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A Practical Approach to Discontinuing NSAID Therapy Prior to a Procedure

The process of stopping NSAIDs should be based on pharmacokinetics, cyclooxygenase selectivity, comorbid renal or hepatic dysfunction, pain level and pain tolerability, overall bleeding risk from specific surgeries or procedures, and overall effect on the patient’s well-being during the perioperative timespan.
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In 2010, there were a total of 51.4 million inpatient procedures performed in the United States.1 The perioperative management of chronic medications is an important consideration for healthcare providers.2 This entails adequately evaluating all vital signs, including pain, and counseling the patient accordingly.3,4

For many candidates undergoing elective surgery or interventional procedures, non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used medications for a multitude of chronic and acute pain syndromes. In 2012, for example, 98 million prescriptions for NSAIDs were filled in the United States. In addition, 23 million Americans reported using over-the-counter NSAIDs daily.5

A directive to discontinue NSAIDs prior to surgery or interventional procedure is a serious concern often creating significant angst for chronic pain patients who otherwise rely on these medications to preserve daily function, obtain restful sleep, and maintain comfort.6 This review will discuss the historical risks related to NSAID use, appropriate timing for stopping NSAIDs, and other practical guidelines.

Recommendations Vary

Increased bleeding risk from NSAID use in the perioperative period is well known. However, clinicians’ recommendations regarding appropriate timing for discontinuation of NSAIDs prior to surgery may be outdated and devoid of scientific evidence specific to unique NSAID half-lives and pharmacology. Minimal clinical studies are available in this area, compelling practitioners to base their decisions on clinical experience, which result in inconsistent recommendations to patients.

Fifteen clinicians responded to an informal email survey the authors sent to pain practitioners nationwide to ascertain their policy on NSAID discontinuation prior to surgery or intervention. The respondents represented a variety of medical specialties, including anesthesiology, pain management, neurosurgery, and pharmacy. Not surprisingly, their answers about the best time to discontinue NSAIDs varied between 0 to 10 days prior to procedure date, with 14% recommending 0 days, 14% recommending 3 days, 29% recommending 7 days, and the majority (43%) of responders recommending discontinuation at 5 days.

Why do practitioners routinely recommend discontinuing NSAID use 5 to 10 days prior to a surgical procedure? Perhaps this is erroneously based on the misconception that all NSAIDs affect platelets similarly to aspirin; that all have the same binding affinity to cyclooxygenase (COX)-1; and that all have an identical half-life. However, the authors suspect that the lack of evidence has influenced most clinicians to take a conservative approach, emphasizing patient safety considering the potential for perioperative bleeding if NSAIDs are continued. This policy may lead to pain patients being left without adequate pain control prior to a procedure.

Historical Record

Willow bark has been recognized for centuries for its antipyretic, anti-inflammatory, and analgesic effects.7,8 In 1838, it was purified to salicylic acid, the first NSAID. It was heavily used in inflammatory disorders, limited only by its poor gastrointestinal tolerability. In 1858, salicylic acid was buffered with sodium and acetyl chloride, creating acetyl salicylic acid, significantly improving its gastrointestinal tolerability. It was not produced commercially in significant amounts, however, until a more stable form was produced in 1899 by the Bayer Company and marketed as Aspirin.7,8 Aspirin quickly became the most popular painkiller worldwide, commonly used for backache, headache, and arthritis.8

Mechanisms of Action

Aspirin’s acetyl group confers receptor binding properties unique among all NSAIDs because it binds irreversibly to Ser529 in platelets, which ultimately affects COX-1.9 Unlike nucleated cells expressed in body tissues, which can recycle and express new COX enzymes, when COX is irreversibly bound in platelets it inhibits platelet aggregation and vasoconstriction for their entire life-cycle (7-10 days).9 Aspirin’s cardioprotective effect and increased bleeding risk are results of this effect and studies have shown it to be achievable with doses as low as 40 mg per day.9

Traditional NSAIDs reversibly inhibit COX enzyme, but may compete with aspirin for the binding site. For this reason, patients requiring aspirin for prevention of cardiovascular disease should be counseled to take it at least 30 minutes prior to non- aspirin NSAIDs to receive the intended cardioprotective effects.9 There are more than 6 distinct chemical classes of NSAIDs with significant differences in pharmacology, pharmacokinetics, and COX selectivity, all of which contribute to their unique efficacy and safety profile.10,11

Arachidonic acid is hydrolyzed from the phospholipid bilayer of cellular membranes by phospholipases and converted into prostaglandins via cyclooxygenase enzymes.9 There are 2 major subtypes of the cyclooxygenase enzyme, COX-1 and COX-2. COX-1 is constitutively expressed in most cells and is responsible for GI mucosa protection, renal homeostasis, and hemodynamic stability.12-15 Prostaglandins produced by the COX-1 enzyme are further metabolized into thromboxane A2(TXA2) and prostacyclin I2 (PGI2), which are produced in equal amounts to maintain a balance.9 In platelets, TXA2 increases platelet aggregation and vasoconstriction.14,16 In tissues and vessels, PGI2 inhibits platelet aggregation and thrombosis formation.9,14

Unlike COX-1, COX-2 is expressed only in the brain, kidney, colon, and vessels. However, its expression can be induced by cytokines at the site of inflammation.12,13,11,17 COX-2 produces PGI2 and PGE2, but not TXA2, and is believed to be the primary mediator of pain and inflammation.11 PGE2 is the primary prostaglandin produced in the presence of inflammation and has an interesting concentration-dependent effect. At low levels, PGE2 will favor platelet aggregation and vasoconstriction whereas at high levels, PGE2 inhibits platelet aggregation and promotes vasodilation.9,12,14

Determining Bleeding Risks

Because COX-1 inhibition directly affects platelet aggregation, the degree of COX-1 inhibition by an NSAID plays an integral part in determining a patient’s bleeding risk.9,12

Theoretically, NSAIDs with COX-2 greater than COX-1 inhibition will have an increased analgesic benefit while minimizing bleeding risk. The NSAIDs currently marketed vary in their degree of COX-1 to COX-2 inhibition and selectivity; and familiarity with these properties can be useful to determine bleeding risk. In fact, since celecoxib (Celebrex) has an 11-hour half-life, it is reasonable to begin therapy at least 55 hours prior to a procedure (5 half-lives) to reach steady state in advance. The final preemptive dose could be given with dinner the evening prior to a scheduled procedure in order to reduce inflammation perioperatively.

Last updated on: December 9, 2013
First published on: December 1, 2013