Intravenous opioids for chemotherapy-induced severe mucositis pain in children: Systematic review and single-center case series of management with patient- or nurse-controlled analgesia (PCA/NCA)

BACKGROUND: Chemotherapy-induced oral mucositis can result in severe pain. Intravenous (IV) opioids are recommended, but management protocols vary. We systematically reviewed studies reporting IV opioid use for pain related to chemotherapy-induced severe oral mucositis in children and conducted a large single-center case series. METHODS: Ovid MEDLINE, PubMed, and Cochrane databases were searched for studies reporting IV opioid duration and/or dose requirements for severe mucositis. Secondly, our pain service database was interrogated to describe episodes of opioid administration by patient- or nurse-controlled analgesia (PCA/NCA) for children with mucositis and cancer treatment-related pain. RESULTS: Seventeen studies (six randomized trials, two prospective observational, three retrospective cohort, six retrospective case series) included IV opioid in 618 patients (age 0.3–22.3 years), but reported parameters varied. Mucositis severity and chemotherapy indication influenced IV opioid requirements, with duration ranging from 3 to 68 days and variable dose trajectories (hourly morphine or equivalent 0-97 mcg/kg/h). Our 7-year series included PCA/NCA for 364 episodes of severe mucositis (302 patients; age 0.12–17.2 years). Duration ranged from 1 to 107 days and dose requirements in the first 3 days from 1 to 110 mcg/kg/h morphine. Longer PCA/NCA duration was associated with: higher initial morphine requirements (ρ = 0.46 [95% CI 0.35, 0.57]); subsequent increased pain and need for ketamine co-analgesia (118/364 episodes with opioid/ketamine 13.9 [9.8–22.2] days vs opioid alone 6.0 [3.9–10.8] days; median [IQR]); but not with age or sex. CONCLUSIONS: Management of severe mucositis pain can require prolonged IV opioid therapy. Individual and treatment-related variability in analgesic requirements highlight the need for regular review, titration, and management by specialist services