Effect of Remote Ischaemic Preconditioning on Liver Injury in Patients Undergoing Major Hepatectomy for Colorectal Liver Metastasis: A Pilot Randomised Controlled Feasibility Trial

Abstract

Background: Liver resection produces excellent long-term survival for patients with colorectal liver metastases but is associated with significant morbidity and mortality from ischaemia reperfusion injury (IRI). Remote ischaemic preconditioning (RIPC) can reduce the effect of IRI. This pilot randomised controlled trial evaluated RIPC in patients undergoing major hepatectomy at the Royal Free Hospital, London.

Methods: Sixteen patients were randomised to RIPC or sham control. RIPC was induced through three 10-min cycles of alternate ischaemia and reperfusion to the leg. At baseline and immediately post-resection, transaminases and indocyanine green (ICG) clearance were measured.

Findings: The RIPC group had lower ALT and AST levels immediately post-resection (ALT: 43% lower 497 ± 165 vs 889 ± 170 IU/L; p = 0.019 AST: 54% lower 408 ± 166 vs 836 ± 167 IU/L; p = 0.001) and at 24 h (ALT: 41% lower 412 ± 144 vs 698 ± 137 IU/L; p = 0.026 AST: 50% lower 316 ± 116 vs 668 ± 115 IU/L; p = 0.02). ICG clearance was reduced in controls versus RIPC immediately after resection (ICG-PDR: 11.1 ± 1.1 vs 16.5 ± 1.4%/min; p = 0.035).

Conclusions: This pilot study shows that RIPC has potential to reduce liver injury following hepatectomy justifying a prospective RCT powered to demonstrate clinical benefits.

Figures

Fig. 1

Trial protocol

Fig. 2

Randomisation according to the CONSORT guidelines

Fig. 3

a In both groups, serum ALT levels at the end of resection and 24 h post-resection were raised versus baseline. At the end of resection, ALT levels were 43% lower in the RIPC group versus control (p = 0.019) and at 24 h was 41% lower versus control (p = 0.026). b In both groups, serum AST levels at the end of resection and at 24 h post-resection were raised versus baseline. At the end of resection, serum AST levels were 54% lower in the RIPC group versus control (p = 0.001). At 24 h post-resection, serum AST levels were 50% lower in the RIPC group versus control (p = 0.02)

Fig. 4

a ICG-PDR of <15%/min indicates borderline liver function. ICG-PDR at baseline in the two groups was not different, but immediately after liver resection there was a significant difference between the two groups (p = 0.035). b ICG retention of >15% after 15 min [ICG-R 15 (%)] after ICG injection is an indicator of severe liver dysfunction. ICG-R 15 (%) at baseline in the two groups were the same, but immediately after liver resection there was a significant difference between the two groups (p = 0.041)