Effects of N-acetylcysteine on microalbuminuria and organ failure in acute severe sepsis: results of a pilot study. N-Acetylcysteine treatment to prevent the progression of multisystem organ failure: a prospective, randomized, placebo-controlled study. The effect of N-acetylcysteine on oxygen transport and uptake in patients with fulminant hepatic failure. The role of glutathione-S-transferase polymorphisms on clinical outcome of ALI/ARDS patient treated with N-acetylcysteine. Phase II, randomized, controlled trial of high-dose N-acetylcysteine in high-risk cardiac surgery patients. The influence of N-acetyl-L-cystein infusion on cytokine levels and gastric intramucosal pH during severe sepsis. N-acetylcysteine for preventing pump-induced oxidoinflammatory response during cardiopulmonary bypass. Influence of N-acetylcysteine on indirect indicators of tissue oxygenation in septic shock patients: results from a prospective, randomized, double-blind study. Does N-acetyl-L-cysteine influence cytokine response during early human septic shock? [The effect of prophylactically administered n-acetylcysteine on clinical indicators for tissue oxygenation during hyperoxic ventilation in cardiac risk patients]. Effects of intraoperative N-acetylcysteine in orthotopic liver transplantation. Does N-acetylcysteine improve hemodynamics and graft function in liver transplantation? N-acetylcysteine in critically ill patients undergoing contrast-enhanced computed tomography: a randomized trial. N-acetylcysteine pretreatment of cardiac surgery patients influences plasma neutrophil elastase and neutrophil influx in bronchoalveolar lavage fluid. The role of N-acetylcystein administration on the oxidative response of neutrophils during cardiopulmonary bypass. Effect of N-acetylcysteine treatment on oxidative stress and inflammation after severe burn. N-acetylcysteine enhances recovery from acute lung injury in man. A randomized, double-blind, placebo-controlled clinical study. N-acetylcysteine increases liver blood flow and improves liver function in septic shock patients: results of a prospective, randomized, double-blind study. N-acetylcysteine for the prevention of kidney injury in abdominal aortic surgery: a randomized, double-blind, placebo-controlled trial. Treatment with N-acetylcysteine during acute respiratory distress syndrome: a randomized, double-blind, placebo-controlled clinical study. N-acetylcysteine for the prevention of postoperative atrial fibrillation: a prospective, randomized, placebo-controlled pilot study. Effects of N-acetylcysteine on pulmonary function in patients undergoing coronary artery bypass surgery with cardiopulmonary bypass. Lack of effect of prophylactic N-acetylcysteine on postoperative organ dysfunction following major abdominal tumour surgery: a randomized, placebo-controlled, double-blinded clinical trial. Lack of renoprotective effect of i.v. N-acetylcysteine in patients with chronic renal failure undergoing cardiac surgery. A trial of antioxidants N-acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group. Effect of intravenous N-acetylcysteine on outcomes after coronary artery bypass surgery: a randomized, double-blind, placebo-controlled clinical trial. N-acetyl-L-cysteine depresses cardiac performance in patients with septic shock. N-acetylcysteine as adjunctive treatment in severe malaria: a randomized, double-blinded placebo-controlled clinical trial. Lack of protection of N-acetylcysteine (NAC) in acute renal failure related to elective aortic aneurysm repair-a randomized controlled trial. Antioxidant treatment with N-acetylcysteine during adult respiratory distress syndrome: a prospective, randomized, placebo-controlled study. N-acetylcysteine prevents reactive oxygen species-mediated myocardial stress in patients undergoing cardiac surgery: results of a randomized, double-blind, placebo-controlled clinical trial. Effects of intravenous N-acetylcysteine on periprocedural myocardial injury after on-pump coronary artery by-pass grafting. Protective effects of N-acetylcysteine and rutin on the lipid peroxidation of the lung epithelium during the adult respiratory distress syndrome. Effects of N-acetylcysteine on myocardial ischemia-reperfusion injury in bypass surgery. N-acetylcysteine does not prevent hepatorenal ischaemia-reperfusion injury in patients undergoing orthotopic liver transplantation. Perioperative N-acetylcysteine to prevent renal dysfunction in high-risk patients undergoing cabg surgery: a randomized controlled trial. N-acetylcysteine for prevention of acute renal failure in patients with chronic renal insufficiency undergoing cardiac surgery: a prospective, randomized, clinical trial. N-acetylcysteine for preventing acute kidney injury in cardiac surgery patients with pre-existing moderate renal insufficiency. Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial. The effect of N-acetylcysteine on nuclear factor-kappa B activation, interleukin-6, interleukin-8, and intercellular adhesion molecule-1 expression in patients with sepsis. Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure.
The level of microalbuminuria is thought to reflect the severity of inflammation-induced systemic vascular permeability and may have prognostic value with regard to organ dysfunction and survival. N-acetylcysteine (NAC) has been shown to decrease capillary leakage in experimental sepsis. The present study investigated the effect of early treatment with NAC on microalbuminuria and organ dysfunction in severe clinical sepsis.
                Prospective, randomized, placebo-controlled study.
                A 24-bed multidisciplinary ICU in a university teaching hospital.
                Thirty-five patients included within 4 h of fulfilling consensus criteria of severe sepsis.
                Patients were randomly assigned to receive either NAC (continuous infusion starting with 50 mg/kg/4 h followed by 100 mg/kg/24 h for 44 h; n = 18) or placebo (n = 17) in addition to standard therapy.
                Urine samples for measurement of microalbuminuria/creatinine ratio (MACR) were collected on inclusion and after 4 h, 24 h, and 48 h. Severity of illness and degree of organ failure were determined by using, respectively, the APACHE (acute physiology and chronic health evaluation) II score and the sequential organ failure assessment (SOFA) score. The MACR did not differ over time between the placebo- and the NAC-treated groups. SOFA scores were comparable between both treatment groups at baseline (6.2 +/- 3.9 vs 6.5 +/- 2.7, NAC vs placebo; p = 0.6) and increased during treatment in the NAC-treated patients but not in the placebo group (7.9 +/- 3.7 vs 5.9 +/- 2.5, p = 0.09 and 7.7 +/- 3.8 vs 5.1 +/- 2.1, p < 0.05; NAC vs placebo, respectively, at 24 h and at 48 h). The cardiovascular SOFA score progressively increased during NAC treatment, reaching higher values as compared to time-matched scores in the placebo group.
                Early NAC administration does not influence the course of MACR in severe clinical sepsis, suggesting that NAC might not attenuate endothelial damage in this condition. NAC treatment even aggravated sepsis-induced organ failure, in particular cardiovascular failure. To investigate whether prolonged infusion of N-acetylcysteine (NAC) that is commenced immediately after admission to the intensive care unit could ameliorate the development or progression of multisystem organ failure and improve mortality.
                Prospective, randomized, double-blinded clinical trial.
                Six-bed intensive care unit in a teaching hospital.
                Of the 100 patients recruited (14 withdrew), 86 patients were studied.
                After randomization, the treatment group (n = 41) received NAC (150 mg/kg bolus followed by a continuous infusion of 12 mg/kg/hr) and the placebo group (n = 45) received 5% dextrose, from a minimum of 3 days up to a maximum of 5 days.
                There was no statistically significant difference between the two groups regarding outcome as indicated by mortality and the required days of inotropic support, mechanical ventilation, and intensive care. The time interval between hospital and intensive care unit admission showed great variability, with a median of 24 hrs for the whole sample. By splitting the groups with this median value, the effect of NAC was examined on patients admitted within 24 hrs and after 24 hrs of arrival to the hospital. There was a nonsignificant difference in mortality in favor of NAC. Patients admitted after 24 hrs of hospital admission had a significantly worse mortality in the NAC-treated group (61% vs. 32% for controls; p = .05).
                We found a nonsignificant difference in outcome between NAC and placebo-treated patients. Our results suggest that the initiation of NAC treatment >24 hrs after hospital admission may potentially be harmful, and further studies should be undertaken to investigate the clinical use of the early application of NAC in critically ill patients. We have investigated the effect of N-acetylcysteine on hemodynamic variables, oxygen delivery (DO2), oxygen consumption (VO2), and oxygen extraction in patients with fulminant hepatic failure using independent methods of determining DO2 and VO2, thereby eliminating the effect of mathematical coupling, which may have biased previous studies. In 11 patients with severe fulminant hepatic failure, we documented the hemodynamic effects of N-acetylcysteine during the first 5 hours of a standard infusion regime and simultaneously measured VO2 using a method based on respiratory gas analysis. We related physiological changes to plasma N-acetylcysteine concentrations, and compared this group with 7 patients who received placebo infusions. A variable hemodynamic response to N-acetylcysteine was observed that did not differ significantly in comparison with the placebo group, and did not correlate with plasma drug concentrations. The most significant relationship observed between DO2 and VO2 in any patient predicted a 13-mL x min(-1) x m(-2) increase in VO2 when DO2 increased by 100 mL x min(-1) x m(-2); in 8 patients, VO2 was independent of DO2 over the range observed. In the group that received N-acetylcysteine, a small (mean 6 [SD 6] mL x min(-1) x m[-2]) increase in VO2 occurred in comparison with baseline after 1 hour of infusion (P < .01), but changes were not significantly different from the placebo group and were not sustained. N-Acetylcysteine infusion did not increase oxygen extraction or result in an improvement in whole-blood lactate levels or base excess during the study period. We conclude that N-acetylcysteine infusion does not result in clinically relevant improvements in global VO2, or in clinical markers of tissue hypoxia in patients with severe fulminant hepatic failure. Oxidative stress has a proven role in pathophysiology of acute respiratory distress syndrome. The antioxidant drugs, especially N-acetylcysteine (NAC) have been used for years to overcome oxidative stress effects in patients. In the present study we have investigated the effects of NAC treatment (IV NAC in 150mg/kg at the first day followed by 50mg/kg/day for three days) on 27 ICU patients with ALI/ARDS considering the glutathione-S-transferase genetic variations, as an important enzyme contributing in oxidative stress pathways. The results indicated that NAC improved oxygenation (increase in PaO(2)/FiO(2)) and decreased mortality rate in treated patients compared to control group (p<0.05). Evaluation of three isoforms of glutathione-S-transferase (GST M1, P1 and T1), in these patients have showed an association between GST M1 null, and GST M1 and T1 double null polymorphisms with increased mortality in control group, suggesting antioxidant therapy critical for this group of patients. To assess the effect of high-dose N-acetylcysteine on renal function in cardiac surgery patients at higher risk of postoperative renal failure.
                Multiblind, placebo-controlled, randomized, phase II clinical trial.
                Operating rooms and intensive care units of two tertiary referral hospitals.
                A total of 60 cardiac surgery patients at higher risk of postoperative renal failure.
                Patients were allocated to either 24 hrs of high-dose N-acetylcysteine infusion (300 mg/kg body weight in 5% glucose, 1.7 L) or placebo (5% glucose, 1.7 L).
                The primary outcome measure was the absolute change in serum creatinine from baseline to peak value within the first five postoperative days. Secondary outcomes included the relative change in serum creatinine, peak serum creatinine level, serum cystatin C, and in urinary output. Further outcomes were needed for renal replacement therapy, length of ventilation, and length of stay in the intensive care unit and hospital. Randomization was successful and patients were well balanced for preoperative and intraoperative characteristics. There was no significant attenuation in the increase in serum creatinine from baseline to peak when comparing N-acetylcysteine with placebo (64.5 +/- 91.2 and 38.0 +/- 42.4 mumol/L, respectively; p = .15). Also, there was no attenuation in the increase in serum cystatin C from baseline to peak for N-acetylcysteine compared with placebo (0.45 +/- 0.43 and 0.30 +/- 0.33 mg/L, respectively; p = .40). Likewise, there was no evidence for differences in any other clinical outcome.
                In this phase II, randomized, controlled trial, high-dose N-acetylcysteine was no more effective than placebo in attenuating cardiopulmonary bypass-related acute renal failure in high-risk cardiac surgery patients. The purpose of the present study was to evaluate the effects of continuously infused N-acetyl-L-cystein (NAC) on serum cytokine levels and gastric intramucosal pH in humans suffering from severe sepsis.
                Fifty-three patients were included in the study. In the NAC group (n = 27), after an initial intravenous bolus of NAC (150 mg/kg over 5 min), a continuous intravenous infusion of 12.5 mg/kg per hour was given for 6 hours. Patients in the control group (n = 26) were administered dextrose (5% solution) at the same dosage. We recorded the following: haemodynamic parameters, nasopharyngeal temperature, arterial blood gas changes, plasma cytokine levels, biochemical parameters, intramucosal pH, length of stay in the intensive care unit, duration of of mechanical ventilation and mortality. All measurements were taken at baseline (15 min before the start of the study) and were repeated immediately after the bolus infusion, and at 24 and 48 hours after initiation of the continuous NAC infusion.
                No differences were found between groups in levels of the major cytokines, duration of ventilation and intensive care unit stay, gastric intramucosal pH and arterial oxygen tension/inspired fractional oxygen ratio (P > 0.05).
                We found that NAC infusion at the doses given did not affect cytokine levels, outcomes, or gastric intramucosal pH in patients with severe sepsis. Because of the limited number of patients included in the study and the short period of observation, our findings need confirmation in larger clinical trials of NAC infused in a dose-titrated manner. However, our results do not support the use of NAC in patients with severe sepsis. To investigate the effect of N-acetylcysteine on preventing pump-induced oxidoinflammatory response during cardiopulmonary bypass (CPB).
                Forty patients undergoing coronary artery bypass grafting (CABG) were randomly divided into a study group (n = 20), given 50 mg kg(-1) N-acetylcysteine intravenously for 3 days, and a control group (n = 20) given saline. Serum samples were collected for measurement of myeloperoxidase (MPO), malondialdehyde (MDA), interleukin-6, Alpha1-acid glycoprotein (AAGP), and C-reactive protein (CRP) during surgery and postoperatively.
                The MPO and MDA values showed a similar pattern during and after CPB in the study group, with significantly less variance than in the control group. Interleukin-6 showed similar patterns in the two groups, but the data from 30 min after the start of CPB and from 6 h post-CPB were significantly different. The AAGP and CRP values were both elevated during CPB in the two groups without a significant difference, but 6 and 24 h post-CPB, the values were significantly higher in the control group than in the study group.
                N-Acetylcysteine decreased pump-induced oxidoinflammatory response during CPB, suggesting that it could be a novel therapy for assisting in the prevention of CBP-induced oxidoinflammatory damage. Deactivation of endothelium-derived relaxing factor due to an increased oxygen radical load during sepsis may contribute to an impairment in microcirculatory blood flow. We investigated whether treatment with the sulfhydryl donor and oxygen radical scavenger, N-acetylcysteine, would improve whole-body oxygen consumption (VO2), gastric intramucosal pH, and veno-arterial CO2 gradient (veno-arterial PCO2) during septic shock.
                Prospective, randomized, double-blind study conducted over 2 yrs.
                Septic shock patients admitted to the intensive care unit.
                Fifty-eight patients requiring hemodynamic monitoring (radial and pulmonary artery catheters) due to septic shock, were included in this study. All patients were examined within 72 hrs after the onset of sepsis. They were optimally resuscitated by conventional means with volume and inotropic agents, and exhibited stable clinical conditions (hemodynamic values, body temperature, hemoglobin, FIO2).
                A gastric tonometer was inserted to measure the gastric intramucosal pH. Subjects randomly received either 150 mg/kg of intravenous N-acetylcysteine or placebo over a 15-min period, then a continuous infusion of 12.5 mg/hr of N-acetylcysteine or placebo over approximately 90 mins.
                Infusion measurements were begun 60 mins after the beginning of infusion and lasted approximately 30 mins. The infusion was then discontinued and 2 hrs later the final measurements were taken.
