Advertisement

Real-time Assessment of Tissue Oxygen Saturation During Endovascular Therapy for Chronic Limb-threatening Ischemia Using a Novel Oximeter

Open AccessPublished:July 21, 2021DOI:https://doi.org/10.1016/j.jvscit.2021.07.001

      Abstract

      This study introduces a novel real-time, near-infrared spectroscopy oximeter, “TOE-20,” that can simultaneously measure regional tissue oxygen saturation (rSO2) in the skin/subcutaneous tissue at three angiosomes of the foot. Seven patients with chronic limb-threatening ischemia (CLTI) who underwent successful revascularization of the superficial femoral artery were included. The analysis revealed a significant correlation between rSO2 values and skin perfusion pressure (SPP). Following revascularization, both rSO2 and SPP increased at the three regions, although the increase at the plantar foot was insignificant. These results indicate that the TOE-20 can successfully monitor rSO2 during endovascular treatment.

      Keywords

      Introduction

      Owing to the growing incidence of diabetes and renal insufficiency, the number of patients with chronic limb-threatening ischemia (CLTI) has increased to more than 6 million globally.
      • Biancari F.
      Meta-analysis of the prevalence, incidence and natural history of critical limb ischemia.
      Endovascular therapy (EVT) is a major treatment for CLTI, particularly for patients with a high surgical risk.
      • Aboyans V.
      • Ricco J.B.
      • Bartelink M.E.L.
      • Björck M.
      • Brodmann M.
      • Cohnert T.
      • et al.
      Editor’s Choice - 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS).
      Previously, the authors introduced a finger-mounted tissue oximeter that relies on near-infrared spectroscopy (NIRS) techniques (Toccare: astem Co., Ltd., Kawasaki, Japan) to assess ischemia severity in patients with peripheral artery disease (PAD).
      • Yata T.
      • Sano M.
      • Kayama T.
      • Naruse E.
      • Yamamoto N.
      • Inuzuka K.
      • et al.
      Utility of a finger-mounted tissue oximeter with near-infrared spectroscopy to evaluate limb ischemia in patients with peripheral arterial disease.
      Subsequently, the team developed an NIRS device to simultaneously facilitate intra-EVT monitoring of tissue oxygenation at multiple sites. Herein, the authors introduce this novel device and present preliminary results for the real-time monitoring of regional tissue oxygen saturation (rSO2) in the skin/subcutaneous tissue at three angiosomes of the foot during EVT.

      Methods

       Study approval

      This study was approved by the Ethical Committee of Hamamatsu University School of Medicine (approval number: 16-057). The study protocol was registered at the UMIN Clinical Trials Registry (UMIN-CTR; ID: UMIN000025021) and Japan Registry of Clinical Trials (CRB4180008). Written informed consent was obtained from all participants.

       Tissue oximeter

      The new NIRS oximeter (TOE-20, astem Co., Kawasaki, Japan) enables real-time monitoring of rSO2 (Supplement Figure 1A). The device’s name, TOE, is an abbreviation for target region oxygenation-based endovascular treatment, which was previously proposed as a new strategy for EVT.
      • Unno N.
      • Inuzuka K.
      • Sano M.
      • Kayama T.
      • Naruse E.
      • Takeuchi H.
      Target region oxygenation-based endovascular treatment in a chronic limb-threatening ischemia patient with multifocal arterial diseases.
      The oximeter comprises three components: a small, box-shaped body (70×72×25 mm; weight: 120 g), including a multiplexer, microcomputer, blue-tooth module, and two size-AA batteries; three sensor probes with 40-cm long cables; and a tablet PC that displays measurement results (Supplement Figure 1B). Each probe has near-infrared light emitting diodes (770 nm, 830 nm) and detectors (photodiodes) (Supplement Figure 1C). Supplement Figure 1D presents the path length distribution obtained from simulation results. Supplement Figure 1E and 1F shows the path length distribution superimposed on a typical magnetic resonance (MRI) image of the foot. Supplement Figure 1G shows the equations used to calculate the concentrations of oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb).
      Figure thumbnail gr1
      Figure 1Regional tissue oxygen saturation (rSO2). A. The rSO2 curve of one patient during the endovascular procedure. The rSO2 values stabilized after a few minutes. B. Relationship between rSO2 and SPP at the surface of the foot. A scatter plot of SPP and rSO2 values (P < .01, r = 0.653). The values reflect data for all seven patients who underwent successful SFA revascularization via endovascular treatment. C. Comparison of rSO2 values at the dorsal foot, plantar foot, and outer ankle between pre- and post-EVT in seven patients. * indicates p < 0.01 in comparison with pre-EVT; n.s., not significant. D. Comparison of SPP values at the dorsal foot, plantar foot, and outer ankle between pre- and post-EVT in seven patients. * indicates p < 0.01 in comparison with pre-EVT; n.s., not significant. E. Changes in rSO2 values at the dorsal foot in seven patients who underwent successful SFA EVT on the day of hospitalization and at pre-EVT, post-EVT, and postoperative day 1 (POD1). * indicates p < 0.05 in comparison with pre-EVT. F. Comparison of rSO2 values at the dorsal foot, plantar foot, and outer ankle between pre- and post-EVT in five patients who underwent failed EVT; n.s., not significant. rSO2, regional tissue oxygen saturation; SPP, skin perfusion pressure; SFA: superficial femoral artery.

