Are non-steroidal anti-inflammatory drugs (NSAIDs) appropriate after cuff repair - if so, which ones? What does ChatGPT say?

Non-steroidal anti-inflammatory drugs (NSAIDs) are powerful analgesics and can provide an important mode of pain management after surgery (see Nonsteroidal antiinflammatory drugs (NSAID) - are we using them enough?). 

There has been concern, however, that NSAIDs may interfere with healing of tendon repair to bone as in rotator cuff repair or subscapularis repair after shoulder arthroplasty (see Do anti inflammatory medications interfere with healing? and Should patients take anti-inflammatory medications after rotator cuff repair?) 

Selective COX-2 inhibitors are a class of NSAIDs that reduce the risk of peptic ulceration, which can be a problem with the non-selective NSAIDS. However, clinical trials have revealed that COX-2 inhibitors significantly increase the risk of heart attacks and strokes. For that reason, most COX-2 inhibitors have been removed from the market, only Celebrex (generic name of celecoxib) is still available for purchase in the United States.

In addition to concerns about heart attacks and strokes, there is a particular concern about the effect of selective COX-2 inhibitors, such as Celebrex, on tendon healing (see Does Celebrex interfere with tendon healing?).

The authors of Non-selective NSAIDs do not increase retear rates post-arthroscopic rotator cuff repair: A meta-analysis sought to investigate the effect of postoperative NSAIDs on retear rates and clinical outcomes for cuff repair.

They included 6 studies in their meta-analysis with 443 (48.3%) patients in the NSAID group and 473 (51.6%) patients in the Control group. 

There were no statistically significant differences in early and late post-operative VAS scores and latest ASES score. In the NSAID group, the pooled retear rate was 25%; in the control group, the pooled retear rate was 21%. Meta-analysis of odds ratio did not yield any statistical significance between the two groups.

However, they conducted a subgroup analysis which demonstrated that inclusion of selective COX-2 inhibitors (‘COX-2 only OR both’ subgroup) leads to significantly higher retear rates when compared to non-selective COX inhibitors (‘Non-selective COX only’ subgroup). 

The authors concluded that NSAIDs use in post-arthroscopic rotator cuff repair pain relief does not increase retear rates and can provide similar clinical outcomes compared to a non-NSAID regime.

Comment:  While selective COX-2 inhibitors may have a potential advantage over traditional, non-selective NSAIDs in terms of the risk of gastrointestinal problems, the potential impact on healing probably outweighs the benefits it offers. And, of course, there's the increased risk of heart attacks and strokes.The risk of gastritis and ulcers with non-selective NSAIDS can often be mitigated through the use of proton-pump-inhibitors (PPIs).

We asked ChatGPT "why do COX-2 drugs interfere with soft tissue healing? " Its response is quoted below

"COX-2 drugs, also known as selective COX-2 inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs), have been associated with potential interference in soft tissue healing. While the exact mechanisms are not fully understood, several factors contribute to this phenomenon:

Inhibition of prostaglandin synthesis: COX-2 inhibitors selectively block the enzyme cyclooxygenase-2 (COX-2), which is responsible for the production of prostaglandins. Prostaglandins play a crucial role in the inflammatory response and are involved in various stages of tissue healing, including inflammation, angiogenesis (formation of new blood vessels), and collagen synthesis. By inhibiting prostaglandin synthesis, COX-2 inhibitors can disrupt these processes, potentially slowing down tissue healing.

Impaired inflammation response: Inflammation is a necessary and natural part of the healing process, as it helps to clear away damaged tissues, recruit immune cells, and initiate tissue repair. COX-2 inhibitors, by reducing the production of prostaglandins, can dampen the inflammatory response. While this anti-inflammatory effect may be beneficial in controlling pain and swelling, it can also interfere with the timely and appropriate inflammatory phase of healing, potentially impacting tissue repair and regeneration.

Altered angiogenesis: Angiogenesis is a critical step in tissue healing, as it brings oxygen and nutrients to the healing site, aiding in the formation of new blood vessels. Prostaglandins, which are inhibited by COX-2 drugs, play a role in promoting angiogenesis. By reducing prostaglandin levels, COX-2 inhibitors may interfere with the proper formation of blood vessels, negatively impacting tissue healing.

Collagen synthesis disruption: Collagen is the main structural component of soft tissues, providing strength and stability. Prostaglandins are involved in collagen synthesis, and their inhibition by COX-2 drugs can disrupt the proper formation and organization of collagen fibers. This interference can affect the tensile strength and integrity of the healing tissue."

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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).

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. 

You can support cutting edge shoulder research that is leading to better care for patients with shoulder problems, click on this link.

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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 non-steroidal medications after cuff repair

The effects of nonsteroidal anti-inflammatory medications after rotator cuff surgery: a randomized, double-blind, placebo-controlled trial

As these authors point out nonsteroidal 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 after commonly performed procedures such as rotator cuff repair. 

They sought to evaluate the effects of postoperative NSAID use on opioid use, pain control, and outcomes after primary arthroscopic rotator cuff repair in a randomized, double-blind, placebo-controlled trial. Patients were randomized to receive ibuprofen (n=51) or placebo (n=50) for 2 weeks postoperatively, in addition to opioid medication. Over 80% of the tears in both groups were of small or medium size and involved only the supraspinatus. 

