Oral N-acetylcysteine Therapy Research Articles

The efficacy of N-acetylcysteine in chronic obstructive pulmonary disease patients: a meta-analysis.

N-acetylcysteine (NAC) may reduce acute exacerbations of chronic obstructive pulmonary disease through an antioxidant effect. Due to the heterogeneity in studies, the currently available data do not confirm the efficacy of oral NAC therapy in chronic obstructive pulmonary disease patients. We hypothesize that chronic obstructive pulmonary disease patients receiving regular oral NAC therapy do not achieve improved clinical outcomes. The purpose of this meta-analysis was to determine the efficacy of long-term oral NAC therapy in chronic obstructive pulmonary disease patients. The literature search was performed using the PubMed, Web of Science, and Cochrane Library databases to identify all included clinical studies. Studies were eligible for inclusion only if they directly compared the outcomes of NAC versus placebo in adults with chronic obstructive pulmonary disease between 1 January 2000 and 30 May 2022. All studies were included if they reported one or more of the following outcomes: number of patients with no acute exacerbations, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), St George's Respiratory Questionnaire score, glutathione level, and adverse events. Nine randomized controlled trials were included in the meta-analysis. There were 1061 patients in the NAC group and 1076 patients in the placebo group. The current meta-analysis provides evidence that the number of patients with no acute exacerbations (965 patients receiving NAC therapy, 979 control group patients), change in FEV1 (433 patients receiving NAC therapy, 447 control group patients), change in FVC (177 patients receiving NAC therapy, 180 control group patients), change in St George's Respiratory Questionnaire score (128 patients receiving NAC therapy, 131 control group patients), change in glutathione levels (38 patients receiving NAC therapy, 40 control group patients), and adverse events (832 patients receiving NAC therapy, 846 control group patients) were not significantly different between the two groups. NAC did not reduce the risk of acute exacerbation or ameliorate the decline in lung volume in chronic obstructive pulmonary disease patients.

ISPD peritonitis guideline recommendations: 2022 update on prevention and treatment.

Peritoneal dialysis (PD)-associated peritonitis is a serious complication of PD and prevention and treatment of such is important in reducing patient morbidity and mortality. The ISPD 2022 updated recommendations have revised and clarified definitions for refractory peritonitis, relapsing peritonitis, peritonitis-associated catheter removal, PD-associated haemodialysis transfer, peritonitis-associated death and peritonitis-associated hospitalisation. New peritonitis categories and outcomes including pre-PD peritonitis, enteric peritonitis, catheter-related peritonitis and medical cure are defined. The new targets recommended for overall peritonitis rate should be no more than 0.40 episodes per year at risk and the percentage of patients free of peritonitis per unit time should be targeted at >80% per year. Revised recommendations regarding management of contamination of PD systems, antibiotic prophylaxis for invasive procedures and PD training and reassessment are included. New recommendations regarding management of modifiable peritonitis risk factors like domestic pets, hypokalaemia and histamine-2 receptor antagonists are highlighted. Updated recommendations regarding empirical antibiotic selection and dosage of antibiotics and also treatment of peritonitis due to specific microorganisms are made with new recommendation regarding adjunctive oral N-acetylcysteine therapy for mitigating aminoglycoside ototoxicity. Areas for future research in prevention and treatment of PD-related peritonitis are suggested.

Oral N-acetylcysteine for prophylaxis of contrast-induced nephropathy in patients following coronary angioplasty: A meta-analysis.

It is acknowledged that contrast-induced nephropathy (CIN) is a common cause of acute renal insufficiency after cardiac catheterization and affects mortality and morbidity. To date, it is unknown whether oral N-acetylcysteine (NAC) is able to prevent contrast-induced nephropathy (CIN) in patients undergoing coronary angioplasty. A meta-analysis of randomized controlled trials was performed to assess the effects of NAC in the prevention of CIN in patients following coronary angioplasty. A total of 19 studies published prior to January 2015 that investigated the efficacy of oral NAC for the prevention of CIN were collected from Medline, Cochrane and Embase databases and conference proceedings from cardiology and nephrology meetings. The primary point of investigation was CIN, and the secondary points were renal failure requiring dialysis, mortality and length of hospitalization. The meta-analysis was performed using fixed- or random-effect models according to heterogeneity. Up to January 2015, 19 randomized placebo-controlled clinical trials met the inclusion criteria for the meta-analysis, including 4,514 patients. The pooled data showed that oral NAC did not reduce the CIN incidence [relative risk 0.84, 95% confidence interval (CI) 0.65–1.10; P=0.20], without heterogeneity among trials (I2=29%). Thus, the present meta-analysis suggests that oral NAC therapy is not effective as an alternative treatment to prevent CIN in patients following angioplasty. Further high quality randomized clinical controlled trials are required to confirm the usage and availability of this treatment.

