A randomized controlled trial on pharmacological preconditioning in liver surgery using a volatile anesthetic.
OBJECTIVE
To evaluate the effects of pharmacological preconditioning with a volatile anesthetic in patients undergoing liver resection with inflow occlusion.


BACKGROUND
In liver surgery, ischemic preconditioning and intermittent clamping are the only established protective strategies to reduce tissue damage due to ischemia during inflow occlusion. Preconditioning with volatile anesthetics has provided protection against cardiac and renal ischemic injury in several animal models through NO and HO-1 pathways. But pharmacological preconditioning has never been tested in patients undergoing liver surgery in a randomized trial.


METHODS
Sixty-four patients undergoing liver surgery with inflow occlusion were randomized intraoperatively for preconditioning with sevoflurane or not (ClinicalTrials.gov NCT00516711). Anesthesia was performed intravenously with propofol. Thirty minutes before inflow occlusion propofol was replaced by sevoflurane in the preconditioning group. Primary endpoint was postoperative liver injury assessed by peak values of liver transaminases. Postoperative complications were recorded according to an established scoring system.


RESULTS
Sevoflurane preconditioning significantly limited the postoperative increase of serum transaminase levels by 261 U/L (95% CI, 65 to 458; P = 0.01) for the ALT and by 239 (95% CI, -2 to 480; P = 0.05) for the AST corresponding to decreases of baseline levels of 35% and 31%, respectively. Patients with steatosis had an even better benefit than patients without steatosis. The rates of any complication (risk ratio 0.46; 95% CI, 0.25 to 0.85; P = 0.006) and of severe complications requiring invasive procedures (risk ratio 0.25; 95% CI, 0.06 to 1.08; P = 0.05) were also lowered by preconditioning.


CONCLUSIONS
This first randomized trial of pharmacological preconditioning in liver surgery in humans showed a protective effect of preconditioning with volatile anesthetics. This strategy may provide a new and easily applicable therapeutic option to protect the liver and to lower complication rates.
Beck-Schimmer
Beatrice
B
Swiss HPB (Hepato-Pancreatico-Biliary) Center, University of Zurich, Zurich, Switzerland.
Breitenstein
Stefan
S
Urech
Severin
S
De Conno
Elisena
E
Wittlinger
Moritz
M
Puhan
Milo
M
Jochum
Wolfram
W
Spahn
Donat R
DR
Graf
Rolf
R
Clavien
Pierre-Alain
PA
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D001219:Aspartate Aminotransferases / Q000097:blood; D015179:Colorectal Neoplasms / Q000473:pathology; D015897:Comorbidity; D004444:Echinococcosis, Hepatic / Q000453:epidemiology / Q000601:surgery; D005234:Fatty Liver / Q000453:epidemiology; D005260:Female; D006498:Hepatectomy / Q000379:methods; D006801:Humans; D019194:Ischemic Preconditioning / Q000379:methods*; D007902:Length of Stay; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000453:epidemiology / Q000556:secondary / Q000601:surgery; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane; D052247:Nitric Oxide Synthase Type II; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase