What is the recommended dosing and titration of naloxone (opioid receptor antagonist) infusion for treating opioid-induced pruritus in pediatric patients on Patient-Controlled Analgesia (PCA) or opioid infusion?

Naloxone Infusion for Opioid-Induced Pruritus in Pediatric Patients on PCA/Infusion

For pediatric patients experiencing opioid-induced pruritus while on PCA or continuous opioid infusion, start a continuous naloxone infusion at 0.25 mcg/kg/h and titrate up to 1 mcg/kg/h as needed for symptom control without reversing analgesia. 1, 2, 3

Initial Dosing Strategy

• Begin naloxone infusion at 0.25 mcg/kg/h as the starting dose when initiating treatment for opioid-induced pruritus in pediatric patients on morphine PCA or continuous infusion 1, 3
• This low starting dose has been shown to significantly reduce the incidence and severity of pruritus (from 77% to 20%) and nausea (from 70% to 35%) without affecting morphine consumption, pain scores, or analgesia 3
• At this dose, plasma naloxone levels remain below 0.1 ng/mL, which is below the level of assay quantification, indicating minimal systemic antagonist effect 2

Titration Protocol

• If pruritus persists at 0.25 mcg/kg/h, titrate upward incrementally through the following doses: 0.40 mcg/kg/h, 0.65 mcg/kg/h, and up to 1 mcg/kg/h 2
• The optimal dose for most pediatric patients is 1 mcg/kg/h, which achieved a <10% side effect/failure rate in dose-finding studies 2
• Plasma naloxone levels increase linearly with infusion rates >0.25 mcg/kg/h, but remain low enough to preserve analgesia 2
• Monitor for symptom control at each dose level before escalating further 2

Critical Threshold for Reversing Analgesia

• Naloxone infusions up to 1 mcg/kg/h do not reverse opioid analgesia in pediatric patients, as demonstrated by unchanged pain scores at rest and with coughing, and no difference in morphine consumption compared to placebo 2, 3
• The guideline-recommended maximum titration endpoint is "mcg/kg/h" (specific upper limit not fully specified in adult guidelines, but pediatric data supports up to 1.65 mcg/kg/h without analgesia reversal) 1, 2
• Careful dose titration is essential to produce relief without reversing analgesic efficacy, as emphasized across multiple guidelines 1, 4

Alternative Treatment Approach: Admixture Strategy

• A naloxone-opioid-saline admixture (NOSA) at a ratio of 12 mcg naloxone per 1 mg morphine per 1 mL normal saline has been studied but is NOT recommended 5
• This admixture approach (delivering approximately 0.37 mcg/kg/h naloxone) did not decrease the incidence (22% vs 36%, p=0.164) or severity of opioid-induced pruritus compared to morphine alone 5
• Separate administration of naloxone via dedicated infusion is the more effective strategy for prevention of opioid-induced pruritus 5

Stepwise Management Algorithm

First-Line Treatment

• Start antihistamines: diphenhydramine 25-50 mg IV/PO every 6 hours or promethazine 12.5-25 mg PO every 6 hours 1, 4, 6
• Rule out other causes of pruritus (other medications, skin conditions) 1, 6

Second-Line Treatment (If Antihistamines Fail)

• Initiate continuous naloxone infusion at 0.25 mcg/kg/h 1, 4, 3
• Consider mixed agonist-antagonist nalbuphine 0.5-1 mg IV every 6 hours as needed (though this carries higher risk of reversing analgesia in opioid-tolerant patients) 1

Third-Line Treatment (If Pruritus Persists)

• Titrate naloxone infusion up to 1 mcg/kg/h 2
• Consider opioid rotation to a different opioid (e.g., fentanyl or buprenorphine) that may not cause cross-reactivity 1, 4, 6

Important Clinical Considerations

• Naloxone is more effective in preventing pruritus than nausea and vomiting, so supplemental antiemetics may still be required 2
• Pruritus is more likely to occur early in the course of opioid treatment, making prophylactic naloxone infusion particularly valuable when initiating PCA 1, 4, 6
• Do not use ondansetron as first-line treatment for opioid-induced pruritus despite its efficacy for opioid-induced nausea, as recent evidence shows it does not reduce incidence or time to onset of pruritus 1, 7
• Sedating antihistamines will compound opioid-induced sedation and require close monitoring 4, 6

Common Pitfalls to Avoid

• Do not administer naloxone to patients whose mothers are suspected of long-term opioid use due to risk of acute withdrawal and seizures 1
• Avoid using full doses of opioid antagonists in opioid-dependent patients as this may precipitate withdrawal 1, 7
• Do not rely on admixture preparations of naloxone with morphine, as separate infusion is more effective 5
• Patients who fail therapy at lower naloxone doses generally have comparable plasma naloxone and morphine levels to those who achieve symptom control, suggesting that success or failure is unrelated to plasma levels and may require dose escalation 2

Monitoring Requirements

• Continuously monitor vital signs and oxygen saturation when initiating naloxone infusion 1
• Assess pain scores at rest and with movement to ensure analgesia is maintained 2, 3
• Track morphine consumption to verify that naloxone is not increasing opioid requirements 2, 3
• Observe for at least 2 hours after the last dose of naloxone for recurrence of symptoms 1