N-acetylcysteine increases liver blood flow and improves liver function in septic shock patients: results of a prospective, randomized, double-blind study.
OBJECTIVE
In septic shock, decreased splanchnic blood flow is reported, despite adequate systemic hemodynamics. Aacetylcysteine (NAC) was found to increase hepatosplanchnic blood flow in experimental settings. In septic shock patients, NAC improved the clearance of indocyanine green and the relationship of systemic oxygen consumption to oxygen demand. We investigated the influence of NAC on liver blood flow, hepatosplanchnic oxygen transport-related variables, and liver function during early septic shock.


METHODS
Prospective, randomized, double-blind study.


METHODS
Septic shock patients admitted to an interdisciplinary surgical intensive care unit.


METHODS
We examined 60 septic shock patients within 24 hrs after onset of sepsis. They were conventionally resuscitated with volume and inotropes and were in stable condition. A gastric tonometer was inserted into the stomach and a catheter into the hepatic vein. Microsomal liver function was assessed by using the plasma appearance of monoethylglycinexylidide (MEGX).


METHODS
Subjects randomly received either a bolus of 150 mg/kg iv NAC over 15 mins and a subsequent continuous infusion of 12.5 mg/kg/hr NAC over 90 mins (n = 30) or placebo (n = 30).


RESULTS
Measurements were performed before (baseline) and 60 mins after beginning the infusion (infusion). After NAC, a significant increase in absolute liver blood flow index (2.7 vs. 3.3 L/min/m2; p = .01) and cardiac index (5.0 vs. 5.7 L/min/m2; p = .02) was observed. Fractional liver blood flow index (cardiac index-related liver blood flow index) did not change. The difference between arterial and gastric mucosal carbon dioxide tension decreased (p = .05) and MEGX increased (p = .04). Liver blood flow index and MEGX correlated significantly (r(s) = .57; p < or = .01).


CONCLUSIONS
After NAC treatment, hepatosplanchnic flow and function improved and may, therefore, suggest enhanced nutritive blood flow. The increase of liver blood flow index was not caused by redistribution to the hepatosplanchnic area, but by an increase of cardiac index. Because of its correlation with liver blood flow index, MEGX may be helpful in identifying patients who benefit from NAC treatment in early septic shock.
Rank
N
N
Department of Anesthesiology and Operative Intensive Care Medicine, University Hospital Benjamin Franklin, Freie Universität Berlin, Germany.
Michel
C
C
Haertel
C
C
Lenhart
A
A
Welte
M
M
Meier-Hellmann
A
A
Spies
C
C
D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity / Q000187:drug effects; D004396:Coloring Agents / Q000493:pharmacokinetics; D004311:Double-Blind Method; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007208:Indocyanine Green / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects*; D008111:Liver Function Tests; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D011446:Prospective Studies; D012772:Shock, Septic / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology / Q000401:mortality / Q000503:physiopathology; D016019:Survival Analysis
D004396:Coloring Agents; D016166:Free Radical Scavengers; D008012:Lidocaine; C001173:monoethylglycinexylidide; D007208:Indocyanine Green; D000111:Acetylcysteine