Opioid Antagonists for Bowel Dysfunction

Although receptors in the central nervous system (CNS) are involved in the pathophysiology of opioid-induced constipation, the effect appears to be mediated predominantly by GI mu opioid receptors (Thomas, Karver, Cooney, et al., 2008). This observation led to a search for a peripherally acting mu opioid antagonist that could specifically reverse opioid-induced bowel dysfunction without reversing analgesia (Thomas, 2008).

When taken orally, the opioid antagonists naloxone, naltrexone, and nalmefene are absorbed systemically, and although they can effectively reverse bowel dysfunction, they can cross the blood-brain barrier, reverse central opioid receptors and analgesia, and produce withdrawal symptoms (Becker, Galandi, Blum, 2007; Goodheart, Leavitt, 2006; Liu, Wittbrodt, 2002; Thomas, 2008). This outcome is least likely to occur with naloxone, which has a very limited oral bioavailability (around 3%). Although there is a risk of systemic absorption with associated return of pain and withdrawal, the risk with this drug is low, and oral naloxone (20 to 40 mg) has been used clinically for refractory constipation (Meissner, Leyndecker, Mueller-Lissner, et al., 2009).

In contrast to these other antagonists, methylnaltrexone (Relistor) and alvimopan (Entereg) have the potential to block opioid actions mediated by peripheral opioid receptors while sparing actions mediated by opioid receptors in the CNS (Portenoy, Thomas, Moehl Boatwright, et al., 2008). Methylnaltrexone has approval in the United States for the treatment of opioid-induced constipation in patients with advanced illness (Wyeth Pharmaceuticals, 2009), and alvimopan is approved for acceleration of the time to upper and lower GI recovery following partial large or small bowel resection with primary anastomosis (GlaxoSmithKline, 2009). Methylnaltrexone is given subcutaneously (8 mg for patients weighing 38 to 62  kg every other day and no more than one dose in a 24-hour period), and alvimopan is taken orally (12 mg 30 minutes to 5 hours prior to surgery, then 12 mg twice daily for up to 7 days for a maximum of 15 doses). Methylnaltrexone is not approved for IV use but has been used by this route for treatment of nausea, pruritus, and urinary retention (Gold Standard Clinical Pharmacology, 2009).

A systematic review of 20 studies that were conducted on the use of methylnaltrexone and alvimopan for treatment of constipation concluded that further research with larger numbers of patients and varying types of pain are required (Becker, Galandi, Blum, 2007). Another analysis of 22 studies concluded that there is insufficient evidence for the safety and efficacy of naloxone or nalbuphine for the treatment of opioid-induced bowel dysfunction and that further research is needed to fully assess the role of alvimopan and methylnaltrexone in therapy (McNicol, Boyce, Schumann, et al., 2008). Following is a discussion of some of the research on methylnaltrexone. See pp. 491-493, Postoperative Ileus, for more on alvimopan.

One of the first studies conducted on methylnaltrexone was a double-blind study of 22 adults who were enrolled in a methadone maintenance program and had methadone-induced constipation (Yuan, Foss, O’Connor, et al., 2000). The subjects were randomized to receive either IV methylnaltrexone (up to 0.365  ) or placebo infusion over 9 minutes. All of the subjects who received methylnaltrexone had abdominal cramping followed by laxation on day 1 or day 2; none of those who received placebo had these effects. The effects of methadone maintenance were not reversed in this study.