                Basic patient characteristics (age, sex, Acute Physiology and Chronic Health Evaluation [APACHE] II scores, Multiple Organ Failure scores) did not differ significantly, nor did pre- and 2-hr postinfusion measurements differ between any of the groups. Thirteen (45%) patients responded (i.e., showed an increase in VO2 > 10%, reaching a mean of 19%) to the N-acetylcysteine infusion. The N-acetylcysteine responders also showed an increase in gastric intramucosal pH, a decrease in veno-arterial PCO2, an increase in oxygen delivery, cardiac index, stroke index, and left ventricular stroke work index, as well as a significant decrease in systemic vascular resistance in comparison to baseline. The N-acetylcysteine nonresponders, as well as the patients in the placebo group, did not show any significant changes in any of these variables. The N-acetylcysteine responders had a higher survival rate (69%) than the non-responders (19%) and were studied earlier after onset of sepsis (37 hrs) than the nonresponders (61 hrs). The only significant difference between the entire N-acetylcysteine group (which included responders plus nonresponders) and the placebo group was an increased VO2 in the entire N-acetylcysteine group during infusion measurements.
                N-acetylcysteine provided a transient improvement in tissue oxygenation in about half of the septic shock patients, as indicated by an increase in VO2 and gastric intramucosal pH and a decrease in veno-arterial PCO2. The higher survival rate in the N-acetylcysteine responders and the fact that half of the patients receiving N-acetylcysteine did not respond, suggests that, in some patients, sepsis irreversibly damages the microvasculature to the extent that N-acetylcysteine has no effect. If analyzed by intention to treat, the N-acetylcysteine did not produce effects that were significantly different from the placebo. Whether the N-acetylcysteine challenge was merely diagnostic or whether N-acetylcysteine can be effective in the treatment of sepsis deserves further investigation. To assess the effects of adjunctive treatment with N-acetyl-L-cysteine (NAC) on hemodynamics, oxygen transport variables, and plasma levels of cytokines in patients with septic shock.
                Prospective, randomized, double-blind, placebo-controlled study.
                A 24-bed medicosurgical ICU in a university hospital.
                Twenty-two patients included within 4 h of diagnosis of septic shock.
                Patients were randomly allocated to receive either NAC (150 mg/kg bolus, followed by a continuous infusion of 50 mg/kg over 4 h; n= 12) or placebo (n=10) in addition to standard therapy.
                Plasma concentrations of tumor necrosis factor-alpha (TNF), interleukin (IL)-6, IL-8, IL-10, and soluble tumor necrosis factor-alpha receptor-p55 (sTNFR-p55) were measured by sensitive immunoassays at 0, 2, 4, 6 and 24 h. Pulmonary artery catheter-derived hemodynamics, blood gases, hemoglobin, and arterial lactate were measured at baseline, after infusion (4 h), and at 24 h.
                NAC improved oxygenation (PaO2/FIO2 ratio, 214+/-97 vs 123+/-86; p<0.05) and static lung compliance (44+/-11 vs 31+/-6 L/cm H2O; p<0.05) at 24 h. NAC had no significant effects on plasma TNF, IL-6, or IL-10 levels, but acutely decreased IL-8 and sTNFR-p55 levels. The administration of NAC had no significant effect on systemic and pulmonary hemodynamics, oxygen delivery, and oxygen consumption. Mortality was similar in both groups (control, 40%; NAC, 42%) but survivors who received NAC had shorter ventilator requirement (7+/-2 days vs 20+/-7 days; p<0.05) and were discharged earlier from the ICU (13+/-2 days vs 32+/-9 days; p<0.05).
                In this small cohort of patients with early septic shock, short-term IV infusion of NAC was well-tolerated, improved respiratory function, and shortened ICU stay in survivors. The attenuated production of IL-8, a potential mediator of septic lung injury, may have contributed to the lung-protective effects of NAC. Hyperoxic ventilation, used to prevent hypoxia during potential periods of hypoventilation, has been reported to paradoxically decrease whole-body oxygen consumption (VO2). Reduction in nutritive blood flow due to oxygen radical production is one possible mechanism. We investigated whether pretreatment with the sulfhydryl group donor and O2 radical scavenger N-acetylcysteine (NAC) would preserve VO2 and other clinical indicators of tissue oxygenation in cardiac risk patients.
                Thirty patients, requiring hemodynamic monitoring (radial and pulmonary artery catheters) because of cardiac risk factors, were included in this randomized investigation. All patients exhibited stable clinical conditions (hemodynamics, body temperature, hemoglobin, F1O2 < 0.5). Cardiac output was determined by thermodilution and VO2 by cardiovascular Fick. After baseline measurements, patients randomly received either 150 mg kg-1 NAC (n = 15) or placebo (n = 15) in 250 ml 5% dextrose i.v. over a period of 30 min. Measurements were repeated 30 min after starting NAC or placebo infusion, 30 min after starting hyperoxia (F1O2 = 1.0), and 30 min after resetting the original F1O2.
                There were no significant differences between groups in any of the measurements before treatment and after the return to baseline F1O2 at the end of the study, respectively. NAC, but not placebo infusion, caused a slight but not significant increase in cardiac index (CI), left ventricular stroke work index (LVSWI) and a decrease in systemic vascular resistance. Significant differences between groups during hyperoxia were: VO2 (NAC: 108 +/- 38 ml min-1m-2 vs placebo: 79 +/- 22 ml min-1m-2; P < or = 0.05), CI (NAC: 4.6 +/- 1.0 vs placebo: 3.7 +/- 1.11 min-1m-2; P < or = 0.05) and LVSWI (NAC: 47 +/- 12 vs placebo: 38 +/- 9; P < or = 0.05). The mean decrease of VO2 was 22% in the NAC group vs 47% in the placebo group (P < or = 0.05) and the mean difference between groups in venoarterial carbon dioxide gradient (PvaCO2) was 14% (P < or = 0.05). ST segment depression ( > 0.2 mV) was significantly less marked in the NAC group (NAC: -0.02 +/- 0.17 vs placebo: -0.23 +/- 0.15; P < or = 0.05).
                NAC helped preserve VO2, oxygen delivery, CI, LVSWI and PvaCO2 during brief hyperoxia in cardiac risk patients. Clinical signs of myocardial ischemia did not occur such as ST-depression if patients were prophylactically treated with NAC. This suggests that pretreatment with NAC could be considered to attenuate impaired tissue oxygenation and to preserve myocardial performance better in cardiac risk patients during hyperoxia. N-acetylcysteine (NAC) is an antioxidant agent which has been shown to benefit patients with fulminant hepatic failure. We have examined its effect in patients with chronic liver disease undergoing orthotopic liver transplantation by giving NAC during operation. In a prospective, randomized, double-blind, placebo-controlled study of 50 patients, NAC appeared to induce mild vasodilatation, improve oxygen delivery and consumption, and reduce base deficit, but data interpretation was difficult. There were no significant effects on mortality, morbidity or postoperative graft function. The release of toxic oxidative free radicals induced by ischemia and reperfusion may jeopardize liver graft function. N-acetylcysteine (NAC) has shown protective effects on hypothermic and warm ischemia reperfusion liver injury in animals. NAC improves hemodynamics and survival rates in patients with fulminant hepatic failure. The aim of this study was to investigate whether intraoperative treatment with NAC would improve hemodynamics and postoperative graft function in liver transplantation. Sixty patients with chronic end-stage liver disease were included in a prospective randomized placebo-controlled study. NAC or the same volume of 5% glucose was started during the anhepatic phase. Hemodynamic data and calculated tissue oxygenation parameters were compared throughout the procedure. Postoperative graft function was assessed by measurements of aminotransferases, prothrombin time, and monoethylglycinexylidide test over the 3 first postoperative days. Patient demographics were similar before the infusion of NAC or glucose. Hemodynamic parameters, oxygen consumption, oxygen delivery, oxygen extraction ratio, and lactates were not different throughout the procedure. One hour after the revascularization of the hepatic artery, the oxygen extraction ratio by the liver was similar (17% +/- 7.6% v 17% +/- 6.2%) in both groups. Postoperative graft function was comparable within the 3 first postoperative days. This study failed to show any beneficial effect of the intraoperative administration of NAC on hemodynamics and graft function in liver transplantation in patients with chronic liver disease. nan Study of leukocyte activation and release of toxic mediators during extracorporeal circulation (ECC). ECC can be used to study the potential protective effect of a pharmacon against neutrophil-mediated lung injury. Clinical studies have indicated that N-acetylcysteine (NAC) may improve systemic oxygenation and reduce the need for ventilatory support when given to patients with acute lung injury.
                Cardiac surgery patients were pretreated with high-dose NAC in order to assess the potential role of NAC to interfere with neutrophil-mediated inflammation and lung injury.
