Anesth Analg 2005;101:1341-1342
© 2005 International Anesthesia Research Society
doi: 10.1213/01.ANE.0000181329.07214.D8
ANESTHETIC PHARMACOLOGY
James G. Bovill
Opiate-Induced Nausea and Vomiting: What Is the Challenge?
Martin Redmond, MD, and
Peter Glass, MBChB
Department of Anesthesiology, SUNY at Stony Brook, Stony Brook, New York
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{at}stonybrook.edu.
Postoperative pain management is an ever-changing and challenging conundrum.
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% opiate-sparing 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 meta-analysis, these data required verification by a prospective study.
In this issue of Anesthesia & Analgesia, Roberts et al. (8) have confirmed, in a prospective study, that the incidence of nausea and vomiting are both increased in a dose-dependent manner by the amount of opiate administered. This study included epidural, IV, and oral opiate administration for patients after either orthopedic or abdominal surgery, thereby covering a wide spectrum of opiate requirements. They found an exponential relationship between opiate dose and nausea, with each halving of the opiate dose reducing the incidence of vomiting by 6% (and a little more for nausea). Although there are several design problems in the study by Roberts et al. (which are well discussed by the authors) and although the percentage reduction in postoperative nausea and vomiting for each milligram of opiate is not identical between the two studies, they together provide credence to the notion that opiate-induced nausea and vomiting is dose-dependent and that measures to provide opiate sparing are likely to reduce their incidence. One caveat of the Roberts et al. study is that pain itself may induce nausea and vomiting (9). This makes it difficult to determine if pain or the opiate is causing the nausea and vomiting. The meta-analysis by Marret et al. (7) would support that this is opiate-induced, as patients in the various studies analyzed generally had equal pain relief whether this was provided primarily by the opiate or the NSAID plus reduced opiate.
In many instances, the use of large-dose opiates is unavoidable. In these incidences, administering prophylactic antiemetics is clearly indicated. The choices for first-line antiemetics are multiple and controversial. With the knowledge that reducing opiate requirements decreases nausea and vomiting, it makes sense to choose an antiemetic that is effective in opiate-induced nausea and vomiting and also enhances analgesic efficacy. Dexamethasone (10), small-dose promethazine (11), and droperidol (12) have demonstrated, at least in some models of pain, both opiate-sparing activity and efficacy in opiate-induced nausea and vomiting. All of these antiemetics are relatively inexpensive, effective, and can be used alone or in combination. When used at appropriate doses they also have limited side effects.
The articles by Roberts et al. and Marret et al. have confirmed the notion that opiate-induced nausea and vomiting is dose dependent. Based on this information we should consider moving away from the concept that opiate analgesics are the cornerstone of moderate-to-severe pain management but are rather simply one component of multimodel pain therapy. Unfortunately, all therapies used for pain management are fraught with adverse events. The challenge for the clinician today is to minimize the opiate component of their pain management (thereby reducing the incidence of side effects) while still insuring optimal pain relief.
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Footnotes
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Accepted for publication July 11, 2005.
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References
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- Research AfHCPa. Acute Pain Management Guideline Panel: Acute Pain Management: Operative or Medical Procedures and Trauma Clinical Practice Guideline Rockville, MD: US Department of Health and Human Services, Public Health Service, 1992.
- Wheeler M, Oderda GM, Ashburn MA, Lipman AG. Adverse events associated with postoperative opioid analgesia: a systematic review. J Pain 2002;3:159–80.[Web of Science][Medline]
- Smetzer JL, Cohen MR. Pain scales don’t weigh every risk. J Pain Palliat Care Pharmacother 2003;17:67–70.[Medline]
- Romsing J, Moiniche S, Mathiesen O, Dahl JB. Reduction of opioid-related adverse events using opioid-sparing analgesia with COX-2 inhibitors lacks documentation: a systematic review. Acta Anaesthesiol Scand 2005;49:133–42.[Medline]
- Zhao SZ, Chung F, Hanna DB, et al. Dose-response relationship between opioid use and adverse effects after ambulatory surgery. J Pain Symptom Manage 2004;28:35–46.[Web of Science][Medline]
- Gan TJ, Joshi GP, Zhao SZ, et al. Presurgical intravenous parecoxib sodium and follow-up oral valdecoxib for pain management after laparoscopic cholecystectomy surgery reduces opioid requirements and opioid-related adverse effects. Acta Anaesthesiol Scand 2004;48:1194–207.[Web of Science][Medline]
- Marret E, Kurdi O, Zufferey P, Bonnet F. Effects of nonsteroidal antiinflammatory drugs on patient-controlled analgesia morphine side effects: meta-analysis of randomized controlled trials. Anesthesiology 2005;102:1249–60.[Web of Science][Medline]
- Roberts GW, Becker TB, Carlsen HH, et al. Postoperative nausea and vomiting is strongly influenced by postoperative opioid use in a dose related manner. Anesth Analg 2005;101:1343–8.[Abstract/Free Full Text]
- Andersen R, Krohg K. Pain as a major cause of postoperative nausea. Can Anaesth Soc J 1976;23:366–9.[Web of Science][Medline]
- Baxendale BR, Vater M, Lavery KM. Dexamethasone reduces pain and swelling following extraction of third molar teeth. Anaesthesia 1993;48:961–4.[Web of Science][Medline]
- Chia YY, Lo Y, Liu K, et al. The effect of promethazine on postoperative pain: a comparison of preoperative, postoperative, and placebo administration in patients following total abdominal hysterectomy. Acta Anaesthesiol Scand 2004;48:625–30.[Medline]
- Lo Y, Chia YY, Liu K, Ko NH. Morphine sparing with droperidol in patient-controlled analgesia. J Clin Anesth 2005;17:271–5.[Web of Science][Medline]
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