A 2-week double-blind trial randomized 133 patients with incurable cancer or other end-stage disease who had been taking stable doses of opioid analgesics for 2 or more weeks to receive either SC methylnaltrexone (0.15  ) or placebo (Thomas, Karver, Cooney, et al., 2008). The median dose of morphine equivalent the patients were taking was 100 mg and 150 mg in the methylnaltrexone and placebo groups, respectively, and the patients were constipated at baseline. Laxation occurred within 4 hours of the first study dose in 48% of those who received methylnaltrexone compared with 15% of those who received placebo, and 52% had laxation without a rescue laxative within 4 hours after two or more of the first four study doses compared with 8% in the placebo group. Adverse effects were mild or moderate (e.g., abdominal pain, flatulence, nausea, increased body temperature, and dizziness) in 8% and 13% of those in the methylnaltrexone and placebo groups, respectively. Life-threatening adverse events were assessed as related to the primary illness. Eighty-nine of the patients in this study entered a 3-month, open-label extension study in which methylnaltrexone was administered to all of them. The response rate in those who had received methylnaltrexone and placebo in the double-blind phase was 45% to 58% and 48% to 52%, respectively. Similar adverse effects occurred in the open-label phase as in the double-blind phase. Analgesia was maintained throughout both phases of this study.

Methylnaltrexone was studied in a randomized, parallel-group, repeated dose, dose-ranging trial that included a one-week double-blind phase followed by an open-label phase for up to 3 weeks (Portenoy, Thomas, Moehl Boatwright, et al., 2008). The patients (N = 33) in this study had terminal or end-stage diseases and were receiving palliative care and long-term opioid therapy with stable doses for at least 2 weeks (mean and median opioid morphine equivalent dose = 289.9 mg and 180 mg, respectively) and reported ongoing constipation. They were randomized to receive 1, 5, 12.5, or 20 mg of SC methylnaltrexone. Doses between 5 mg and 20 mg (0.05 to 0.5  ) induced a bowel movement within 4 hours of drug administration significantly more often than a dose of 1 mg (less than 0.05  ), and there was no dose-response relationship above 5 mg/day. Approximately 50% of the patients responded with doses 5 mg or more within 4 hours and maintained favorable effects with repeated doses. These doses produced effective and rapid relief of constipation without producing pain flare or opioid withdrawal symptoms. All of the patients in this study experienced at least one adverse effect related to treatment; however, most were mild and not related to the dose of methylnaltrexone; abdominal pain was the most common. More recent research (N = 52) showed methylnaltrexone (0.15  ) given SC every other day for 2 weeks to patients with advanced illness resulted in a higher percentage of patient-rated improvements in bowel status, prompt and predictable laxation, and less use of other laxation techniques (e.g., laxatives and enemas) compared with placebo (Chamberlain, Cross, Winston, et al., 2009) (see Table 19-1).

Opioid Antagonists for Management of Ileus

A major advance in the management of postoperative ileus is the approval of alvimopan (Entereg) for the acceleration of the time to upper and lower GI recovery following partial large or small bowel resection with primary anastomosis (GlaxoSmithKline, 2009). Alvimopan is a synthetic peripherally acting mu opioid receptor antagonist taken orally (12 mg 30 minutes to 5 hours prior to surgery, then 12 mg twice daily for up to 7 days for a maximum of 15 doses) (Kraft, 2007). Randomized controlled trials have shown that the drug can reduce ileus, shorten hospital length of stay, and is well tolerated with adverse effects similar to placebo after major abdominal surgery (Becker, Blum, 2009; Leslie, 2005; Neary, Delaney, 2005; Sinatra, 2006; Viscusi, Gan, Leslie, et al., 2009; Viscusi, Goldstein, Witkowski, et al., 2006). Methylnaltrexone, another peripherally acting mu opioid antagonist, has also been shown to reduce ileus (Viscusi, Gan, Leslie, et al., 2009) but is approved and used most often for the treatment of opioid-induced constipation in patients with advanced illness (see previous discussion earlier in the chapter). The opioid antagonists naloxone and nalmefene are not selective for the mu opioid receptors in the GI tract and should not be used for the prevention or treatment of ileus (Kraft, 2007).

In summary, postoperative ileus has multiple underlying mechanisms and is influenced by a number of factors. Management requires the implementation of a multimodal approach that focuses on prevention. Strategies include continuous thoracic epidural analgesia, opioid-sparing analgesic techniques, peripheral mu opioid antagonists, laparoscopic surgical techniques, and avoidance of routine NG tube, fluid excess, and immobility (see Table 19-1).

