Effects of Perioperative Antiinflammatory and Immunomodulating Therapy on Surgical Wound Healing

Anthony J. Busti, PharmD; Justin S. Hooper, PharmD; Christopher J. Amaya, PharmD; Salahuddin Kazi, MBBS


Pharmacotherapy. 2005;25(11):1566-1591. 

In This Article

Abstract and Introduction

Patients with various rheumatologic and inflammatory disease states commonly require drugs known to decrease the inflammatory or autoimmune response for adequate control of their condition. Such drugs include nonsteroidal antiinflammatory drugs (NSAIDs), cyclooxygenase (COX)-2 inhibitors, corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and biologic response modifiers. These drugs affect inflammation and local immune responses, which are necessary for proper wound healing in the perioperative setting, thereby potentially resulting in undesirable postoperative complications. Such complications include wound dehiscence, infection, and impaired collagen synthesis. The end result is delayed healing of soft tissue and bone wounds. The current literature provides insight into the effect of some of these drugs on wound healing. For certain drugs, such as methotrexate, trials have been conducted in humans and direct us on what to do during the perioperative period. Whereas with other drugs, we must rely on either small-animal studies or extrapolation of data from human studies that did not specifically look at wound healing. Unfortunately, no clear consensus exists on the need and optimum time for withholding therapy before surgery. Likewise, clinicians are often uncertain of the appropriate time to resume therapy after the procedure. For those drugs with limited or no data in this setting, the use of pharmacokinetic properties and biologic effects of each drug should be considered individually. In some cases, discontinuation of therapy may be required up to 4 weeks before surgery because of the long half-lives of the drugs. In doing so, patients may experience an exacerbation or worsening of disease. Clinicians must carefully evaluate individual patient risk factors, disease severity, and the pharmacokinetics of available therapies when weighing the risks and benefits of discontinuing therapy in the perioperative setting.

Patients with osteoarthritis, rheumatoid arthritis, or other autoimmune diseases frequently require corticosteroids, nonselective nonsteroidal antiinflammatory drugs (NSAIDs), cyclooxygenase (COX)-2-selective inhibitors, disease-modifying antirheumatic drugs (DMARDs), and/or biologic response modifiers for the treatment of disease-related pain and disease progression. In addition to their therapeutic effects, these compounds have physiologic effects on the bone marrow, kidneys, adrenal glands, and central nervous system. Some of these effects are believed to be detrimental to the process of normal soft tissue and bone healing. For example, suppressive effects on the human immune system may increase the tendency toward infection of surgical wounds. Several recent publications have reported that infection may develop among nonsurgical patients receiving tumor necrosis factor (TNF)-α inhibitors such as etanercept, infliximab, and adalimumab.[1,2,3,4,5] All three TNF-α blocking agents also have been noted to cause pancytopenia. In addition, leflunomide has been reported to cause pancytopenia.[6] Consequently, these extratherapeutic effects may contribute to morbidity due to poor wound healing in the postoperative setting. We review the physiologic mechanisms involved in soft tissue and bone healing and the proposed consequences of common antiinflammatory and immuno-suppressive drug therapy on the wound healing process. Furthermore, we propose evidence-based recommendations that are based on the current literature in reference to perioperative management of antiinflammatory and immuno-modulating therapy in patients undergoing orthopedic and other surgical procedures.


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