Nielsen, B.N., Aagaard, G., Henneberg, S.W., Schmiegelow, K., Hansen, S.H., & Romsing, J. (2012). Topical morphine for oral mucositis in children: Dose finding and absorption. Journal of Pain and Symptom Management, 44(1), 117–123.

To investigate the dose-response relationship of topical morphine and pain in pediatric cancer patients with oral mucositis; to investigate, after topical morphine administration, the plasma levels of morphine and metabolites
 

The sample included 12 children receiving treatment for chemotherapy-induced oral mucositis. Seven patients were in the dose-response study and five were in the absorption group.

Both groups received oral morphine for pain relief. All children in the study received an oral solution containing morphine hydrochloride, 1 or 2 mg/ml, administered as a spray by means of an atomizer. The child was then to retain the solution in the mouth for 10 seconds before spitting out the solution. All children in the study also received 10‐15 mg/kg acetaminophen every 6 hours. Supplemental analgesics were allowed in the study either by patient-controlled analgesia pump or intravenously.
 

• The sample was composed of 12 patients.                         
• Mean patient age was 9 years (SD = 7 years). In the dose-relationship study, the age range of participants was 6‐15 years, with the mean age being 8 years. In the absorption study, the age range of participants was 2‐17 years, with mean age being 10.4 years.
• Of all participants, 66.6% were male and 33.3% were female.
• Diagnoses in both groups were varied and included non-Hodgkin lymphoma (NHL); neuroblastoma (NBL); hematopoietic stem cell transplantation (HSCT), including concomitant radiation therapy; and acute lymphoblastic leukemia (ALL). ALL was the most common diagnosis. The list that follows specifies diagnosis by percentage of all patients.
  • 50% (n = 6) ALL.
  • 16.6% (n = 2) NHL.
  • 25% (n = 3) NBL.
  • 8.3% (n = 1) HSCT, including concomitant radiation therapy.

• Single site
• Inpatient
• Department of Pediatrics, Copenhagen University Hospital, Sweden

• Phase of care: active treatment
• Clinical application: pediatrics

Prospective observational sequential study

• Age-appropriate 11-point pain scale, to assess pain intensity, with 0 = no pain and 10 = worst pain
• Visual analog scale (VAS), 0–10, for children older than age 8
• Wong-Baker FACES Pain Rating Scale, a VAS consisting of six faces, to assess the pain of children ages 6–8
• Face, Legs, Activity, Cry, Consolability (FLACC) Scale, composed of five behavioral components to access the pain of preverbal children age 5 and younger
• World Health Organization (WHO) Oral Mucositis Scale, on which 0 = no oral mucositis and 4 = severe oral mucositis
• Analysis of plasma and metabolites to show morphine level

In the dose-response group, the morphine mouthwash was associated with a decrease of at least 36% in the oral pain score of six of seven patients. Thirty minutes after topical doses of 0.25–0.4 mg/kg morphine, pain decreased by approximately 36%. The absorption study reported concentrations of morphine and metabolites well below effective analgesic levels; authors reported no increase in plasma concentration of morphine.

The extremely small sample size prevents applying study results to the pediatric population of patients diagnosed with oral mucositis. Further research should investigate the reliability of these findings.
 

• The study had a small sample size, with fewer than 30 patients.
• The use of a systemic opiod as a rescue medication may have caused inconsistent results.

The evidence from this study is insufficient to allow researchers to draw conclusions about the effect of topical morphine on the pain associated with oral mucositis. However, oral analgesics such as morphine could be effective supplements, causing few side effects, to established treatments. More research is needed.