       Application to patients

      Three sensor probes can be placed at the operator’s discretion to monitor tissue perfusion. Supplement Figure 2A and 2B show the placement of probes according to the angiosome model: one on the dorsal aspect of the foot, one on the outer ankle (Supplement Figure 2A), and one on the plantar aspect of the foot (Supplement Figure 2B). Supplement Figure 2C shows the actual monitoring setup for measuring rSO2 during EVT.

       Participants

      This prospective study included seven patients with CLTI who underwent successful revascularization of the superficial femoral artery (SFA) without intervention in the tibial arteries and five patients with CLTI who underwent failed EVT (four with failed tibial artery intervention and one with failed SFA intervention) (Table I). All patients were categorized as Rutherford classification 5 with intractable toe ulcers. Successful revascularization of the SFA was defined as <30% residual stenosis of the target lesion on completion angiogram without peripheral emboli. The rSO2 values were measured within 0.5 seconds per point. Although rSO2 was monitored continuously, the authors waited for 5 minutes to observe the effect of revascularization after each procedure because values required a few minutes to stabilize (Figure 1A). Skin perfusion pressure (SPP) was also measured at the above-mentioned regions in the ambulatory clinic before and after treatment using an SPP system (SensiLase PAD 3000, Vasamed Eden Prairie, MN, USA).
      Table IDemographic and clinical characteristics of the included patients
      Successful SFA revascularizationFailed EVT
      Patients, n75
      Age, years, median, interquartile range76, 62-8574, 57-85
      Men, n (%)4 (57)3 (60)
      Hypertension, n (%)5 (71)6 (60)
      Dyslipidemia, n (%)3 (43)6 (60)
      Diabetes mellitus, n (%)5 (71)6 (60)
      History of smoking, n (%)5 (71)8 (80)
      End-stage renal disease, n (%)4 (57)6 (60)
      Coronary artery disease, n (%)2 (29)6 (60)
      Limbs, n75
      Location of ulcer
      Toe74
      Plantar foot01
      Outer ankle00
      Ankle-brachial index0.63 ± 0.130.58 ± 0.25
      SFA: superficial femoral artery, EVT: endovascular treatment

       Statistical analysis

      The correlations between the rSO2 and SPP values were analyzed using the nonparametric Spearman rank correlation tests. Results are expressed as mean ± standard deviation. Paired t-tests were used to compare rSO2 and SPP values between pre- and post-revascularization at the same sites. One-way analysis of variance and nonparametric Friedman tests with post hoc Tukey’s test were used to examine differences in the time course of rSO2 values in the dorsal foot among the seven patients. The level of statistical significance was set at P <0.05. (IBM SPSS version 25.0 software, IBM Corp., Armonk, NY, USA)

      Results

      SFA revascularizations were successfully performed via endovascular interventions with balloon angioplasty in five patients, a Viabahn stent-graft (W.L. Gore & Associates, Flagstaff, AZ, USA) in one patient, and stent placement in one patient. In outflow arteries below the knee, completion angiography revealed two run-off vessels in four patients and one run-off vessel in three patients. Therefore, all seven patients had at least one straight-line flow on below-the-knee angiography. Following revascularization, the sensor probes gradually responded to the increased blood flow to increase rSO2 to a stable value. There was a significant correlation between SPP and rSO2 values (p<0.01) (Figure 1B). After revascularization, both rSO2 and SPP increased at the dorsal foot and outer ankle (Figure 1C,D). Figure 1E shows the time course of rSO2 values in the seven patients on the day of hospitalization and at pre-EVT, post-EVT, and postoperative day (POD) 1. By 3 months after EVT, all ulcers had healed in all seven patients. In contrast, there was no significant increase in rSO2 at any region in patients with failed EVT (Figure 1F).