                18 patients who underwent ECC: group 1 (n = 8) no premedication (only placebo); group 2 (n = 10) NAC (72 mg/kg i.v. as a bolus, later 72 mg/kg over 12 h).
                In group 2, the partial pressure of oxygen in arterial blood/fractional inspired oxygen 4 h after surgery was significantly higher than in group 1 (213 +/- 31 vs 123 +/- 22; p = 0.044). NAC pretreatment prevented an increase in plasma neutrophil elastase activity (18.9 +/- 6.9 vs 49.9 +/- 5.6 ng/ml in group 1 at the end of ECC; p = 0.027). Release of myeloperoxidase (MPO) was not affected (group 1:1105 +/- 225 ng/ml vs group 2:1127 +/- 81 at the end of ECC; p = 0.63). At the end of ECC, total antigenic human neutrophil elastase (group 1:671 +/- 72 ng/ml vs group 2:579 +/- 134; p = 0.37) and complex formation between elastase and alpha 1-proteinase inhibitor were no different in the two groups. There were no significant difference in cellular composition and mediators in the lavage fluid, although values for total number of neutrophils, elastase, MPO and interleukin-8 were lower in group 2.
                Pretreatment with NAC may prevent lung injury by diminishing elastase activity. Since the release of mediators, especially MPO, is not affected, this diminished activity of elastase may be achieved by enhanced inactivation by antiproteases after initial treatment. The role of N-acetylcystein (NAC) administration on the oxidative response of neutrophils during cardiopulmonary bypass (CPB) was evaluated in a double-blind study. Twenty-four adult patients undergoing coronary artery bypass were included in the study. Twelve patients received NAC as a bolus of 100 mg/kg followed by a continuous infusion of 20 mg/kg/h in the bypass circuit from the beginning to the end of bypass. A further 12 patients received placebo. Citrated blood samples for measurement of oxidative burst response of neutrophils were obtained at different time points during bypass. The oxidative burst response of neutrophils in the patients receiving NAC was significantly low at all times during bypass. Based on these findings NAC appears to act as an oxygen free radical scavenger during open-heart surgery. Oxidative stress and inflammation generate edema in burns. The aim of our study was to assess effect of N-acetylcysteine (NAC) on oxidative stress, inflammation, fluid requirement, multiple organ dysfunction (MOD) score and vasoactive drug requirement. In this study 15 patients were on standard therapy, whereas for other 15 patients NAC was supplemented. Blood samples were taken on admission and on the next five consecutive mornings. Levels of malondialdehyde, protein sulfhydril (PSH) groups, reduced gluthation (GSH), activity of myeloperoxidase, catalase and superoxide dismutase enzymes and induced free radical generating capacity were measured as well as concentrations of TNF-α, IL-6, IL-8, and IL-10. MOD score, use of vasopressor agents and fluid utilisation were recorded daily. NAC treatment increased GSH level on days 4-5 (p<0.05) and PSH level on days 2-6 (p<0.05) compared to controls. Plasma IL-6 was lower on days 4-5 (p<0.05), IL-8 on days 4-6 (p<0.05) and IL-10 on days 4-6 (p<0.05) in NAC group. NAC group received less catecholamines than controls (p<0.01) from day 4 without significant differences in MOD score. NAC treatment is associated with a diminished oxidative stress reflected in preserved antioxidant levels, lower inflammation mirrored in lower interleukin levels and less vasopressor requirement.
                Copyright Â© 2011 Elsevier Ltd and ISBI. All rights reserved. To determine the effects of intravenous N-acetylcysteine (NAC) on the development of severe adult respiratory distress syndrome (ARDS) and mortality rate in patients with mild-to-moderate acute lung injury and to analyze the duration of ventilatory support and FIO2 required as well as the evolution of the lung injury score.
                Three university hospital ICUs and one regional ICU in Switzerland.
                Sixty-one adult patients presenting with mild-to-moderate acute lung injury and various predisposing factors for ARDS received either NAC, 40 mg/kg/d, or placebo intravenously for 3 days.
                Respiratory dysfunction was assessed daily according to the need for mechanical ventilation and FIO2, the evolution of the lung injury score, and the PaO2/FIO2 ratio. The cardiovascular state, liver function, and kidney function were also monitored. Data were collected at admission (day 0), during the first 3 days, and on the day of discharge from the ICU.
                The NAC and placebo groups (32 and 29 patients, respectively) were comparable at ICU admission for severity of illness assessed by the simplified acute physiology score (SAPS) (10.8 +/- 4.6 vs 10.9 +/- 4.8) and lung injury score (LIS) (1.39 +/- 0.95 vs 1.11 +/- 1.08) (mean +/- SD). Three patients in each group developed ARDS. The 1-month mortality rate was 22 percent for the NAC group and 35 percent for the placebo group (difference not statistically significant). At admission, 22 of 32 patients (69 percent) in the NAC group were mechanically ventilated compared with 22 of 29 (76 percent) in the placebo group. At the end of the treatment period (day 3), 5 of 29 (17 percent) in the NAC group and 12 of 25 (48 percent) in the placebo group were still receiving ventilatory support (p = 0.01), The FIO2 was 0.37 less than admission value (day 0) in the NAC group, and 0.20 less in the placebo group (p < 0.04); the oxygenation index (PaO2/FIO2) improved significantly (p < 0.05) from day 0 to day 3 only in the NAC-treated group. The LIS showed a significant regression (p = 0.003) in the NAC-treated group during the first 10 days of treatment: no change was observed in the placebo group. No adverse effects were observed during the treatment with NAC.
                Intravenous NAC treatment during 72 h improved systemic oxygenation and reduced the need for ventilatory support in patients presenting with mild-to-moderate acute lung injury subsequent to a variety of underlying diseases. Development of ARDS and mortality were not reduced significantly by this therapy. 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.
                Prospective, randomized, double-blind study.
                Septic shock patients admitted to an interdisciplinary surgical intensive care unit.
                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).
                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).
                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).
                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. In this prospective, randomized, placebo-controlled, double-blind trial we studied the effects of IV N-acetylcysteine for prevention of renal injury in patients undergoing abdominal aortic surgery. Seventy patients without previously documented renal dysfunction were randomly allocated to receive either N-acetylcysteine (150 mg/kg mixed in 250 mL of 5% dextrose infused in 20 min, followed by an infusion of 150 mg/kg in 250 mL of 5% dextrose over 24 h) or placebo. The infusion was started after the induction of anesthesia. The primary outcome measure was renal injury as measured by the increases in urinary N-acetyl-beta-d-glucosaminidase (NAG)/creatinine ratio (indicator of renal tubular injury) and urinary albumin/creatinine ratio (indicator of glomerular injury). Renal function was assessed by measuring plasma creatinine and serum cystatin C concentrations. The urinary NAG/creatinine ratio increased significantly from baseline to before crossclamp and remained increased on day 5 in both groups. The urinary albumin/creatinine ratio increased significantly from baseline to 6 h after declamping in the N-acetylcysteine group. However, the changes in the NAG/creatinine ratio and the albumin/creatinine ratio were not significantly different between the two groups. Plasma creatinine and serum cystatin C values remained unchanged during the study period in both groups. In conclusion, N-acetylcysteine did not offer any significant protection from renal injury during elective aortic operation in patients with normal preoperative renal function, and some degree of tubular injury seems to occur before aortic crossclamp. Intravenous N-acetylcysteine (NAC) has been reported to improve systemic oxygenation and reduce the need for ventilatory support in patients with an acute lung injury. In the more serious form, namely established adult respiratory distress syndrome (ARDS) (PaO2/FIO2 < or = 200 mm Hg), we tested the hypothesis that treatment with intravenous NAC may be beneficial.
                Respiratory dysfunction was graded daily according to the need for mechanical ventilation and FIO2 and to the evolution of the lung injury score (LIS) and the PaO2/FIO2 ratio in 42 patients with established ARDS receiving either NAC 190 mg/kg/day or placebo as a continuous intravenous infusion over the first 3 days of their clinical course.