• Identify patients at high risk for PONV (see Box 19-1). There is no consensus on how many risk factors a patient must have to warrant the designation of high risk (Apfel, Kranke, Eberhart, et al., 2002; Gan, Meyer, Apfel, et al., 2003; van den Bosch, Kalkman, Vergouwe, et al., 2005). A simple scoring system (the Apfel risk score) developed by Apfel and colleagues (1999) is widely used and has been shown to be reliable and valid for this purpose. It is based on four predictors: female gender, prior history of motion sickness or PONV, nonsmoking status, and the use of postoperative opioids. If no or only one factor is present, the incidence of PONV varies from 10% to 21%. If two or more are present, the risk rises to 39% to 78% (Apfel, Laara, Koivuranta, et al., 1999).

• Reduce baseline risk factors, e.g., implement multimodal analgesic strategies to treat postoperative pain so that no opioid or the lowest effective dose of opioid can be given. This may also include the use of effective nonpharmacologic strategies such as relaxation techniques, acupuncture, and acupressure (Lee, Done, 1999; Nunley, Wakim, Guinn, 2008; Roscoe, Bushunow, Jean-Pierre, et al., 2009). Although nondrug interventions may be helpful, the mainstay of PONV treatment is pharmacologic (Wilhelm, Dehoorne-Smith, Kale-Pradhan, 2007). The use of regional rather than general anesthesia is widely recommended to reduce PONV, although some surgical procedures (e.g., cesarean, some major orthopedic surgeries) are associated with a high incidence of PONV despite using regional anesthesia (Borgeat, Ekatodramis, Schenker, 2003).

• Administer PONV prophylaxis using one to two interventions to patients at moderate risk for PONV. For example, administer dexamethasone (Decadron) before anesthesia induction and a serotonin receptor antagonist (e.g., ondansetron [Zofran]) at the end of surgery. It is important to consider that research has shown that single-drug prophylaxis has a high failure rate and is associated with a resultant increased cost of care (Gan, Meyer, Apfel, et al., 2007; Watcha, 2000), so combinations of two antiemetics rather than a single antiemetic prophylactically are preferred.

• Administer PONV prophylaxis using two or more interventions (multimodal approach) to patients at high risk for PONV. For example, administer dexamethasone before anesthesia induction, IV total anesthesia (IVTA) propofol (Diprivan), a serotonin receptor antagonist at the end of surgery, and IV propofol rescue doses in the PACU. A prospective study of 376 patients at high risk for PONV revealed that the administration of three or more prophylactic antiemetics produced the largest reduction in PONV, but despite this aggressive treatment, 30% still experienced symptoms severe enough to interfere with function (White, O’Hara, Roberson, et al., 2008). A prospective observational study concluded similarly that compared with lower Apfel risk scores, a high Apfel risk score (see above) was associated with a higher incidence of emetic sequelae in the first 24 hours after surgery despite the prophylactic administration of multiple antiemetics (White, Sacan, Nuangchamnong, et al., 2008).

• Do not administer prophylactic antiemetic treatment to low-risk patients as this is not supported by current practice (Apfel, Korttila, Abdalla, et al., 2004; Gan, Meyer, Apfel, et al., 2003, 2007); however, provide antiemetic treatment to patients with PONV who did not receive prophylaxis or in whom prophylaxis failed.

