Salvador, P., Azusano, C., Wang, L., & Howell, D. (2012). A pilot randomized controlled trial of an oral care intervention to reduce mucositis severity in stem cell transplant patients. Journal of Pain and Symptom Management, 44, 64–73.

To assess the effectiveness and feasibility of implementing an oral cryotherapy plus oral care protocol to reduce oral mucositis (OM) severity in patients with multiple myeloma undergoing autologous stem cell transplant (ASCT)

Participants were randomized into an oral cryotherapy study group or a standard oral care control group. Patients in the oral cryotherapy study group received verbal and written instructions on oral cryotherapy plus an oral care protocol in place at the study site. Oral cryotherapy consisted of sucking on ice chips five minutes before, during, and after melphalan administration for a total of 60 minutes. The standard oral care protocol included education regarding oral self care, brushing with Toothette® brushes dipped in sodium bicarbonate, mouth rinsing with sodium bicarbonate mouthwash, and applying moisturizer to lips or the oral cavity. Patients were permitted to floss until their platelet counts fell below 50,000. Patients in the standard oral care control group received only the instructions on the oral care protocol (no cryotherapy). Outcomes were evaluated on days 3, 6, 9, and 12 after stem cell rescue. A research assistant who was blinded to group assignment assessed each participant and recorded the results of the assessment on data collection forms.

• The study reported on 46 patients aged 18 years and older.
• Patients' ages ranged from 43–72 years.
• The sample was 58% male and 42% female.
• Patients had been diagnosed with multiple myeloma and were undergoing ASCT. They were scheduled to receive 200 mg/m² high-dose melphalan. Additionally, they were scheduled to receive growth factors. They had no preexisting oral disease.
• Statistically significant differences existed between the study group and the control group related to age and education.

The study was conducted at a single-site, inpatient setting in Ontario, Canada.

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for palliative care.

This was a prospective, pilot, randomized control trial with repeated measures.

• The World Health Organization (WHO) mucositis grading scale was used.
• Pain was assessed using a 100-mm visual analog scale.
• Opioid use was assessed quantiatively by converting into morphine-equivalent units.
• A nutritional assessment form was used to record functional intake of food and fluids.
• Lengths of stay were recorded from medical records.
• An oral therapy questionnaire was used to assess the tolerability of cryotherapy.

• All participants were free of OM symptoms on days -1 and +3. Signs and symptoms of OM were observed on day +6 and were most pronounced on day +9. Symptoms of OM began to resolve on day +12.
• The overall mean severity scores for OM on the WHO scale were statistically significant (0.43 to 1.14, p < 0.001) on days +9 and +12 (p = 0.03), both in favor of the study group. On day +6, the statistically significant difference (p = 0.02) favored the control group.
• Pain scores were lower for the study group (p  < 0.01), and more participants in the control group used opioid analgesics than in the experimental group (41% versus 13%).
• No significant differences were found related to functional intake of food and fluids.
• The study group experienced a one-day decrease in length of stay, but this was not statistically significant.
• Cryotherapy was somewhat or well tolerated by 87% of patients. Side effects of teeth sensitivity and chills were reported by 17.4% of participants in the study group.

Cryotherapy in addition to an oral care protocol (as described above) is likely to be beneficial in reducing the severity of OM as well as decreasing pain and the need for opioid analgesics. In terms of lengths of stay, cryotherapy offered a clinical benefit, although not statistically significant.

• The sample size was small with fewer than 100 patients.
• Some data collection required patients to self-report.
• The study observed only adult patients diagnosed with multiple myeloma and undergoing stem cell tranplant.
• The study was limited in that the only OM-causing agent was melphalan.
• The study was not blinded.

Cryotherapy is inexpensive, and the protocol is relatively simple. In conjunction with an oral care protocol, this is a reasonable approach to take. A larger trial would be helpful.