Metalloproteinase expression after desflurane preconditioning in hepatectomies: A randomized clinical trial

Abstract

BACKGROUND Hepatectomy with inflow occlusion results in ischemia-reperfusion injury; however, pharmacological preconditioning can prevent such injury and optimize the postoperative recovery of hepatectomized patients. The normal inflammatory response after a hepatectomy involves increased expression of metalloproteinases, which may signal pathologic hepatic tissue reformation. AIM To investigate the effect of desflurane preconditioning on these inflammatory indices in patients with inflow occlusion undergoing hepatectomy. METHODS This is a single-center, prospective, randomized controlled trial conducted at the 4 th Department of Surgery of the Medical School of Aristotle University of Thessaloniki, between August 2016 and December 2017. Forty-six patients were randomized to either the desflurane treatment group for pharmacological preconditioning (by replacement of propofol with desflurane, administered 30 min before induction of ischemia) or the control group for standard intravenous propofol. The primary endpoint of expression levels of matrix metalloproteinases and their inhibitors was determined preoperatively and at 30 min posthepatic reperfusion. The secondary endpoints of neutrophil infiltration, coagulation profile, activity of antithrombin III (AT III), protein C (PC), protein S and biochemical markers of liver function were determined for 5 d postoperatively and compared between the groups. RESULTS The desflurane treatment group showed significantly increased levels of tissue inhibitor of metalloproteinases 1 and 2, significantly decreased levels of matrix metalloproteinases 2 and 9, decreased neutrophil infiltration, and less profound changes in the coagulation profile. During the 5-d postoperative period, all patients showed significantly decreased activity of AT III, PC and protein S ( vs baseline values, P < 0.05). The activity of AT III and PC differed significantly between the two groups from postoperative day 1 to postoperative day 5 ( P < 0.05), showing a moderate drop in activity of AT III and PC in the desflurane treatment group and a dramatic drop in the control group. Compared to the control group, the desflurane treatment group also had significantly lower international normalized ratio values on all postoperative days ( P < 0.005) and lower serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase values on postoperative days 2 and 3 ( P < 0.05). Total length of stay was significantly less in the desflurane group ( P = 0.009). CONCLUSION Desflurane preconditioning can lessen the inflammatory response related to ischemia-reperfusion injury and may shorten length of hospitalization.

Repetitive Treatment with Volatile Anesthetics Does Not Affect the In Vivo Plasma Concentration and Composition of Extracellular Vesicles in Rats

“…Even the prolonged repetitive AIP scenario, as presented in this study, is not realistic. Therefore, the available data about preconditioning in clinical scenarios are limited to short 3 min sequences of AIP before and during cardiac surgery, for example [37], or to a replacement of propofol by desflurane at 30 min before the onset of ischemia during hepatectomy, for example, in [38]. Nevertheless, both settings show beneficial effects in reducing the inflammatory response.…”

Possibilities of inhalation anesthetics in blocking an excessive inflammatory response: a review

“…В обеих группах использовалась 1,0-1,5 МАК ингаляционного анестетика. Было выявлено, что десфлуран достоверно больше индуцировал увеличение количества Treg в периферической кро- В аналогичном исследовании изучалось влияние прекондиционирования десфлураном на воспалительные показатели у пациентов, перенесших гепатэктомию [54]. В группу лечения десфлураном (с помощью фармакологического прекондиционирования путем замены пропофола на десфлуран, вводимого за 30 мин до индукции ишемии с минимальной альвеолярной концентра цией, равной 1) были включены 46 пациентов.…”