Pharmacological Modulation of Ischemic-Reperfusion Injury during Pringle Maneuver in Hepatic Surgery. A Prospective Randomized Pilot Study.
The Pringle maneuver, which is performed during liver surgery to reduce blood loss, may result in liver ischemia/reperfusion injury resulting in metabolic, immunological, and microvascular changes, which may lead to hepatocellular damage. The aim of this study was the investigation of the effects of N-acetylcysteine (NAC) and methylprednisolone (MET) in the modulation of liver warm ischemia during hepatic resection.



Forty-eight patients were enrolled in a pilot double-blind, randomized clinical trial. The patients received either NAC, MET, or placebo. The primary endpoint was the reduction in postoperative alanine aminotransferase and bilirubin. The secondary endpoint was the difference in morbidity and mortality.



All the 48 patients had liver resection with no mortality. Morbidity was observed in 8 (16 %) patients equally distributed among the groups. There was a significant favorable recovery of liver function tests in patients treated with NAC or MET compared with the placebo when the Pringle maneuver exceeded 70 min.



The administration of NAC or MET prior to the Pringle maneuver during hepatic resection is associated with lower postoperative aberration in liver function tests compared with placebo when the Pringle maneuver exceeded 70 min. Larger studies are required to validate our findings and to investigate the specific role of NAC and MET in liver surgery.
Department of Hepatobiliary and General Surgery, Humanitas University, Humanitas Research Hospital, Via Manzoni, 56, 20089, Rozzano, Milan, Italy.
Matteo
M
Donadon
Department of Anesthesiology and Intensive Care, Humanitas University, Humanitas Research Hospital, Via Manzoni, 56, 20089, Rozzano, Milan, Italy.
Andrea Forastieri
AF
Molinari
Department of Anesthesiology and Intensive Care, Humanitas University, Humanitas Research Hospital, Via Manzoni, 56, 20089, Rozzano, Milan, Italy.
Francesco
F
Corazzi
Department of Anesthesiology and Intensive Care, Humanitas University, Humanitas Research Hospital, Via Manzoni, 56, 20089, Rozzano, Milan, Italy.
Laura
L
Rocchi
Department of Anesthesiology and Intensive Care, Humanitas University, Humanitas Research Hospital, Via Manzoni, 56, 20089, Rozzano, Milan, Italy.
Paola
P
Zito
Department of Hepatobiliary and General Surgery, Humanitas University, Humanitas Research Hospital, Via Manzoni, 56, 20089, Rozzano, Milan, Italy.
Matteo
M
Cimino
Department of Hepatobiliary and General Surgery, Humanitas University, Humanitas Research Hospital, Via Manzoni, 56, 20089, Rozzano, Milan, Italy.
Guido
G
Costa
Department of Anesthesiology and Intensive Care, Humanitas University, Humanitas Research Hospital, Via Manzoni, 56, 20089, Rozzano, Milan, Italy.
Ferdinando
F
Raimondi
Department of Hepatobiliary and General Surgery, Humanitas University, Humanitas Research Hospital, Via Manzoni, 56, 20089, Rozzano, Milan, Italy. guido.torzilli@humanitas.it.
Guido
G
Torzilli
D000111:Acetylcysteine / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000410:Alanine Transaminase / Q000097:blood; D001663:Bilirubin / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D016166:Free Radical Scavengers; D005938:Glucocorticoids; D006498:Hepatectomy / Q000379:methods*; D006801:Humans; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000601:surgery; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D013525:Surgical Instruments; D014111:Tourniquets; D055815:Young Adult
D016166:Free Radical Scavengers; D005938:Glucocorticoids; D000410:Alanine Transaminase; D001663:Bilirubin; D000111:Acetylcysteine; D008775:Methylprednisolone