Hemodynamics of the oral mucosa during cooling: A crossover clinical trial.

Objective: Oral cryotherapy is used to prevent the onset of oral mucositis, a common and debilitating adverse effect following cancer chemotherapy. A protective mechanism associated with oral cooling is thought to be mediated through reduced tissue microcirculation. The aim of the present study was to examine the underlying mechanism associated with oral mucosal cooling by measuring oral microcirculation and tissue oxygen saturation after cooling with ice chips (IC) and an intraoral cooling device (ICD). Study design: In a single-center randomized crossover study, 10 healthy volunteers were assigned (1:1) randomly to the order in which the two intraoral cooling procedures (IC/ICD) were to be commenced. On day 1, half of the study participants started with IC and then crossed over to intraoral cooling with the ICD on day 2, while the other half of the participants undertook the same two procedures in the reverse order. Total and functional capillary density (T/FCD) and tissue oxygen saturation (StO2) measurements were obtained at baseline and 30 min following oral cooling. Results: Following 30 min of oral cooling, a statistically significant difference was found for FCD between IC and ICD (percentage points; +2 vs. -13; p < 0.05). A statistically significant decrease in StO2 was observed with both IC and ICD (%; 13 vs. 10) after 30 min of cooling as compared to baseline (p < 0.05). As for the participants' preference the ICD was preferred over IC by 9 out of 10 participants (p = 0.021). Conclusions: Both microcirculation parameters and tissue oxygen saturation are altered in conjunction with oral cooling, indicating their potential mechanistic contribution towards cryoprevention of oral mucositis.

An extraoral approach to intraoral cooling-a feasibility study in non-cancer patients.

BACKGROUND: Cryotherapy, using ice chips (IC) is an effective strategy to prevent chemotherapy-induced oral mucositis (OM) in selected cancer patient cohorts. However, although effective, use of IC may cause adverse reactions, e.g., nausea, numbness, and shooting pain in the teeth, which could have an adverse impact on the medical treatment. Furthermore, IC requires water of good quality to minimize risk of serious systemic infections. To eliminate these disadvantages, novel cooling devices have emerged as alternative cooling modalities. Thus, the aim was to evaluate the efficacy and tolerability profile of extraoral cooling for intraoral temperature reduction. SUBJECTS AND METHODS: This experimental pilot study was conducted at the Institute of Odontology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. In total, six healthy volunteers were enrolled in this study. At baseline and following 30-, and 60 min of cooling with the extraoral cooling device, intraoral mucosal temperatures were measured using a thermographic camera, and a questionnaire related to tolerability was completed. RESULTS: Following 30-, and 60 min of cooling, the intraoral temperature decreased with 2.0 °C and 2.3 °C, respectively. Extraoral cooling was well tolerated, and all subjects endured the entire cooling session of 60 min. CONCLUSION: Extraoral cooling reduces intraoral mucosal temperatures and is a well-tolerated cooling modality.

Cryopreventive temperatures prior to chemotherapy.

The superiority of oral cryotherapy (OC) for prevention of chemotherapy-induced oral mucositis (OM) has been demonstrated in several trials. In clinical settings, cooling is usually initiated prior to the chemotherapy infusion. It then continues during the infusion, and for a period after the infusion has been completed. While the cooling period post-infusion depends on the half-life of the chemotherapeutic drug, there is no consensus on when cooling should be initiated prior to the infusion. The lowest achieved temperature in the oral mucosa is believed to provide the best condition for OM prevention. Given this, it was of interest to investigate when along the course of intraoral cooling this temperature is achieved. In total, 20 healthy volunteers participated in this randomized crossover trial. Each subject attended three separate cooling sessions of 30 min each, with ice chips (IC) and the intraoral cooling device (ICD) set to 8 and 15 °C, respectively. At baseline and following 5, 10, 15, 20 and 30 min of cooling, intraoral temperatures were registered using a thermographic camera. The greatest drop in intraoral temperature was seen after 5 min of cooling with IC, ICD8°C and ICD15°C, respectively. A statistically significant difference, corresponding to 1.4 °C, was seen between IC and the ICD15°C (p < 0.05). The intraoral temperature further declined throughout the 30 min of cooling, showing an additional temperature reduction of 3.1, 2.2, and 1.7 °C for IC, ICD8°C and ICD15°C, respectively.

Moderate temperature reduction is sufficient for prevention of 5-fluorouracil-induced oral mucositis: an experimental in vivo study in rats.

PURPOSE: The current idea of how oral mucositis (OM) develops is primarily based on hypotheses and the early events which precede clinically established OM remain to be demonstrated. Cryotherapy (CT) continues to have considerable promise in clinical settings to reduce chemotherapy-induced OM. Although being effective, the knowledge is scarce regarding the ideal temperature for prevention of OM. Thus, the present study had two main objectives: (i) to develop an animal model to investigate the early events of OM; (ii) to study at what cooling temperature these early events could be abolished. METHODS: Male Sprague-Dawley rats were anaesthetized and given an intravenous bolus dose with the cytostatic drug fluorouracil (5-FU). During the first hour following injection with 5-FU, the oral cavity of the rats was cooled to a mucosal temperature at the range of 15-30 â—‹C, or left uncooled (35 â—‹C), serving as control. After 3-5 days, the rats were euthanized, and the buccal mucosa was excised. Subsequently, mucosal thickness and expression of IL-6 and TNF-α were analyzed with immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). RESULTS: Five days following treatment with 5-FU, a statistically significant thickening of the oral mucosa occurred, and a distinct expression of both IL-6 and TNF-α were observed. The cryo-treated groups (15-30 °C) displayed statistically significantly thinner mucosa as compared to the control group (35 °C). The ELISA showed an increase in expression of the proinflammatory cytokines IL-6 and TNF-α in tissues exposed to 5-FU that were treated with increasing temperatures (15-30 °C). CONCLUSION: Bolus i.v. injection with 5-FU in rats can be used to create a functional animal model for chemotherapy-induced OM. Further, moderate temperature reduction is sufficient to reduce the early events which may precede clinically established OM.

Can cryoprevention of oral mucositis be obtained at a higher temperature?

OBJECTIVES: Ice chips (IC) have successfully been used to prevent the development of chemotherapy-induced oral mucositis (OM). Although effective, IC entails several shortcomings and may open avenues for systemic infections as the water used may be contaminated by microorganisms, which may jeopardise the medical rehabilitation of an already immunosuppressed patient. This study aimed to investigate the efficacy and tolerability profile of a novel intraoral cooling device (ICD). SUBJECTS AND METHODS: In total, 20 healthy volunteers were enrolled in this randomised crossover study. Intraoral temperatures were registered using an IR camera, at baseline and following 30 and 60 min of cooling with the ICD, set to 8 °C or 15 °C. Following each cooling session, tolerability was assessed using a questionnaire. RESULTS: A statistically significant difference in the intraoral temperature was observed using 8 °C compared with 15 °C, following both 30 (1.87 °C, p < 0.001) and 60 min (2.48 °C, p < 0.001) of cooling. Thus, the difference of the intraoral temperatures was less than the 7 °C difference between 8 °C and 15 °C. Furthermore, 60 min of cooling with 15 °C compared with 8 °C was better tolerated and preferred by 15 out of 20 participants (p < 0.001). CONCLUSION: Cooling was better tolerated when the ICD was set to 15 °C compared with 8 °C, although the difference in reduction of the intraoral mucosal temperature was marginal and may not affect cryoprevention of oral mucositis. CLINICAL RELEVANCE: The ICD has the potential to improve the care for patients with cancer at high risk of developing OM.