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Date: October 9th, 2020

Guest Skeptic: Dr. Sergey Motov is an Emergency Physician in the Department of Emergency Medicine, Maimonides Medical Center in New York City. He is also one of the world’s leading researchers on pain management in the emergency department, specifically the use of ketamine. His twitter handle is @PainFreeED.

Reference: Friedman et al. Ibuprofen Plus Acetaminophen Versus Ibuprofen Alone for Acute Low Back Pain: An Emergency Department-based Randomized Study. AEM 2020.

Case: A 41-year-old man without a significant past medical history presents to the emergency department (ED) with a chief complaint of lower back pain that started 48 hours prior to the ED visits after attempting to move a couch in his house. He describes the pain as sharp, constant, non-radiating, and 6/10 in intensity. Pain gets worse with movement and minimal bending. The pain is limiting his usual activities included his ability to go to work. He denies weakness or numbness of the legs as well as bowel or bladder dysfunctions. You perform a physical exam and note prominent tender area to palpation at the right lumbar region. You explain to the patient the most likely diagnosis is a muscle strain. Your usual approach is to treat this type of case scenario with Ibuprofen. The patient asked you if Ibuprofen alone will be strong enough to control his pain.

Background: Pain is one of the most frequent reasons to attend an ED. Low back pain (LBP) is responsible for 2.3% of all ED visits resulting in 2.6 million visits each year in the USA (Friedman et al Spine 2010). We have covered back pain a number of times on the SGEM.

  • 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

The SGEM bottom line from SGEM#240 was:

There appears to be no long-term analgesics benefits from prescribing opioids for chronic non-cancer pain (nociceptive and neuropathic). However, their use is associated with increased adverse events.

The American College of Emergency Physicians (ACEP) has updated their clinical policy on prescribing opioids for adult ED patients. There are no Level A recommendations, one Level B recommendation and multiple Level C recommendations (ACEP June 2020)

  • In adult patients experiencing opioid withdrawal, is emergency department-administered buprenorphine as effective for the management of opioid withdrawal compared with alternative management strategies?
    • Level B Recommendations: When possible, treat opioid withdrawal in the emergency department with buprenorphine or methadone as a more effective option compared with nonopioid-based management strategies such as the combination of α2-adrenergic agonists and antiemetics

Many other pharmaceutical treatments besides opioids have been tried to address acute LBP pain with limited success. These include: 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) and benzodiazepines (Friedman et al Ann Emerg Med 2017).

Pain outcomes for patients with LBP are generally poor; One week after an ED visit in an unselected LBP population, 70% of patients report persistent back pain–related functional impairment and 69% report continued analgesic use (Friedman et al AEM 2012).

There are a number of non-pharmaceutical treatment modalities that have also been tried to treat low back pain. They include: CBT and mindfulness (Cherkin et al JAMA 2016), chiropractic (Paige et al JAMA 2017), physical therapy (Paolucci et al J Pain Research 2018) and acupuncture (Colquhoun and Novella Anesthesia and Analgesia 2013). None of these other treatments has high-quality evidence supporting their use.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line medication therapy for patients with acute LBP.  Acetaminophen is often used for acute LBP, although it is unlikely to be effective when used as monotherapy. Whether or not combining an NSAID with acetaminophen can improve patient outcomes is unknown.

Clinical Question: Is the addition of acetaminophen to ibuprofen better than ibuprofen alone in treating ED patients with acute, non-traumatic, non-radicular low back pain?

Reference: Friedman et al. Ibuprofen Plus Acetaminophen Versus Ibuprofen Alone for Acute Low Back Pain: An Emergency Department-based Randomized Study. AEM 2020.

  • Population: Adults aged 21 to 69 years who presented to the ED primarily for management of acute non-traumatic, non-radicular, musculoskeletal LBP with Roland Morris Disability Questionnaire (RMDQ)score of >5.
    • The RMDQ is a 24-item questionnaire commonly used to measure LBP and related functional impairment. The scale goes from 0 (no impairment) to 24 (maximum impairment).
    • Exclusions: “non- musculoskeletal etiology of low back, such as urinary tract infection or influenza-like illness; radicular pain, defined as pain radiating below the gluteal folds in a dermatomal distribution; pain duration > 2 weeks (336 hours); or a baseline LBP frequency of once per month or more frequently. Patients with substantial, direct trauma to the back within the previous month were excluded as were those who were unavailable for follow-up, those who were pregnant or breastfeeding, patients with a chronic pain syndrome defined as use of any analgesic medication on a daily or near-daily basis, and those who were allergic to or intolerant of the investigational medications.”
  • Intervention: Combination ofibuprofen 600mg plus acetaminophen 500 to 1000mg, orally, every 6 hours.
  • Comparison: Monotherapy of Ibuprofen 600mg plus placebo,orally, every 6 hours.
  • Outcome:
    • Primary Outcome: Improvement of LBP on the RMDQ between ED discharge and the 7-day telephone follow-up. 
    • Secondary Outcomes: 1 week and 48 hours after ED discharge were as follows: 1) participants’ worst LBP during the previous 24 hours, using a four-item ordinal scale (severe, moderate, mild, or none); 2) the frequency of LBP during the previous 24 hours using a five-item scale (not at all, rarely, sometimes, usually, always); 3) the frequency of any analgesic or LBP medication use during the previous 24 hours; 4) satisfaction with treatment, as measured by response to the question, “The next time you have back pain, do you want to take the same medications you’ve been taking this past week?”; 5) the day post–ED discharge the participant was able to return to usual activities; and 6) the frequency of visits to any health care provider.

