Effects of remote ischemic conditioning on microcirculatory alterations in patients with sepsis: a single-arm clinical trial

Abstract

Background: Remote ischemic conditioning (RIC) is a promising technique that may protect organs and tissues from the effects of additional ischemic episodes. However, the therapeutic efficacy of RIC in humans with sepsis remains unknown. We hypothesized that RIC might improve sublingual microcirculation in patients with sepsis.

Methods: This prospective single-arm trial was performed in a mixed ICU at a tertiary teaching hospital. We included patients with sepsis or septic shock within 24 h of ICU admission. The RIC procedure comprised 3 cycles of brachial cuff inflation to 200 mmHg for 5 min followed by deflation to 0 mmHg for another 5 min. The procedure took 30 min. RIC was performed at the time of study inclusion and repeated after 12 and 24 h. Sublingual microcirculatory measurements were obtained before and after each RIC procedure using a Cytocam®-incident dark-field (IDF) device (Braedius Medical, Huizen, The Netherlands). The microcirculatory data were compared with a historical control. Data are reported as the medians along with the 25th and 75th percentiles.

Results: Twenty-six septic patients with a median age of 65 (57-81) years were enrolled in this study. The median Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores at admission were 20 (13-23) and 10 (9-12), respectively. All patients were receiving vasopressors. After the 1st RIC procedure, the microvascular flow index (MFI) and the proportion of perfused vessels (PPV) among small vessels were significantly higher than before the procedure, with pre- and post-treatment values of 2.17 (1.81-2.69) and 2.59 (2.21-2.83), respectively, for MFI (p = 0.003) and 87.9 (82.4-93.8) and 92.5 (87.9-96.1) %, respectively, for PPV (p = 0.026). This result was confirmed by comparison with a historical control group. We found no change in microcirculatory flow or density parameters during repeated RIC after 12 h and 24 h.

Conclusion: In patients with sepsis, the first remote ischemic conditioning procedure improved microcirculatory flow, whereas later procedures did not affect sublingual microcirculation. Trial registration NCT04644926, http://www.clinicaltrials.gov . Date of registration: 25 November 2020. Retrospectively registered, https://ichgcp.net/clinical-trials-registry/NCT04644926 .

Keywords: IDF imaging; Microcirculation; Remote ischemic conditioning.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1

Microcirculatory parameters before and after RIC over 24 h. a Microvascular flow index; b proportion of perfused vessels (PPV) of small vessels; c perfused vessel density (PVD) of small vessels; d total vessel density (TVD) of small vessels. *p < 0.05 significant difference before and after remote ischemic conditioning (RIC). #p < 0.05 compared with the historical control

Fig. 2

Correlation of the change in IL-6 after 24 h with a microvascular flow index (MFI) and b proportion of perfused vessels (PPV) of small vessels during the first application of RIC

Fig. 3

Line and scatter plot showing the median (interquartile range) of microcirculatory parameters over 24 h in the RIC and historical control groups. MFI microvascular flow index, PPV proportion of perfused vessels, TVD total vessel density, PVD perfused vessel density. *p < 0.05 compared with the historical control

Fig. 4

Linear regression and Pearson correlation analysis of the basal microvascular flow index (MFI) of small vessels and the change in MFI of small vessels during the first RIC period in the historical control and RIC groups