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Where has all the meperidine gone?

Dobbins, Elizabeth H. PhD, RN, CNE, FNP-BC

doi: 10.1097/01.NURSE.0000365924.16631.a4

The pitfalls of meperidine

Elizabeth H. Dobbins is an associate professor of nursing at Walters State Community College in Morristown, Tenn.

AFTER TAKING TIME off to raise her children, Jane Collins, RN, resumed her nursing career in the surgical unit that she left a few years before. One day, she realized that something was different: The surgeons were no longer ordering meperidine (Demerol) for postoperative pain management. Instead, they were prescribing morphine and hydromorphone. Meperidine wasn't even in the automated medication dispensing devices! Where had all the meperidine gone?

Once the most widely prescribed opioid analgesic, meperidine is now used only for the prevention and treatment of postoperative shivering, drug-induced rigors, and short-term pain management in patients who can't tolerate other opioids.1 (These exceptions should be clearly defined by hospital policy.) The change in meperidine use is based on recommendations of The Joint Commission, Agency for Healthcare Research and Quality, American Pain Society, and Institute for Safe Medication Practices.

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Fall from grace

Meperidine causes less hypotension, respiratory depression, urine retention, and gastrointestinal adverse reactions than morphine, which explains its popularity in the past.2 But as medication monitoring systems improved, the high number of reported adverse reactions revealed hidden dangers.

The problem with meperidine lies in how it's metabolized in the liver, where some of the drug is converted into normeperidine, a potentially neurotoxic, nonopioid active metabolite. Normeperidine can cause altered mental status, nervousness, myoclonus, seizures, delirium, and psychosis.

Although the half-life of meperidine is 3 to 4 hours, researchers have found the half-life of normeperidine to be anywhere from 14 to 48 hours, depending on renal function. The metabolite also accumulates in the body. Significant accumulation has been noted in healthy patients within 2 days of beginning meperidine therapy.

Because meperidine is excreted by the kidneys, the risk of toxicity is greater in patients with impaired renal function, such as older adults and patients with sickle-cell disease. Although meperidine was a first-line drug in the control of pain in patients in sickle-cell crisis in the past, both the American Pain Society and National Institutes of Health now discourage its use in those patients.3

Signs and symptoms of normeperidine toxicity include irritability, muscle twitching, tremors, myoclonus jerking, disorientation, agitation, intestinal spasms, tachycardia, and hypertension. The accumulation of normeperidine in the central nervous system lowers the seizure threshold.1 But because the signs and symptoms of normeperidine toxicity can be vague and highly variable, they can be misinterpreted as indications of inadequate pain management, leading to further meperidine administration.

Meperidine also blocks the reuptake of both serotonin and norepinephrine by the neurons and can precipitate serotonin syndrome. This potentially fatal condition has been reported in patients taking monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, and triptan migraine medications such as sumatriptan and zolmitriptan. The signs and symptoms of serotonin syndrome are similar to those of normeperidine toxicity and, like normeperidine toxicity, vary greatly from patient to patient. They include a sudden onset of confusion, delirium, diaphoresis, hyperpyrexia, nausea, severe muscle twitching, exaggerated reflexes, and rigidity.1 Serotonin syndrome can lead to life-threatening hyperthermia, rhabdomyolysis, disseminated intravascular coagulation, and cardiac dysrhythmias.

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Using meperidine safely

Every national clinical practice guideline for pain management published since 1990 has discouraged the use of meperidine.4 But it's still appropriate in certain cases as previously described. Follow these tips and guidelines for administering it safely:

  • Patients should receive no more than 600 mg/day for no more than 2 consecutive days.3 Closely observe older adults, who are more likely to have decreased renal function (and should be prescribed lower doses). For all patients, administer the medication by slow I.V. injection over 4 to 5 minutes. Don't give meperidine orally or via patient-controlled analgesia pump.
  • Watch for signs and symptoms of normeperidine toxicity and serotonin syndrome—irritability, nervousness, agitation, tremors, and seizures—particularly in older patients and patients with renal impairment. Assess for tremor and ask the patient and family members or caregivers if the patient is experiencing any involuntary tremors, twitches, or jerks, particularly while sleeping.
  • If you suspect an adverse drug reaction, immediately discontinue the drug and notify the healthcare provider. Don't administer the opioid antagonist naloxone, which is ineffective against normeperidine toxicity and enhances the drug's proconvulsant effect, precipitating grand mal seizures.1 Using naloxone also can compromise pain management. Increase fluids to promote normeperidine excretion, initiate seizure precautions, monitor the patient for seizures, and administer antiepileptic drugs, if indicated.5
  • Be aware of possible drug interactions and incompatibilities. Admixture and Y-site incompatibilities can occur with various I.V. drugs, including barbiturates, aminophylline, heparin, morphine, methicillin, phenytoin, sodium bicarbonate, sulfisoxazole, cefoperazone, and tetracycline.
  • Follow the Institute for Safe Medication Practices' recommendation to remove meperidine from all preprinted orders and protocols for patient-controlled analgesia. Adhere to your facility's stop order policy, which commonly limits meperidine orders to 48 hours to prevent normeperidine accumulation.6,7

Keeping up-to-date on the latest evidence-based practices will help keep patients as safe as possible. Now you know where all the meperidine went—and why.

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1. Latta KS, Ginsberg B, Barkin RL. Meperidine: a critical review. Am J Ther. 2002;9(1):53–68.
2. Quinn TE. Pain topics: what's all the fuss?.
3. National Institutes of Health. Management of Sickle Cell Disease (publication No. 02–2177). 4th ed. National Institutes of Health, National Heart, Blood, and Lung Institute, Bethesda, Md.; 2002 .
4. Weissman DE. Fast fact and concept #71: meperidine for pain—What's all the fuss? 2nd ed .
5. McDermot P. Recognizing normeperidine toxicity. Nursing. 2003;33(3):24.
6. Institute for Safe Medication Practices. ISMP medication safety alert: let's put a stop to problem-prone automatic stop order policies .
7. Institute for Safe Medication Practices. High alert medication feature: reducing patient harm from opiates .
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