Antiemetics

There are numerous antiemetic drug options available (Carlisle, Stevenson, 2006), and selection should be based on evidence of efficacy and safety as well as consideration of cost (see Table 19-1). A systematic review concluded that no one antiemetic agent is superior to another (Wilhelm, Dehoorne-Smith, Kale-Pradhan, 2007). A multicenter study of over 4000 patients at high risk for PONV (greater than 40% risk per Apfel risk scoring system [Apfel, Laara, Koivuranta, et al., 1999]) and undergoing a variety of types of surgeries were randomized to receive one of the following interventions: ondansetron (4 mg IV) or no ondansetron; dexamethasone (4 mg IV) or no dexamethasone; droperidol (Inapsine) (1.25 mg IV) or no droperidol; propofol or a volatile anesthetic (i.e., isoflurane, desflurane, or sevoflurane); nitrogen or nitrous oxide; and remifentanil or fentanyl. Because propofol has been shown to reduce PONV (see the paragraphs that follow), twice as many patients were assigned to the propofol group to ensure adequate power to compare treatments. All of the antiemetics were similarly effective; ondansetron, dexamethasone, and droperidol reduced risk by approximately 26%, propofol by 19%, and nitrogen by 12%. Droperidol, which has a “Black Box” warning for potential QTc prolongation and torsades de pointes, was safe (see later in the chapter for more on droperidol). The researchers pointed out that the clinical implication of their findings is that, because the interventions were similarly effective, the safest and least expensive treatment should be used first.

The glucocorticoid dexamethasone is an excellent choice antiemetic because numerous studies have shown it to be effective, safe, and inexpensive (Gan, Meyer, Apfel, et al., 2007) (see Table 19-1). It may be given prophylactically before induction of anesthesia as well as for established PONV (Golembiewski, Chernin, Chopra, 2005) and has been shown to have similar efficacy to the serotonin antagonist tropisetron, which is not available in the United States (Wang, Ho, Uen, et al., 2002). Dexamethasone is administered as a single 4 mg to 8 mg IV bolus dose most often and has been combined in multimodal treatment plans with a number of other agents including ondansetron (Zofran) (Paech, Rucklidge, Lain, et al., 2007; Pan, Lee, Harris, 2008), granisetron (Kytril) (Fujii, Saitoh, Tanaka, et al., 1999; Gan, Coop, Philip, et al., 2005), dolasetron (Anzemet) (Coloma, White, Markowitz, et al., 2002; Rusch, Arndt, Martin, et al., 2007), droperidol (Sanchez-Ledesma, Lopez-Olaondo, Pueyo, et al., 2002), metoclopramide (Reglan) (Wallenborn, Gelbrich, Bulst, et al., 2006), and haloperidol (Haldol) (Chu, Shieh, Tzeng, et al., 2008; Rusch, Arndt, Martin, et al., 2007). Adverse effects are rare with short-term use (Gan, Meyer, Apfel, et al., 2007).

The serotonin receptor antagonists dolasetron, granisetron, and ondansetron are most effective when administered at the end of surgery (Gan, Meyer, Apfel, et al., 2007) (see Table 19-1). The newest serotonin antagonist palonosetron (Aloxi) is approved for prevention of chemotherapy-induced nausea and has been shown to significantly decrease PONV in a dose-related manner (0.075 mg IV significantly better than 0.025 mg IV) when administered immediately prior to anesthesia induction (Candiotti, Kovac, Melson, et al., 2008). The serotonin receptor antagonists are often combined with other antiemetics in multimodal PONV prophylaxis regimens. This practice is supported by a meta- analysis of 33 randomized controlled trials (3447 patients), which concluded that various combinations of a serotonin antagonist with dexamethasone or droperidol were equally effective with similar adverse effects, and the combinations were more effective than a serotonin antagonist alone (Habib, El-Moalem, Gan, 2004). A 2001 systematic review of the literature found that the serotonin antagonists available at the time were similarly effective for treatment of established PONV and that lower doses were as effective as higher doses, so the lowest dose in the dosing range was recommended (Kazemi-Kjellberg, Henzi, Tramer, 2001).

