Post-op PCA adverse effects?

A 45-year-old woman, B.R., who is 5 ft. 5 in. tall, 80 kg in weight, is hospitalized following a total abdominal hysterectomy. For 36 hours she's been using a meperidine patient-controlled analgesia (PCA) to control pain (loading dose = 30 mg, incremental dose = 20 mg, lockout interval = eight minutes, four-hour limit of 200 mg). During your team rounds, you find B.R. is agitated and irritable, with uncontrollable twitching. The resident asks you to recommend a sedative. Checking the chart, you notice B.R.'s serum creatinine (SrCr) prior to surgery was 1 mg/dl, but today it is 2.0 mg/dl. What do you recommend?

B.R.'s signs and symptoms of central nervous system irritability certainly lead one to suspect normeperidine toxicity. However, in postsurgical patients with agitation, mixed drug withdrawal must also be considered. Drugs such as sedative hypnotics or alcohol can produce withdrawal that may resemble normeperidine toxicity. Therefore, the first recommendation is to discontinue the meperidine PCA, then administer a benzodiazepine (dosed appropriately for renal function) to control the agitation and twitching.

To control pain, a short-acting oral opiate (oxycodone, morphine, hydromorphone) might be adequate. If a PCA is to be used this late, morphine, hydromorphone, or fentanyl can be safely used. I would also recommend exploring the cause of B.R.'s SrCr elevation.

Peter J. Koo, Pharm.D.

Associate Clinical Professor of Pharmacy
Pharmacist Specialist, Pain Management
University of California, San Francisco

Although meperidine has agonist effects similar to morphine, its adverse-effect profile limits its utility in patients with renal insufficiency, seizure disorders, or the elderly. Meperidine is N-demethylated to normeperidine, a metabolite that accumulates with repeated administration and with renal insufficiency. This metabolite has twice the potential to induce seizures and one-half the analgesic potency as the parent compound. Accumulation of normeperidine can cause CNS effects including mood changes, tremors, and seizures. Because other opioid agonists are available, meperidine use in acute pain management is not recommended.

B.R.'s CNS adverse effects most likely result from normeperidine accumulation. The doubling of SrCr in 36 hours has decreased metabolite elimination. Although the total amount of meperidine received is not available, she has the potential to receive 1,200 mg/24 hours (recommended maximum is 600 mg/24 hours.)

Based on B.R.'s symptoms, discontinue the meperidine PCA. Do not administer naloxone because it can precipitate seizures by reversing the depressant effects of meperidine and allowing the normeperidine seizure potential to manifest. If B.R. still requires PCA opioid for pain control, change to a hydromorphone (no active metabolites.) The physician must also assess fluid status. One of the most common causes of increasing creatinine in post-op patients is fluid depletion. By correcting fluid status, renal function will improve. This will eliminate normeperidine more efficiently.

Leslie N. Schechter, Pharm.D.

Clinical Pharmacy Specialist
Thomas Jefferson University Hospital
Philadelphia