Original article
Walker SM, Selers EL, Jay MA; Great Ormond Street Hospital Inpatient Pain Service. 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). Paediatr Anaesth. 2022 Jan;32(1):17-34. PMID: 34731511
One of the big differences between adult and pediatric cancer is the nature of associated pain. In adults, tumors often result from cancer invasion into surrounding tissues and slow, agonizing pain. In children, most cancer pain is related to medical therapy, either from therapeutic interventions, think lumbar puncture and bone marrow aspiration or from chemotherapy induced mucositis.
Rapid turnover cells in the gastrointestinal mucosa are susceptible to anti-neoplastic drugs, and oral erythema and ulceration results in pain and difficulty swallowing, while more generalized gastrointestinal involvement can be associated with abdominal pain, diarrhea, and inability to absorb oral medications or nutrients. “This manuscript focuses on the use of IV opioids by intermittent bolus and/or continuous infusion for pain related to chemotherapy-induced severe oral mucositis in children” and is based on the experience at the Great Ormond Street Hospital.
At Great Ormand Ormond Street, IVPCA as well as IV nurse PCA and surrogate (parental) PCA is managed by the acute pain service for ALL patients (surgery, medicine, oncology, etc.). In this single center study, morphine was the primary opioid for almost all mucositis patients who received a continuous infusion (0.02 mg/kg/hr) and IV demand (bolus) dose ((0.02 mg/kg/bolus). Dosing and duration of therapy was titrated by the acute pain service. “If analgesia was inadequate or patients experienced dose-limiting side effects with IV opioids alone, racemic ketamine was added to the opioid syringe (initial 20 mcg/kg/ml to maximum 1 mg/ml for patients >50 kg; double strength if further escalation required).” “Continuous monitoring includes pulse oximetry. Vomiting and itch are recorded, but specific relationships with opioid intake can be confounded by clinical status, routine use of anti-emetics to minimize chemotherapy side effects, and itch related to graft versus host disease.” The duration of therapy and dose requirements are based on the severity of mucositis. “Mouth care to remove debris and reduce the risk of secondary infection is an important aspect of care, but this and other local interventions such as cryotherapy, may be poorly tolerated by children as the severity of mucositis and pain increases.” The authors also present a systematic review of the literature of opioid treatment of mucositis pain in children which identifies little difference in efficacy or side effects among different opioids administered by PCA with prolonged course of treatment due to severity of mucositis similar to that seen in the Great Ormond Street case series.
Detailed GOSH Pain Service protocols are available online (https://www.gosh.nhs.uk/wards-and-departments/departments/clinical-specialties/pain-control-service-information-parents-and-visitors/download-documentation/).
Unlike the protocol described in this study, when I worked on the acute pain service at Johns Hopkins, we started ketamine almost immediately and it was administered by a separate infusion pump. In this study, ketamine was added to the morphine solution when pain was inadequately treated by morphine alone. Additionally, at Hopkins methadone was occasionally used instead of the continuous morphine infusion.
Mucositis produces terrible pain and suffering. This is a must read for any of us who treat acute oncologic pain. Myron Yaster MD