Treating pancreatic pain with meperidine: preferred analgesic or antiquated practice?
Acute or chronic pancreatitis is the result of chronic alcohol abuse in about 70% of the cases. Although usually a condition that affects adults, it can also occur in adolescents who drink excessively and in children with cystic fibrosis (Toskes, 1999). The pain associated within the pancreatitis ranges from tolerable to incapacitating and often requires opioids for adequate analgesia. Unfortunately, meperidine (Demerol, pethidine) has traditionally been considered the opioid of choice, because it was thought to cause less spasm of the sphincter of Oddi (SO). Several current references continue to recommend meperidine for pancreatic pain, thus promoting this antiquated this practice (Munoz & Katerndahl, 2000; Schlapman, 2001).
Research, however, does not support meperidine's superiority for treating pancreatic pain. In a review of the English literature from 1966 to 2000, Thompson (2001) found no evidence that morphine is contraindicated for use in acute pancreatitis. Of the 9 studies that were reviewed, all of the opioids - morphine, meperidine, pentazocine (Talwin), tramadol (Ultram), phenazocine, butorphanol (Stadol), nalbuphine (Nubain), buprenorphine (Buprenex), and fentanyl - restricted flow at the SO with an increase in bile pressure.
In another review of 12 studies, which included the additional drug, oxycodone, Isenhower and Mueller (1998) could not draw a firm conclusion. Their review of two studies using the most accurate measurement of pressure in the SO, endoscopic retrograde cholangiopancreatography (ERCP), found evidence for morphine increasing SO pressure and increasing contraction frequency (study had seven subjects) and for meperidine increasing contraction frequency but not SO pressure (study had 18 subjects). Based on ERCP manometry, three other analgesics, nalbuphine, buprenorphine, and tramadol, showed no change in pressure.
The authors concluded in a German review of 11 studies in the English abstract that all the opioids have a spasmogenic affect on SO. They found no good evidence to suggest that the spasmogenic effect impairs the course of acute pancreatitis and stated that the side effects of meperidine exceed those of other available opioids (Van Voorthuizen, Helmers, Tjoeng, and Otten, 2000).
Some studies have compared the effect of different opioids on the SO, using less accurate methods than ERCP for measuring biliary pressure. For example, one study compared the equianalgesic doses of fentanyl (1.25 mcg/kg), morphine (0.125 mg/kg), meperidine (1.0 mg/kg), and pentazocine (0.5 mg/kg) on common bile duct pressure to determine which drug had the least effect on SO and was best suited for use in biliary tract surgery (Radnay, et al, 1980). Forty patients scheduled for elective cholecystectomy were randomly assigned to the four drug groups. Common bile duct pressure measurements were obtained intraoperatively by intubating the common bile duct with a 24-inch 16-gauge angiocath. Pressure measurements were taken with a manometer attached with a 3-way stopcock to the catheter; the results were read in centimeters of saline. The largest average increases in pressure were 99.5% for fentanyl, 52.7% for morphine, 61.3% for meperidine, and 15.1% for pentazocine. Fentanyl, morphine, and meperidine were not statistically different from each other, but were significantly higher than pentazocine. The authors concluded that pentazocine was the drug of choice for relief of biliary colic. However, in a study using ERCP manometry, pentazocine (30 mg intravenously) increased SO pressure (Staritz and others, 1986).
Unfortunately, nalbuphine and pentazocine are mixed agonist-antagonist drugs. They produce analgesia by binding to kappa opioid receptors but antagonize the action of morphine-like agonists at the mu receptor. When given to patients receiving morphine-like agonists, these drugs can precipitate acute opioid withdrawal and may cause confusion and hallucinations. Buprenorphine is a partial agonist-antagonist that can also precipitate withdrawal in patients taking pure mu agonists. For this reason these analgesics are not recommended as first-line drugs for treatment of pain unless the patient is unable to tolerate other opioids (APS, p. 32, 1999).
Transdermal fentanyl (Duragesic patch) was compared to meperidine in 32 subjects with pancreatic pain. The experimental group received Duragesic with intramuscular IM meperidine for break-through pain and the control group received a placebo patch and IM meperidine. There was no significant difference in pain ratings between the groups on day one, which was probably due to the slow onset of Duragesic (about 12 to 24 hours). There was a significant difference in pain scores at 36 and 45 hours. The Duragesic group had lower pain scores and a shorter hospital stay, even though they had more previous hospitalizations and a higher mean pain score on admission (Stevens, Esler, and Asher, 2002).
