Indications for Administration of Acetaminophen or NSAIDs

NONOPIOIDS are flexible analgesics and may be used for a wide spectrum of painful conditions. Box 5-1 provides a summary of indications for nonopioids based on the discussion that follows. They typically are first-line analgesics for pain of mild to moderate intensity related to tissue injury (so-called nociceptive pain). This includes inflammatory pain following trauma or surgery, and pain caused by damage to bone, joint, or soft tissue. Given a relatively rapid onset of analgesia and the ability to initiate administration at a dose that is usually effective, it is reasonable to consider this class for both acute and persistent (chronic) pain. (See Patient Medication Information Forms III-1 through III-5 on pp. 250-259.)

Guidelines

Box 5-1

Indications for Nonopioid Analgesics

Mild pain: Start with a nonopioid. Acetaminophen or an NSAID alone often provides adequate relief.

Moderate to severe pain: Pain of any severity may be at least partially relieved by a nonopioid. For some types of moderate pain, especially muscle and joint pain, NSAIDs alone or in combination with acetaminophen may provide adequate relief. However, an NSAID alone usually does not relieve severe pain.

Postoperative pain: Perioperative use of acetaminophen and an NSAID, especially parenteral ketorolac (Toradol) when not contraindicated, should be part of a multimodal analgesic plan begun preoperatively and continued throughout the postoperative course.

Persistent (Chronic) pain: Various types of persistent pain, including cancer-related bone pain, OA, and RA, are appropriate indications for an NSAID.

Pain that requires an opioid: Whenever pain is severe enough to require an opioid, always consider adding a nonopioid for the following reasons:

• Opioid dose-sparing effect (i.e., opioid dose may be lowered without decreasing pain relief. A decreased opioid dose can result in a reduction in opioid-induced adverse effects). A common example is oral or rectal acetaminophen and IV ibuprofen or IV ketorolac plus an opioid postoperatively.

• Opioids and nonopioids relieve pain by different mechanisms.

From Pasero, C., & McCaffery, M. Pain assessment and pharmacologic management, p. 182, St. Louis, Mosby. Pasero C, McCaffery M. May be duplicated for use in clinical practice.

Acetaminophen and aspirin are equi-effective at conventionally-used doses and have long been recognized as multipurpose analgesics (Toms, McQuay, Derry, et al., 2008). As shown in Table 5-1, 650 mg of aspirin or acetaminophen may relieve as much pain as 3 to 5 mg of oral oxycodone or 5 mg of hydrocodone. Single doses of these drugs may be effective. Acetaminophen has a very low incidence of adverse effects. Aspirin is used less today because its adverse effect liability, particularly GI toxicity, is greater than most of the newer NSAIDs, and it must be taken multiple times per day to provide continuous effects.

Table 5-1

Equianalgesic Chart: Approximate Equivalent Doses of Nonopioids and Opioids for Mild to Moderate Pain

From Pasero, C., & McCaffery, M. (2011). Pain assessment and pharmacologic management, p. 182, St. Louis, Mosby. Data from American Pain Society. (2003). Principles of analgesic use in the treatment of acute pain and cancer pain, ed 5, Glenview, IL, APS; Bradley, R. L., Ellis, P. E., Thomas, P., et al. (2007). A randomized clinical trial comparing the efficacy of ibuprofen and paracetamol in the control of orthodontic pain. Am J Orthod Dentofacial Ortho, 132, 511-517; Burke, A., Smyth, E., & FitzGerald, G. A. (2006). Analgesic-anti-pyretic agents: Pharmacotherapy of gout. In L. L. Brunton, J. S. Lazo, & K. L. Parke (Eds.), Goodman & Gilman’s the pharmacological basis of therapeutics, ed 11, New York, McGraw-Hill; Friday, J. H., Kanegaye, J.T., McCaslin I., et al. (2009). Ibuprofen provides analgesia equivalent to acetaminophen-codein in the treatment of acute pain in children with extremity injuries: A randomized clinical trial. Acad Emerg Med, 16(8), 711-716; McCaffery, M., & Portenoy, R. K. (1999). Nonopioid analgesics. In M. McCaffery, & C. Pasero C: Pain: Clinical manual, ed 2, St Louis, Mosby; Raeder, J. C., Stein, S., & Vatsgar, T. T. (2001). Oral ibuprofen versus paracetamol plus codeine for analgesia after ambulatory surgery. Anesth Analg, 92(6), 1470-1472. Pasero C, McCaffery M. May be duplicated for use in clinical practice.