N-acetylcysteine interference of Trinder-based assays

ObjectivesThe primary objective of this study was to evaluate potential interference of Trinder-based chemistry assays by N-acetylcysteine (NAC). A secondary objective was to look for evidence of interference in patients treated with NAC for acetaminophen (APAP) overdose. Design and methodsDilutions of NAC in plasma were tested for interference using the following Roche Diagnostics Trinder-based assays on a cobas 8000 system: enzymatic creatinine (Cr), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), triglycerides (TRIG), and uric acid (UA). Two non-Trinder Roche assays — urea nitrogen (BUN) and glucose (GLUC) — were tested as controls. Sekisui N-geneous® low-density lipoprotein cholesterol (LDL-C) reagent was also evaluated. Retrospective chart review of APAP overdose cases over 49months was conducted to look for differences in plasma Cr before and after intravenous (IV) NAC administration. ResultsNAC concentrations (shown in parentheses) that caused ≥10% inhibition for individual assays were (in order of sensitivity to interference): TRIG (570mg/L)>CHOL (740mg/L)≈Cr (790mg/L)>UA (1100mg/L)>HDL-C (1760mg/L)>LDL-C (2900mg/L). Neither BUN nor GLUC achieved significant inhibition up to 10,000mg/L NAC. Evidence for relatively minor inhibition of Cr was observed in patients after NAC administration. ConclusionsNAC inhibition of the assays investigated typically occurs at concentrations higher than expected during IV and oral NAC therapy.

Assessment of the Clinical Use of Intravenous and Oral N-Acetylcysteine in the Treatment of Acute Acetaminophen Poisoning in Children: A Retrospective Review

Background N-acetylcysteine (NAC) is the most effective therapy for acetaminophen (APAP) toxicity and is currently available for oral and intravenous (IV) administration. Although both routes are effective, use of the IV formulation has been increasing since becoming available in the United States in 2004, raising questions about cost/benefit comparisons between the 2 formulations. Decreased length of treatment and hospital stay have been used to justify the use of IV NAC; however, some patients may receive extended therapy of either NAC regimen. Objective This retrospective review assessed the clinical use of oral and IV NAC in pediatric patients with APAP intoxication from June 1, 2004 through May 31, 2008. Methods Electronic medical charts for patients aged ≤21 years were identified with International Classification of Diseases, Ninth Revision (ICD-9) codes for APAP overdose. Descriptive statistics were used to describe the overall patient population and route of NAC administration. The primary outcome variable was the length of treatment with IV and oral NAC therapy. Results A total of 62 charts for patients with APAP toxicity were reviewed; 37 patients (60%) received IV NAC and 25 patients (40%) received oral NAC. The average lengths of treatment and stay for IV dosing were 23.5 hours (range, 17.6–54.9 hours) and 1.6 days (range, 1–3 days), respectively; those for oral dosing were 69.5 hours (range, 33–133 hours) and 1.95 days (range, 1–5 days), respectively. Of 16 patients who received oral NAC and were admitted for <3 days, 14 were transferred to an inpatient psychiatric unit and completed the 72-hour therapy. A total of 3 patients received extended NAC dosing—2 with IV dosing and 1 with oral dosing. Conclusions Based on our review, the majority of patients received recommended dosing of NAC therapy; however, 3 patients received extended NAC therapy. Patient-specific factors should be considered when assessing whether NAC therapy should be extended and if one route of administration may be preferred. ClinicalTrials.gov identifier: NCT00725179.

