Clinical Trial Assessment of Intermittent and Continuous Infusion Dose of N-Acetylcysteine on Redox Status of the Body in Patients with Sepsis Admitted to the ICU

Abstract

Purpose: Conflicting results exist regarding the efficacy of N-acetyl cysteine (NAC) in sepsis treatment. A pivotal factor affecting the therapeutic potency of NAC in sepsis is timing and dosing of its infusion. We aimed to assess the effect of NAC on redox status of patients with sepsis and to compare its efficacy in intermittent and continuous infusion with the objective of developing the infusion regimen and optimizing the timing. Materials and Methods: A prospective, randomized clinical trial was designed to compare the antioxidative effect of NAC in intermittent infusion group (IV: 25 mg/kg bolus and then 25 mg/kg/8 hours 3 times) and continuous infusion group (IV: 25 mg/kg bolus and then 75 mg/kg over 24 hours) in 60 critically ill patients with sepsis (20 patients in each group). Blood samples were collected immediately before and after intervention for total antioxidant capacity (TAC) and malondialdehyde (MDA) assessment. Results: N-acetyl cysteine considerably increased TAC levels in both intermittent (0.68 ± 0.60; P value = .036) and continuous (0.69 ± 0.64; P value = .015) infusion groups when compared to placebo (0.61 ± 0.10); however, the difference in TAC levels between the intermittent and the continuous infusion did not reach statistical significance ( P value = .942). Likewise, NAC treatment decreased MDA levels in both intermittent (19.45 ± 4.18; P value = 0.001) and continuous (22.47 ± 6.68; P value = .002) infusion groups when compared to placebo (31.76 ± 11.06), while the difference in MDA levels between the intermittent and the continuous infusion did not reach statistical significance ( P value = .481). Conclusion: Our data confirmed the antioxidative effect of NAC treatment in patients with sepsis, with no significant difference in intermittent and continuous infusion.

Serum reactive oxygen species and apoptosis markers in septic patients

“…Also, in a study with septic rats, the administration of intraperitoneal NAC, associated with deferoxamine, decreased the production of superoxide, the activity of enzyme catalase, superoxide dismutase, and myeloperoxidase in all organs, in addition to improving survival [54]. In several clinical trials in which septic patients were supplemented with antioxidants, the length of mechanical ventilation or oxygen levels were not reduced [55][56][57][58][59][60][61][62][63][64][65][66][67][68]. There are many works that describe differences between animal models of sepsis and patients, and the difficulty of transferring the results of the animal model to patients [69][70][71].…”

The Effect of N-Acetyl Cysteine and Vitamin E on Oxidative Status and Hemoglobin Level in Transfusion-Dependent Thalassemia Patients: A Systematic Review and Meta-Analysis

“…The bene cialantioxidanteffect of NAC as adjunct therapyhas been described in some diseases, including patients with sepsis 19 , hospitalized patients with HIV associated tuberculosis 20 , and in combination with glycine in older adults for improvement of the insults of human agingsuch as mitochondrial dysfunction and in ammation 21 . However, high dose infusion of NAC for 24 hours revealed no signi cant improvement in the total antioxidant potential in critically ill patients 22 .…”

Nrf2—A Molecular Target for Sepsis Patients in Critical Care

“…Restoration of the intracellular glutathione pool by the glutathione precursor molecule N-acetyl cysteine (NAC) has already been described in animal experiments to reduce pro-inflammatory cytokine expression and to improve disease outcome [62,145] and administration of the synthetic GSH peroxidase mimic, ebselen, has broad anti-inflammatory activity in infectious and non-infectious conditions [146][147][148]. According to these preclinical data, NAC has also been used in the sepsis patient, however with controversial results [149][150][151][152][153]. In a prospective, randomized clinical trial, including 60 critical ill patients with sepsis in total, intermittent NAC infusion was compared with continuous infusion [149].…”

“…According to these preclinical data, NAC has also been used in the sepsis patient, however with controversial results [149][150][151][152][153]. In a prospective, randomized clinical trial, including 60 critical ill patients with sepsis in total, intermittent NAC infusion was compared with continuous infusion [149]. In this study, blood samples were collected to determine the total antioxidant capacity (TAC) and malondialdehyde (MDA) content.…”