                NAC and placebo groups (22 and 20 patients, respectively) were comparable for demographic characteristics, ARDS categories, severity of illness (simplified acute physiology score [SAPS II]) LIS and PaO2/FIO2 ratio. Mortality rate was 32% for the NAC and 25% for the placebo group (difference not significant). At admission (day 1), 91% of patients in the NAC and 95% in the placebo group required ventilatory support; at days 2, 3, 5, and 7 after admission, the percentage of patients receiving ventilatory support was not significantly reduced for both groups in comparison with day 1. Moreover, there were no differences between the two groups at the same observation days. In both groups, the FIO2 was significantly lower and the PaO2/FIO2 ratio was significantly higher than the initial values during the evolution (FiO2 at day 3, P < .01 for NAC and P < .05 for placebo; PaO2/FIO2 at day 3: P < .01 for NAC and P < .02 for placebo), but this improvement was similar for both groups and, moreover, the between-group comparison was never significantly different at the various collection days. The LIS decreased significantly in NAC group between days 1 and 3 (2.23 +/- 0.62 v 1.76 +/- 0.17; P < .05), whereas no changes were observed in the placebo group; at day 5, there was a significant difference between the two groups (1.53 +/- 0.21 for the NAC v 2.15 +/- 0.19 for the placebo group; P < .05). In the prevalent sepsis category (10 patients in the NAC and 9 in the placebo group), the mortality rate, the need of ventilatory support, the intensive care unit stay, and the PaO2/FIO2 evolution did not differ significantly in both subgroups.
                In this relatively small group of patients presenting with an established ARDS subsequent to a variety of underlying diseases, intravenous NAC treatment during 72 hours neither improved systemic oxygenation nor reduced the need for ventilatory support. Oxidative stress has recently been implicated in the pathophysiology of atrial fibrillation (AF). The aim of the present study was to evaluate the effects of antioxidant agent N-acetylcysteine (NAC) on postoperative AF.
                The population of this prospective, randomized, double-blind, placebo-controlled study consisted of 115 patients undergoing coronary artery bypass and/or valve surgery. All the patients were treated with standard medical therapy and were randomized to NAC group (n = 58) or placebo (saline, n = 57). An AF episode >5 min during hospitalization was accepted as endpoint. During follow-up period, 15 patients (15/115, 13%) had AF. The rate of AF was lower in NAC group compared with placebo group (three patients in NAC group [5.2%] and 12 patients in placebo group [21.1%] had postoperative AF; odds ratio [OR] 0.20; 95% confidence interval [CI] 0.05 to 0.77; P = 0.019). In the multivariable logistic regression analysis, independent predictors of postoperative AF were left atrial diameter (OR, 1.18; 95% CI, 1.06-1.31; P = 0.002) and the use of NAC (OR, 0.20; 95% CI, 0.04-0.91; P = 0.038).
                The result of this study indicates that NAC treatment decreases the incidence of postoperative AF. Cardiopulmonary bypass (CPB) has been implicated in causing poor pulmonary gas exchange postoperatively in patients undergoing coronary artery bypass grafting (CABG) procedures. In this prospective, randomized, double-blind, placebo-controlled study, we examined the pulmonary effects of N-acetylcysteine (NAC) in patients undergoing CABG. Twenty patients undergoing elective CABG and early tracheal extubation were randomized into two groups. Group I (ten patients) received a physiologic salt solution as a placebo in a continuous intravenous infusion for one hour before CPB and 24 hours after CPB; Group II (ten patients) received 100 mg/ kg NAC intravenously for one hour before CPB and 40 mg/kg/day at 24 hours after CPB. Perioperative hemodynamic and pulmonary data were recorded. Postoperative tracheal extubation was accomplished at the earliest appropriate time. The postoperative clinical course was similar in the two groups. Both groups exhibited significant postoperative increases in A-a oxygen gradient (p < 0.01), but patients in Group II exhibited significantly lower increases in postoperative A-a oxygen gradient (p < 0.006). Other hemodynamic and pulmonary data (pulmonary capillary wedge pressure, pulmonary vascular resistance (PVR), cardiac index (CI), shunt flow, dynamic lung compliance and static lung compliance) exhibited no differences between the groups. There was no significant difference in terms of intubation time. The malondialdehyde (MDA) increase in Group II following CPB was found to be significantly lower than in Group I (p = 0.043). This clinical study reveals that administration of NAC to patients undergoing elective CABG with CPB improves systemic oxygenation. There was no effect in other pulmonary parameters and in terms of intubation time. Sepsis and respiratory dysfunction leading to multiple system organ failure remains the leading cause of postoperative morbidity and mortality following major surgical procedures. It has been suggested the oxygen free radicals might play a pivotal role in this process. The aim of this study was to investigate whether short-term infusion of N-acetylcysteine (N-acetylcysteine), a potent antioxidant, administered before and during extensive abdominal surgery, could ameliorate the progression of early postoperative organ dysfunction and improve oxygenation. Out of the 93 patients, 47 received N-acetylcysteine and 46 were given placebo in a randomized, controlled, double-blinded fashion. Patients received N-acetylcysteine (150 mg.kg-1 bolus followed by a continuous infusion of 12 mg.kg-1.h-1) or the same volume of placebo (5% dextrose) during surgery. Treatment effect on organ function was assessed by organ dysfunction scores according to physiological parameters of six main organ systems: respiratory, cardiovascular, renal, hepatic, haematological and central nervous system. The scores were obtained on admission, then daily during the first three postoperative days. For statistical analysis Mann-Whitney U and Chi-squared tests were used. There was no significant difference between the two groups in any of the six organ dysfunction parameters, length of intensive care stay, days of mechanical ventilation and mortality. Our results do not support the routine use of N-acetylcysteine as a prophylactic measure during surgery, and reinforce previous evidence which challenges the indication of N-acetylcysteine in the critically ill. Pre-existing chronic renal failure is a significant risk factor for acute renal failure (ARF) after cardiac surgery. N-acetylcysteine (NAC) has been shown to prevent contrast media-induced ARF. Our objective was to evaluate whether i.v. NAC has renoprotective effects in patients with mild renal failure undergoing cardiac surgery.
                In this prospective, randomized, double-blind study, 80 patients with mild to moderate renal failure undergoing elective heart surgery with cardiopulmonary bypass were recruited. All received either i.v. NAC (n=38) or placebo (n=39) at induction of anaesthesia and then up to 20 h. Urine N-acetyl-beta-D-glucosaminidase (NAG) and urine creatinine ratio, plasma creatinine, and serum cystatin C levels indicated renal function.
                Levels of urinary NAG/creatinine ratio, plasma creatinine and serum cystatin C did not significantly differ between NAC and placebo groups during five postoperative days. Urine NAG/creatinine ratio increased over 30% in 100% of patients in the NAC group vs 92.3% in the placebo group (P=0.081). Plasma creatinine increased by 25% from baseline or over 44 mumol litre(-1) in 42.1% in NAC group vs 48.7% in placebo group (P=0.560). Serum cystatin C exceeded 1.4 mg litre(-1) in 78.9% in NAC group vs 61.5% in placebo group (P=0.096).
                Prophylactic treatment with i.v. N-acetylcysteine had no renoprotective effect in patients with pre-existing renal failure undergoing cardiac surgery. To determine the levels of glutathione and cysteine in patients with ARDS and examine the effect of treatment with N-acetylcysteine (NAC) and L-2-oxothiazolidine-4-carboxylate (Procysteine; Clintec Technologies Inc; Chicago [OTZ]) on these levels and on common physiologic abnormalities, and organ dysfunction associated with ARDS.
                Randomized, double-blind, placebo-controlled, prospective clinical trial.
                ICUs in five clinical centers in the United States and Canada.
                Patients meeting a predetermined definition of ARDS and requiring mechanical ventilation.
                Standard care for ARDS and I.V. infusion, every 8 h for 10 days, of one of the following: NAC (70 mg/kg, n=14), OTZ (63 mg/kg, n=17), or placebo (n=15).
                Both antioxidants effectively repleted RBC glutathione gradually over the 10-day treatment period (47% and 49% increases from baseline values for NAC and OTZ, respectively). There was no difference in mortality among groups (placebo, 40%; NAC, 36%; OTZ, 35%). However, the number of days of acute lung injury was decreased and there was also a significant increase in cardiac index in both treatment groups (NAC/OTZ [+]14%; placebo [-]6%).
