SGEM#419: Welcome Back – To Another Episode on Back Pain

• SGEM#87:Let Your Back Bone Slide (Paracetamol for Low-Back Pain)
• SGEM#173: Diazepam Won’t Get Back Pain Down
• SGEM#240: I Can’t Get No Satisfaction for My Chronic Non-Cancer Pain
• SGEM#304: Treating Acute Low Back Pain – It’s Tricky, Tricky, Tricky
• SGEM#366: Relax, Don’t Do It – Skeletal Muscle Relaxants for Low Back Pain

Back pain and neck pain are leading causes of disability on a global scale [2,3]. The substantial disability burden imposes enormous costs both directly on healthcare systems, and indirectly through productivity losses [4,5].

Not only are these conditions common and painful they are difficult to treat. Many pharmacologic treatments have been tried with limited efficacy.

• Acetaminophen (Williams et al Lancet 2014)
• Muscle relaxants (Friedman et al JAMA 2015)
• NSAIDs (Machado et al  Ann Rheum Dis 2017)
• Steroids (Balakrishnamoorthy et al Emerg Med J 2014)
• Benzodiazepines (Friedman et al Ann Emerg Med 2017)

Many non-pharmacologic therapies have also been tried with limited efficacy.

• Cognitive Behavioral Therapy and mindfulness (Cherkin et al JAMA 2016)
• Chiropractic (Paige et al JAMA 2017)
• Physical therapy (Paolucci et al J Pain Research 2018)
• Acupuncture (Colquhoun and Novella Anesthesia and Analgesia 2013)

One treatment modality, opioids, can be effective but comes with very real potential harms. The American College Physicians (ACP) has a 2017 policy on guidelines for treating non-radicular low back pain (Qaseem et al Annals of Int Med). Their third recommendations states:

• Clinicians should only consider opioids as an option in patients who have failed the aforementioned treatments and only if the potential benefits outweigh the risks for individual patients and after a discussion of known risks and realistic benefits with patients. (Grade: weak recommendation, moderate-quality evidence)

The American College of Emergency Physicians (ACEP) has addressed the issue of opioid use in patients being discharged home after an acute episode of pain. They give a Level C Recommendations saying:

• Do not routinely prescribe, or knowingly cause to be co-prescribed, a simultaneous course of opioids and benzodiazepines (as well as other muscle relaxants/sedative-hypnotics) for treatment of an acute episode of pain in patients discharged from the emergency department (Consensus recommendation). 

Despite guidelines and policy recommendations for prudent short-term opioid use only after other analgesics fail [6], opioid medications are frequently prescribed as the initial treatment for patients presenting with acute low back pain or neck pain. Estimates suggest up to two-thirds of these patients in Australia may receive opioids first-line [7].

Opioid prescription rates remain high in many countries including the USA. One study reported 43 prescriptions dispensed per 100 people in the US in 2020, though efforts have been made recently to curtail this use [8]. The prevalent use of opioids for acute back and neck pain is concerning given the lack of direct, high-quality evidence supporting efficacy [9].

Clinical Question: Is a short course of an opioid analgesic effective at reducing pain severity and improving function and quality of life in patients with acute non-specific low back pain or neck pain compared to placebo?

Reference: Jones et al. Opioid analgesia for acute low back pain and neck pain (the OPAL trial): a randomised placebo-controlled trial placebo-controlled trial. Lancet July 2023

