Treatment with N-acetylcysteine during acute respiratory distress syndrome: A randomized, double-blind, placebo-controlled clinical study

Domenighetti, Guido; Suter, Peter M.; Schaller, Marie-Denise; Ritz, R; Perret, C

doi:10.1016/s0883-9441(97)90029-0

Cited by 145 publications

(92 citation statements)

References 20 publications

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“…Clinical trials with antioxidants for acute illnesses, such as ALI or sepsis, have been disappointing, and no agent has been shown to be effective in critically ill patients (63)(64)(65)(66)(67)(68).…”

Section: Discussionmentioning

confidence: 99%

Antiinflammatory Effects of Hydrogen Peroxide in Neutrophil Activation and Acute Lung Injury

Żmijewski¹,

Lorne²,

Zhao³

et al. 2009

Am J Respir Crit Care Med

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Rationale: Although reactive oxygen species (ROS) are generally considered to be proinflammatory and to contribute to cellular and organ dysfunction when present in excessive amounts, there is evidence that specific ROS, particularly hydrogen peroxide (H 2 O 2 ), may have antiinflammatory properties. Objectives: To address the role that increases in intracellular H 2 O 2 may play in acute inflammatory processes, we examined the effects of catalase inhibition or the absence of catalase on LPS-induced inflammatory responses. Methods: Neutrophils from control or acatalasemic mice, or control neutrophils incubated with the catalase inhibitor aminotriazole, were treated with LPS, and levels of reactive oxygen species, proteasomal activity, NF-kB activation, and proinflammatory cytokine expression were measured. Acute lung injury (ALI) was produced by intratracheal injection of LPS into control, acatalasemic-, or aminotriazole-treated mice. Measurements and Main Results: Intracellular levels of H 2 O 2 were increased in acatalasemic neutrophils and in neutrophils exposed to aminotriazole. Compared with LPS-stimulated neutrophils from control mice, neutrophils from acatalasemic mice or neutrophils treated with aminotriazole demonstrated reduced 20S and 26S proteasomal activity, IkB-a degradation, NF-kB nuclear accumulation, and production of the proinflammatory cytokines TNF-a and macrophage inhibitory protein (MIP)-2. The severity of LPS-induced ALI was less in acatalasemic mice and in mice treated with aminotriazole as compared with that found in control mice. Conclusions: These results indicate that H 2 O 2 has antiinflammatory effects on neutrophil activation and inflammatory processes, such as ALI, in which activated neutrophils play a major role.

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Section: Discussionmentioning

confidence: 99%

Antiinflammatory Effects of Hydrogen Peroxide in Neutrophil Activation and Acute Lung Injury

Żmijewski¹,

Lorne²,

Zhao³

et al. 2009

Am J Respir Crit Care Med

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“…The prednisolone dosage was tapered after high-dose corticosteroid pulse therapy, and immunosuppressants were also prescribed for some patients. Several reports have indicated that antioxidant therapy, such as N-acetylcysteine [23,24,25] or anticoagulation therapy [26,27,28], is useful for ALI/ARDS; however, none of the study patients received antioxidant or anticoagulation therapy.…”

Section: Methodsmentioning

confidence: 99%

Direct Hemoperfusion Using Immobilized Polymyxin B in Patients with Rapidly Progressive Interstitial Pneumonias: A Retrospective Study

et al. 2010

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Background: Rapidly progressive interstitial pneumonia (IP), including acute exacerbation of IP, has a high mortality rate. Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) was recently identified as an effective treatment for sepsis-associated acute respiratory distress syndrome. However, little is known about the effectiveness of PMX-DHP for rapidly progressive IP. Objectives: The present study investigates whether PMX-DHP is safe and effective against rapidly progressive IP. Methods: We retrospectively examined the effects of PMX-DHP in 33 consecutive patients with rapidly progressive IP who were resistant to steroid pulse therapy. Patients were hospitalized at Nagasaki University Hospital between 2006 and 2009. Results: Seventy-two hours after PMX-DHP, the arterial oxygen tension/inspiratory oxygen fraction ratio (median 127–153 mm Hg) had significantly improved. One week after PMX-DHP, the arterial oxygen tension/inspiratory oxygen fraction ratio (median 127–227 mm Hg), the alveolar-arterial difference of oxygen (median 371–177 mm Hg) and the number of positive criteria for systemic inflammatory response syndrome had significantly improved, despite the ineffectiveness of corticosteroid pulse therapy. The serum level of monocyte chemotactic protein 1 was significantly decreased immediately after PMX-DHP. Conclusions: PMX-DHP was safe and effective in improving oxygenation and systemic inflammatory response syndromein patients with rapidly progressive IP. The beneficialeffects of PMX-DHP may be at least partially due to the inhibition of monocyte activation.

