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Background: Perioperative thermal disturbances during orthotopic liver transplantation (OLT) are common. We hypothesized that in patients undergoing OLT the use of a humidified high flow CO2 warming system maintains higher intraoperative temperatures when compared to standardized multimodal strategies to maintain thermoregulatory homeostasis.Methods: We performed a randomized pilot study in adult patients undergoing primary OLT. Participants were randomized to receive either open wound humidification with a high flow CO2 warming system in addition to standard care (Humidification group) or to standard care alone (Control group). The primary end point was nasopharyngeal core temperature measured 5 min immediately prior to reperfusion of the donor liver (Stage 3 - 5 min). Secondary endpoints included intraoperative PaCO2, minute ventilation and the use of vasoconstrictors.Results: Eleven patients were randomized to each group. Both groups were similar for age, body mass index, MELD, SOFA and APACHE II scores, baseline temperature, and duration of surgery. Immediately prior to reperfusion (Stage 3 - 5 min) the mean (SD) core temperature was higher in the Humidification Group compared to the Control Group: 36.0 °C (0.13) vs. 35.4 °C (0.22), p = 0.028. Repeated measured ANOVA showed that core temperatures over time during the stages of the transplant were higher in the Humidification Group compared to the Control Group (p < 0.0001). There were no significant differences in the ETCO2, PaCO2, minute ventilation, or inotropic support.Conclusion: The humidified high flow CO2 warming system was superior to standardized multimodal strategies in maintaining normothermia in patients undergoing OLT. Use of the device was feasible and did not interfere with any aspects of surgery. A larger study is needed to investigate if the improved thermoregulation observed is associated with improved patient outcomes.Trial Registration: ACTRN12616001631493 . Retrospectively registered 25 November 2016. [ABSTRACT FROM AUTHOR]