• Population: Adults aged 18 years or older with acute low back pain, neck pain, or both with or without radiation to the leg or arm of at least moderate severity that has been lasting for 12 weeks or less and preceded by at least a 1-month period free from back and neck pain. Participants were recruited via emergency department, primary care offices or through a social media campaign.
  • Exclusions: Known or suspected serious spinal pathology; contraindications to opioid analgesics; taken a prescription opioid analgesic for the current episode of low back pain or neck pain at a dose higher than 15 mg of oral morphine equivalent per day for 5 or more consecutive days; spinal surgery in the preceding 6 months; scheduled or being considered for surgery or interventional procedures for low back pain or neck pain (or both) during the 6-week treatment period; younger than 18 years; insufficient English language skills or if interpretation was unavailable; and female participants who were planning conception, pregnant, or breastfeeding.
• Intervention: Oxycodone-naloxone modified release tablets (5mg oxycodone/2.5mg naloxone) given orally for up to 6 weeks twice daily with allowable titration up to a maximum of 10mg oxycodone/5mg naloxone twice daily based on pain severity, tolerability, and sedation scores. Down-titration and cessation occurred once adequate pain improvement was achieved (pain score 0-1 out of 10 for 3 consecutive days or for a maximum of 6 weeks)
• Comparison: Identical-appearing placebo tablets containing inactive ingredients that followed the same dosing regimen and schedule as the intervention group. Both groups also received guideline-recommended care for acute spinal pain in addition to the study medication/placebo.
• Outcome:
  • Primary Outcome: Pain intensity measured on a 0–10 scale by the Brief Pain Inventory Pain Severity Subscale at 6 weeks after randomization.
  • Secondary Outcomes:
    • Global Perceived Effect Scale: Assessed at weeks 2, 4, 6, and 12.
    • Physical Functioning (Generic): Measured by the Brief Pain Inventory Interference Subscale (BPI-IS) at weeks 2, 4, 6, and 12.
    • Physical Functioning (Back): Measured by the Roland Morris Disability Questionnaire (RMDQ) at week 6.
    • Physical Functioning (Neck): Measured by the Neck Disability Index (NDI) as a percentage at week 6.
    • Quality of Life (Physical Score): Measured by the SF-12v2 at weeks 2, 4, 6, and 12.
    • Quality of Life (Mental Score): Measured by the SF-12v2 at weeks 2, 4, 6, and 12.
    • Pain severity at other timepoints (2, 4, 12, 26, 52 weeks)
    • Time to recovery
    • Healthcare utilization
    • Work absenteeism
    • Adverse events
    • Risk of opioid misuse (Current Opioid Misuse Measure scale)
• Type of Study: A randomized, triple-blinded, placebo-controlled trial with parallel groups and intention-to-treat analysis.

Authors’ Conclusions: “Opioids should not be recommended for acute non-specific low back pain or neck pain given that they found no significant difference in pain severity compared with placebo. This finding calls for a change in the frequent use of opioids for these conditions.”

Quality Checklist for Randomized Clinical Trials:

1. The study population included or focused on those in the emergency department. No
2. The patients were adequately randomized. Yes
3. The randomization process was concealed. Yes
4. The patients were analyzed in the groups to which they were randomized. Yes
5. The study patients were recruited consecutively (i.e. no selection bias). Unsure
6. The patients in both groups were similar with respect to prognostic factors. Yes
7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Unsure
8. All groups were treated equally except for the intervention. Yes
9. Follow-up was complete (i.e. at least 80% for both groups). No
10. All patient-important outcomes were considered. Yes
11. The treatment effect was large enough and precise enough to be clinically significant. No
12. Financial conflicts of interest. The authors stated that the funders of the study had no role in the study design, data collection, analysis, interpretation, or reporting. The sources of funding included government agencies and academic institutions. No industry funding was reported. All authors declared no competing interests related to the submitted work. Two authors received research fellowships from the National Health and Medical Research Council of Australia. No other financial relationships or conflicts of interest were reported.

Results: 347 participants were recruited to be randomized. The mean age was 45 years with an even male/female split. The cohort consisted of 97% from primary care sites, 3% from the ED, and no participants from social media. The majority of people (~80%) had low back pain and about one-third had used opioids in the past.

Key Result: No statistical difference in pain reported between groups at six weeks.

