- USES: Meperidine is a narcotic analgesic used for the relief of moderate to severe pain, obstetrical analgesia, as a preoperative medication, and for support of anesthesia. PHARMACOLOGY: Meperidine is a mu and kappa opioid agonist. In therapeutic doses, it produces euphoria and analgesia. TOXICOLOGY: Therapeutic and toxic effects are mediated by different opioid receptors. Mu 1: Supraspinal and peripheral analgesia, sedation, and euphoria. Mu 2: Spinal analgesia, respiratory depression, physical dependence, GI dysmotility, bradycardia and pruritus. Kappa 1: Spinal analgesia and miosis. Kappa 2: Dysphoria and psychotomimesis. Kappa 3: Supraspinal analgesia. Chronic opioid users develop tolerance to the analgesic and euphoric effects, but not to the respiratory depression effects. Meperidine has an active metabolite (normeperidine) which may accumulate after repeated high doses or in patients with renal failure and cause seizures and myoclonus. Meperidine inhibits serotonin uptake and may also precipitate serotonin syndrome in combination with other serotonergic drugs. EPIDEMIOLOGY: Meperidine overdose is uncommon as the medication is decreasingly used. Severe toxicity can occur. MILD TO MODERATE TOXICITY: Lightheadedness, dizziness, nausea, vomiting, urinary retention, sedation, and disorientation. SEVERE TOXICITY: Higher doses and longer-term administration have been associated with central nervous system excitatory effects such as agitation, tremors, myoclonus, motor weakness, and seizures. Excitatory symptoms are thought to be due to the metabolite, normeperidine, which has a longer half-life than the parent compound and thus accumulates with frequently repeated high dose use of meperidine. Respiratory and CNS depression can occur from large doses. Meperidine can cause signs of serotonin toxicity such as muscle rigidity, tremor, confusion, behavioral changes, and autonomic instability usually when used with other serotonergic drugs. A syndrome closely resembling moderate to severe idiopathic Parkinson’s disease has been described in intravenous and intranasal drug users following use of a derivative of meperidine, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Orofacial dyskinesias, arm flexion, and stiffening of the legs have been observed. DRUG INTERACTION: Concomitant administration with monoamine oxidase inhibitors can cause a severe reaction (eg, hyperthermia, hypertension, muscle rigidity, coma, mental status changes, seizures, death). Meperidine may precipitate serotonin syndrome when administered with other serotonergic drugs. ADVERSE EFFECTS: COMMON: Lightheadedness, dizziness, sedation, nausea, vomiting, and sweating. OTHER EFFECTS: Asthenia, confusion, headache, weakness, syncope, constipation, dry mouth, seizures, tremors, myoclonus, delirium, euphoria, dysphoria, agitation, transient hallucinations and disorientation, urinary retention, hypotension, tachycardia, bradycardia, palpitations, pruritus, flushing, urticaria, injection site pain and irritation, visual disturbances, anaphylactic reactions, muscle rigidity, biliary tract spasm, and respiratory depression. Histamine release, leading to hypotension and/or tachycardia, flushing, sweating, and pruritus, has been reported in patients receiving meperidine.
Range of Toxicity:
- TOXICITY: Meperidine-related seizures have been reported with patient-controlled analgesia pump administration. One retrospective review has shown that patients who receive more than 10 mg/kg/day of intravenous patient-controlled analgesia (IV PCA) meperidine are at higher risk of central nervous system excitatory effects. A 17-year-old girl developed coma after ingesting 15 g of meperidine. She later experienced seizures, tremor, hyperreflexia, myoclonus, clonus, dilated pupils, and tachycardia. Following supportive therapy, including naloxone, she gradually improved over the next 48 hours. THERAPEUTIC DOSES: ADULTS: 50 to 150 mg every 3 to 4 hours as necessary, given IM, orally, or SubQ. CHILDREN: Pain: 1.1 to 1.8 mg/kg orally, up to the adult dose, every 3 or 4 hours as necessary. Premedication for procedure: 1.1 to 2.2 mg/kg IM or SubQ 30 to 90 minutes before anesthesia.
- Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Patients may need only observation for CNS excitation or depression and respiratory depression. MANAGEMENT OF SEVERE TOXICITY: Administer oxygen and assist ventilation for respiratory depression. Naloxone is the antidote indicated for respiratory or CNS depression. Orotracheal intubation for airway protection should be performed early in cases of obtundation and/or respiratory depression that do not respond to naloxone, or in patients who develop severe acute lung injury. Treat seizures with benzodiazepines.
