Nonsteroidal antiinflammatory drugs (NSAID) - are we using them enough?

The authors of A Rallying Call for Nonsteroidal Anti-Inflammatory Drugs in Musculoskeletal Pain: Improving Value of Care While Combating the Opioid Epidemic point out that despite being only 2% of all medical providers, orthopaedic surgeons represent 11% of the high-volume opioid prescribers and are in the top 10% of opioid prescription writers yearly.

Among us there is a high rate of opioid prescription generation for non-postoperative pain; for example, among patients presenting to a single center for arthritic hip or knee pain, 22.8% were prescribed opioids on their initial visit. 19% of orthopaedic trainees wrote prescriptions for amounts of opioids exceeding the recommended limits. These authors opine that the pain-relieving capabilities of nonsteroidal anti-inflamatory drugs (NSAIDs) represents a untapped opportunity for us to impact the opioid crisis. 

They make several important points:

First, for nonoperative management of osteoarthritis, NSAIDs represent a key value-based treatment option that fulfills the requirements for efficacy and lower costs. The efficacy of NSAIDs is supported by clinical practice guidelines from the American Academy of Orthopaedic Surgeons (AAOS) and the American College of Rheumatology (ACR) based on high quality published studies. As an example, the Strategies for Prescribing Analgesics Comparative Effectiveness (SPACE) trial was a randomized study that compared the effect of opioid versus nonopioid medications (including NSAIDs) on pain-related function, pain intensity, and adverse events in patients with chronic back pain or hip and knee OA. While pain-related function was comparable over 12 months, both pain intensity and adverse events were significantly lower in the non-opioid treatment arm.

Second, in contrast to the clear positions of the AAOS and the ACR, other medical specialties (e.g., family medicine, internal medicine, geriatrics, and physical therapy) do not have recommendations pertaining to the use of NSAIDs. The lack of clear indications and contraindications among different specialties often results in variable interpretations at the provider level, leading to confusion among patients as to whether NSAIDs can be used safely and effectively. As a result, in clinical practice, treatments such as injections and opioids are used more frequently for OA treatment than NSAIDs even though they have not been supported by the current AAOS CPGs.

Third, several safety concerns exist about NSAIDs, including the potential for gastrointestinal (GI) and cardiovascular (CV) adverse events, renal toxicity, and impaired bone-healing. 

    (a) While the potential GI side effects of NSAIDs have been well-established, most studies have focused on nonselective cyclooxygenase (COX) inhibitors and have failed to exclude patients who concurrently have been taking other medications that are known to cause GI side effects (e.g., aspirin). The gastrointestinal safety of celecoxib versus naproxen in patients with cardiothrombotic diseases and arthritis after upper gastrointestinal bleeding (CONCERN) trial was a double-blinded RCT that compared the GI safety of celecoxib (a selective COX-2 inhibitor) with naproxen (a nonselective COX inhibitor) in patients with OA, cardiovascular disease (CVD), and recent upper GI bleeding. Recurrent GI bleeding was found in 5.6% of individuals who were taking celecoxib compared with 12.3% of those taking naproxen. This study also found that NSAIDs should not be considered contraindicated simply based on advanced age; rather, the decision should be guided by patient risk factors. In addition, adding proton pump inhibitors (PPIs) to NSAIDs reduces adverse GI events when compared with the use of NSAIDs alone. The combination of selective COX-2 inhibitors and PPIs may further reduce the risk of adverse GI events.

    (b) The potential adverse CV effects of NSAIDs are another common concern. The Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION) trial was a large RCT that compared the CV safety of celecoxib, naproxen, and ibuprofen when utilized for arthritis treatment. Compared with nonselective COX inhibitors, including naproxen and ibuprofen, celecoxib had a lower risk of adverse CV events. Collectively, these studies demonstrate the differential effects of NSAIDs on CV health and emphasize the need to identify high-risk patients.

    (c) The potential nephrotoxicity of NSAIDs is another concern. The International Society of Nephrology recommends the avoidance of NSAIDs in those with chronic kidney disease especially those with a glomerular filtration rate (GFR) of <30 mL/min/1.73 m². However, more rigorous studies and clearer guidelines are necessary to help clinicians navigate the use of NSAIDs in the subset of patients with CKD.

