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

Disclosures

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

In This Article

Recommendations Based on Current Literature

The use of aspirin leads to an irreversible inhibition of platelet function, thereby placing any patient undergoing surgery at higher risk of intraoperative or postoperative bleeding. Because of its irreversible effects on COX-1 and the life span of the platelet, it would be prudent to hold aspirin or aspirin-containing products for at least 7-10 days before surgery. Nonselective NSAIDs do not exhibit the same irreversible actions on platelet aggregation; however, they should be held for approximately 3-4 half-lives to allow for adequate elimination from the systemic circulation. Based on the evidence described, knowing that bone healing has been inhibited for up to 6 weeks postoperatively, it would be prudent in certain patients to withhold NSAIDs for this duration.

The current data, however, regarding COX-2 inhibitors in this setting reflect different outcomes compared with the nonselective NSAIDs. For patients undergoing orthopedic surgery who are at high risk for postoperative complications, such as cigarette smokers or those with diabetes mellitus, it may be prudent to avoid therapy with COX-2 inhibitors until further safety data have been established. However, patients having minor surgery, such as dental procedures or procedures involving superficial skin layers, or patients with no risk factors for poor outcomes can probably receive COX-2 inhibitors with little or no effect on postoperative healing or bleeding complications.

The use of methotrexate has been associated with an increased rate of infection, which may contribute to postoperative complications.[73,74,75,76,77,78,79,80] The withdrawal of methotrexate in patients whose rheumatoid arthritis is stable before surgery may lead to a disease flare. The delicate balance between risk of complications and quality-of-life benefit must be weighed carefully by the clinician. The effect of methotrexate on postoperative outcomes has been extensively studied, with no clear-cut answer in terms of the appropriate perioperative administration of methotrexate. Patient-specific characteristics should be considered important in the decision-making process. We suggest it may be appropriate to hold methotrexate for 2-4 weeks before surgery and during the first week postoperatively in high-risk patients such as the elderly or those with renal insufficiency. Methotrexate therapy should then be promptly restarted to avoid worsening of rheumatologic disease.

Few studies involving the perioperative management of D-penicillamine and azathioprine are available. Though no definitive data are available, it appears reasonable to continue D-penicillamine with no concern for delays in postoperative recovery or wound healing in patients with rheumatoid arthritis. Because of its potential for bone-marrow toxicity, it is reasonable to hold azathioprine at least 1 day before the surgery and resume treatment a few days after surgery.

Limited data have been published that analyze surgical outcomes after administration of biologic response modifiers, including TNF-α receptor antagonists. The half-lives of these agents are generally long; hence, to allow for complete drug elimination, they must be withdrawn up to 6 weeks before surgery. This may worsen arthritic symptoms, leading to a poorer quality of life. An exception is anakinra, which has a half-life of 4-6 hours. The prudent clinician should exercise caution when administering these drugs in the perioperative setting due to the potential for infection. Because of limited human data with these agents in the surgical setting, we recommend that a conservative management strategy be used for moderate- to high-risk patients. This may include discontinuation of these agents 1 week before surgery with resumption within 1 month after surgery.

Patients taking long-term glucocorticoid therapy should maintain their therapy throughout the perioperative period. However, clinicians should bear in mind that some reports have cited an increase in complications associated with corticosteroid administration. Patients who are taking supraphysiologic dosages of glucocorticoids (e.g., prednisone > 5-7 mg/day) may need supplementation during the surgical period due to suppression of the hypothalamus-pituitary-adrenal axis. These guidelines have been published elsewhere.[152,153] The risk of infection increases and postoperative complications may increase with the amount of corticosteroid given. Caution should be exercised during this situation, and consideration should be given to other patient-specific issues.

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