All patients received a single-shot interscalene regional anesthetic preoperatively. Rotator cuff tears were repaired with either single or double-row constructs. Patients with biceps pathology were

treated with arthroscopic debridement or tenotomy. Those who underwent open biceps tenodesis were excluded from the study to reduce the introduction of confounding factors from a larger, open approach that may influence postoperative pain control.

All patients were immobilized in a shoulder sling with an abduction pillow for 6 weeks after surgery.

The mean total morphine milligram equivalents (MMEs) used in the first postoperative week was lower in the ibuprofen group than in the placebo group (168 MMEs vs. 211 MMEs, P ..04). 

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

At 6 months, mean forward flexion and the mean ASES score were higher in the ibuprofen group than in the placebo group: 162 vs. 153 (P ..03) and 86 vs. 78 (P ..02), respectively.

There were no differences in shoulder motion or 12-item Short Form Survey, Disabilities of the Arm, Shoulder and Hand, or ASES scores at 1 year. 

At 1 year after surgery, 85 patients underwent ultrasound examination at 1 year after surgery. 7 (16%) patients in the ibuprofen group had evidence of tendon retear diagnosed on ultrasound (5 partial and 2 full thickness) compared with 13 (30%) patients in the placebo group (5 partial and 8 full thickness).

There was no difference in the ASES and DASH scores at 1 year between patients with retears and those with intact repairs in either group.

Comment: This is a well done and much needed study. Patients with rotator cuff repair often have substantial postoperative pain. This study provides evidence that ibuprofen can help in postoperative pain management without increasing the rate of re-tear. 

It is of interest that (1) the rate of re-tear of these repairs of small-moderate cuff tears was substantial and (2) that re-tear did not appear to affect the patients' self-assessed functional outcome.

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)

The smooth and move for irreparable cuff tears (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).

Shoulder rehabilitation exercises (see this link).

Follow on twitter: Frederick Matsen (@shoulderarth)

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).

Do anti inflammatory medications interfere with healing?

Ibuprofen impairs capsulolabral healing in a rat model of anterior glenohumeral instability

These authors used a rat model to determine the effect of nonsteroidal antiinflammatory drugs (NSAIDs) on the healing glenoid labrum and capsule after glenohumeral dislocation.

Sixty-six rats had surgically induced anterior-inferior labral tears and anterior glenohumeral dislocation. Postoperatively, the animals were assigned to either normal (n = 32) or ibuprofen drinking water (n = 31). Animals were euthanized at 2 and 4 weeks postoperatively for biomechanical testing and histologic analysis.

They found that the postinjury administration of ibuprofen resulted in decreased capsulolabral healing as indicated by decreased stiffness and maximal load to failure.

and delayed histologic evidence of healing

These authors point to a clinical study investigating the effect of NSAIDs on capsulolabral healing in 477 patients from the Norwegian shoulder instability registry with a primary arthroscopic Bankart procedure (see this link). The Western Ontario Shoulder Instability Index and the reoperation rate of the patients who received NSAIDs postoperatively were not statistically significant from those who did not.

Comment: There are substantial data suggesting that non-steroidal anti-inflammatory medications can interfere with the progress of healing of soft tissue injuries and repairs, fractures and surgical fusions.
On the other hand, these medications are effective non-narcotic analgesics with great utility in the postoperative period. They may also be effective in combatting stiffness after arthroplasty.

In situations where healing is likely to be robust (e.g. in healing the subscapularis repair after a shoulder arthroplasty) we use immediate postoperative NSAIDs because the benefit seems to outweigh the resk.
However, where healing is uncertain, for example in rotator cuff repair, there may be a consideration to avoid these medications, although again the evidence comes primarily from animal models (see this link).
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The reader may also be interested in these posts:

Healing through joint replacement

Supporting progress in shoulder surgery

Consultation for those who live a distance away from Seattle.

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Click here to see the new Rotator Cuff Book

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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 as well as the 'ream and run essentials'

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Effect of asprin on healing

Effect of Aspirin on Bone Healing in a Rabbit Ulnar Osteotomy Model

What does this have to do with rotator cuff repair? 

Well, we think that in cuff repair surgery, the bone heals to the tendon, so it seems that drugs that impair bone healing may interfere with the healing of cuff repairs. 

It is recognized that nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with delayed bone healing. These authors study effects of aspirin on bone healing.

Following ulnar osteotomy, fifty-six rabbits were administered a placebo (nine rabbits), indomethacin (nine rabbits given 12.5 mg/kg daily), or aspirin at various doses and schedules (2.7 mg/kg daily for ten rabbits, 10 mg/kg daily for nine rabbits, 50 mg/kg twice daily for ten rabbits, and 100 mg/kg three times daily for nine rabbits). The aspirin doses were chosen to span the clinical dosing range. The indomethacin group served as a positive control and as a relative comparison with the effect of aspirin. Radiographs were obtained every two weeks and the animals were killed at eight weeks. Mechanical testing was performed on all rabbits except for six selected for histological evaluation.

The authors found that aspirin delayed bone healing in a dose-dependent fashion at salicylate levels equivalent to those resulting from typical human dosing (low-dose aspirin 325 mg). Receiver operating characteristic analysis demonstrated a plasma salicylate threshold above 20.7 μg/mL predicting delayed bone healing. This approximates a single human dose of 325 mg. Salicylate levels above this threshold were associated with delayed bone healing similar to that caused by indomethacin. 

This study should cause us to consider the possibility that asprin and non-steroidal anti-inflammatory medications may impair healing after surgery.

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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 as well as the 'ream and run essentials'


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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.

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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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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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