N-acetylcysteine and cardiac dysfunction in human septic shock

Abstract

Objective: To determine which patients in septic shock may develop myocardial depression during adjuvant therapy with N-acetylcysteine (NAC). Design: Open, interventional study. Setting: Medicosurgical intensive care unit in a university hospital. Subjects: Twelve consecutively enrolled patients with acute pneumonia-induced septic shock. Interventions: Following fluid and catecholamine resuscitation, all patients received NAC as a 150 mg/kg "bolus" over 15 min, followed by a continuous infusion of 50 mg/kg/4 h and 100 mg/kg/16 h. Measurements and main results: Assessment of left ventricular (LV) function by transoesophageal echocardiography and plasma measurements of cardiac troponin I (cTnI) were performed after haemodynamic stabilization and repeated 24 h later. Total plasma NAC amount was measured by HPLC before administration and 0.5, 2, 6 and 24 h post-infusion. Six patients were cTnI-positive (cTnI values exceeding 0.4µg/l) at baseline (mean value 3.8(0.5-12.3)µg/l) and at 24h (mean value 4.7(0.7-17.0)µg/l). All had underlying cardiac disease and echocardiographically documented LV dysfunction. Only one of the six cTnI-negative subjects had LV dysfunction at baseline which resolved after 24 h. Mean plasma NAC levels were consistently higher in cTnI-positive vs.cTnI-negative patients. Values became significant 6 h (268±121 vs. 135±63 mg/l;p = 0.04) and 24 h (126±84 vs. 8±5 mg/l;p = 0.002) after start of infusion. 4 of 6 cTnI-positive but no cTnI-negative patients died in refractory shock within 120 h after the start of NAC administration. Conclusions: NAC metabolism during septic shock is disturbed in patients with underlying cardiac disease. The resulting high plasma NAC concentrations may expose these patients to adverse cardiovascular events. Increased plasma cTnI levels in association with LV dysfunction as assessed by transoesophageal echocardiography may identify patients "at risk".