    (d) Orthopaedic surgeons are frequently concerned about the potential negative impact of NSAIDs on bone-healing. However, a recent study by the Orthopaedic Trauma Association (OTA) Musculoskeletal Pain Task Force determined that there is no conclusive evidence demonstrating the detrimental effect of NSAIDs on bone-healing and recommended the routine use of NSAIDs in fracture care. Currently, there is no definitive clinical evidence that NSAIDs impair fracture-healing.

In summary, NSAIDs remain an underutilized class of medications in orthopaedic surgery. Available evidence suggests that opioids are not superior to NSAIDs in improving pain-related function, including in patients with back pain and major-joint arthritis. While concerns regarding the use of NSAIDs are valid, providers should maintain a level of realistic caution so as not to deprive patients of their potential benefits. All NSAIDs are not equal in terms of their safety profiles. To date, there exists a major gap in our knowledge regarding clear and well-accepted interdisciplinary contraindications for NSAID use. Without clear guidance—in part due to the lack of high-quality evidence and clinical guidance from major medical societies—conflicting interpretations and recommendations have become mainstream. 

To summarize:

The potential GI risks can be minimized by prescribing selective COX-2 inhibitors along with PPIs. 

The risk of CV events may potentially be diminished by using lower-dose NSAIDs with shorter durations in at-risk patients. 

With routine screening, the risk of nephrotoxicity among patients with stage-I and II renal dysfunction appears to be similar to that in the general population. 

The effect of NSAIDs on bone-healing is so far unproven and remains a topic of debate. 

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Here are some videos that are of shoulder interest

Shoulder arthritis - what you need to know (see this link).

How to x-ray the shoulder (see this link).

The ream and run procedure (see this link).

The total shoulder arthroplasty (see this link).

The cuff tear arthropathy arthroplasty (see this link).

The reverse total shoulder arthroplasty (see this link).

The smooth and move procedure for irreparable rotator cuff tears (see this link).

Shoulder rehabilitation exercises (see this link).

Should patients take anti-inflammatory medications after rotator cuff repair?

 The Effects of Non-Steroidal Anti-Inflammatory Medications After Rotator Cuff Surgery: A Randomized Double-Blinded Placebo-Controlled Trial

These authors point out that non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used for postoperative pain management. However, animal studies have demonstrated negative effects of NSAIDs on bone and tendon healing in commonly performed procedures such as rotator cuff repair. Their goal was to evaluate the effects of postoperative NSAID use on opioid use, pain control, and shoulder outcomes after arthroscopic rotator cuff repair using a randomized, double-blinded, placebo-controlled trial.

Patients were randomized using a computer-generated number to receive either ibuprofen (400mg every eight hours for 14 days continuously) or placebo (for the same duration) for postoperative pain control in addition to opioid medication. A total of 50 patients in the placebo group and 51 patients in the ibuprofen group were included. There were no differences in age, race, gender, history of preoperative NSAID or opioid use, or operative findings between groups. 

Findings and repair details are shown for the ibuprofen group (left) and the placebo group (right).

Mean total morphine milligram equivalents (MME) used in the first postoperative week was lower in the ibuprofen group compared to the  placebo group (168 vs 211, P = 0.04). 

Early VAS scores on postoperative day 3, 4, 5, and 6 were lower in the ibuprofen group but there was no difference in mean VAS scores between groups by6 weeks after surgery. 

At 6 months, mean forward flexion and ASES scores were higher in the ibuprofen group compared to placebo (162  vs 153 , P = 0.03) and (86 vs 78, P = 0.02), respectively. There were no differences in shoulder motion, SF-12, DASH or ASES scores at 1 year. 

At 1 year after surgery, 7 patients in the ibuprofen group had evidence of tendon retear diagnosed on ultrasound (5 partial-thickness, 2 full-thickness) compared to 13 patients in the  placebo group (5 partial-thickness, 8 full-thickness) (P = 0.20). Interestinhgly, there was no difference in ASES and DASH scores at 1 year between patients with retears and those with intact repairs in either group.