The question remains - what is the best opioid to treat pancreatic pain? Probably the clearest answer is what not to use. With no strong evidence to support its benefit in regard to SO pressure, meperidine should not be used because of its well-known risks. In the liver, meperidine is metabolized to normeperidine, which is a potent central nervous system stimulant. Normeperidine has a long-half life from 14 to 48 hours. Normeperidine can cause anxiety, tremors that progress to muscle twitches, gross jerking of extremities, weakness in extremities, hallucinations, sensitivity to sudden noise, and even generalized seizures. Patients with alcoholic pancreatitis are already at risk for neurologic complications from ethanol withdrawal and often have liver dysfunction. Parenteral meperidine has a short duration (about 2 hours) and given intramuscularly can cause pain and eventual muscle fibrosis and nerve damage. Unlike other opioids, it has a unique euphoric effect that lasts about five minutes in some patients. The euphoria is described as feeling high, floating, drunk, coasting, confused, or having difficulty concentrating (Walker and Zacny, 1999). This intoxicating effect has made it an opioid of choice among drug addicts.
An underrecognized side effect of meperidine is the "serotonin syndrome" (SS). SS is an iatrogenic disorder that only results from some drugs, such as the selective serotonin (5HT)-reuptake inhibitor (SSRI) antidepressants, fluoxetine (Prozac), paroxitine (Paxil), sertraline (Zoloft), citalopram (Celexa), and fluvoxamine (Luvox). Meperidine is thought to inhibit both 5-HT and norepinephrine. Meperidine-induced SS is potentiated by monoamine oxidase inhibitors (MAOIs). Symptoms of SS include (Latta and others, 2002):
Meperidine is also a strong anticholinergic drug due to its blockade of the muscarinic/acetylcyholine receptor. It causes peripheral effects of blurred vision, constipation (in addition to opioid-induced constipation), decreased sweating, dry mouth, tachycardia, and possible worsening of narrow-angle glaucoma. The central manifestations may include confusion, disorientation, agitation, belligerence, delirium, memory loss, and visual hallucinations (Latta and others, 2002).
In addition to the many behavioral/cognitive effects of meperidine, the drug also causes a more negative than positive mood (Kaiko and others, 1983). Since unrelieved pain is often associated with fear, anxiety, depression, and anger, it is irrational to use an analgesic that promotes a sense of suffering ((Kaiko and others, 1983).
In an excellent review of meperidine that is supported by 203 references, Latta, Ginsberg, and Berkin (2002) conclude: "Clinically, the preferential use of meperidine over any other opioids cannot be supported using scientific findings. Meperidine has as much effect on smooth muscle as do other opioids when done in equianalgesic amounts. When the neurotoxic effects are taken into pharmacotherapeutic consideration, other drugs must become the preferential treatment" (p. 56).
Nurses are often confronted with physician orders prescribing meperidine for pancreatic pain. It is difficult to dispel long standing traditional practice. But we must advocate for our patients because "First Do No Harm." The logical starting place is to discuss the lack of evidence for meperidine's beneficial effects on the SO and the risks of meperidine, especially in patients who may also have liver damage. The next step is to suggest alternative opioids, such as morphine, hydromorphone (Dilaudid), levolorphanol (Levodromoran), and fentanyl. If these educational approaches are unsuccessful, emphasize to the physician that every pain guideline in the U.S. recommends against the use of meperidine. With these official publications and the JCAHO pain standards, offer the advice that in our litigious society the use of meperidine will be very difficult to defend in a lawsuit.
Finally, if none of these arguments result in an appropriate analgesic order, suggest that your patients list Demerol in their allergy history. Educate them on the dangers of this drug, especially if they are taking SSRIs or MAOIs. And if your patients do receive meperidine, assess them every 8 hours for neurotoxicity, which is easily diagnosed in the early stages as tremors of the hand and arms. If tremors are present in a patient who did not have them before receiving meperidine, report the tremors as an adverse drug reaction (ADR) to the pharmacy.
Once your facility has accumulated documentation of neurotoxic side effects, the next step is to take the data to risk management to review the legal ramification of continuing the use of meperidine in their institution. Such action can result in meperidine being removed from the formulary and retained only as a treatment for rigors from anesthesia or drugs such as amphotericin. Finally, if your facility refuses to change its policy regarding the use of meperidine as an analgesic, consider contacting the Joint Commission on Accreditation of Healthcare Organizations. JCAHO has established pain assessment and management standards and a toll free hot line (800-994-6610) to encourage patients, their families, caregivers, and others to share concerns regarding quality of care issues at accredited health care organizations. Complaints can be anonymous and sent by email to complaint@jcaho.org; faxed to the office of Quality Monitoring at 630-792-5636; or mailed to the Office of Quality Monitoring, Joint Commission, One Renaissance Blvd, Oakbrook Terrace, IL, 60181. The pain standards are available from jcaho.org/standard/pm_hap.html.
March 7, 2003