The serotonin antagonists are reported to prevent postoperative vomiting better than nausea (Gan, Meyer, Apfel, et al., 2007; Kazemi-Kjellberg, Henzi, Tramer, 2001); however, an analysis of data from 5161 patients concluded that ondansetron prevents both symptoms equally well (Jokela, Cakmakkaya, Danzeisen, et al., 2009). Ondansetron 8 mg twice daily is effective in an orally disintegrating tablet formulation (Zofran ODT) (Gan, Franiak, Reeves, 2002; Grover, Mathew, Hegde, 2009; Hartsell, Long, Kirsch, 2005). The most common adverse effect of the serotonin antagonists is headache (Kazemi-Kjellberg, Henzi, Tramer, 2001).

The anticholinergic scopolamine delivered via a transdermal patch (Transderm-Scop, Transderm-V) has been shown to prevent PONV with minimal adverse effects when applied preoperatively (White, Tang, Song, et al., 2007) (see Table 19-1). One patch (1.5 mg) should be applied behind the ear preoperatively, taking into account its 2- to 4-hour onset of action, and it can provide relief for up to 72 hours. A second patch may be applied after the first is removed at 72 hours. Transdermal scopolamine may be combined with other antiemetics in a multimodal treatment plan (Kranke, Morin, Roewer, et al., 2002). A randomized study of 126 patients undergoing cosmetic surgery found that the transdermal scopolamine patch combined with IV ondansetron (4 mg) was more effective in reducing PONV than ondansetron plus a placebo patch (Sah, Ramesh, Kaul, et al., 2009). Another study also found the combination to be more effective than ondansetron alone (Gan, Sinha, Kovac, et al., 2009). Transdermal scopolamine has also been used to reduce nausea and vomiting associated with intrathecal morphine post–cesarean section (Harnett, O’Rourke, Walsh, et al., 2007). Adverse effects include dry mouth, sedation, and visual disturbances; older patients may be more sensitive to CNS adverse effects, such as dizziness and agitation (Golembiewski, Chernin, Chopra, 2005).

Research in the 1990s demonstrated that the IV sedative hypnotic propofol at subhypnotic doses (5 to 10 mg IV push q 4 to 6 h or 0.5 to 1 per hour continuous infusion) reduced the overall incidence of PONV in patients at high risk for PONV without untoward sedative or cardiovascular (CV) effects compared with placebo (Ewalenko, Janny, Dejonckheere, et al., 1996). Since then, the drug has gained in popularity as a component of multimodal approaches designed to reduce PONV (Eberhart, Mauch, Morin, et al., 2002; Scudieri, James, Harris, et al., 2000) (see Table 19-1). A randomized controlled study administered 90 patients undergoing laparoscopic cholecystectomy one of the following regimens: (1) a multimodal management strategy that involved the use of TIVA propofol plus droperidol and ondansetron, (2) IV propofol at induction followed by inspired isoflurane/nitrous oxide-based anesthesia, droperidol, and ondansetron, or (3) TIVA with no other antiemetic prophylaxis (Habib, White, Eubanks, et al., 2004). The droperidol (0.625 mg) was administered at induction and ondansetron (4 mg) was administered at the end of surgery in groups 1 and 2. Complete response rate (no PONV and no rescue antiemetic) at 2 hours and 24 hours after surgery was 90% and 80% in group 1, 63% and 63% in group 2, and 66% and 43% in group 3. Patient satisfaction was also higher in group 1. The researchers noted, however, that the higher cost of propofol compared with volatile anesthetics and its short-lived antiemetic effect (limited to early postoperative period) makes it suitable for use only in patients at very high risk for PONV.

Novel Approaches to the Management of PONV

Some novel and relatively inexpensive approaches have been tried for the management of PONV. Researchers applied nicotine patches to patients undergoing laparoscopic cholecystectomy under general anesthesia based on research that shows cigarette smoking reduces risk of PONV (Ionescu, Badescu, Acalovschi, 2007). Patients in this study (N = 75) were randomized according to their cigarette smoking status: (1) nonsmokers, (2) patients who had stopped smoking at least 5 years prior and received one 16.6 mg nicotine patch, and (3) patients who currently smoked. There was a 20% reduction in PONV in patients in group 2 compared with group 1 and no difference between group 2 and group 3.