The authors concluded that (1) postoperative ibuprofen use reduces opioid requirements and decreases patient pain levels in the first week after arthroscopic rotator cuff repair and (2) ibuprofen use after rotator cuff repair is not associated with increased risk of tendon retear.

Comment: This is a well done randomized controlled study. While the investigation did not concern the effect of anti-inflammatory medication on subscapularis healing after arthroplasty, we routinely use scheduled NSAIDs after joint replacement to assist in pain control and early motion; we have not noted problems with subscapularis healing in those patients. 

How you can support research in shoulder surgery Click on this link.

Here are some videos that are of shoulder interest

Shoulder arthritis - what you need to know (see this link).

How to x-ray the shoulder (see this link).

The total shoulder arthroplasty (see this link).

The ream and run technique is shown in this link.

The cuff tear arthropathy arthroplasty (see this link).

The reverse total shoulder arthroplasty (see this link).

The smooth and move procedure for irreparable rotator cuff tears (see this link).

Shoulder rehabilitation exercises (see this link).

Naproxen after joint surgery

Effect of Naproxen Prophylaxis on Heterotopic Ossification Following Hip Arthroscopy: A Double-Blind Randomized Placebo-Controlled Trial.

These authors performed a Level I study to determine the effect of postoperative naproxen therapy on the development of unwanted bone formation (HO) following arthroscopic surgery for femoroacetabular impingement.

Those in the treatment group were prescribed 500 mg of Naproxen twice a day. The prevalence of HO was 46% in the control group versus 4% in the naproxen group.  Minor adverse reactions to the study medications were reported in 42% of the patients taking naproxen versus 35% of those taking the placebo (p = 0.45).

Comment: While the shoulder is not the hip, and femoroacetabular impingement surgery is not arthroplasty, we are interested in the use of Naproxen as a means of increasing comfort and decreasing stiffness after shoulder arthroplasty. In the past we avoided anti-inflammatory medications (NSAIDs) after shoulder arthroplasty out of concern for bleeding and delayed healing. Currently, however, Naproxen has become a part of our postoperative program. Our initial observations are that the postoperative course is smoother for the patient and we've not observed significant side effects.
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Steroid vs NSAID injection for shoulder pain

A double-blind randomized controlled trial comparing the effects of subacromial injection with corticosteroid versus NSAID in patients with shoulder impingement syndrome.

The inclusion criteria included shoulder pain with passive and/or active abduction, diagnosis of subacromial bursitis based on tenderness to palpation about the acromion, positive Neer’s sign, positive Hawkin’s sign, and pain exacerbated with the shoulder held in internal rotation. It is not clear how many of these had to be present for inclusion. As is pointed out recently, the diagnosis of 'impingement syndrome' can in most cases be replaced with a more specific anatomical diagnosis, because many of the 'classical' signs have been shown to be non-specific. While MRI imaging was not used in all patients, a number of patients meeting the inclusion criteria were found to have cuff tears.

Nevertheless, this study is of interest because it was a double-blinded randomized controlled clinical trial comparing the subacromial injection of either 40 mg triamcinolone or 60 mg of ketorolac.

While both group were improved, the authors noted that an injection of ketorolac resulted in greater improvements in the UCLA scale than an injection of triamcinolone at 4 weeks follow-up. They suggest that ketorolac may have fewer potential side effects that steroid injection.

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Use the "Search" box to the right to find other topics of interest to you.

You may be interested in some of our most visited web pages including:shoulder arthritis, total shoulder, ream and run, reverse total shoulder, CTA arthroplasty,  and rotator cuff surgery.

See from which cities our patients come.

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Cardiovascular safety of non-steroidal anti-inflammatory drugs for arthritis, NSAIDS

The British Medical Journal recently published a network meta-analysis to analyze the evidence on cardiovascular safety of non-steroidal anti-inflammatory medications. These are medications that are commonly used to manage the symptoms of arthritis. They looked at the rates of myocardial infarction (heart attacks), as well as strokes, death from cardiovascular disease, and death from any causes. They included 31 randomized controlled trials with data from over 100,000 patients. Patients included those taking naproxen (Aleve), ibuprofen (Advil), diclofenac (Voltaren), celecoxib (Celebrex), etoricoxib (Arcoxia), rofecoxib (Vioxx), lumiracoxib (Prexige), or placebo (a pill with no biological activity). Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction, followed by lumiracoxib. Ibuprofen was associated with the highest risk of stroke, followed by diclofenac. Etoricoxib and diclofenac were associated with the highest risk of cardiovascular death. However, none of these drugs appeared to be free of cardiovascular risk. Among them, naproxen seemed to be the safest. While this study does not indicate that these medications should be avoided, it does suggest that moderate and intermittent use may be advisable to minimize the risk.
See also Drugs for arthritis: the good and the bad and our post on the relative safety of these medications.

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Use the "Search the Blog" box to the right to find other topics of interest to you.

You may be interested in some of our most visited web pages including: shoulder arthritis, total shoulder, ream and run, reverse total shoulder, CTA arthroplasty, and rotator cuff surgery.

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Relative safety of non-steroidal anti-inflammatory medications

A recent study has made some important observations on the cardiovascular risk of different NSAIDs. The summary of this study is presented below.

For those patients with normal kidney function, who are not on anticoagulants, who do not have other contraindications, we commonly suggest naproxen (Aleve) used according to the manufacturer's specifications.


"Data from a study published online in the journal PLoS Medicine suggest that, among widely used non-steroidal anti-inflammatory drugs (NSAIDs), naproxen and low-dose ibuprofen are the least likely to increase cardiovascular risk. The authors conducted a systematic review of 30 case-control studies covering 184,946 cardiovascular events, and 21 cohort studies that described outcomes in more than 2.7 million exposed individuals. Of the most extensively studied drugs, the highest overall risks were seen with rofecoxib and diclofenac, and the lowest with ibuprofen and naproxen. In a sub-set of studies, risk was elevated with low doses of rofecoxib, celecoxib, and diclofenac, with risk increasing with higher doses. Ibuprofen risk was seen only with higher doses, while naproxen was risk-neutral at all doses."

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You may be interested in some of our most visited web pages including:shoulder arthritis, total shoulder, ream and run, reverse total shoulder, CTA arthroplasty,  and rotator cuff surgery.

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Drugs for arthritis: the good and the bad

Oral medications are often used to manage the symptoms of shoulder arthritis. While drugs such as Enbrel or Humira can modify the course of rheumatoid arthritis, there is little evidence that medications can change the course of osteoarthritis, chondrolysis, or capsulorrhaphy arthropathy, the commonest forms of shoulder arthritis.

The most common medications used for the symptoms of shoulder arthritis are basic pain relievers and NSAIDs (non-steroidal anti inflammatory medications). Taking these medications is not without risks -some of which are substantial - such as the increased risk of heart attack and stroke, bleeding, ulcers, interactions with alcohol, interactions with other medications (including blood thinners, heart medications, blood pressure medications, seizure medications, antibiotics and over the counter medications), kidney failure, liver failure, pregnancy or breast feeding problems, dizziness, vision changes, allergic reactions and increased risk of surgery.

I've listed some of the more commonly used drugs below. If you click on the name of the drug, it will take you to the National Library of Medicine Public Health site that tells you of the potential side effects and risks of the medication. If you are taking or considering taking any of these medications, you may wish to review the material the government has provided.

Tylenol (also a part of many compound drugs)
Asprin/Bufferin
Advil/Motrin
Aleve/Naproxen
Orudis
Torodol
Clinoril
Indocin
Feldene
Dolobid
Relafen

The Arthritis Foundation has a useful drug guide.

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Use the "Search the Blog" box to the right to find other topics of interest to you.

You may be interested in some of our most visited web pages including: shoulder arthritis, total shoulder, ream and run, reverse total shoulder, CTA arthroplasty, and rotator cuff surgery.

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