- Decontamination: PREHOSPITAL: Prehospital decontamination is not recommended because of the potential for CNS depression and seizures. HOSPITAL: Activated charcoal is not routinely administered in these patients because they are at risk for the abrupt onset of seizures or mental status depression and subsequent aspiration in the event of spontaneous emesis. Gastric lavage is generally not recommended.
- Airway management: Endotracheal intubation should be performed in patients with CNS depression not responsive to naloxone, recurrent seizures or severe CNS excitation, and the inability to protect their own airway.
- Antidote: Naloxone can be given intravascularly, intramuscularly, subcutaneously, intranasally or endotracheally. The usual dose is 0.4 to 2 mg IV. In patients with suspected opioid dependence, incremental doses of 0.2 mg IV should be administered, titrated to reversal of respiratory depression and coma, to avoid precipitating acute opioid withdrawal. Doses may be repeated every 2 to 3 minutes up to 20 mg. Very high doses are rarely needed. DURATION of effect is usually 1 to 2 hours. Meperidine has a longer duration of effect, so it is necessary to observe the patient at least 4 hours after the last dose of naloxone to ensure that the patient does not have recurrent symptoms of toxicity. Naloxone can precipitate withdrawal in an opioid-dependent patients, which is usually not life-threatening; however it can be extremely uncomfortable for the patient. Naloxone will not treat meperidine-induced seizures or myoclonus.
- Seizure: Administer a benzodiazepine for initial control. Consider phenobarbital or propofol if seizures are not controlled with benzodiazepines. Hyperthermia, lactic acidosis, and muscle destruction may necessitate use of neuromuscular blocking agents with continuous EEG monitoring.
- Hypotensive episode: Administer IV fluids and place patient in supine position. If unresponsive to these measures, administer vasopressors and titrate as need to desired response. Direct acting agents (norepinephrine, epinephrine, phentolamine) are theoretically preferred.
- Serotonin syndrome: Benzodiazepines (lorazepam 1 to 2 mg IV every 5 to 10 minutes titrated to sedation and decreased rigidity) are the mainstay of therapy. Cyproheptadine, a 5-HT antagonist, is also commonly used. Severe cases have been managed with benzodiazepine sedation and neuromuscular paralysis with non-depolarizing agents.
- Body temperature above reference range: Control agitation and muscle activity. Undress patient and enhance evaporative heat loss by keeping skin damp and using cooling fans. Ice water immersion may be needed in severe cases. Muscle activity: Benzodiazepines are the drug of choice to control agitation and muscle activity. Non-depolarizing paralytics may be used in severe cases.
- Hypertensive episode: Monitor vital signs regularly. For mild-moderate asymptomatic hypertension, pharmacologic intervention is usually not necessary.
- Enhanced elimination procedure: Methods to enhance elimination are not likely to be useful because of the large volume of distribution.
- Monitoring of patient: Monitor for decreased respiratory rate, decreased oxygen saturation, or other signs of respiratory depression. Monitor level of consciousness or arousability for excess CNS depression. Monitor for tremors, myoclonic jerking or seizures as an indication of normeperidine accumulation. Monitor CPK in patients with prolonged coma or repeated seizure activity. Plasma meperidine levels are not clinically useful to guide therapy. Treatment is based on clinical presentation than on specific laboratory data.
- Patient disposition: HOME CRITERIA: Respiratory depression may occur at doses just above a therapeutic dose. Children should be evaluated in the hospital and observed as they are generally opioid-naive and may develop respiratory depression. Adults should be evaluated by a health care professional if they have received a higher than recommended (therapeutic) dose, especially if opioid-naive. OBSERVATION CRITERIA: Patients with deliberate ingestions and all children with ingestions should be sent to a health care facility for observation for at least 4 hours, as peak plasma levels and symptoms will likely develop within this time period. Patients who are treated with naloxone should be observed for 4 to 6 hours after the last dose, for recurrent CNS depression or acute lung injury. ADMISSION CRITERIA: Patients with significant persistent central nervous depression should be admitted to the hospital. Patients needing more than 2 doses of naloxone should be admitted as they may have taken a longer-acting opioid and may need additional doses. Patients with coma, seizures, dysrhythmias, or delirium or those needing a naloxone infusion or intubated patients should be admitted to an intensive care setting. CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.