Cardiovascular effects of high dose N-acetylcysteine in severe pneumonia-induced sepsis.

Herbert Spapen, Nam NGUYEN Duc, Luc Huyghens

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Cardiovascular effects of high dose N-acetylcysteine treatment in severe pneumonia-induced sepsis.

Background : Hig IV doses of N-acetylcysteine (hNAC) have been used as antioxidant adjuvant treatment in severe sepsis. hNAC is considered safe with optimal efficacy during early sepsis. However, significant cardiac depression and higher mortality was observed during hNAC infusion in a heterogenous group of newly diagnose septic shock patients (1). We assessed hemodynamic effects and safety of hNAC in a distinct population of patients with severe pneumonie-induced sepsis.
Methods : 16 patients with bacteriologically confirmed pneumonia and severe sepzsis were consecutively enrolled. All patients were mechanically ventilated and received routine resuscitation therapy including fluids, dobutamine to maintain cardiac index (CI) > 4 L min-1 m-2 and noradrenaline to maintain mean arterial pressure (MAP) > 65 mm Hg. Patients received either NAC in 5% dextrose (150 mg/kg over 15 min, followed by 50 mg/kg/4h and then 100 mg/kg/24 h ; hNAC group, n = 8) or an equivalent volume of 5% dextrose (placebo group, n = 8). Heart rate (HR), MAP, CI, systemic vascular resistance index (SVRI) and pulmonary capillary wedge pressure (PCWP) were recorded before start of treatment and 4 and 24 h later.
Results : New APACHE II score and age were not different between both treatment groups (respectively 22 + 4 vs 21 + 4 and 67 + 11 vs 56 + 16 yrs ; hNAC vs. placebo, both p > 0.05). Baseline values of all hemodynamic variables were not different betweens groups. At 4 h, hNAC infusion caused a slight but non-significant increase in CI (from 4.7 + 1.3 vs 4.8 + 1.2 to 5.0 + 1.2 vs 4.9 + 1.6 L min-1 m-2 ; hNAC vs. placebo), and a decrease in SVRI. MAP increased in both groups but at higher PCRP in the placebogroup (15 + 3 vs. 19 + 3 ; mmHg hNAC vs. placebo p w 0.05). At 24 h, SVRI returned to baseline in the hNAC group, CI and MAP remained stable within and between treatment groups, but HR significantly fell in the placebo-treated subjects (113 + 16 vs. 96 + 11 b/min ; hNAC vs. placebo, p <0.05). During the study, dobutamine infusion could be more rapidly reduced in the hNAC-treated subjects (from 8.1 + 6.5 to 3.1 + 2.6 µg/kg/min ; p <0.05).
Conclusion : Adjuvant hNAC treatment in severe pneumonia-induced sepsis is not associated with a depression of cardiovascular performance. hNAC better maintains at lower filling pressures and may in facilitate weaning from inotropic support.
Originele taal-2English
Aantal pagina's1
TijdschriftEuropean Respiratory Journal
Volume22
Nummer van het tijdschrift45
StatusPublished - 2003

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