Authors’ Conclusions: “Among ED patients with acute, nontraumatic, non-radicular LBP, adding acetaminophen to ibuprofen does not improve outcomes within 1 week.”

Quality Checklist for Randomized Clinical Trials:

  1. The study population included or focused on those in the emergency department. Yes
  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). Yes
  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. Yes
  8. All groups were treated equally except for the intervention. Yes
  9. Follow-up was complete (i.e. at least 80% for both groups). Yes
  10. All patient-important outcomes were considered. Yes
  11. The treatment effect was large enough and precise enough to be clinically significant. No

Key Results: They screened 605 patients for eligibility and were able to randomize 120. The mean age was 41 years, 52% were men, mean duration of symptoms was 48 hours and 80% were working at least 30 hours a week.

No statistical difference between ibuprofen plus acetaminophen and ibuprofen alone in back pain improvement at one week.

  • Primary Outcome: Mean improvement of RMDQ (+/-SD) at 1 week
    • Combo 11.1 (+/- 10.7) vs Mono 11.9 (+/- 9.7)
    • Between group difference 0.8 (95% CI -3.0 to 4.7)
  • Secondary Outcomes: 
    • Participants’ worst LBP during the previous 24 hours, using a four-item ordinal scale (severe, moderate, mild, or none): No statistical difference
    • Frequency of LBP during the previous 24 hours using a five-item scale (not at all, rarely, sometimes, usually, always): More frequent in combination group
    • Frequency of any analgesic or LBP medication use during the previous 24 hours: No statistical difference
    • Satisfaction with treatment, as measured by response to the question, “The next time you have back pain, do you want to take the same medications you’ve been taking this past week?” No statistical difference
    • How many days post–ED discharge the participant was able to return to usual activities: No statistical difference
    • Frequency of visits to any health care provider: No statistical difference

1. Ibuprofen Dosing: They used 600mg of ibuprofen in this trial rather than 400mg. Unlike opioid analgesics, NSAID dosing is limited by their “analgesic ceiling”, meaning there is a dose-analgesic response. Above certain doses, NSAIDs produce more side effects or harms without providing additional analgesia. Our team has published evidence supporting this on both ibuprofen (Motov et al Ann Emerg Med 2019) and ketorolac (Motov et al Ann Emerg Med 2017). The ketorolac paper was covered on SGEM#175.

2. External Validity: This study was conducted in two urban EDs serving a socioeconomically depressed population. Socioeconomic factors have been shown to be associated with an increased risk of pain (Poleshuckand Green Pain 2008). It is unclear if this data could be applied to other populations.

3. Exclusion Criteria: Patients were excluded if they had LBP greater than two weeks. The mean duration of LBP varied from 12 to 96h prior to enrollment in the study. We could not find if patients were patients taking any medications prior to enrollment. They also listed a number of other exclusion criteria including patients who were “intolerant of the investigational medications.” The authors did not explicitly state if patients were excluded if they had renal/hepatic insufficiency or co-medications such as coumadin, aspirin, direct oral anti-coagulants, etc.

4 Concordance: The loss to follow-up was less than the quality indicator of 20%. However, more than one-third of both groups did not take their study medication as instructed 24 hours prior to the 1-week phone call. Similarly, about one-fifth of patients did not take their study medications as instructed 24 hours prior to 48h phone call.

5. Other Medication: It was not stated in the manuscript that patients were told/advised not to take any other medications other than those used in the trial. While this would be pragmatic, it could mask any difference between the ibuprofen plus acetaminophen compared to the ibuprofen alone group.

Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with authors’ conclusion.

SGEM Bottom Line: We cannot recommend the addition of acetaminophen to Ibuprofen for adult patients presenting to the ED with acute, non-traumatic, non-radicular low back pain.

Case Resolution: You recommend ibuprofen 400mg as a first line agent and try to set reasonable expectations.

Clinical Application: There still appears to be no great treatment options for patients presenting with acute low back pain. Evidence for individual pharmaceutical therapies are limited and this trial provides evidence that a combination therapy of acetaminophen and ibuprofen is not better than ibuprofen alone. This agrees with the previous SGEM episode looking at a combination of diazepam and naproxen (SGEM#173). We also don’t have high-quality evidence that non-pharmacological treatments work well.

One final thing that is important is to discuss expectations with the patient. They need to know that their pain might not be completely relieved in the ED. The goal should be about about limiting suffering, not eliminating pain.  Most patients will have persistent symptoms a week after presentation and many will have continued pain and functional impairment months after symptom onset (Itz et al 2013 , Donelson et al 2012  and Costa et al 2012). We need to be supportive and realistic when discussing the natural history of acute low back pain with patients.

Dr. Sergey Motov

What Do I Tell My Patient?  You have a muscle strain in your back. This is a very common problem and can be very painful. Ibuprofen can help lower your pain, but it is unlikely get rid of your pain completely. Adding medications like acetaminophen or even a benzodiazepam has not shown to be more effective. People have tried many other medications and non-medications to try and help. One thing we know is that opioids are not usually recommended. Unfortunately, you may have pain over the next few weeks or months. Try to stay active and, if your pain is getting worse, you can’t function, or are otherwise worried please return to the ED for re-assessment. 

Keener Kontest: Last weeks’ winner was Drew McMillan. He knew the definition of a TIA was changed in 2009.

Listen to the SGEM podcast to hear this weeks’ question. Send your answer 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.