JUNE 2002

Meperidine Use Guidelines

At the March 2002 meeting, the Pharmacy and Therapeutics Committee approved guidelines for the inpatient use of meperidine at KU Med Center. Meperidine (Demerol) is an effective, rapidly acting opioid analgesic. However, on repeated dosing, patients (especially those with renal impairment) will experience an accumulation of the toxic metabolite, normeperidine. Normeperidine is a very weak analgesic (less than 1/3 the potency of racemic meperidine) and a potent central nervous system irritant. Symptoms of normeperidine accumulation progress from irritability to tremors and myoclonus, to generalized seizures. In many cases, when patients have normeperidine-induced seizures, naloxone is administered, which results in an exacerbation of the seizures, due to antagonism of the seizure-suppressing effects of meperidine.

Numerous reviews of meperidine’s pharmacodynamic properties have failed to demonstrate any benefit to using meperidine in the treatment of common pain problems, including biliary cholic, pancreatitis, labor, and migraine. Two such reviews are listed in the references following this article.

Healthcare professionals frequently underestimate the analgesic potency of meperidine. Standard references, including the American Pain Society’s Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain (4^th Edition), indicate that 75 mg of IV meperidine has an analgesic potency equal to that of 10 mg of IV morphine or 100 mg of IV fentanyl. The fact that many patients state that meperidine is the only medication they have found effective in treating their pain may be due, in part, to underdosing of other medications related to failure to consider this equianalgesic relationship.

The Pharmacy & Therapeutics Committee has adopted the following guideline on meperidine use as a means of insuring that this medication is used in a safe manner. For assistance in finding alternative medication regimens for patients using meperidine, please contact the pharmacy (588-2321) or the Pain Management Resource Team (588-3692).

References

Chalverus, CA. Clinically significant meperidine toxicities. J Pharm Care in Pain & Symptom Control 2001; 9(3):37-55

Latta, KA, Ginsberg, B, Barkin, RL. Meperidine: A critical review. Am J Therapeutics, 2002, 9:53-68.

Meperidine: Guidelines for Use

A.	Background
Problems associated with meperidine use have resulted in inadequate pain control and adverse effects for many patients through the years. First‑line opioids such as morphine, hydromorphone or oxycodone should be used in preference to meperidine, which should be utilized only as outlined below. Meperidine, in spite of its Food and Drug Administration-labeled indication, is not suitable for chronic pain. To promote safe medication usage and optimal pain management, the Pharmacy and Therapeutics Committee has established the following guidelines for use of meperidine.
B.	Appropriate Indications for Use
	1.0	Management of acute episodes of moderate to severe pain if the patient has a history of one or more of the following problems:
		1.1	Unmanageable adverse reactions to other first-line opioids.
		1.2	Treatment failure to other first-line opioids given in adequate doses.
	2.0	Prevention or treatment of drug-induced or blood product-induced rigors (e.g., amphotericin B, muromonab, platelets), and treatment of post-anesthesia shivering.
	3.0	Management of pain during medical procedures.
	4.0	Research protocols specifying the use of meperidine.
	5.0	Neuraxial analgesia for acute pain management, administered by the anesthesiology service.
C.	Dose, Route and Duration of Therapy
	1.0	Meperidine should not be used for longer than 48 hours or at doses greater than 600 mg/24 hours in patients with normal renal function.
	2.0	Adult parenteral doses may range from 25 to 100 mg intravenously or subcutaneously every 3 hours as needed. The slow intravenous (IV) push route may be used, at a starting dose of 25 mg, increasing in 25 mg increments to a maximum of 100 mg, every 2 to 3 hours as needed, within the limitations noted in point 1.0 above. Intramuscular (IM) absorption is erratic and IM injections are painful; therefore, they are to be used only in emergent situations where another route is not immediately available.
	3.0	For the prevention of rigors, 12.5 to 50 mg should be administered via slow IV push. For treatment of rigors or post-anesthesia shivering, 12.5 to 50 mg should be given by slow IV push every 15 to 20 minutes until symptoms are controlled.
	4.0	Meperidine is seldom indicated for analgesia in children. The analgesic dose is 0.75 to 1.0 mg/kg SC or slow IV push every 3 hours as needed. For the prevention or treatment of rigors, a single dose of 0.5 mg/kg may be administered via slow IV push.
	5.0	For pre-procedural sedation, single doses of 25 to 100 mg IV 30 minutes prior to procedures may be given.
	6.0	The oral dosage form is non-formulary and is, therefore, not available. In addition, this dosage form SHOULD NOT BE USED due to high first pass metabolism and increased concentration of normeperidine.
	7.0	Meperidine is inappropriate therapy for migraine headache, although it is very commonly used. Meperidine is not recommended for this use because of its very short duration, its toxic metabolite, and because it is painful to inject. While IM meperidine has a slightly faster onset than morphine, its disadvantages outweigh this very small advantage.
D.	Contraindications
	1.0	Hypersensitivity to meperidine.
	2.0	Patients who are receiving MAO inhibitors or those who have received MAO inhibitors in the past 14 days. Concurrent use of meperidine and MAO inhibitors may result in hypertensive crisis, hyperpyrexia and cardiovascular system collapse, and may be fatal.
	3.0	Patients with renal insufficiency (creatinine clearance less than 50 ml/min).
	4.0	Patients with untreated hypothyroidism, Addison's disease, benign prostatic hypertrophy, or urethral stricture.
E.	Inappropriate Indications
	1.0	Meperidine has not been shown to have any specific benefit compared to other narcotic analgesics in patients with biliary colic. (See Chalverus, CA. J Pharm Care in Pain & Symptom Control 2001; 9(3):37-55 for a review).
	2.0	Meperidine has not been shown to have any unique benefit compared to other narcotic analgesics in the treatment of pain due to acute pancreatitis.
	3.0	Routine use of meperidine prior to the first dose of amphotericin is inappropriate. If a patient does develop rigors, prophylactic use prior to subsequent doses is warranted.

F.	Precautions
	1.0	Meperidine should be discontinued when the following central nervous system effects occur:
		Anxiety	Fluctuations in awareness levels
		Hallucinations	Agitation
		Illusions	Disorientation
		Restlessness	Bizarre feelings (feeling frightened)
		Seizures	Diaphoresis
		Shakiness	Myoclonic jerks
		Nervousness	Tremors
		Confusion

2.0	In cases of normeperidine neurotoxicity, naloxone should not be used. Naloxone does not reverse the effects of normeperidine, and may actually precipitate seizure activity as the sedative effects of meperidine are reversed allowing the full effect of normeperidine to act on the central nervous system. Naloxone is effective in reversing episodes of apnea induced by meperidine. The following management guidelines have been recommended:
	2.1	Discontinue meperidine completely.
	2.2	Add an alternative opioid agonist (morphine or hydromorphone).
	2.3	Use diazepam, phenytoin or other anticonvulsants for seizure control (Kaiko RF, et al. Ann Neurol 1983;13:180-5.).
3.0	In all cases, meperidine should be given with caution. The initial dose should be reduced in all patients with decreased renal or hepatic function, and in the elderly.
4.0	Meperidine should be used with extreme caution in patients with pre-existing convulsive disorders, and in patients receiving drugs that are known to predispose patients to seizures (e.g., imipenem).