                Our findings suggest that repletion of glutathione may safely be accomplished with NAC or OTZ in patients with acute lung injury/ARDS. Such treatment may shorten the duration of acute lung injury, but larger studies are needed to confirm this. N-acetylcysteine, a potent anti-inflammatory and antioxidant agent, is known to decrease the production of reactive oxygen species after cardiac surgery. The objective of this study was to evaluate the effects of intravenous N-acetylcysteine on clinical and biochemical outcomes after coronary artery bypass surgery with cardiopulmonary bypass.
                One hundred patients (mean age 60.5 years, range 43-78 years, 89% male) undergoing coronary artery bypass grafting at the Montreal Heart Institute were randomized to receive either N-acetylcysteine (600 mg orally the day before and the morning of the operation, a bolus of 150 mg/kg of intravenous N-acetylcysteine before skin incision, followed by perfusion at 12.5 mg x kg(-1) x h(-1) over 24 hours; n = 50) or placebo (n = 50). The patients and clinical team were blinded to group assignments. Preoperative characteristics were similar between the two groups. Postoperative clinical data (death, myocardial infarction, low-output syndromes, arrhythmias, bleeding, transfusion requirements, and intensive care unit and hospital lengths of stay) and biochemical markers (creatine kinase MB, troponin T, creatinine, hemoglobin, and platelet levels) were evaluated serially over 4 days.
                Clinical outcomes were not significantly different between the two groups with regard to the incidence of death, myocardial infarction, bleeding, transfusion requirements, intubation time, and hospital length of stay. No differences were found in postoperative biochemical markers (troponin T, creatine kinase MB, creatinine, hemoglobin, and platelets) between the groups. No differences were observed between the groups in interleukin-6 production (P = not significant).
                Prophylactic use of N-acetylcysteine in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass does not lead to improvement in clinical results or biochemical markers. Further strategies to decrease reperfusion injury should be devised. To investigate the effects of adjunctive therapy with parenteral N-acetyl-L-cysteine in patients with newly diagnosed septic shock.
                Prospective, randomized, double-blind, placebo-controlled study.
                Multidisciplinary intensive care unit at a university teaching hospital.
                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.
                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).
                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 Score 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/m2, 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, Pao2/Fio2 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.
                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. Markers of oxidative stress are reported to be increased in severe malaria. It has been suggested that the antioxidant N-acetylcysteine (NAC) may be beneficial in treatment. We studied the efficacy and safety of parenteral NAC as an adjunct to artesunate treatment of severe falciparum malaria.
                A randomized, double-blind, placebo-controlled trial on the use of high-dose intravenous NAC as adjunctive treatment to artesunate.
                A provincial hospital in Western Thailand and a tertiary referral hospital in Chittagong, Bangladesh.
                One hundred eight adult patients with severe falciparum malaria.
                Patients were randomized to receive NAC or placebo as an adjunctive treatment to intravenous artesunate.
                A total of 56 patients were treated with NAC and 52 received placebo. NAC had no significant effect on mortality, lactate clearance times (p = 0.74), or coma recovery times (p = 0.46). Parasite clearance time was increased from 30 hours (range, 6-144 hours) to 36 hours (range, 6-120 hours) (p = 0.03), but this could be explained by differences in admission parasitemia. Urinary F2-isoprostane metabolites, measured as a marker of oxidative stress, were increased in severe malaria compared with patients with uncomplicated malaria and healthy volunteers. Admission red cell rigidity correlated with mortality, but did not improve with NAC.
                Systemic oxidative stress is increased in severe malaria. Treatment with NAC had no effect on outcome in patients with severe falciparum malaria in this setting. N-acetylcysteine (NAC) is an antioxidant drug largely tested in different clinical situations. Recently, NAC has been employed with variable success in the prevention of radiocontrast nephropathy. Since aortic aneurysm surgical repair is a condition that is frequently accompanied by acute renal failure (ARF), we sought to investigate whether NAC has any role in preventing ARF in this scenario.
                A randomized, placebo-controlled, double-blind trial with the following inclusion criteria: elective aortic aneurysm repair in patients with stable renal function. The groups were randomly matched for age, gender, presence of diabetes and pre-existent renal failure. NAC or placebo (control) was administered p.o. for 24 h before operation and maintained i.v. for 48 h after operation. The dose of NAC was 1200 mg b.i.d. the day before surgery and 600 mg b.i.d. after. The primary endpoint was the development of ARF up to the third post-operative day, defined as an increase in SCr > or = 25% from baseline. Secondary endpoints were: ICU mortality and ICU length of stay.
                Forty-two patients (n = 18 for NAC group and n = 24 for control) were studied. The baseline SCr and calculated GFR did not differ between the groups (1.19 +/- 0.33 vs 1.37 +/- 0.49 mg/dl; and 64.6 +/- 26.22 vs 65.7 +/- 28.32 ml/min, NAC vs control, respectively, P = 0.17 and P = 0.90). Need for suprarenal aortic cross-clamping and its duration, occurrence of major bleeding, intra-operative hypotension and the post-operative peak of CPK did not differ between NAC and control groups. The overall incidence of ARF in the study was 36% (13/36), but it was not significantly different between groups (7/14, 50% in NAC vs 6/22, 27.3% in control, P = 0.16). The overall mortality was 23% (10/42) and was not different (P = 0.209) in NAC group (33.3%) when compared with control (16.7%), the same occurring with the length of ICU stay (2.93 +/- 1.53 vs 2.52 +/- 1.36 days, P = 0.40).
                This study suggests that the putative beneficial effects of NAC on radiocontrast nephropathy might not be applicable to other situations, such as ARF associated with elective aortic aneurysm repair. To examine whether the antioxidant N-acetylcysteine could ameliorate the course of the adult respiratory distress syndrome (ARDS) in man.
                Randomized, double-blind, placebo-controlled study.
                Medical and surgical ICU in a regional hospital.
                Sixty-six ICU patients with ARDS.
                Patients with ARDS (PaO2/FiO2 ratio less than 250 torr) were treated with either the antioxidant N-acetylcysteine 150 mg/kg as a loading dose and then 20 mg/kg/hr, or with placebo for 6 days.
                No improvement could be demonstrated in the PaO2/FiO2 ratio in the study group as compared with the control group on any day. Pulmonary compliance was higher in the N-acetylcysteine group than in the placebo group on all days, but this difference did not reach the chosen 5% level of significance. No difference between the two groups could be demonstrated on chest radiograph or on survival rate. We documented that N-acetylcysteine acts as an anticoagulant and perhaps decreases pulmonary fibrin uptake during ARDS.
                N-acetylcysteine might be of benefit in ARDS. Before further clinical studies are started, problems with N-acetylcysteine and coagulation have to be elucidated in order to find out whether N-acetylcysteine could have a beneficial effect in the treatment of ARDS. Reactive oxygen species have been shown to contribute to myocardial stress in patients undergoing cardiac surgery, as demonstrated by myocardial 8-iso-prostaglandin-F(2)alpha and nitrotyrosine formation. We hypothesized that the reactive oxygen species scavenger N-acetylcysteine attenuates reactive oxygen species-mediated myocardial stress in patients undergoing cardiac surgery.
                Forty patients undergoing coronary artery surgery (mean age +/- SD, 66 +/- 9 years; 9 women and 31 men) were randomized to receive either N-acetylcysteine (100 mg/kg into cardiopulmonary bypass prime followed by infusion at 20 mg.kg(-1).h(-1), n = 20) or placebo (n = 20). Patients and clinical staff were blinded to group assignment. Transmural left ventricular biopsy specimens collected before and at the end of cardiopulmonary bypass were subjected to immunocytochemical staining against 8-iso-prostaglandin-F(2)alpha (primary measure) as an indicator for reactive oxygen species-mediated lipid peroxidation and nitrotyrosine (coprimary measure) as a marker for peroxynitrite-mediated tissue injury. Cardiomyocyte staining was quantitatively determined by using densitometry (in gray units). Global left ventricular function was measured on the basis of fractional area of contraction by using transesophageal echocardiography.
