Pharmacologic Management of Postoperative Pain

Pharmacologic management of mild to moderate postoperative pain should begin, unless there is a contraindication, with an NSAID. Moderately severe to severe pain normally should be treated initially with an opioid analgesic. After many relatively noninvasive surgical procedures, NSAIDs alone can achieve excellent pain control (Davie, Slawson, and Burt, 1982; Rosen, Absi, and Webster, 1985). NSAIDs decrease levels of inflammatory mediators generated at the site of tissue injury. Even when insufficient alone to control pain, NSAIDs have a significant opioid dose–sparing effect upon postoperative pain and can be useful in reducing opioid side effects (Guideline Report, in press; Hodsman, Burns, Blythe, Kenny, McArdle, and Rotman, 1987; Martens, 1982). The concurrent use of opioids and NSAIDs often provides more effective analgesia than either of the drug classes alone. Although it is likely that NSAIDs also act within the central nervous system, in contrast to opioids, they do not cause sedation or respiratory depression, nor do they interfere with bowel or bladder function. Acetaminophen does not affect platelet aggregation, nor does it provide peripheral anti– inflammatory activity. Some evidence exists that two salicylates do not affect platelet aggregation profoundly; these are saisalate (Estes and Kaplan, 1980) and choline magnesium trisalicylate (Danesh, Saniabadi, Russell, and Lowe, 1987). All other NSAIDs appear to produce a risk of platelet dysfunction that may impair blood clotting and carry a small risk of gastrointestinal bleeding. At present, one NSAID (ketorolac) is approved by the Food and Drug Administration for parenteral use. The analgesic dosage tables in appendixes B and C include information on NSAIDS, opioids, and other analgesic drugs.

Opioid analgesics are the cornerstone of pharmacological postoperative pain management, especially for more extensive surgical procedures that cause moderate to severe pain. Other agents such as NSAIDs or single injections of local anesthetics may control mild to moderate pain after relatively minor procedures or reduce opioid dose requirements after more extensive operations when this is a goal (Guideline Report, in press; Egan, Herrnan, Doucette, Normand, and McLeod, 1988; Engberg, 1985a, 1985b; Kaplan, Miller and Gallagher, 1975; Patel, Lanzafame, Williams, Mullen, and Hinshaw, 1983; Sabanathan, Meams, Bickford Smith, Eng, Berrisford, Bibby, and Majid, 1990; Toledo–Pereyra and DeMeester, 1979). Even in the absence of preemptive efforts targeted at postoperative analgesia, adequate postoperative pain control can usually be achieved with opioid analgesics. When increasing doses of opioids are ineffective in controlling postoperative pain, a prompt search for residual pathology is indicated, and other diagnoses such as neuropathic pain should be considered.

Opioid tolerance or physiological dependence is unusual in short–term postoperative use in opioid naive patients. Likewise, psychologic dependence and addiction are extremely unlikely to develop after patients without prior drug abuse histories use opioids for acute pain (Porter and Jick, 1980). Proper use of opioids involves selecting a particular drug and route of administration and judging: 1) suitable initial dose; 2) frequency of administration; 3) optimal doses of non– opioid analgesics, if these are also to be given; 4) incidence and severity of side effects; and 5) whether the analgesic will be given in an inpatient or ambulatory setting. Titration to achieve the desired therapeutic effect in the immediate postoperative period and to maintain that effect over time should be emphasized.

Opioids produce analgesia by binding to opioid receptors both within and outside the central nervous system. Opioid analgesics are classified as full agonists, partial agonists, or mixed agonist–antagonists, depending on the manner in which they interact with opioid receptors. Full agonists produce a maximal response within the cells to which they bind; partial agonists produce a lesser response, regardless of their concentration; and mixed agonist–antagonists activate one type of opioid receptor while simultaneously blocking another type. Several types and subtypes of such receptors exist. The most important receptor type for clinical analgesia is named "mu" because of its affinity for morphine. Other commonly used mu opioid agonists include hydromorphone, codeine, oxycodone and hydrocodone, methadone, levorphanoll and fentanyl. All mu opioid agonists have the potential to cause constipation, urinary retention, sedation, and respiratory depression and frequently also produce nausea or confusion. Mixed agonist– antagonists in clinical use include pentazocine [Talwin], butorphanol tartrate [Stadol], and nalbuphine hydrochloride [Nubain]; each of these blocks or is neutral at the mu opioid receptor while simultaneously activating a different type of opioid receptor termed "kappa." Patients receiving mu opioid agonists should not be given a mixed agonist–antagonist because doing so may precipitate a withdrawal syndrome and increase pain. Mixed agonist–antagonists and partial agonists may exhibit a ceiling effect not only with respect to respiratory depression (Nagashima, Karamanian, Malovany, Radnay, Ang, Koerner, and Foldes, 1976; Kallos and Caruso, 1979) but also in regard to their analgesic activity. In the awake patient, there is a clinical ceiling analgesic effect even with morphine because side effects such as respiratory depression limit the dose that may be safely given. However, this does not limit the ability of clinicians to effectively increase the drug dose when the painful stimulus increases and respiratory status is monitored.