Continuing Education Activity

Meperidine is in the class of phenylpiperidine as a hydrochloride salt synthetic form of the opioid. Meperidine is used for the treatment of moderate to severe pain. It has intramuscular, subcutaneous, intravenous injection, syrup, and tablet forms. In the 20th century, it was the drug of choice among the opioids in the management of acute pain and the management of some patients with chronic pain. It has also become a drug commonly abused. Meperidine is used as an adjunct to preoperative medications to reduce shivering. This activity outlines the indications, action, and contraindications for meperidine as an analgesic and other related disorders.

Objectives:

• Identify the mechanism of action of meperidine.
• Describe the adverse effects and contraindications of meperidine.
• Review the routes of administration of meperidine.
• Summarize interprofessional team strategies for improving care coordination and communication to advance the safe use of meperidine and improve outcomes.

Indications

Meperidine, also known as pethidine, is in the class of phenylpiperidine as a hydrochloride salt synthetic form of the opioid, which is a white crystalline with a melting point of 186 degrees C. This medication has calcium sulfate, dibasic calcium phosphate, starch, stearic acid, and talc as inactive ingredients. Clinicians use meperidine is used for the treatment of moderate to severe pain. It has intramuscular, subcutaneous, intravenous injection, syrup, and tablet forms. In the 20th century, it was the drug of choice amongst the opioids in the management of acute pain by most of the physicians and the management of some patients with chronic pain. Meperidine is also being used as an adjunct to preoperative medications to reduce shivering.[1][2][3]

Meperidine appeared to be safer with a lower risk of addiction when compared to other opioids and because of the anticholinergic effects associated with less biliary spasm or renal colic. However, it appears that risks of addiction, biliary spasm, and renal colic are equal to other opioids. Additionally, due to its toxic metabolite is known as normeperidine, which has serotonergic properties, it correlates with an increased risk of serotonin syndrome and seizure. These issues have led to the removal of meperidine from the World Health Organization’s list of essential medicines, the list of most effective and safe medicines in the health system in 2003.[4][5][6]

Mechanism of Action

Meperidine has the same mechanism of action as morphine, which is acting as an agonist to the mu-opioid receptor. The anti-shivering effect may involve the stimulation of k-opioid receptors.[7]

Meperidine also has some local anesthetic effects because of interactions with sodium ion channels. Also, meperidine has stimulant effects by inhibition of the dopamine transporter (DAT) and norepinephrine transporter (NET).

Administration

Oral form: (not recommended for acute pain control)

• Tablet form: 50 mg to 100 mg
• Syrup form: 50 mg/5 ml

Injectable solution form: 25 mg/ml, 50 mg/ml, 75 mg/ml, 100 mg/ml 

Intravenous (IV) injection: inject the dose of 10 mg/ml slowly. The injection should be a consideration only when an opiate antagonist and the administration of oxygen and respiratory monitoring facilities are available.

For continuous IV infusion: 15 to 35 mg/hr

Intramuscular: Injection should be into large muscle mass, and it is preferable to subcutaneous injection.

Using Meperidine for pain control should be considered if no other options are available, in which case duration of medication use should be limited to less than 48 hours, and the total dosage administered should not exceed 600 mg in 24 hours.

For pain management:

• In adults: 50 mg to 150 mg orally, IM, subcutaneously (SC) every 3 to 4 hours as needed.
• In pediatrics: 1 mg/kg to1.8 mg/kg orally, IM, subcutaneously (SC) every 3 to 4 hours as needed. (each dose should not exceed 100mg)

Continuous infusion: 15 mg to 35 mg per hour

Obstetrical pain management: 50 mg to 100 mg IM/SC, every 1 to 3 hours as needed

Preoperatively:

• In adults: 50 mg to 150 mg IM/SC every 3 to 4 hours as needed.
• In pediatrics: 1.1 mg/kg to 2.2 mg/kg SC/IM 30 to 90 minutes before anesthesia

Adverse Effects

Serious Reactions

Shock, seizure, syncope, hallucination (especially among the geriatric population), potential opioid dependency, withdrawal symptoms if discontinued without tapering down, opioid-induced androgen deficiency (chronic use), bradycardia, cardiac arrest, severe hypotension, apnea, respiratory failure.

Common Reactions

Tachycardia, urinary retention, tremor, involuntary movements, xerostomia, constipation, dysphoria, weakness, palpitation, headache, rash, pruritus, urticaria, visual disturbances, involuntary movements, confusion, dysphoria, delirium (especially in geriatric population), nausea, vomiting, lightheadedness, diaphoresis, agitation, orthostatic hypotension, weakness, bradycardia, flushing.