• Primary Outcome: Mean pain score at 6 weeks
  • 2.78 (SE 0.20) in the opioid group vs 2.25 (SE 0.19) in the placebo group
  • The adjusted mean difference between groups was 0.53 (95% CI -0.00 to 1.07) which was not statistically significant (p=0.051)
  • No difference was found between male and female participants as well (MD of 0.50 (95% CI -0.03 to 1.03, p=0.064).
• Secondary Outcomes: 
  • Pain scores over time favored placebo, with a statistically significant difference at 52 weeks.
  • No significant differences were seen in:
    • Generic physical functioning scores or condition-specific scale for participants with neck pain
    • Gime to recovery, healthcare utilization, or work absenteeism.
    • Proportion of participants reporting adverse events ( both non-serious and non-serious)
  • A significant difference was found in condition-specific functioning scale (RMDQ) for back pain favoring placebo at week 6.
  • Mental health quality of life scores significantly favored placebo at 6 and 12 weeks.
  • More opioid-related adverse effects occurred in the opioid group like nausea and constipation.
  • Risk of opioid misuse was significantly higher with opioid use at 52 weeks.

1) Masking: We are unsure if masking was maintained with patients. Those allocated to the opioid group had much more nausea and constipation. The observed increase in constipation was interesting because the opioid was combined with naloxone that should mitigate this side effect. These adverse events could have unmasked the trial. However, that would have biased the study to find superiority. Since they did not report a statistically significant difference, we are more certain in the conclusions’ opioids do not provide a meaningful patient-oriented outcome (POO).

• Dr. Caitlin Jones (lead author) reached out to us after the episode was published. She let us know that  Appendix 12 of the supplementary material reported on masking fidelity. This is an excellent thing to do. It appears there were only about 10% difference in participants correctly identifying group allocation with have being unsure.

2) Follow-Up: The loss to follow-up rate was greater than the standard 20% threshold at the primary endpoint of 6 weeks (76% in opioid group, 80% in placebo) and even lower at 1 year (73-74% follow-up) which a limitation of this study. Missing data reduces statistical power, precision of results, and raises risk of attrition bias. However, the authors used appropriate statistical methods as mixed effects models and multiple imputation to account for missing data in the analysis with reported reasons for dropout appeared balanced between groups.

3) Show Me the Details: The paper states both groups received guideline-recommended care for acute spinal pain in addition to the study medication, but details of the specific care provided are not reported. This makes it difficult to ascertain whether the groups truly received equivalent concomitant treatment, which is an important component of a placebo-controlled trial. Any differences in care like use of physical therapy or additional analgesics could influence outcomes. The lack of transparency around the co-interventions is a limitation when judging the internal validity of the comparison between groups.

• Dr. Caitlin Jones (lead author) pointed out there were details on the guideline-recommended care provided in Table 3 of the manuscript. We are sorry to have missed this information and appreciate her being skeptical of our appraisal. This helps us have more confidence that each group received equivalent concomitant treatment.

4) Mean Difference: The adjusted mean difference between groups was 0.53 points on the 0-10 Brief Pain Inventory pain severity scale, with the opioid group having a mean of 2.78 (SE 0.20) compared to the placebo group mean of 2.25 (SE 0.19). The 95% confidence interval for this estimated difference spanned from no effect to a small effect favoring placebo (-0.00 to 1.07), and the p-value was 0.051, trending towards but not reaching the predefined threshold for statistical significance (p<0.05).

5) Minimum Clinically Important Difference (MCID): The authors stated that a 1-point difference on the 10-point pain scale was predefined as the minimum clinically important difference (MCID) for the study. However, a review of the literature does not provide robust evidence to support this threshold as an appropriate MCID for pain intensity. Multiple prior studies have estimated MCID values on visual analog or numeric rating scales for pain to be in the range of 15-33% reduction from baseline, which equates to a 2-to-3-point change on a 10-point scale [10,11,12].  Thus, the authors’ predefined 1-point MCID for pain reduction lacks substantive justification from prior literature. This raises some uncertainty around the clinical interpretation of group differences under 1 point found in this study.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with authors’ conclusion that short-term, judicious use of an opioid analgesic for people with acute low back pain or neck pain did not confer analgesic benefits when compared with placebo.

SGEM Bottom Line: Opioids analgesics prescribed for a short course at discharge from the ED does not appear to provide better pain relief for people with acute low back pain or neck pain and opioids should be used with caution due to the potential harms.

Case Resolution: You explained to the patient that there is a lack of good evidence to support an opioid will help his back pain and can increase potential harm, including substance use disorder. Therefore, the best evidence suggests starting with a non-steroidal anti-inflammatory drug Ibuprofen and then reassess his pain.

Dr. Sergey Motov

Clinical Application: Short-term, judicious prescribing of oral opioids either alone or as an adjunct to a guideline-specific care in the ED and at discharge for patients with acute low back or neck pain lacks good evidence for analgesic efficacy and does have evidence for increased potential for harm.

What Do I Tell the Patient? Many people think only opioids will work for back pain. There is no good evidence they will help your back pain or your back function. Also, opioids have many side effects like nausea and constipation. It can increase your risk of addiction. I want you to get the best treatment, based upon the best evidence. The best evidence suggests an anti-inflammatory like Ibuprofen has the best chance of working. A short course of anti-inflammatories has less side effects than opioids. You should also try to stay somewhat active. Lying around can make your back pain worse. You should come back to the ED if the pain gets much worse, you develop a fever, lose function in your leg, have saddle numbness, lose bowel/bladder control, rash, etc or are worried. We will give you some written instructions on discharge with more details.

Keener Kontest: Last weeks’ winner was Dr. Corey Hazekamp. He knew the largest settlement in a spinal abscess case in the USA was $19,250,000 from a case in Florida in 2014.

Listen to this weeks’ episode to hear the trivia question. If you think you know the answer, send an email to TheSGEM@gmail.com  with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

References:

1. Vos T, Lim SS, Abbafati C, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 2020; 396: 1204–22.
2. Wu A, March L, Zheng X, et al. Global low back pain prevalence and years lived with disability from 1990 to 2017: estimates from the Global Burden of Disease Study 2017. Ann Transl Med 2020; 8: 299.
3. Safiri S, Kolahi AA, Hoy D, et al. Global, regional, and national burden of neck pain in the general population, 1990–2017: systematic analysis of the Global Burden of Disease Study 2017. BMJ 2020;
   368: m791.
4. Hartvigsen J, Hancock MJ, Kongsted A, et al. What low back pain is and why we need to pay attention. Lancet 2018; 391: 2356–67.
5. Walker BF, Muller R, Grant WD. Low back pain in Australian adults: the economic burden. Asia Pac J Public Health 2003; 15: 79–87.
6. Chiarotto A, Koes BW. Nonspecific low back pain. N Engl J Med 2022; 386: 1732–40.
7. Ferreira GE, Machado GC, Abdel Shaheed C, et al. Management of low back pain in Australian emergency departments. BMJ Qual Saf 2019; 28: 826–34.
8. Centers for Disease Control and Prevention. US opioid dispensing rate map. https://www.cdc.gov/drugoverdose/rxrate-maps/index.html (accessed October 16, 2023).
9. Deyo RA, Von Korff M, Duhrkoop D. Opioids for low back pain. BMJ 2015; 350: g6380
10. Katz NP, Paillard FC, Ekman E. Determining the clinical importance of treatment benefits for interventions for painful orthopedic conditions. J Orthop Surg Res. 2015 Feb 3;10:24. doi: 10.1186/s13018-014-0144-x. PMID: 25645576; PMCID: PMC4327973.
11. Olsen MF, Bjerre E, Hansen MD, Hilden J, Landler NE, Tendal B, Hróbjartsson A. Pain relief that matters to patients: systematic review of empirical studies assessing the minimum clinically important difference in acute pain. BMC Med. 2017 Feb 20;15(1):35. doi: 10.1186/s12916-016-0775-3. PMID: 28215182; PMCID: PMC5317055
12. Atthakomol P, Tongsu R, Ngamsuprom K, Wangtrakunchai V, Phinyo P, Manosroi W. Minimal clinically important difference of the Michigan Hand Outcomes Questionnaire score and the pain visual analogue scale in conservative treatment of trigger finger. Journal of Hand Surgery (European Volume). 2023;48(9):863-871. doi:10.1177/17531934231176663