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Opiate-induced nausea and vomiting: what is the challenge?

The Agency for Healthcare Research and Quality (previously known as the Agency for Health Care Policy and Research) was created by Congress in 1989 was charged with the development of practice guidelines. In 1992, they released the publication “Acute Pain Management in Operative or Medical Procedures and Trauma,” which stated, “Opioid analgesics are the cornerstone of pharmacological postoperative pain management, especially for more extensive surgical procedures that cause moderate to severe pain.” (1) This was followed by the Joint Commission on Accreditation of Healthcare Organizations’ emphasis on pain management and the recognition of pain as the fifth vital sign. These aggressive efforts to enhance postoperative pain management led to increasing opiate administration. Opioid use was further increased by the availability of newer, simpler, and more effective drug delivery systems, including central neuraxial administration, patient-controlled analgesia pumps, drug patches, and slow release oral formulations. Although the practice of increasing opiate administration has resulted in more effective pain therapy and patient satisfaction, it has also come at a price of increased opiate side effects (2,3) including sedation, respiratory depression, urinary retention, pruritus, constipation, and nausea and vomiting. Certainly the incidence and severity of sedation and respiratory depression are dose-related phenomenon, but is the incidence of these other adverse events dichotomous (all or none), or are they also dose-dependent? This is an important question because if these adverse events occur independent of dose, then the many efforts to provide opiate sparing have limited value. Unfortunately, although numerous studies have demonstrated that a variety of interventions or therapies can result in opiate sparing, they are generally underpowered to demonstrate an improvement in outcomes (4). Several recent articles have, at least in general, evaluated if opiate sparing reduces the incidence or severity of opiate side effects or what the authors have termed “clinically meaningful events” (CMEs) (5,6). This work resulted from the development of cyclooxygenase (COX)-2 analgesics for perioperative pain. In the control group, the incidence of a CME and the number of CMEs was related to the dose of opiate analgesic administered. Interestingly, the authors also found that below a morphine equivalent threshold of approximately 10 mg, opiate-related symptoms did not occur. In another study, Gan et al. (6) found after a cholecystectomy and using the same symptom distress questionnaire that the opiate sparing produced by the coadministration of a COX-2 similarly reduced the incidence of CMEs proportional to the reduction in opiate administration. The authors, however, were unable to discriminate the effect of dose on individual adverse events produced by opiates. These studies confirmed that opiate-related side effects, in general, were reduced by decreasing opiate administration, but they could not confirm if the incidence of specific adverse events were decreased by reduced opiate administration. More recently, Marret et al. (7) performed a meta-analysis of studies investigating the opiate-sparing effects of nonsteroidal antiinflammatory drugs (NSAIDs). By combining these studies, they demonstrate that the approximately 30% opiatesparing effect that these drugs provided also resulted in a decreased relative risk of nausea and vomiting. More importantly, their analysis showed there was a dose-response relationship between the amount of opiate administered and the incidence of both nausea and vomiting. They found a linear relationship, with each reduction of 10 mg of morphine decreasing the incidence of nausea by 9%. Being a retrospective metaanalysis, these data required verification by a prospective study. Accepted for publication July 11, 2005. Address correspondence to Peter S. Glass, MB.ChB., FFA (S.A.), University Medical Center at Stony Brook, Department of Anesthesiology, Nicolls Rd HSC Level 4, Rm 060, Stony Brook, NY 11794– 8480. Address e-mail to Peter.Glass@stonybrook.edu.