Top POEMs of 2018: Pain Management

Top 20 POEMs of 2018

Nonopiods Equivalent to Opioids for Severe Chronic Back, Hip, or Knee Pain with Fewer Adverse Outcomes

Clinical question
Are opioid medications preferable for improving pain-related function in adults with severe chronic back, hip, or knee pain?

Bottom line
Nonopioid medications were at least as effective as opioid medications for improving pain-related function over 12 months in adults with severe chronic back pain or knee or hip osteoarthritis pain. The evidence that opioids are NOT superior to nonopioid medications for both chronic and acute pain continues to mount. The tough job will be getting patients and their clinicians to believe the evidence. (LOE = 1b)

Reference
Krebs EE, Gravely A, Nugent S, et al. Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain. The SPACE randomized clinical trial. JAMA 2018;319(9):872-882.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (primary care)

Synopsis
For decades both patients and clinicians have believed/assumed that opioids are superior for reducing pain and improving function in patients with severe chronic pain. These investigators identified adults with chronic back pain or hip or knee osteoarthritis pain that rated at least moderately severe on a standard pain rating scale and persisted every day for at least 6 months. Patients with severe depression or posttraumatic stress disorder symptoms were NOT excluded. Study participants (N = 240) randomly received assignment (concealed allocation) to either an opioid or nonopioid pain management group. Patients in the opioid group started taking immediate release (IR) oral opioids with escalation to sustained-released (SA) oral opioids and finally to transdermal fentanyl, if needed. Titration continued to a maximum daily dose of 100 morphine-equivalent milligrams. Patients in the nonopioid medication group started with acetaminophen and nonsteroidal anti-inflammatory drugs, with step-up as needed to adjuvant oral medications (eg, amitriptyline, gabapentin) and topical analgesics (eg, capsaicin, lidocaine), and finally to pregabalin, duloxetine, and/or tramadol, if needed. Medication adherence was monitored by urine drug testing and with regular checking of a state prescription monitoring program. Individuals who assessed outcomes remained masked to treatment group assignment. Follow-up rates ranged from 90% to 98% of patients at 12 months. Mean age was 58.3 years (range = 21 – 80 years) and 13% were women. Using intention-to-treat analyses, there was no significant group difference in pain-related function over 12 months based on standard rating scales. Overall, pain intensity was significantly better in the nonopioid group over 12 months. Drop-outs due to adverse medication-related symptoms were significantly higher in the opioid group than in the nonopioid group (19% vs 8%, respectively). No deaths or diversions were detected in either group. Tramadol was dispensed to 11% of patients in the nonopioid group over the 12 months of follow-up.

David C. Slawson, MD
Professor and Vice Chair of Family Medicine for Education and Scholarship
Atrium Health
Professor of Family Medicine, UNC Chapel Hill
Charlotte, NC

Ibuprofen + Acetaminophen Equals Opioid + Acetaminophen for Acute Severe Extremity Pain

Clinical question
What oral analgesic combinations are effective for reducing the pain of an acute extremity injury in adults in the emergency department?

Bottom line
In adults presenting to the emergency department with acute extremity pain severe enough to warrant radiologic investigation, ibuprofen plus acetaminophen was equally effective in reducing pain intensity at 2 hours compared with 3 different opioid and acetaminophen combination analgesics. In a similar study (Friedman BW, et al. JAMA 2015;314(15):1572-80), naproxen alone was as effective as naproxen plus oxycodone/acetaminophen or naproxen plus cyclobenzaprine for reducing pain from acute musculoskeletal low back pain. It's time we stopped believing that opioids are superior to nonsteroidal anti-inflammatory drugs for acute pain control. We'd save a lot of lives. (LOE = 1b)

Reference
Chang AK, Bijur PE, Esses D, Barnaby DP, Baer J. Effect of a single dose of oral opioid and nonopioid analgesics on acute extremity pain in the emergency department. A randomized clinical trial. JAMA 2017;318(17):1661-1667.

