M1), which has a significantly higher affinity for the mu-opioid receptor than tramadol. The M1 metabolite is up to 6 times more potent than tramadol in producing analgesia! (And oxycodone is metabolized by CYP3A4 to noroxycodone and by CYP2D6 to oxymorphone. Noroxycodone is a weaker opioid agonist than the parent compound, but the presence of this active metabolite increases the potential for interactions with other drugs metabolized by the CYP3A4 pathway.)
We will review the remaining key action statements in tomorrow’s PAAD. Send your thoughts and comments to Myron who will post in a Friday reader response.
References
1. Hadland SE, Agarwal R, Raman SR, et al. Opioid Prescribing for Acute Pain Managet in Children and Adolescents in Outpatient Settings: Clinical Practice Guideline. Pediatrics 2024.
2. Kharasch ED, Clark JD, Adams JM. Opioids and Public Health: The Prescription Opioid Ecosystem and Need for Improved Management. Anesthesiology 2022; 136(1): 10-30.
3. Goyal MK, Johnson TJ, Chamberlain JM, et al. Racial and Ethnic Differences in Emergency Department Pain Management of Children With Fractures. Pediatrics 2020; 145(5).
4. Groenewald CB, Rabbitts JA, Hansen EE, Palermo TM. Racial differences in opioid prescribing for children in the United States. Pain 2018; 159(10): 2050-7.
5. Hauer J, Houtrow AJ. Pain Assessment and Treatment in Children With Significant Impairment of the Central Nervous System. Pediatrics 2017; 139(6).
6. Cranfield E, Ashcroft E, Forget P. Mortality by opioid poisoning in children and teenagers and opioid prescriptions. BMC Pediatr 2021; 21(1): 569.
7. Szalavitz M. How Fentanyl Drove a Tsunami of Death in America. New York Times. 2024 09/27/2024.
8. Tanz LJ, Dinwiddie AT, Mattson CL, O'Donnell J, Davis NL. Drug Overdose Deaths Among Persons Aged 10-19 Years - United States, July 2019-December 2021. MMWR Morbidity and mortality weekly report 2022; 71(50): 1576-82.
9. Hunsberger JB, Hsu A, Yaster M, et al. Physicians Prescribe More Opioid Than Needed to Treat Pain in Children After Outpatient Urological Procedures: An Observational Cohort Study. Anesthesia and analgesia 2020; 131(3): 866-75.