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“…It has been shown to enter the cell and to be deacetylated to cysteine (14), which can replete intracellular glutathione. In adults with adult respiratory distress syndrome, NAC treatment reduced lung injury in some studies (15,16) but not in others (17). We carried out a randomized, multicenter, controlled trial to test the hypothesis that NAC administration during the first week of life would decrease the incidence of BPD in extremely low birth weight infants (ELBWIs).…”

mentioning

confidence: 99%

Plasma 8-Isoprostane Is Increased in Preterm Infants Who Develop Bronchopulmonary Dysplasia or Periventricular Leukomalacia

et al. 2004

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Our aim was to assess the plasma free 8-epi-prostaglandin F 2␣ (8-isoprostane) and ascorbyl radical as risk indicators for oxidative damage in extremely low birth weight infants (ELBWIs) and the effect of N-acetylcysteine (NAC) on these markers. Plasma samples were collected on days 3 and 7 of life from infants who were enrolled in a randomized, controlled trial in which i.v. NAC or placebo was administered to ELBWIs during the first week of life, with the aim of preventing bronchopulmonary dysplasia (BPD). Plasma 8-isoprostane was analyzed in 83 infants using an enzyme immunoassay kit. Ascorbyl radical concentration was measured in 61 infants with electron spin resonance spectroscopy. The 8-isoprostane concentrations were similar in the NAC and placebo groups. In infants who later developed BPD or died (n ϭ 29), the median (range) 8-isoprostane concentration was significantly higher (p ϭ 0.001) on day 3 and day 7 [50.0 pg/mL (19 -360) and 57.0 pg/mL (14 -460), respectively] than in survivors without BPD [n ϭ 54; 34.5 pg/mL (5-240) and 39.5 pg/mL (7-400), respectively]. The 8-isoprostane levels increased significantly more (p Ͻ 0.05) in infants who later developed periventricular leukomalacia. NAC treatment or the later development of BPD was not related to the ascorbyl radical levels. The ascorbyl radical level decreased significantly in all groups from day 3 to day 7, but the difference between the groups was not significant. The mean (SD) ascorbyl radical level on day 3 was significantly higher (p Ͻ 0.01) in infants who later developed periventricular leukomalacia [287 (124) Free radical generation and oxidative injury have been implicated as causal factors in several complications of prematurity, such as bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and periventricular leukomalacia (PVL) (1). Despite improved perinatal care, BPD remains one of the most important causes of long-term morbidity after preterm birth (2). Oxygen therapy and inflammatory neutrophil activation are considered important in increasing the production of reactive oxygen species (ROS) and the release of proinflammatory cytokines resulting in abnormal lung development. Evidence for increased oxidant production and oxidant-induced macromolecular damage has been demonstrated during the first week of life in infants who develop BPD (2,3). Increased levels of volatile lipid peroxidation products have been shown to correlate with poor respiratory outcome and death in very low birth weight infants (4).Preterm newborn infants are considered vulnerable to oxidative stress because of deficient antioxidant capacity. Even though the enzymatic antioxidant defenses of preterm infants seem relatively well developed, with the exception of catalase (5)

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Treatment with N-acetylcysteine during acute respiratory distress syndrome: A randomized, double-blind, placebo-controlled clinical study

Cited by 145 publications

References 20 publications

Antiinflammatory Effects of Hydrogen Peroxide in Neutrophil Activation and Acute Lung Injury

Antiinflammatory Effects of Hydrogen Peroxide in Neutrophil Activation and Acute Lung Injury

Direct Hemoperfusion Using Immobilized Polymyxin B in Patients with Rapidly Progressive Interstitial Pneumonias: A Retrospective Study

Plasma 8-Isoprostane Is Increased in Preterm Infants Who Develop Bronchopulmonary Dysplasia or Periventricular Leukomalacia

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