Contraindications

Meperidine is contraindicated in patients that are actively receiving or have been exposed during the past 14 days to monoamine oxidase inhibitors (MAOI) because of unpredictable severe, and occasionally fatal reactions such as coma, severe respiratory depression, hypotension, cyanosis, and acute narcotic overdose. Also, convulsion, hyper-excitability, tachycardia, hyperpyrexia, and hypertension have been reported. Intravenous hydrocortisone or prednisone have been used to treat severe reactions. In those cases exhibiting hypertension and hyperpyrexia, intravenous chlorpromazine is added.

Meperidine has respiratory depressant effects and capacity to elevate cerebrospinal fluid pressure especially in patients with head injury or other intracranial lesions. In this group of patients using Meperidine should be with extreme caution. Like other narcotics, using meperidine in patients having an acute asthma attack and chronic obstructive pulmonary disease should be with caution, and these patients should be monitored for any signs of increased airway resistance or apnea.

Meperidine has several Black Box warnings:

1. The potential risk of opioid addiction which can cause overdose and death. Physicians should evaluate their patients continuously for developing these conditions.
2. Life-threatening respiratory failure may occur, therefore monitoring for respiratory depression during the initiation and following dose increase should be considered.
3. Parallel use with cytochrome P450 3A4 inhibitors or discontinuation of P450 inducers causes the increase of the meperidine concentration that can result in a fatal overdose.
4. Concomitant use of meperidine and monoamine oxidase inhibitors (MAOI) can cause coma, severe respiratory failure, cyanosis, and hypotension.
5. Chronic use of meperidine during pregnancy can cause neonatal opioid withdrawal syndrome, which needs to be diagnosed and managed by guidelines of neonatology, which otherwise can be fatal.
6. Concomitant use of another central nervous system (CNS) depressant like benzodiazepines or alcohol with meperidine may cause profound sedation, respiratory depression, coma, and death.
7. There is a risk of medication errors, which can be prevented by ensuring accuracy when prescribing, dispensing, and administrating. This is especially important as confusing mg and ml when dosing can result in an accidental fatal overdose.

Toxicity

Meperidine is a potent opioid analgesic that has the potential for habit-forming and misuse, which increases the risk of overdose.[8][4] Overdose on meperidine happens in:

• Having an underlying or unknown condition that increases the sensitivity to meperidine
• Accidentally or intentionally using more than the prescribed dosage
• Concomitant use of meperidine with alcohol, other CNS depressants, or illicit drugs that make changes in the body’s sensitivity to the medication.

The signs of an overdose of meperidine:

Patients can have shallow or no breathing, signs of cyanosis like blue lips or fingernails, fatigue, convulsion, low blood pressure, bradycardia, constipation, stomach cramps, nausea and vomiting, cold and clammy skin, drowsiness, lightheadedness, and twitching muscles. In severe overdose, patients may experience circulatory relapse, cardiac arrest, apnea, and in some cases, death.

Treatment of meperidine overdose:

First, because of potential respiratory failure, the patients’ airway should be reestablished by ventilation. Then the patient can be managed by activated charcoal to reduce the absorption of the medication in the gastrointestinal (GI) tract by almost 60% (time-dependent). IV fluids are useful for flushing the medication from patients’ system while balancing the acid/base equilibrium and minerals of the body. The use of gastric lavage or stomach pumping will wash out the stomach content. Laxatives can be an option to induce defecation to remove the poison from the GI tract. Hemodialysis may help to filter the patient’s blood. Administration of opioids antagonists like naloxone to reverse the drug’s effects is another means of addressing overdose. Intravenous hydrocortisone or prednisone is also a choice to treat severe reactions. Clinicians can add intravenous chlorpromazine in those cases exhibiting hypertension and hyperpyrexia.

After the recovery, these patients should participate in addiction treatment programs for the treatment of underlying causes of addiction and support the patient in the process of rehabilitation.

Enhancing Healthcare Team Outcomes

All healthcare workers, including the pharmacist and nurse practitioner, should be aware that meperidine is no longer considered to be safer than other opiates. It appears that risks of addiction, biliary spasm, and renal colic are equal to other opioids. Additionally, due to its toxic metabolite is known as normeperidine, which has serotonergic properties, it correlates with an increased risk of serotonin syndrome and seizure. This correlation has led to meperidine's removal from the World Health Organization's list of essential medicines, the list of most effective and safe medicines in the health system in 2003. 

When prescribed, the patients require close monitoring, and the duration of prescription should not be more than a few days. Experts recommend alternate means of pain control.[9]