                Patient characteristics in both groups were comparable. The change in left ventricular cardiomyocyte staining (end of cardiopulmonary bypass--before cardiopulmonary bypass) differed significantly between groups for both primary measures: 8-iso-prostaglandin-F(2)alpha, -1.8 +/- 7.5 gray units (mean +/- SD, N-acetylcysteine group) versus 5.0 +/- 4.1 gray units (placebo group; 95% confidence interval, 2.6-11.0, P =.003); nitrotyrosine, -6.4 +/- 10.0 gray units (N-acetylcysteine group) versus 9.2 +/- 8.4 gray units (placebo group; 95% confidence interval, 9.4-21.7, P <.001). Hemodynamics and clinical outcomes were comparable in both groups.
                Reactive oxygen species scavenging with N-acetylcysteine attenuates myocardial oxidative stress in the hearts of patients subjected to cardiopulmonary bypass and cardioplegic arrest. Myocardial ischemia/reperfusion injury in patients undergoing coronary artery by-pass grafting (CABG) involves the reperfusion-induced conversion of reversible injured myocardial and endothelial cells. N-acetylcysteine (NAC) has a potential being the minimization of the impact of reperfusion injury. The aim of this study was to evaluate the effects of intravenous NAC on periprocedural myocardial injury after CABG.
                The population of this prospective-randomized, double blind, placebo controlled study consisted of 40 patients undergoing on-pump CABG. All the patients were treated with standard medical therapy and eligible patients were randomized to NAC group (N.=19; intravenous infusion for 1 hour before the procedure at a dose of 50 mg/kg, followed by intravenous infusion for 48 hours after the operation at a dose of 50 mg/kg/day) and placebo (saline) group (N.=21). The study drug and placebo infusions were set to infuse at the same rate.
                Demographic and procedural variables were similar in the both groups (All P>0.05). Creatine kinase MB isoform (CK-MB) mass levels did not significantly differ between the groups at both preoperative and postoperative periods. Similarly, cTnT levels were similar in the groups at all periods. Eight patients in the NAC group and 7 in the placebo group had increased CK-MB >3 times normal value. However, only 3 patients in the NAC group experienced CK-MB>5 times normal value.
                Results of this study indicated that periprocedural use of NAC as intravenously did not attenuate myocardial damage after on-pump CABG surgery. This study investigates the effects of N-acetylcysteine (NAC) and rutin on the lung oxidative burden of patients with early adult respiratory distress syndrome (ARDS). The protection was evaluated by measuring expired ethane and malondialdehyde (MDA), and oxidized (GSSG) and reduced glutathione (GSH) in the epithelial lining fluid of 36 patients who developed ARDS less than 24 hours before enrollment in the study. The patients were randomly assigned to 3 groups, receiving 250 mL 5% dextrose in water (group 1), NAC 50 mg/kg body weight in 5% dextrose (group 2), and NAC 50 mg/kg + rutin 5 mg/kg in 5% dextrose (group 3). Ethane and MDA concentrations were significantly reduced in the treatment groups after day 6. GSH was 30% increased in the treatment groups. No significant variations were observed in the control group until day 9. The trial confirms that NAC and rutin are efficient in protecting the lungs of patients with ARDS. Myocardial ischemia-reperfusion injury may complicate coronary artery bypass grafting (CABG) operations. N-Acetylcysteine (NAC) had antioxidant and microcirculatory effects, and inhibits neutrophil aggregation. The aim of this study was to determine the effects of NAC in limiting myocardial ischemia-reperfusion injury in CABG operations. Twenty patients undergoing elective coronary bypass operation with cardiopulmonary bypass were enrolled and randomly assigned to two groups: a control group operated with a routine CABG protocol, and one where NAC was administered intravenously during the operation (NAC group). Blood samples from coronary sinus for tumor necrosis factor-alpha assay, myocardial biopsy specimens for chemiluminescent luminol, and lucigenin measurements of reactive oxygen species were taken. The luminol (specific for (*)OH, H(2)O(2), and HOCl(-) radicals) and lucigenin (specific for O(2) (*-)) levels and the difference ratios after reperfusion were significantly lower in the NAC group. Tumor necrosis factor-alpha levels increased in the control group but, in contrast, a significant decrease was detected in the NAC group (P < 0.01). Creatine kinase-MB levels at 6 and 12 hours were significantly lower in the NAC group (P = 0.02). N-Acetylcysteine has potential effects to limit ischemia reperfusion injury during CABG operations. We believe that its effects on clinical outcome may be more apparent in patients prone to ischemia-reperfusion injury. Glutathione (GSH) acts as a free radical scavenger that may be helpful in preventing reperfusion injury. N-acetylcysteine (NAC) replenishes GSH stores. The aims of this study were to evaluate the efficacy of NAC in improving liver graft performance and reducing the incidence of post-operative acute kidney injury (AKI).
                Our study was a randomized, double-blind, placebo-controlled trial of 100 patients; 50 received placebo and 50 received a loading dose of 140 mg/kg of intravenous (IV) NAC over 1 h followed by 70 mg/kg IV repeated every 4 h for a total of 12 doses. Both groups were followed up for 1 year post-orthotopic liver transplant (OLT). We recorded liver function tests, renal function tests, graft survival, patient survival, plasma GSH and duration of hospital and ICU stay. In addition to serum creatinine (SCr) levels, we analysed cystatin C and beta-trace as independent measures of glomerular filtration. All clinical data were recorded daily for the first week after the surgery, then on Days 14, 21, 30, 90 and 180 and at the end of the first year.
                IV NAC did not affect survival, graft function or risk of AKI. However, GSH levels were highly variable with only 50% of patients receiving NAC exhibiting increased levels and fewer patients developed AKI when GSH levels were increased. Additional risk factors for AKI in the post-transplant period were female gender (P = 0.05), increased baseline serum bilirubin (P = 0.004) and increased baseline SCr levels (P = 0.02).
                IV NAC was not effective in reducing renal or hepatic injury in the setting of liver transplantation. The dose and duration of NAC used, though higher than most renal protection studies, may have been ineffective for raising GSH levels in some patients. Renal dysfunction is a complication of coronary artery bypass graft (CABG) surgery performed with cardiopulmonary bypass (CPB) that is associated with increased morbidity and mortality. N-acetylcysteine, an antioxidant and vasodilator, counteracts renal ischemia and hypoxia.
                To determine whether perioperative intravenous (IV) N-acetylcysteine preserves renal function in high-risk patients undergoing CABG surgery with CPB compared with placebo.
                Randomized, quadruple blind, placebo-controlled trial (October 2003-September 2004) in operating rooms and general intensive care units (ICUs) of 2 Ontario tertiary care centers. The 295 patients required elective or urgent CABG and had at least 1 of the following: preexisting renal dysfunction, at least 70 years old, diabetes mellitus, impaired left ventricular function, or undergoing concomitant valve or redo surgery.
                Patients received 4 (2 intraoperative and 2 postoperative) doses of IV N-acetylcysteine (600 mg) (n = 148) or placebo (n = 147) over 24 hours.
                The primary outcome was the proportion of patients developing postoperative renal dysfunction, defined by an increase in serum creatinine level greater than 0.5 mg/dL (44 micromol/L) or a 25% increase from baseline within the first 5 postoperative days. Secondary outcomes included postoperative interventions and complications, the requirement for renal replacement therapy (RRT), adverse events, hospital mortality, and ICU and hospital length of stay.
                There was no difference in the proportion of patients with postoperative renal dysfunction (29.7% vs 29.0%, P = .89; relative risk [RR], 1.03 [95% confidence interval {CI}, 0.72-1.46]) in the N-acetylcysteine and placebo groups, respectively. We noted nonsignificant differences in postoperative interventions and complications, the need for RRT (0.7% vs 2.1%; P = .37), total (6.1% vs 9.6%; P = .26) and serious adverse events, hospital mortality (3.4% vs 2.7%; P>.99), and ICU and hospital length of stay between the N-acetylcysteine and placebo groups. A post hoc subgroup analysis of patients (baseline creatinine level >1.4 mg/dL [120 micromol/L]) showed a nonsignificant trend toward fewer patients experiencing postoperative renal dysfunction in the N-acetylcysteine group compared with the placebo group (25.0% vs 37.1%; P = .29).