Use of N-acetylcysteine to reduce post-cardiothoracic surgery complications: a meta-analysis

Post-cardiothoracic surgery (CTS) complications (e.g. myocardial injury, renal dysfunction, atrial fibrillation) may occur as a result of enhanced systemic inflammation, perhaps provoked by an oxidative stress response. N-acetylcysteine (NAC) is a free radical scavenger antioxidant agent that may attenuate this physiologic response and reduce post-CTS complications. Thus, a meta-analysis was performed to help characterize the potential beneficial effects of perioperative NAC administration in patients undergoing CTS. A systematic literature search in MEDLINE, EMBASE and the Cochrane Library was conducted through April 2008. A search strategy using medical subject headings and text keywords was performed. Results are reported as odds ratios or weighted mean differences with accompanying 95% confidence intervals (CIs). Studies were pooled using a fixed-effect model. The primary outcomes included atrial fibrillation (AF), myocardial infarction (MI), stroke, acute kidney injury (AKI), need for renal replacement therapy (RRT), mortality and total hospital length-of-stay (LOS). Upon meta-analysis of 13 trials (n=1338 subjects), the use of NAC appeared to statistically significantly lower the odds of developing post-CTS AF by 36% (95%CI 2-58%) (n=6 studies). This corresponded to an 8% (1-15%) pooled risk difference and a number-needed-to-treat of 13. NAC did not appear to significantly alter any of the other meta-analysis endpoints. The exclusion of the study utilizing only oral NAC therapy and the study with lower internal validity did not affect the overall conclusions of our meta-analysis. Currently, the most compelling data for using NAC in CTS patients is in post-CTS AF prevention. However, additional, larger randomized controlled trials evaluating this and other postoperative complication endpoints are needed.

Effects of N-Acetyl-Cysteine on Endothelial Function and Inflammation in Patients with Type 2 Diabetes Mellitus

Endothelial dysfunction has been associated with premature vascular disease. There is increasing data that N-acetyl-cysteine (NAC) may prevent or improve endothelial dysfunction. The aim of this study was to assess the effects of NAC on endothelial function in patients with type 2 diabetes mellitus, a population at high risk for endothelial dysfunction. Twenty-four patients with diabetes mellitus were assigned randomly to initial therapy with either 900 mg NAC or placebo twice daily in a double-blind, cross-over study design. Flowmediated vasodilation (FMD) of the brachial artery was assessed at baseline, after four weeks of therapy, after a four-week wash-out period, and after another four weeks on the opposite treatment. Plasma and red blood cell glutathione levels and high-sensitivity C-reactive protein (CRP) were measured at all four visits. At baseline, FMD was moderately impaired (3.7±2.9%). There was no significant change in FMD after four weeks of NAC therapy as compared to placebo (0.1±3.6% vs. 1.2±4.2%). Similarly, there was no significant change in glutathione levels. However, median CRP decreased from 2.35 to 2.14 mg/L during NAC therapy (p=0.04), while it increased from 2.24 to 2.65 mg/L with placebo. No side effects were noted during the treatment period. In this double-blind, randomized cross-over study, four weeks of oral NAC therapy failed to improve endothelial dysfunction in patients with diabetes mellitus. However, NAC therapy decreased CRP levels, suggesting that this compound may have some efficacy in reducing systemic inflammation.

Acetaminophen intoxication and length of treatment: how long is long enough?

The currently recommended dosing scheme for treating acetaminophen overdose in the United States consists of a loading dose of oral N-acetylcysteine 140 mg/kg, followed by 70 mg/kg every 4 hours for 17 doses, for a total of 72 hours of oral N-acetylcysteine therapy. This protocol has been both effective and safe. We critically evaluated the evidence that supports reducing the course of N-acetylcysteine therapy from 72 hours to 24 or 36 hours. This shorter regimen offers important benefits for both the patient and the patient's family, such as increased drug tolerability and reduced hospital stay. Patients who intentionally ingested acetaminophen with harmful intent could receive appropriate psychosocial treatment more quickly. In addition, shorter courses of N-acetylcysteine therapy have positive financial ramifications by reducing the hospital stay by 1 or 2 days. Clearly, a shorter treatment regimen would not be appropriate for all patients, particularly those who seek treatment late (> 24 hrs after ingestion) and those with evidence of organ toxicity. In order to provide the necessary evidence to support a change in accepted clinical practice, further investigation on the safety and efficacy of a shorter N-acetylcysteine regimen should be conducted by clinical researchers in a controlled manner.