      Discussion

      The present results demonstrate the utility of the TOE-20 for simultaneous monitoring of rSO2 in the skin/subcutaneous tissue in three angiosomes of the foot during EVT. Previous NIRS oximeters focused on measuring oxygen levels in the brain or muscles at a depth of 10–20 mm below the skin surface,
      • Rao R.
      • Saint-Cyr M.
      • Ma A.M.
      • Bowling M.
      • Hatef D.A.
      • Andrews V.
      • et al.
      Prediction of post-operative necrosis after mastectomy: a pilot study utilizing optical diffusion imaging spectroscopy.
      ; however, these devices may not be able to measure oxygen levels in the skin/subcutaneous tissue of the toe because the bones or tendons are present at depths less than 10 mm from the skin surface. In contrast, the TOE-20 is specifically designed to measure rSO2 in the skin and subcutaneous tissue. The superimposed MRI of the foot revealed that the TOE-20 reflects rSO2 levels up to 5 mm under the skin surface and can measure rSO2 of the skin and subcutaneous tissue without the influence of bone. This characteristic is quite unique when compared with those of other NIRS devices, which mainly measure cerebral oxygen levels using an algorithm that diminishes the contribution of the skin and scalp.
      • Hyttel-Sorensen S.
      • Sorensen L.C.
      • Riera J.
      • Greisen G.
      Tissue oximetry: a comparison of mean values of regional tissue saturation, reproducibility and dynamic range of four NIRS-instruments on the human forearm.
      One of the biggest advantages of the TOE-20 is the speed with which rSO2 can be measured. Continuous monitoring allows one to obtain the values almost instantly (within approximately 0.5 s), thereby reducing the influence of the patient’s bodily movements on measurements. Because high and low rSO2 areas are observed even within the same angiosome, peripheral tissue perfusion in the foot in patients with CLTI (especially those with diabetes) is determined by the peripheral microvascular blood flow in the skin and subcutaneous tissue.
      • Kagaya Y.
      • Ohura N.
      • Suga H.
      • Eto H.
      • Takushima A.
      • Harii K.
      ‘Real angiosome’ assessment from peripheral tissue perfusion using tissue oxygen saturation foot-mapping in patients with critical limb ischemia.
      After revasculatization, increases in rSO2 and SPP at the plantar foot were not significant. The lack of a patent pedal arch in some patients may explain why plantar rSO2 did not increase significantly after EVT. Because all seven patients had toe ulcers, the authors assumed that rSO2 in the dorsal foot most likely reflects oxygenation in the toe ulcers.
      The authors previously investigated the use of a finger-mounted oximeter that relies on the same algorithm as the TOE-20 in 34 patients with CLTI without infection who underwent EVT. All patients with rSO2 ≥50 % in the dorsal foot on POD1 exhibited improved ulcer healing, indicating that rSO2 ≥50% may be a cut-off value for wound healing.
      • Kayama T.
      • Sano M.
      • Yata T.
      • Inuzuka K.
      • Katahashi K.
      • Yata T.
      • et al.
      A pilot study investigating the use of regional oxygen saturation as a predictor of ischemic wound healing outcome after endovascular treatment in patients with chronic limb-threatening ischemia.
      Further studies with longer observation periods are required to verify the cut-off value of rSO2 for wound healing.

      Supplementary data

      Figure thumbnail figs1
      Figure thumbnail figs2

      References

        • Biancari F.
        Meta-analysis of the prevalence, incidence and natural history of critical limb ischemia.
        J Cardiovasc Surg. 2013; 54: 663-669
        • Aboyans V.
        • Ricco J.B.
        • Bartelink M.E.L.
        • Björck M.
        • Brodmann M.
        • Cohnert T.
        • et al.
        Editor’s Choice - 2017 ESC guidelines on the diagnosis and treatment of peripheral arterial diseases, in collaboration with the European Society for Vascular Surgery (ESVS).
        Eur J Vasc Endovasc Surg. 2018; 55: 305-368
        • Yata T.
        • Sano M.
        • Kayama T.
        • Naruse E.
        • Yamamoto N.
        • Inuzuka K.
        • et al.
        Utility of a finger-mounted tissue oximeter with near-infrared spectroscopy to evaluate limb ischemia in patients with peripheral arterial disease.
        Ann Vasc Dis. 2019; 12: 36-43
        • Unno N.
        • Inuzuka K.
        • Sano M.
        • Kayama T.
        • Naruse E.
        • Takeuchi H.
        Target region oxygenation-based endovascular treatment in a chronic limb-threatening ischemia patient with multifocal arterial diseases.
        J Vasc Surg Cases Innov Tech. 2020; 6: 228-232
        • Rao R.
        • Saint-Cyr M.
        • Ma A.M.
        • Bowling M.
        • Hatef D.A.
        • Andrews V.
        • et al.
        Prediction of post-operative necrosis after mastectomy: a pilot study utilizing optical diffusion imaging spectroscopy.
        World J Surg Oncol. 2009; 7: 91
        • Hyttel-Sorensen S.
        • Sorensen L.C.
        • Riera J.
        • Greisen G.
        Tissue oximetry: a comparison of mean values of regional tissue saturation, reproducibility and dynamic range of four NIRS-instruments on the human forearm.
        Biomed Opt Express. 2011; 2: 3047-3057
        • Kagaya Y.
        • Ohura N.
        • Suga H.
        • Eto H.
        • Takushima A.
        • Harii K.
        ‘Real angiosome’ assessment from peripheral tissue perfusion using tissue oxygen saturation foot-mapping in patients with critical limb ischemia.
        Eur J Vasc Endovasc Surg. 2014; 47 (433-44)
        • Kayama T.
        • Sano M.
        • Yata T.
        • Inuzuka K.
        • Katahashi K.
        • Yata T.
        • et al.
        A pilot study investigating the use of regional oxygen saturation as a predictor of ischemic wound healing outcome after endovascular treatment in patients with chronic limb-threatening ischemia.
        Ann Vasc Dis. 2021; 14: 23-30