Pharmacy & Therapeutics- July 2008 - (Page 421) Pain Management and Medication Errors The drop-off in the usage of meperidine probably represents better recognition of this drug’s neuropsychiatric side effects. These adverse effects are mediated by a toxic metabolite (normeperidine), which tends to accumulate because of its relatively long half-life, particularly in patients with impaired renal function.11 As the only active metabolite of meperidine, normeperidine has excitatory central nervous system effects that can lead to anxiety, hyperreflexia, myoclonus, seizures, and mood changes.12 Because of these concerns, meperidine has been supplanted by hydromorphone as the first-line parenteral opioid alternative to morphine in some institutions. Consistent with the trend of increasing opioid use, a study by Pletcher et al. demonstrated that opioid-prescribing rates for patients presenting with pain in emergency departments have increased markedly.13 Documented increases in average consumption of opioids have also been reported in the perioperative setting in the time period before and after The Joint Commission’s standards were implemented (see Table 1).14 Unfortunately, a significant amount of this increased use in the U.S. reflects the growing problem of illicit abuse of prescription opioids. According to a February 2007 study from the Office of National Drug Control Policy,15 prescribed medications, most frequently Purdue’s OxyContin (oxycodone) and Abbott’s Vicodin (hydrocodone/acetaminophen), are now the second most common drugs of abuse among teenagers, trailing only marijuana. At our institution, there has been a growing recognition, as well as discomfort, that our hospital’s formulary is the source of a considerable amount of this type of drug abuse, mainly via diversion of drugs obtained through visits to our emergency depar tment. It is also known that teenagers are obtaining opioid medications from their parents’ prescription bottles and online via the Internet.16 increased focus on pain and the attendant increased opioid use have been accompanied by a greater number of adverse drug events (ADEs) in hospitals. Vila et al. reported more than a twofold increase in the incidence of adverse drug reactions (ADRs) from opioid oversedation, from 11 per 100,000 inpatient hospital days before implementation of The Joint Commission’s pain standards to 24.5 per 100,000 afterward.17 During that period, pain satisfaction scores increased by a modest but statistically significant 5.7%.17 The same investigators noted a similar pattern over the same time period in an analysis of the MedMarx database, which tracks hospital medication errors nationwide.17 Their analysis was unlikely to be confounded by secular trends in reporting frequency, because the rates of ADRs reported over the comparable time period for other dangerous drugs such as insulin and heparin were unchanged.17 In 2002, the Institute for Safe Medication Practices (ISMP) published a paper in response to an increased number of reports it had received concerning opioid-related respiratory depression and deaths.18 In an analysis of ADEs reported to the Adverse Event Reporting System of the Food and Drug Administration (FDA), Moore et al. found a 2.6-fold increase in serious ADEs and a comparable 2.7-fold increase in fatal ADEs between 1998 and 2005.19 Four of the six drugs (oxycodone, fentanyl, morphine, and methadone) most commonly associated with fatal ADEs were opioids.19 An observational study of 53 patients at the University of Connecticut demonstrated that patients had reached dangerous levels of sedation in the first 24 hours postoperatively, particularly in those who were using patient-controlled analgesia (PCA) devices.20 By contrast, among 1,082 postoperative patients in a postanesthesia care unit, Frasco et al. found no association between their observed increase in opioid use, expressed in morphine equivalents, after The Joint Commission’s pain standards were implemented, in terms of length of stay, naloxone use, or postoperative nausea and vomiting.14 Whether or not opioid-related ADEs have increased in real numbers, they have been reported to be not only common but also costly.21–23 In the postoperative setting, problems associated with opioids have been the most common sequelae in the early hours following surgery.20,24 Opioid-Related Adverse Consequences Are Also Increasing In addition to the growing number of problems associated with drug diversion and addiction, there is concern that this Table 1 Distribution of Opioids in Grams per 100,000 U.S. Population Real Change 1997– 2005 0.7 6.6 3.1 2.9 0.7 10.0 2.4 5.0 1.9 % Change 1997– 2005 −27.4% 561.1% 212.2% 185.9% −28.8% 895.4% 144.1% 400.0% 91.8% Lessons Learned from the Recent Experience Of a Community Teaching Hospital In our hospital, we have experienced a number of opioidrelated ADEs that have heightened our concern that the intense “focus on the pain score number,” engendered by Joint Commission standards, might be having an unintended negative effect. Several of these ADEs have resulted in mandatory reports to our state Department of Health because of the severity of the outcomes. In reviewing these events, we have discovered several common themes. First, we found that opioid prescribing trends varied widely among individual physicians and also among specialties. This variance is likely to be found in any clinical setting where there has not been a concerted effort to standardize the approach to pharmacological pain management. Because variance in clinical practice often contributes to a risk of errors, standardization of ordering practices (e.g., as in Figure 1) can Drug Codeine Oxycodone Hydromorphone Hydrocodone Meperidine Methadone Morphine Fentanyl Total 1997 9,396 1668 90 3,249 2161 194 2,220 28 19,006 2005 6,826 11,027 281 9,290 1,538 1,931 5,420 140 36,453 From Automation of Reports and Consolidated Orders System (ARCOS). Available at: www.deadiversion.usdoj.gov/arcos/index. html.10 Vol. 33 No. 7 • July 2008 • P&T® 421 http://www.deadiversion.usdoj.gov/arcos/index.html http://www.deadiversion.usdoj.gov/arcos/index.html
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