Multimodal analgesia

Published on 07/02/2015 by admin

Filed under Anesthesiology

Last modified 22/04/2025

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Multimodal analgesia

Roy A. Greengrass, MD

Traditionally, perioperative pain has been treated with systemic opioids as the only analgesic drug (monomodal therapy); unfortunately, this approach often resulted in inadequate analgesia because the dose of opioids necessary to completely attenuate the pain was associated with unacceptable side effects. Poorly treated pain has significant physiologic and psychological consequences that adversely affect patient satisfaction and convalescence and is associated with increased costs. To address this problem, the concept of multimodal analgesia, which incorporates the use of different analgesic agents acting, often times synergistically, at specific sites along nociceptive pathways to decrease or eliminate the need for administration of systemic opioids, has developed. It is generally agreed that it is better to prevent, rather than treat, pain; thus, these multimodal strategies should be initiated prior to surgery. Medications should be administered at scheduled times rather than on an as-needed basis. Agents utilized for multimodal analgesia include nonselective and cyclooxygenase-2 (COX-2) selective nonsteroidal antiinflammatory drugs (NSAIDs), acetaminophen, steroids, local anesthetic agents (e.g., for regional anesthesia), α2-receptor agonists, ketamine, opioids, and α2δ ligands.

The nonsteroidal antiinflammatory drugs

Surgical injury causes activation of COX-2 receptors, which enhance prostaglandin production, resulting in hyperalgesia at the site of injury (primary hyperalgesia). Central release of prostaglandins results in secondary hyperalgesia. The use of NSAIDs, thus, presents an opportunity to block these components of the nociceptive pathway. NSAIDs are considered to be the drugs of choice for mild to moderate postoperative pain. NSAIDs have a ceiling effect for analgesia but not for side effects.

Nonselective NSAIDs may result in gastrointestinal erosions, particularly in the elderly. COX-2 NSAIDS decrease, but do not eliminate, gastrointestinal erosion. All NSAIDs decrease renal blood flow and may result in sodium retention and edema. Nonselective NSAIDs also impair platelet function and have been associated with increased blood loss in some surgical procedures.

Acetaminophen

Acetaminophen has no antiinflammatory or peripheral activity. Its antipyretic and analgesic properties are thought to emanate via two possible mechanisms: stimulation of descending central inhibitory pathways or inhibition of central COX-3 (COX-3 being a variant of COX-2) pathways.

Published trials evaluating acetaminophen have demonstrated opioid-sparing effects in the range of 20%, less than that of NSAIDs. Acetaminophen, when administered orally, has a bioavailability of 80% to 90%; however, important variation in individual absorption of acetaminophen occurs in the early postoperative period as a result of delayed gastric emptying. Rectal administration of acetaminophen results in poor and unpredictable absorption. Intravenous acetaminophen is now approved for use in the Unites States.

Steroids

Steroids have potent antiinflammatory and immunosuppressive effects, which decrease the inflammatory response at the site of surgery, thereby decreasing nociceptive input into the spinal cord. A direct effect of steroids of decreasing signal transmission in nociceptive C fibers has also been demonstrated. A single dose of glucocorticoids has been demonstrated to inhibit the synthesis and release of proinflammatory and antiinflammatory mediators in major abdominal and cardiovascular operations. Among the steroids, glucocorticoids are preferred for perioperative antiinflammatory use due to enhanced efficiency and avoidance of mineralocorticoid effects of fluid retention and edema. Suppression of the hypothalamic-pituitary-adrenal axis after single-dose steroid therapy is not an issue. Additionally, there is no evidence in the literature that single-dose steroid administration will increase the risk of wound infection, though a single dose administered to obese patients has been associated with hyperglycemia during the perioperative period.