                N-acetylcysteine did not prevent postoperative renal dysfunction, interventions, complications, or mortality in high-risk patients undergoing CABG surgery with CPB. Further research is required to identify CABG patients at risk for postoperative renal events, valid markers of renal dysfunction, and to establish renal thresholds associated with important clinical outcomes. To assess the preventive effect of the antioxidant N-acetylcysteine on postoperative acute renal failure in patients with renal insufficiency undergoing cardiac surgery.
                Randomized, placebo-controlled, prospective study.
                University cardiology center.
                Two hundred fifty-four consecutive patients with chronic renal insufficiency (estimated creatinine clearance < or = 60 mL/min) undergoing elective cardiac surgery.
                Patients were randomized to receive N-acetylcysteine (n = 129) or placebo (n = 125). Patients of the N-acetylcysteine group received four boluses of intravenous N-acetylcysteine (1200 mg every 12 hrs, starting immediately before cardiac surgery).
                The incidence of postoperative acute renal failure (> 25% increase in serum creatinine from baseline) and the in-hospital clinical course were evaluated. Acute renal failure occurred in 46% of patients and was associated with increased in-hospital mortality (7% vs. 0.7%; p = .024). It occurred in 52% of control patients and 40% of N-acetylcysteine-treated patients (p = .06). In-hospital mortality and need for renal replacement therapy were not affected by N-acetylcysteine, but a lower percentage of N-acetylcysteine-treated patients required mechanical ventilation prolonged for > 48 hrs (3% vs. 18%; p < .001) and had an intensive care unit stay > 4 days (13% vs. 33%; p < .001).
                Intravenous administration of N-acetylcysteine does not clearly prevent postoperative acute renal failure in patients with renal insufficiency undergoing cardiac surgery. N-acetylcysteine may prevent acute kidney injury after cardiac surgery. To determine if N-acetylcysteine warrants definitive evaluation in a large multicentre trial, we evaluated its effects on a surrogate outcome, estimated glomerular filtration rate (eGFR), in a randomized trial.
                One-hundred-seventy-seven cardiac surgery patients with moderate pre-existing renal insufficiency (eGFR <or= 60 mLxmin(-1)) were recruited in a blinded (patients, clinicians, data-collectors) placebo-controlled randomized trial. Eighty-nine were randomized to N-acetylcysteine (100 mgxkg(-1) i.v. bolus, 20 mgxkg(-1)xhr(-1) infusion until four hours after cardiopulmonary bypass), and 88 to placebo. The primary outcome was the percent change in eGFR during the first 72 postoperative hours. Secondary outcomes included renal replacement therapy, mortality, atrial fibrillation, vasoactive medications, and adverse effects. A future multicentre trial was deemed to be warranted if N-acetylcysteine was associated with a percent change in eGFR that was 3.8 better (small benefit), and with an upper 95% confidence interval including 9.5 (moderate benefit).
                The median percent change in eGFR was 5.2% better (absolute difference) in the N-acetylcysteine arm (95% confidence interval 2.4% worse to 12.1% better; P=0.22). With regard to secondary outcomes, all-cause mortality was lower in the N-acetylcysteine arm (0% vs 8%; P=0.007).
                N-acetylcysteine did not cause a statistically significant improvement in postoperative eGFR in this single-centre study. Nonetheless, its treatment effect was consistent with a plausible small-to-moderate benefit. Given this finding, N-acetylcysteine should be definitively evaluated in a large randomized trial. To see whether intravenous acetylcysteine would improve outcome in patients with fulminant hepatic failure after paracetamol overdose.
                A prospective randomised controlled study.
                The Institute of Liver Studies, King's College Hospital, London.
                50 consecutive patients (21 male) aged 16-60 with fulminant hepatic failure after paracetamol overdose who had not previously received acetylcysteine.
                Conventional intensive liver care plus either acetylcysteine (25 patients) in the same dose regimen as used early after a paracetamol overdose, except that the infusion was continued until recovery from encephalopathy or death, or an equivalent volume of 5% dextrose (25 patients).
                Survival; incidence of cerebral oedema, renal failure, and hypotension requiring inotropic support; liver function as assessed by prolongation of the prothrombin time; and degree of encephalopathy.
                The rate of survival was significantly higher in the acetylcysteine treated group than in the controls (48% (12/25 patients) v 20% (5/25); p = 0.037, 95% confidence interval for difference in proportions surviving 3% to 53%). Acetylcysteine treated patients had a lower incidence of cerebral oedema (40% (10/25) v 68% (17/25); p = 0.047, 95% confidence interval for difference in incidence 2% to 54%), and fewer developed hypotension requiring inotropic support (48% (12/25) v 80% (20/25); p = 0.018, 95% confidence interval 7% to 57%). Rates of deterioration and recovery of liver function, however, were similar in the two groups. No adverse reactions to acetylcysteine were seen.
                Acetylcysteine is safe and effective in fulminant hepatic failure after paracetamol overdose. Expression of inflammatory mediators is controlled in part at the transcriptional level via nuclear factor-kappa B. Inhibition of nuclear factor-kappa B activation may be beneficial in critically ill patients. N-acetylcysteine is an antioxidant that inhibits nuclear factor-kappa B activation in vitro. In this pilot study we investigated the effect of N-acetylcysteine on nuclear factor-kappa B activation and circulating cytokine and adhesion molecules in patients with sepsis.
                Prospective, randomized, double blind, placebo-controlled pilot trial.
                Eight-bed intensive care unit in a university teaching hospital.
                Twenty consecutive patients within 12 hrs of fulfilling the consensus criteria for sepsis.
                A bolus of 150 mg/kg N-acetylcysteine in 100 mL of 0.9% saline over 15 mins, then 50 mg/kg in 100 mL of 0.9% saline over 4 hrs as a loading dose, and then a maintenance infusion of 50 mg/kg in 200 mL of 0.9% saline over each 24-hr period for a total of 72 hrs, or an equivalent volume of saline.
                Nuclear factor-kappa B activation was measured in mononuclear leukocytes using electrophoretic mobility shift assay, at baseline and 24, 48, 72, and 96 hrs later. Activation decreased significantly in patients treated with N-acetylcysteine (p =.016) but not placebo and was significantly reduced at 72 hrs compared with both preinfusion values (p =.028) and patients receiving placebo (p =.01). Plasma interleukin-6, interleukin-8, and soluble intercellular adhesion molecule-1 concentrations were measured using enzyme immunoassay. Interleukin-6 concentrations were high initially and then decreased in all patients, regardless of whether they received N-acetylcysteine or placebo. Interleukin-8 decreased significantly only in those who received N-acetylcysteine (p =.0081). Soluble intercellular adhesion molecule-1 concentrations remained unchanged in all patients.
                Administration of N-acetylcysteine results in decreased nuclear factor-kappa B activation in patients with sepsis, associated with decreases in interleukin-8 but not interleukin-6 or soluble intercellular adhesion molecule-1. These pilot data suggest that antioxidant therapy with N-acetylcysteine may be useful in blunting the inflammatory response to sepsis. Further studies are warranted. N-acetylcysteine (NAC), an antidote for acetaminophen poisoning, might benefit patients with non-acetaminophen-related acute liver failure.
                In a prospective, double-blind trial, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were stratified by site and coma grade and assigned randomly to groups that were given NAC or placebo (dextrose) infusion for 72 hours. The primary outcome was overall survival at 3 weeks. Secondary outcomes included transplant-free survival and rate of transplantation.
                A total of 173 patients received NAC (n = 81) or placebo (n = 92). Overall survival at 3 weeks was 70% for patients given NAC and 66% for patients given placebo (1-sided P = .283). Transplant-free survival was significantly better for NAC patients (40%) than for those given placebo (27%; 1-sided P = .043). The benefits of transplant-free survival were confined to the 114 patients with coma grades I-II who received NAC (52% compared with 30% for placebo; 1-sided P = .010); transplant-free survival for the 59 patients with coma grades III-IV was 9% in those given NAC and 22% in those given placebo (1-sided P = .912). The transplantation rate was lower in the NAC group but was not significantly different between groups (32% vs 45%; P = .093). Intravenous NAC generally was well tolerated; only nausea and vomiting occurred significantly more frequently in the NAC group (14% vs 4%; P = .031).
                Intravenous NAC improves transplant-free survival in patients with early stage non-acetaminophen-related acute liver failure. Patients with advanced coma grades do not benefit from NAC and typically require emergency liver transplantation.