Urinary and Plasma Homocysteine and Cysteine Levels during Prolonged Oral N-Acetylcysteine Therapy

Acute administration of N-acetylcysteine (NAC) may induce alterations in plasma and urinary levels of homocysteine (Hcy) and cysteine (Cys). We studied the effects of continuous oral NAC therapy on different Hcy and Cys plasma and urinary forms in 40 healthy subjects assigned to three groups (groups A: n = 13, no therapy; group B: n = 14, NAC 600 mg/day, and group C: n = 14, NAC 1,800 mg/day) for 1 month (T₁). After a 1-month washout period without therapy (T₂), all subjects were treated with oral NAC (1,800 mg/day) for 2 months and (T₃ and T₄) reassessed monthly for plasma and urinary thiols. The treated subjects showed a significant decrease in plasma total Hcy and a slight increase in total Cys levels; the alterations of different forms of plasma thiols suggested an NAC-induced increase in disulfide forms and an increase in urinary Hcy and Cys excretion as disulfide forms. The effects appeared to be dose dependent, being more marked in subjects treated with higher dosages. This approach may be important, as an association or alternative therapy in hyperhomocysteinemic conditions of poor responses to vitamins.

The effect of N-acetylcysteine on plasma total homocysteine levels in hemodialysis: A randomized, controlled study

Background: The chronic hemodialysis population has an accelerated rate of cardiovascular morbidity and death. Furthermore, elevated levels of the putative atherothrombotic risk factor homocysteine are almost ubiquitous in this population. Attempts to normalize elevated plasma total homocysteine (tHcy) levels in dialysis patients using pharmacological-dose vitamin therapy or other strategies generally have been unsuccessful. Preliminary uncontrolled evidence suggests that N-acetylcysteine (NAC) may be an effective tHcy-lowering agent. We designed a randomized placebo-controlled study to determine the effect of prolonged oral NAC therapy on lowering tHcy levels in vitamin-replete chronic hemodialysis patients. Methods: Thirty-eight subjects were treated before intervention with a standard dialysis vitamin supplement to ensure a uniform vitamin-replete state. They were then block randomized to treatment with NAC, 1.2 g twice a day, for 4 weeks or matched placebo. Results: There were no significant baseline differences between the two groups, although differences in pyridoxal 5′-phosphate (active form of vitamin B6) levels approached significance (P = 0.06). In a paired analysis, there was no statistically significant difference between the NAC and placebo groups. NAC was very well tolerated in hemodialysis patients. Conclusion: This randomized placebo-controlled trial found that chronic oral NAC therapy did not significantly reduce tHcy levels in hemodialysis patients. Although a larger sample size theoretically could have increased the statistical significance between groups, implications of the potentially very modest reduction in tHcy levels are not yet known. Finally, based on this limited study, NAC appears to be a safe and well-tolerated therapy in the hemodialysis population. Am J Kidney Dis 41:442-446.

Shorter duration of oral N -Acetylcysteine therapy for acute acetaminophen overdose

Study objective: We sought to evaluate the safety and efficacy of a shorter N -acetylcysteine (NAC) regimen in the treatment of acute acetaminophen overdose. Methods: We performed a retrospective case series in a large urban county hospital. Of 305 patients identified through the emergency department, 75 patients met the criteria inclusion: an acute overdose ingestion, serum acetaminophen concentration in toxic range according to the Rumack-Matthew nomogram, and oral NAC treatment initiated within 24 hours of the ingestion. The regional poison control center recommended oral treatment with NAC 140 mg/kg, followed by maintenance doses of 70 mg/kg every 4 hours until the serum acetaminophen level was no longer detectable, rather than the standard 72-hour treatment regimen. Results: The primary outcome measure was the development of hepatotoxicity. Twenty-five (33.3%) patients were treated for a period of less than 24 hours, 25 (33.3%) were treated for 24 to 36 hours, and 25 (33.3%) were treated for 37 to 64 hours; the mean and median duration of treatment was 31 hours. None of the patients treated for less than 24 hours had evidence of hepatotoxicity (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] level >1,000 IU/L); hepatotoxicity developed in 2 (8%) patients treated for 24 to 36 hours and 4 (16%) patients treated for 37 to 64 hours. There were no deaths or patients who received liver transplantation. The overall incidence of hepatotoxicity in our patients was similar to that found in other protocols with administration of oral NAC for 72 hours or intravenous NAC for 20 or 48 hours. Conclusion: This observational study suggests that a shorter course of oral NAC therapy in patients who do not show evidence of hepatotoxicity within 36 hours of an acute acetaminophen overdose is safe and effective. [Woo OF, Mueller PD, Olson KR, Anderson IB, Kim SY. Shorter duration of oral N -acetylcysteine therapy for acute acetami-nophen overdose. Ann Emerg Med . April 2000;35:363-368.]

