The most common adverse effects of NSAIDs involve the GI system. NSAID-induced GI toxicity usually is addressed in the literature as an adverse effect resulting from long-term NSAID use; however, GI ulceration can occur with short-term perioperative administration as well (Pasero, Portenoy, & McCaffery, 2011). This is particularly true in individuals with elevated risk for GI toxicity, such as older adults and those with a previous GI complication. The use of the least ulcerogenic nonselective NSAID or a COX-2 selective NSAID, if not contraindicated by cardiovascular risk, is encouraged. The lowest effective NSAID dose for the shortest period of time necessary is also recommended (Pasero, Portenoy, & McCaffery, 2011).
The possibility of increased bleeding time is of special concern when NSAIDs are used for postoperative pain. Aspirin has an irreversible effect on platelets and will increase bleeding time for up to 7 days after the last dose (i.e., until the damaged platelets are replaced by new ones). For that reason, aspirin therapy is usually discontinued 1 week or more before surgery, and aspirin is not recommended for perioperative analgesic use (Ashraf, Wong, Ronayne, & Williams, 2004). Other nonselective NSAIDs are also sometimes withheld during the perioperative period because of their tendency to prolong bleeding time. However, acetaminophen; the nonselective NSAIDs nabumetone, meloxicam, choline magnesium trisalicylate, magnesium salicylate, and salsalate; and the COX-2 selective NSAID celecoxib have no effect on bleeding time and should be considered instead (Visser & Goucke, 2008).
Shortly after the release of the COX-2 selective NSAIDs, studies revealed an association between the perioperative use of valdecoxib and an increase in adverse cardiovascular events (e.g., myocardial infarction, stroke, pulmonary embolism) in patients who had undergone high-risk cardiac surgery (Nussmeier et al., 2005; Ott et al., 2003). The general recommendation is to avoid the perioperative use of NSAIDs following high-risk, open heart surgery (United States Food and Drug Administration [USFDA], 2007).
Adverse renal effects are relatively rare in otherwise healthy individuals who are given NSAIDs during the perioperative period (Lee, Cooper, Craig, Knight, & Keneally, 2007). In contrast, individuals with acute or chronic volume depletion or hypotension depend on prostaglandin synthesis to maintain adequate renal blood flow (“prostaglandin dependence”) (Helstrom & Rosow, 2006), and NSAID inhibition of prostaglandin synthesis in such patients can cause acute renal ischemia and acute renal failure (ARF) (Helstrom & Rosow, 2006). Acute renal failure as a result of hypovolemia is usually reversed when the NSAID is stopped and volume is replenished (Miyoshi, 2001), but it underscores the importance of adequate hydration and maintenance of acceptable BP before and during NSAID administration. Patients at increased risk for perioperative ARF and who might be more susceptible to NSAID-induced renal injury include those with cardiac failure, liver cirrhosis, ascites, diabetes, preexisting hypertension, and patients being treated with ACE inhibitors (Forrest et al., 2002; Helstrom & Rosow, 2006; Launay-Vacher, Karie, Fau, Izzedine, & Deray, 2005). Other risk factors are preexisting renal impairment, advanced age, and left ventricular dysfunction (Helstrom & Rosow, 2006). It is generally recommended that NSAIDs be avoided in patients with chronic renal failure and in any patient with a creatinine clearance below 30 mL/min (Laine, White, Rostom, & Hochberg, 2008; Launay-Vacher, Karie, Fau, Izzedine, & Deray, 2005). Acetaminophen and opioids (e.g., fentanyl) are better choices in these patients.