Intraoperative supplemental oxygen has been suggested as a strategy to reduce PONV, but research is conflicting. One early study showed that the incidence of PONV was significantly reduced in patients following laparoscopic gynecologic surgery who received 80% supplemental intraoperative oxygen (22%) and those who received 8 mg of ondansetron at induction (30%) compared with patients who received 30% supplemental oxygen intraoperatively (44%) (Goll, Akca, Grief, et al., 2001). However, a later study showed that neither 30% nor 80% intraoperative oxygen administration reduced PONV in 100 patients undergoing ambulatory gynecologic laparoscopy (Purhonen, Turunen, Ruohoaho, et al., 2003). Intraoperative supplemental oxygen did not decrease the incidence of PONV post–cesarean section delivery with neuraxial anesthesia either (Phillips, Broussard, Sumrall, et al., 2007).

Studies have shown that wrist acustimulation/acupressure (acupuncture point P6 [pericardium 6]) (ReliefBand®) reduces PONV (Gan, Jiao, Zenn, et al., 2004; Lee, Fan, 2009; Nunley, Wakim, Guinn, 2008; Roscoe, Bushunow, Jean-Pierre, et al., 2009) and that when combined with ondansetron (4 mg), the response rate to acustimulation is increased and quality of recovery and patient satisfaction are improved (Coloma, White, Ogunnaike, et al., 2002; White, Issioui, Hu, et al., 2002). The optimal time to administer acustimulation for antiemetic prophylaxis is after surgery (White, Hamza, Recart, et al., 2005). Figure 19-2 shows the location of acupuncture point P6.

A meta-analysis of research on gum chewing during the early postoperative period following colectomy concluded that the practice may enhance GI recovery and reduce length of stay (Purkayastha, Tilney, Darzi, et al., 2008). Improved GI recovery may contribute to a lower incidence of PONV.

Effective, Safe, and Inexpensive Treatment

By far, the most effective, safest, and least expensive way to treat PONV is to reduce the opioid dose whenever possible. Postoperative opioid orders should include the expectation that nurses will consider decreasing the opioid dose by 25% prior to or in conjunction with pharmacologic treatment of moderate-to-severe PONV (see following patient example and Form 17-1 on p. 464 for an example of how decreases in opioid dose can be included in opioid order sets). Decreasing the opioid dose is facilitated by adding or increasing a nonopioid, such as an NSAID or acetaminophen, or adding a local anesthetic to the epidural opioid solution to provide additional pain relief. If patients are too nauseated to take oral nonopioids, they may be given rectally (see Section III and Chapter 14 in this section for more on rectal administration).

Approaches with Little or No Effectiveness

In their 2007 guidelines, the American Society for Ambulatory Anesthesia concluded that there is a lack or limited evidence of a prophylactic effect for metoclopramide (10 mg IV), ginger root, and cannabinoids for PONV (Gan, Meyer, Apfel, et al., 2007). Metoclopramide is reported to be no more effective than placebo for its treatment (Gan, 2002); however, one randomized controlled study (N = 3140) found doses of 25 to 50 mg of metoclopramide in combination with dexamethasone administered intraoperatively reduced the frequency of PONV without a high incidence of adverse effects (Wallenborn, Gelbrich, Bulst, et al., 2006). Doses this high are not recommended; the drug has been reported to produce extrapyramidal symptoms, even in low doses (i.e., 10 mg) (Moss, Hansen, 2008).