An adolescent case of sulfhemoglobinemia associated with high-dose metoclopramide and N-Acetylcysteine

We describe the case of an adolescent girl who received high-dose metoclopramide in combination with oral N-acetylcysteine therapy for acute acetaminophen toxicity. Whole blood-sample analysis for abnormal hemoglobin pigments established the diagnosis of sulfhemoglobinemia. Metoclopramide has been shown to cause sulfhemoglobinemia, particularly when used in repeated high doses. Although N-acetylcysteine alone has not been associated as the cause, we suggest that sulfhemoglobinemia is a potential complication in patients treated with metoclopramide for the nausea that often accompanies oral N-acetylcysteine therapy for acetaminophen toxicity. Cyanosis without respiratory distress should suggest this diagnosis.

Systematic review of N‐acetylcysteine in cystic fibrosis

A systematic review was carried out to evaluate whether the use of N‐acetylcysteine to improve lung function in patients with cystic fibrosis is supported by published evidence. Medline and the Cochrane Library were searched and the reference lists of all retrieved papers and of relevant chapters of three major textbooks were scanned. Data on lung function (forced expiratory volume in one second (FEV1)) were extracted from controlled clinical trials and pooled as weighted mean differences for analysis. Twenty‐three studies, mostly uncontrolled clinical observations, were retrieved. Only three randomized controlled clinical trials on nebulized N‐acetylcysteine in cystic fibrosis were found, not showing any beneficial effect on lung function. Six randomized controlled clinical trials on oral N‐acetylcysteine in cystic fibrosis were found, with a total number of 181 patients. There was a tendency towards a beneficial effect on lung function of oral N‐acetylcysteine therapy on FEV1 but it was small (2.3%, 95% CI from (−0.3 to 4.9% of predicted) and of doubtful clinical relevance. In all studies, follow‐up was 3 months or shorter. In conclusion, at present there is no evidence supporting the use of N‐acetylcysteine in cystic fibrosis, although a beneficial effect with long‐term use of N‐acetylcysteine in cystic fibrosis cannot be excluded.

A prospective evaluation of the effect of activated charcoal before oral N-acetylcysteine in acetaminophen overdose

To evaluate whether activated charcoal (AC) reduces the efficacy of subsequent oral N-acetylcysteine therapy during acute acetaminophen overdose. Prospective observational case series of all acute acetaminophen overdoses reported to three certified regional poison centers. TYPES OF PATIENTS: All patients with acute acetaminophen overdose in whom N-acetylcysteine therapy was initiated within 16 hours after ingestion. All patients were treated with oral N-acetylcysteine therapy for 72 hours. The decision to use AC was left to the treating physician without input from the investigator. One hundred twenty-two patients were evaluated. Maximum recorded SGOT levels of more than 125 U/mL were defined as evidence of hepatotoxicity. AC was used in addition to N-acetylcysteine in 82 of 122 patients. Hepatotoxicity developed in four of 82 patients who received AC versus ten of 40 patients who did not receive AC (P < .005). An increasing dose of N-acetylcysteine provided no additional benefit (P > .05). Spacing the administration of AC and oral N-acetylcysteine less than or more than two hours apart did not affect outcome (P > .05). Administration of AC before the administration of oral N-acetylcysteine in acetaminophen overdose does not reduce the efficacy of N-acetylcysteine therapy and may provide some additional hepatoprotective benefit. The practice of increasing the dose of oral N-acetylcysteine therapy after the administration of AC appears unwarranted.