N-acetyl-L-cysteine depresses cardiac performance in patients with septic shock

Objective: To investigate the effects of adjunctive therapy with parenteral N- Design: Prospective, randomized, double-blind, placebo-controlled study. Setting: Multidisciplinary intensive care unit at a university teaching hospital. Patients: Twenty patients (N-acetyl-L-cysteine group [n = 10], placebo group [n = 10]), 15 male and five female, of mean age 64 +/- 15 (SD) yrs and Acute Physiology and Chronic health Evaluation (APACHE) II score 33 +/- 6, with septic shock within 24 hrs of diagnosis. Interventions: After a 2-hr stabilization period (time-zero minus 2 hrs to time zero), patients received either N-acetyl-L- cysteine in 5% dextrose (150 mg/kg in 100 mL over 15 mins, followed by 50 mg/kg in 250 mL over 4 hrs, and then 100 mg/kg/24 hrs in 500 mL for 44 hrs; N-acetyl L-cysteine group) or the equivalent volume of 5% dextrose (placebo group). Measurements and Main Results: Hemodynamic and oxygen transport indices were measured at time-zero minus 2 hrs and time-zero, and at multiple time points thereafter until completion of the trial infusion (time-zero plus 48 hrs). A daily Organ Failure Scare was recorded for 14 days, Treatment group demographics and hemodynamic variables did not differ significantly between the two groups at time-zero. Mean (SD), pooled mean arterial pressure (MAP), and cardiac index were 75 +/- 15 mm Hg and 3.9 +/- 1.2 L/ min/m(2), respectively, Over the next 48 hrs, in the N-acetyl-L-cysteine group, there was a progressive decrease, relative to both time-zero and the placebo group, in MAP, cardiac index, and left ventricular stroke work index (p <.01, repeated-measures analysis of variance), Percentage reductions in these values relative to the placebo group at 48 hrs were 23%, 18%, and 43%, respectively. Oxygen transport indices, arterial blood gas analyses, Pao(2)/Flo(2) ratio, and shunt did not differ over time between the groups. There was no difference in either daily Organ failure Score over time (p > .01, repeated-measures analysis of variance) or hospital mortality rate (90% N-acetyl-L-cysteine group, 50% placebo group) (p >.1, logistic regression) between the two groups. Conclusion: Adjunctive therapy with N-acetyl-L-cysteine in newly diagnosed septic shock was associated with a depression in cardiovascular performance, as indicated by progressive reductions in cardiac index, left ventricular stroke work index, and MAP.