Effects of ischemic conditioning on head and neck free flap oxygenation: a randomized controlled trial

Abstract

Flap failure after microvascular reconstructive surgery is a rare but devastating complication caused by reperfusion injury and tissue hypoperfusion. Remote ischemic conditioning (RIC) provides protection against ischemia/reperfusion injury and reduces tissue infarction. We hypothesized that RIC would enhance flap oxygenation and exert organ-protective effects during head and neck free flap reconstructive surgery. Adult patients undergoing free flap transfer surgery for head and neck cancer were randomized to receive either RIC or sham-RIC during surgery. RIC consisted of four cycles of 5-min ischemia and 5-min reperfusion applied to the upper or lower extremity. The primary endpoint, tissue oxygen saturation of the flap, was measured by near-infrared spectroscopy on the first postoperative day. Organ-protective effects of RIC were evaluated with infarct size of rat hearts perfused with plasma dialysate from patients received RIC or sham-RIC. Between April 2018 and July 2019, 50 patients were randomized (each n = 25) and 46 were analyzed in the RIC (n = 23) or sham-RIC (n = 23) groups. Tissue oxygen saturation of the flap was similar between the groups (85 ± 12% vs 83 ± 9% in the RIC vs sham-RIC groups; P = 0.471). Myocardial infarct size after treatment of plasma dialysate was significantly reduced in the RIC group (44 ± 7% to 26 ± 6%; P = 0.018) compared to the sham-RIC group (42 ± 6% to 37 ± 7%; P = 0.388). RIC did not improve tissue oxygenation of the transferred free flap in head and neck cancer reconstructive surgery. However, there was evidence of organ-protective effects of RIC in experimental models.Trial registration: Registry number of ClinicalTrials.gov: NCT03474952.

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s).

Figures

Figure 1

CONSORT diagram of patient recruitment.

Figure 2

Study protocol of remote ischemic preconditioning or sham in patients undergoing free flap reconstructive surgery for head and neck cancer. (a) Schematic diagram of the study protocol. (b) Langendorff rat heart ischemia/reperfusion injury model using plasma dialysate from patients received remote ischemic conditioning or sham. (c) Protocol of ischemia/reperfusion injury and measurement of infarct size of the rat heart. RIC remote ischemic conditioning, KHB Krebs–Henseleit buffer.

Figure 3

Boxplot of (a) tissue oxygen saturation of the flap on postoperative day 1 and (b) changes in tissue oxygen saturation of the flap site after free flap reconstruction compared to the baseline in the RIC and sham-RIC group. Horizontal line within the box indicates median values; lower and upper boundaries of the box indicate 25th and 75th percentiles, respectively; horizontal lines outside the box indicate the minimum and the maximum values of the data, respectively. Extreme outliers were omitted. RIC remote ischemic conditioning.

Figure 4

Infarct size of the rat hearts perfused with serum dialysate from patients before and after remote ischemic conditioning or sham treatment. RIC remote ischemic conditioning.