Although promethazine (Phenergan) has been used for many years and has efficacy for the treatment of established PONV (Habib, Breen, Gan, 2005; Gan, Meyer, Apfel, et al., 2007; Habib, Reuveni, Taguchi, et al., 2007; Moser, Caldwell, Rhule, 2006), it is associated with significant adverse effects, including excessive sedation, respiratory depression, dysphoria, dystonia, and extrapyramidal symptoms (McGee, Alexander, 1979; Sheth, Verrico, Skledar, et al., 2005). Further, significant tissue damage can occur when promethazine is given intravenously (Institute for Safe Medication Practices, 2006a, 2006b). A “Black Box” warning added to promethazine prescribing information describes these injuries and the risk of unintentional intra-arterial injection and recommends deep IM injection of the drug; SC injection is contraindicated (U.S. FDA, 2009c). It is common practice to administer promethazine based on the belief that it will enhance opioid analgesia; however, early research dispelled this misconception (McGee, Alexander, 1979), and the practice is discouraged (Pasero, Portenoy, McCaffery, 1999). If promethazine is used, low doses are recommended, particularly in older adults (Habib, Breen, Gan, 2005; Moser, Caldwell, Rhule, 2006). Doses of 6.25 mg were found to be as effective as higher doses (e.g., 12 mg) (Habib, Reuveni, Taguchi, et al., 2007).

Prochlorperazine (Compazine) provided better relief of nausea and vomiting than promethazine in patients in the emergency department (ED) (Ernst, Weiss, Park, et al., 2000). Prochlorperazine has a faster onset and causes less sedation than promethazine as well (Golembiewski, Chernin, Chopra, 2005).

Another commonly used drug is hydroxyzine (Vistaril), but the doses that would be required to produce analgesia create significant risk of respiratory depression that is not reversible by naloxone (Gordon, 1995). IM hydroxyzine is especially irritating to the muscle and soft tissue and can produce sterile abscesses, so this practice is discouraged as well. Other older drugs—dimenhydrinate (Dramamine) (Kothari, Boyd, Bottcher, et al., 2000) and diphenhydramine (Benadryl)—are occasionally used for PONV but can cause significant sedation and dizziness. Antiemetics with better efficacy and safety should be considered before these drugs are used for treatment of PONV (Gan, Meyer, Apfel, et al., 2007) (see Table 19-1).

The routine use of NG tubes during surgery as a means of reducing PONV is not recommended. A large case control study (N = 4055) evaluated the association between NG tube use and the incidence of nausea, emesis, and overall PONV and showed no reduction in the incidence of these three outcome measures; the incidence of PONV was 44.4% with intraoperative NG tube versus 41.5% in controls (Kerger, Mascha, Steinbrecher, et al., 2009).

The Meperidine Misconception

Although institutional quality improvement initiatives have resulted in a significant decline in the use of meperidine over the years (Gordon, Jones, Goshman, et al., 2000), the drug continues to be a first-choice analgesic of many prescribers (Seifert, Kennedy, 2004). This is particularly true for the management of pain during GI procedures and in patients with pancreatitis or cholecystitis; however, there are many disadvantages to the use of meperidine for pain management, including accumulation of its toxic metabolite with repeated dosing and its inappropriateness in older adults (Latta, Ginsberg, Barkin, 2002) (see Chapter 13).

A review of the literature concluded that morphine may be of more benefit than meperidine by offering analgesia without the risks associated with meperidine and that there are no studies or evidence to indicate morphine is contraindicated for use in acute pancreatitis (2001). Low-dose transdermal fentanyl (12.5 to 25 mcg) caused no significant changes in sphincter of Oddi pressure in patients with pancreatitis in one study and was described as the ideal analgesic for treatment of pancreatitis pain (Koo, Moon, Choi, et al., 2009). An interesting letter to the editor suggested that the choice of meperidine over other opioids is not based on evidence and persists because of the perpetuation of the misconception that meperidine has no effect on the sphincter of Oddi (Lee, Cundiff, 1998). The authors equated this to the “medical equivalent of an urban legend.” The best course of action is to avoid meperidine for all types of pain, including procedural pain and pancreatitis pain, and rely instead on other mu agonist opioids, such as morphine, hydromorphone, or fentanyl.