MORPHINE IS DRUG OF CHOICE OVER DEMEROL FOR POST-OP ACUTE PAIN, FIRST AHCPR GUIDELINE RECOMMENDS: REPORT CALLS FOR AGGRESSIVE, PROACTIVE PAIN MANAGEMENT
Morphine is the drug of choice rather than Demerol (meperidine) in preventing and controlling acute post-operative pain, HHS' Agency for Health Care Policy and Research recommended in a new guideline, "Acute Pain Management: Operative or Medical Procedures and Trauma." "Opioid analgesics are the cornerstone for management of moderate to severe acute pain," AHCPR says in a "Quick Reference Guide for Clinicians" accompanying the longer guideline. "Morphine is the standard agent for opioid therapy. If morphine cannot be used because of an unusual reaction or allergy, another opioid such as hydromorphone can be substituted." Meperidine, characterized as currently the standard drug of choice in most U.S. hospitals for acute post-op pain, is recommended only for use in "very brief courses" in patients who are healthy and/or have problems with other opioids, such as an allergic response. The guideline, the first in a series of federally-sponsored blueprints for certain areas of medical care, was unveiled March 5 by HHS Secretary Sullivan, Assistant Secretary for Health James Mason, MD, and AHCPR Administrator Jarrett Clinton, MD, among others. Developed by an interdisciplinary panel and endorsed by the department, the document is designed to provide clinicians with an easy-reference pattern of treatment: Mason predicted that the AHCPR recommendations will have the same kind of acceptance as federal guidelines for immunizations. The guideline also has been endorsed by a number of professional groups, including the American Nurses Association. The American Medical Association says it endorses the process followed in developing the pain guideline. The group is currently reviewing the guideline's actual provisions. Asked during a press briefing whether the recommendation of morphine as the drug of choice will prove controversial, panel co- chair Ada Jacox, RN/PhD, Johns Hopkins University School of Nursing, replied: "For more years than I care to think, the common way to deal with post-operative pain was 75 mg of Demerol every three to four hours as necessary. This has been shown to be widely ineffective." Over-reliance on meperidine "is one of the major reasons" why an estimated 50% of surgical patients experience moderate to severe pain post-operatively, Jacox said. Meperidine is manufactured under the brand name Demerol by Sterling Winthrop and is also available in generic versions. The problem with meperidine is multi-fold, Jacox suggested, involving both clinical practice and the toxicology of the drug itself. First, she said, meperidine is routinely underprescribed. The standard order is 75 mg to 100 mg every three to four hours, "as necessary," Jacox noted. However, Demerol is only effective for "roughly" two-and-a-half to three-and-a-half hours, "so if the patient only gets it after four hours, the pain already has started to re-emerge." Also, in order to be as effective in controlling pain as morphine, "one would have to give 100 to 150 mg of Demerol every three hours," she added. "So that from the standpoint of amount of drug administered, it's underprescribed and from the standpoint of length of time it's effective, it's underprescribed." A dosing chart in the guideline recommends 100 mg of meperidine delivered parenterally every three hours in adults, and .75 mg/kg every two to three hours in children. Oral dosing is not recommended. The other panel co-chair, Daniel Carr, MD, Massachusetts General Hospital, noted that adverse side effects from meperidine also factored into the panel's recommendations. Meperidine produces a "very toxic byproduct" when it metabolizes, Carr said. While it is widely known that meperidine is contraindicated in patients with renal problems, the buildup of toxic metabolites can effect even healthy patients adversely, Carr said. However, he noted that "the guideline does not prohibit meperidine or Demerol use whatsoever. It simply recommends that morphine be used as the first drug." The toxic meperidine metabolite is normeperidine (6-N- desmethylmeperidine), which is excreted through the kidney. The guideline notes that in patients with normal renal function, normeperidine has a half-life of 15 to 20 hours. AHCPR says this half-life is "extended greatly" in both the elderly and patients with impaired renal function. Side effects can range from dysphoria and irritability to convulsions, the report states. One reason clinicians may have been reluctant to use morphine is fear of addiction among patients, speakers said. However, a review of the literature showed an addiction rate of only about .04%, according to Jacox. Overall, the report emphasizes the need for "aggressive pain management before, during and after surgery," and recommends against treating pain on an "as-needed" basis. Relying on opioid administration "as-needed," for example, can result in "prolonged delays" in patient relief, the guideline says. "These delays can be eliminated by administering analgesics on a regular time schedule initially. For example, if the patient is likely to have pain requiring opioid analgesics for 48 hours following surgery, morphine could be ordered every four hours by the clock (not 'as needed') for 36 hours. Once the duration of analgesic action is determined for a patient, the dosage frequency should be adjusted to prevent pain from recurring." As soon as the patient is able to tolerate it, oral dosing is "usually the most convenient and least expensive route of administration," the guideline notes. If the patient cannot tolerate oral dosing, I.V. administration is the "parenteral route of choice," whether via bolus or continuous infusion. For intravenous administration, many patients prefer patient controlled analgesia via infusion pump to intermittent injections, the guideline states. PCA is "a safe method for postoperative pain management," suitable both for adults and for children as young as seven, according to the recommendations. Commenting on PCA during the press briefing, Carr said that while the literature is still growing in this area, "in a nutshell, reviewing that literature showed us that patients are clearly more satisfied when they use those devices. Their pain is better controlled; that is, it is statistically significantly lower or of less intensity than during conventional therapy." Carr said there was also "a trend" toward less use of drug than during conventional treatment but added that that data "did not attain statistical significance." For mild to moderate pain, nonsteroidal anti-inflammatory drugs are the first line treatment. "Even when insufficient alone to control pain, NSAIDs, including acetaminophen, have significant dose-sparing effects on postoperative pain and hence can be useful in reducing opioid side effects," the guideline says. For patients who cannot tolerate oral dosing, Syntex' Toradol (ketorolac) has been approved by FDA for parenteral use, the guideline notes. Rectal administration of NSAIDs also may be used. While AHCPR's mission ostensibly is focused on quality of care rather than economics, the guidelines eventually may become a factor in Medicare reimbursement, HHS' Mason told the briefing. Although Mason stressed that cost consideration is "not one of the driving forces" in the creation of the guidelines, he noted that "as these guidelines are voluntarily adopted...I think there will be some reductions in certain procedures that may be less effective." However, any impact on reimbursement practices is likely to show up first among private payers, Mason added. "I think there will be some third-party providers that will say 'Well, we're not going to spend more to get less or spend more to get the same.'" With regard to the pain management guideline specifically, Mason said that better management of pain could lead to a decrease in length of stay, perhaps as much as half a day. At the same time, however, there may be an increase in costs from closer monitoring of pain management. HHS Secretary Sullivan hailed the guideline as "the beginning of a peaceful revolution in American medical care." He added: "Put simply, the findings here indicate that we can do more, and we can do better, to control pain after surgery." AHCPR currently is working on 15 additional guidelines, Clinton said, 12 in-house and three under contract. The agency expects to release the next document, a guideline for treatment of urinary incontinence in adults, later this month (see box, p. 4, for list of AHCPR guidelines under development). The agency is treating cancer pain in a separate guideline, due out at the end of the year. In addition to the 145-page guideline itself, AHCPR also is disseminating two 22-page "Quick Reference Guides," one referring to adults and one to children, and a nine-page patient guide. The agency is working on a Spanish language version of the patient guide, to be available in a few months. The pain control package will be available via an 800 toll-free number, AHCPR's Clinton said. The agency has contracted with outside peer review organizations, including the American Medical Review Research Center, to evaluate the first few guidelines it develops.
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