Oral cryotherapy for preventing oral mucositis during chemotherapy


Oral cryotherapy in the form of ice-cold water, ice cubes or chips is a popular low-cost intervention for oral mucositis which is a common complication of cancer treatment.  A number of trials as well as a 2015 Cochrane review (Dental Elf – 11th Jan 2016) have indicated that oral cryotherapy is effective in patients undergoing chemotherapy.

The aim of this review was to evaluate the efficacy of oral cryotherapy in the prevention of chemotherapy-induced oral mucositis.


Searches were conducted in the Cochrane Central Register of Controlled Trials (Central), Medline and Embase. Randomised controlled trials (RCTs) comparing patients undergoing chemotherapy receiving oral cryotherapy verses patients receiving placebo, no treatment, or other active intervention were considered. Two reviewers independently selected studies extracted data and assessed risk of bias using the Cochrane risk of bias tool. The primary outcome was the incidence of oral mucositis. Random effects meta-analysis was conducted estimating pooled risk ratios (RR) and 95% confidence intervals (CI). The certainty of the evidence was assessed using Grading of Recommendation, Assessment, Development and Evaluation (GRADE) approach.


  • 14 RCTs (13 parallel, 1 crossover) involving 1577 patients were included.
  • Studies were conducted in Italy (3), USA (3), China (2), Iran (2), and one each in Canada, Denmark, Sweden, Turkey.
  • Oral cryotherapy was compared to placebo in 6 studies, normal saline rinse (4 studies), oral care (3 studies) and leucovorin in one study.
  • The overall risk of bias was considered to be high in all 14 studies.
  • Meta-analysis showed that patients treated with oral cryotherapy had a significantly lower risk of developing oral mucositis of any grade (table 1)

Table 1.

Type of malignancy Risk Ratio (95%CI)
Any cancer 0.67 (0.56 to 0.81)
Haematological 0.69 (0.54 to 0.89)
Solid tumours 0.66 (0.58 to 0.75)
  • Meta-analysis also showed a significant reduction in oral mucositis in patients receiving oral cryotherapy of any grade, moderate -severe grade and severe grade (table 2)

Table 2.

Grade of oral mucositis Risk Ratio (95%CI)
Any grade 0.67 (0.56 to 0.81)
Moderate- severe 0.63 (0.49–0.82)
Severe 0.47 (0.34–0.94)
  • The certainty of the evidence was graded as moderate.


The authors concluded: –

Oral cryotherapy is effective in preventing oral mucositis in patients undergoing chemotherapy for the management of solid malignancies. The use of oral cryotherapy in preventing oral mucositis in bone marrow transplantation settings showed promising efficacy, but the evidence is not conclusive and requires more high-quality randomized controlled trials.


This protocol for this review was published on PROSPERO and has followed a standard systematic review approach and searching 3 major databases.  A 2015 Cochrane review (Dental Elf – 11th Jan 2016) has also looked at this question. The Cochrane review included 14 RCTs and all 14 of those studies are included in this new review together with two new RCTs that have been published since 2015. The findings of the new review are very similar to those of the Cochrane review providing support for oral cryotherapy for preventing oral mucositis particularly for patients with solid malignancies undergoing chemotherapy.


Primary Paper

Al-Rudayni AHM, Gopinath D, Maharajan MK, Veettil SK, Menon RK. Efficacy of Oral Cryotherapy in the Prevention of Oral Mucositis Associated with Cancer Chemotherapy: Systematic Review with Meta-Analysis and Trial Sequential Analysis. Curr Oncol. 2021 Jul 29;28(4):2852-2867. doi: 10.3390/curroncol28040250. PMID: 34436016; PMCID: PMC8395421.

Review protocol on PROSPERO

Other references

Dental Elf – 11th Jan 2016

Oral cryotherapy reduces oral mucositis in patients receiving 5FU-based treatment for solid cancers

Picture Credits

Photo by Luigi Pozzoli on Unsplash

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