Although NSAIDs other than aspirin were originally marketed for inflammatory conditions such as rheumatoid arthritis (RA), they too are increasingly used as multipurpose analgesics. Based largely on anecdotal observation, there is a strong likelihood that aspirin and other NSAIDs are relatively more effective for somatic (e.g., musculoskeletal) nociceptive pains, particularly those that involve local inflammation, than they are for other types of pain. Note that, despite having very little peripheral antiinflammatory effect, acetaminophen still may be an effective analgesic for inflammatory conditions, such as RA (Simon, Lipman, Caudill-Slosberg, et al., 2002) and postoperative pain (Schug, Manopas, 2007). As described in Chapter 7, however, there also is evidence that the nonaspirin NSAIDs are more effective than acetaminophen for the pain of osteoarthritis (OA). This has also been shown to be true for postoperative pain. A randomized controlled study demonstrated that oral ibuprofen 800 mg taken three times daily provided better pain relief than 1000 mg of oral acetaminophen taken twice daily after anterior cruciate ligament repair (Dahl, Dybvik, Steen, et al., 2004).

An initial trial of a nonopioid is typical if pain is mild or moderate in severity. Patients usually present to health professionals after having tried acetaminophen, aspirin, and/or an over-the-counter (OTC) NSAID without success.

In some situations, such as the pain associated with serious medical illnesses such as cancer, NSAIDs may be overlooked in the context of moderate to severe pain, while treatment with an opioid is initiated. In other situations, such as neuropathic pain, the likelihood that NSAIDs are relatively less effective may justify the decision to forego trials in lieu of selected drugs in the category of the so-called adjuvant analgesics (see Section V). Moderate to severe somatic pain, such as the pain associated with joint disease, usually is treated first with one of the NSAIDs.

The response to an NSAID, like other analgesics, varies. As noted, some of this variation may be related to the pathophysiologies that sustain the pain. In other cases, it seems to be associated with intensity. Severe pain associated with somatic injury may not decline adequately in response to an NSAID at a maximally safe or effective (ceiling) dose (Schug, Manopas, 2007). Finally, some of the variation in response is related to ill-defined individual patient factors that lead to different levels of response to different drugs in the same category. Moderate to severe pain that does not respond to an NSAID, therefore, may be addressed by a trial of another NSAID, or by the addition or substitution of another drug, such as an opioid. All of the nonopioids are compatible with opioid and adjuvant analgesics.

It is wise to avoid combining NSAIDs. This approach may lead to an increase in adverse effects, particularly GI bleeding, and has not been shown to produce better analgesia than a trial with a single NSAID (Kovac, Mikuls, Mudano, et al., 2006). Studies have shown that the combination of acetaminophen and an NSAID produces an additive analgesic effect, however, and concomitant administration may be recommended (Altman, 2004; Bradley, Ellis, Thomas et al., 2007; Hyllested, Jones, Pedersen, et al., 2002; Miranda, Puig, Prieto, et al., 2006; Pasero, McCaffery, 2007; Schug, Manopas, 2007). An oral formulation of 500 mg acetaminophen combined with 150 mg ibuprofen per tablet (Maxigesic) is available outside of the United States for treatment of pain and fever. A randomized controlled trial of 135 adults undergoing removal of 1 to 4 wisdom teeth under local anesthetic found that the combination formulation provided superior postprocedure pain relief compared with acetaminophen or ibuprofen alone (Merry, Gibbs, Edwards, et al., 2009). Patients in this study took 2 tablets immediately before surgery and then 2 more tablets 4 times/day for 48 hours following surgery. Most adverse effects were mild, and there were no changes in the adverse event profile when the two drugs were combined.