Study design:Randomized controlled trial (double-blinded)

Funding source: Government

Allocation:Concealed

Setting:Emergency department

Synopsis
Opioid use for just 3 days can significantly increase the risk of opioid dependence. These investigators identified adults, aged 21 to 64 years, presenting to the emergency department for acute extremity pain, defined as pain originating distal to and including the shoulder joint in the upper extremities and distal to and including the hip joint in the lower extremities. Eligible patients (N = 411) included those with an injury severe enough to require radiologic imaging according to the judgment of the attending physician. After baseline pain measurement, patients randomly received (concealed allocation assignment) identical capsules containing either ibuprofen 400 mg plus acetaminophen 1000 mg; oxycodone 5 mg plus acetaminophen 325 mg; hydrocodone 5 mg plus acetaminophen 300 mg; or codeine 30 mg plus acetaminophen 300 mg. Patients masked to their treatment group assignment self-assessed pain intensity using a verbal numerical rating scale from 0 (no pain) to 10 (worse pain imaginable). The minimum clinically important difference was predefined as a mean pain scale score of 1.3. Complete follow-up occurred for 100% of patients at 2 hours. Using intention-to-treat analysis, pain intensity significantly declined by 3.5 to 4.4 points at 2 hours compared with baseline in all treatment groups, but was not significantly different among the 4 groups. Pain intensity was also similarly reduced in all treatment groups at 1 hour and there were no group differences in the use of rescue analgesia. Even with post hoc analysis, no statistical difference was present for those with 10/10 pain (severe) and those with acute fractures.

David C. Slawson, MD
Professor and Vice Chair of Family Medicine for Education and Scholarship
Atrium Health
Professor of Family Medicine, UNC Chapel Hill
Charlotte, NC

Gabapentin and Pregabalin Not Effective for Low Back Pain with or Without Radiculopathy

Clinical question
Are anticonvulsants an effective treatment for low back pain?

Bottom line
The use of anticonvulsants like gabapentin for painful conditions has increased greatly in recent years. This review finds good evidence that these drugs are not an effective treatment for low back pain with or without radiculopathy, and are associated with an increased risk for adverse events. (LOE = 1a)

Reference
Enke O, New HA, New CH, et al. Anticonvulsants in the treatment of low back pain and lumbar radicular pain: a systematic review and meta-analysis. CMAJ 2018;190(26):E786-E793.

Study design:Meta-analysis (randomized controlled trials)

Funding source:Self-funded or unfunded

Setting: Various (meta-analysis)

Synopsis
Particularly in this era of heightened awareness of the potential harms of opioids, anticonvulsants are often prescribed for the treatment of painful conditions. Although there is evidence of their effectiveness primarily for peripheral and diabetic neuropathy, they are increasingly prescribed for other conditions, including low back pain. This systematic review included a comprehensive search of the literature and the authors identified 9 randomized trials (3 of which were crossover studies) that compared topiramate, pregabalin, or gabapentin with placebo in patients with low back pain with or without radiculopathy. They excluded studies of pregnant women; pre-operative patients; and patients with mixed conditions, such as neck and back pain. The trials were assessed for risk of bias, and only 1 was at high risk. The studies used a range of pain scales, so the standardized mean difference in pain scores between treatment and placebo groups was the primary outcome. The 9 studies reported a total of 14 comparisons, with only 2 showing a statistically significant benefit. One was a small study of high-dose gabapentin (3600 mg/day) in 43 patients with lumbar radicular pain, and the other was a study of 96 patients with low back pain who were given 300 mg topiramate 300 each day. The other topiramate study found no benefit, as did none of the other studies of pregabalin or gabapentin. Where results could be pooled, there was essentially no difference between groups. Where results could be pooled, there was essentially no difference between groups. There was no difference in serious adverse events: 4 in the pregabalin group, 6 in the placebo group (though these were reported in only 2 studies with a total of 423 patients). Any adverse events, however, were significantly more common with active treatment (relative risk 1.4; 95% CI 1.2 - 1.7).

Mark H. Ebell, MD, MS
Professor
University of Georgia
Athens, GA

POEMs are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com(www.essentialevidenceplus.com).