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. 2020 Jun;9(3):271-283.
doi: 10.21037/hbsn.2020.02.04.

Interpatient heterogeneity in hepatic microvascular blood flow during vascular inflow occlusion (Pringle manoeuvre)

Lucinda Shen  1   2 , Zühre Uz  1   3 , Joanne Verheij  4 , Denise P Veelo  5 , Yasin Ince  1 , Can Ince  1   2 , Thomas M van Gulik  3
Affiliations

Interpatient heterogeneity in hepatic microvascular blood flow during vascular inflow occlusion (Pringle manoeuvre)

Lucinda Shen et al. Hepatobiliary Surg Nutr. 2020 Jun.

Abstract

Background: Vascular inflow occlusion (VIO) during liver resections (Pringle manoeuvre) can be applied to reduce blood loss, however may at the same time, give rise to ischemia-reperfusion injury (IRI). The aim of this study was to assess the characteristics of hepatic microvascular perfusion during VIO in patients undergoing major liver resection.

Methods: Assessment of hepatic microcirculation was performed using a handheld vital microscope (HVM) at the beginning of surgery, end of VIO (20 minutes) and during reperfusion after the termination of VIO. The microcirculatory parameters assessed were: functional capillary density (FCD), microvascular flow index (MFI) and sinusoidal diameter (SinD).

Results: A total of 15 patients underwent VIO; 8 patients showed hepatic microvascular perfusion despite VIO (partial responders) and 7 patients showed complete cessation of hepatic microvascular perfusion (full responders). Functional microvascular parameters and blood flow levels were significantly higher in the partial responders when compared to the full responders during VIO (FCD: 0.84±0.88 vs. 0.00±0.00 mm/mm2, P<0.03, respectively, and MFI: 0.69-0.22 vs. 0.00±0.00, P<0.01, respectively).

Conclusions: An interpatient heterogeneous response in hepatic microvascular blood flow was observed upon VIO. This may explain why clinical strategies to protect the liver against IRI lacked consistency.

Keywords: Liver; microcirculation; perfusion.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/hbsn.2020.02.04). CI developed the Sidestream Dark Field imaging device and is listed as an inventor on the patent which is commercialized by MicroVision Medical under a license from the Amsterdam UMC. He received no royalties nor benefits from this license. He has been a consultant for MicroVision Medical previously, however has not been involved with this company for over 6 years, and holds no shares or stocks. Braedius Medical is a company owned by a relative of CI, which designed and developed the Cytocam-IDF imaging device. CI hold no financial relationship with Braedius Medical, does no hold shares or receive speaker or consultancy fees from the company. CI runs an internet site (www.microcirculationacademy.org) which offers training services that are related to the clinical microcirculation. TM van Gulik serves as an unpaid editorial board member of Hepatobiliary Surgery and Nutrition. The other authors have no conflicts of interest to declare.

Figures

Video 1
Video 1
The hepatic microcirculation of a full responder to VIO.
Video 2
Video 2
The hepatic microcirculation of a partial responder to VIO.
Figure 1
Figure 1
Systemic parameters of the full responders (˜) and partial responder (∇). Data represented as the mean and standard deviation. The observed completed cessation of hepatic microvascular blood flow (i.e., the full responders) at the end of VIO, was accompanied by a significant decrease in the systolic blood pressure and mean arterial pressure. Although no significant differences were observed in the full responders between any timepoints. In the partial responders, termination of VIO was accompanied by a significant decrease in the heart rate, while no other significant differences systemic responses were detected between any timepoints. * = within group one-way ANOVA analysis; *, P<0.002 vs. end of VIO; **, P<0.006 vs. beginning of surgery; ***, P<0.04 vs. beginning of surgery. # = between group unpaired t-test: #, P<0.05. Full responders vs. partial responders. BP, blood pressure; BPM, beats per minute; SpO2, peripheral capillary oxygen saturation; VIO, vascular inflow occlusion.
Figure 2
Figure 2
Hepatic microcirculatory parameters governing convection and flow. All data displayed as mean and standard deviation shown at the beginning of surgery, the end of VIO (20 minutes occlusion time) and within 1-minute following termination of VIO. (A) Functional capillary density. During assessment of the hepatic microcirculation at the end of VIO, perfused micro vessels (i.e., vessels with observable RBC flow) was seen in 8/15 patients; (B) sinusoidal diameter (SinD). The termination of VIO caused a significant increase in the SinD in both full and partial responders; (C) microvascular flow index (MFI). VIO caused a complete cessation of microvascular blood flow in the full responders. However, phenotypes of sluggish, intermittent and continuous blood flow were observed in the partial responders; (D) Percentage of perfused vessel surface. The partial responders showed residual blood flow of up to 10% in the field of view of the analysis screen, whereas the full responders showed complete cessation of microvascular blood flow. * = within group one-way ANOVA analysis; *, P≤0.02 vs. beginning of surgery and termination of VIO; **, P<0.02 vs. Beginning of surgery. # = between group unpaired t-test: #, P<0.03 full responders vs. partial responders. AU, arbitrary units; VIO, vascular inflow occlusion.
Figure 3
Figure 3
Liver function tests of the full responders (˜) and partial responder (∇) shown at timepoints: before surgery (BS), post-operative day (POD) 1, POD 3, POD 5 and POD 7. All values are displayed as the mean and standard deviation. (A) Aspartate aminotransferase (AST); (B) alanine aminotransferase (ALT); (C) alkaline phosphatase (ALP); (D) gamma-glutamyl transferase (GGT); (E) total serum bilirubin (TSB); (F) prothrombin time (PT). * = within group one-way ANOVA analysis: *, P<0.05 vs. BS, POD 3, POD 5 and POD 7; **, P<0.05 vs. POD 1; ***, P<0.05 vs. POD 5, and POD 7; ****, P<0.05 vs. POD 7; *****, P<0.05 vs. POD 5; ******, P<0.05 vs. BS, POD 5 and POD 7. # = between group unpaired t-test: #, P<0.05 full responders vs. partial responders.
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