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N-acetylcysteine use among patients undergoing cardiac surgery: A systematic review and meta-analysis of randomized trials.
Pereira, JEG, El Dib, R, Braz, LG, Escudero, J, Hayes, J, Johnston, BC
PloS one. 2019;(5):e0213862
Abstract
BACKGROUND Cardiac surgeries are complex procedures aiming to re-establish coronary flow and correct valvular defects. Oxidative stress, caused by inflammation and ischemia-reperfusion injury, is associated with these procedures, increasing the risk of adverse outcomes. N-acetylcysteine (NAC) acts as an antioxidant by replenishing the glutathione stores, and emerging evidence suggests that NAC may reduce the risk of adverse perioperative outcomes. We conducted a systematic review and meta-analysis to investigate the addition of NAC to a standard of care among adult patients undergoing cardiac surgery. METHODS We searched four databases (PubMed, EMBASE, CENTRAL, LILACS) from inception to October 2018 and the grey literaure for randomized controlled trials (RCTs) investigating the effect of NAC on pre-defined outcomes including mortality, acute renal insufficiency (ARI), acute cardiac insufficiency (ACI), hospital length of stay (HLoS), intensive care unit length of stay (ICULoS), arrhythmia and acute myocardial infarction (AMI). Reviewers independently screened potentially eligible articles, extracted data and assessed the risk of bias among eligible articles. We used the GRADE approach to rate the overall certainty of evidence for each outcome. RESULTS Twenty-nine RCTs including 2,486 participants proved eligible. Low to moderate certainty evidence demonstrated that the addition of NAC resulted in a non-statistically significant reduction in mortality (Risk Ratio (RR) 0.71; 95% Confidence Interval (CI) 0.40 to 1.25), ARI (RR 0.92; 95% CI 0.79 to 1.09), ACI (RR 0.77; 95% CI 0.44 to 1.38), HLoS (Mean Difference (MD) 0.21; 95% CI -0.64 to 0.23), ICULoS (MD -0.04; 95% CI -0.29 to 0.20), arrhythmia (RR 0.79; 95% CI 0.52 to 1.20), and AMI (RR 0.84; 95% CI 0.48 to 1.48). LIMITATIONS Among eligible trials, we observed heterogeneity in the population and interventions including patients with and without kidney dysfunction and interventions that differed in route of administration, dosage, and duration of treatment. This observed heterogeneity was not explained by our subgroup analyses. CONCLUSIONS The addition of NAC during cardiac surgery did not result in a statistically significant reduction in clinical outcomes. A large randomized placebo-controlled multi-centre trial is needed to determine whether NAC reduces mortality. REGISTRATION PROSPERO CRD42018091191.
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Chinese herbal medicines compared with N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis: Protocol for a systematic review.
Guo, J, Li, B, Li, W, Pan, Y, Wang, Z, Wu, Y, Wang, F
Medicine. 2018;(44):e13077
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Abstract
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a major public health problem worldwide. There is no curative treatment for IPF except lung transplantation. Chinese herbal medicines (CHMs) are widely used in the treatment of IPF in China. However, their effectiveness and safety are still obscure and deserve further investigation. The aim of the study was to assess the efficacy and safety of CHMs in treating IPF compared with N-acetylcysteine (NAC). METHODS This review summarizes and meta-analyzes randomized controlled trials (RCTs) of CHMs for the treatment of IPF. RCTs compare either CHMs alone or in combination with NAC or conventional medicine treatment (CMT) vs NAC alone or in combination with CMT have been included. The following electronic databases have been searched: PubMed, Cochrane Library, Embase, CNKI, CBM, VIP, and WANFANG DATA. The methodologic quality of RCTs has been assessed using the Cochrane risk assessment tool. All trials included are analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.3, R-3.5.1 software, and GRADE pro GDT web solution are used for data synthesis and analysis. RESULTS This review evaluates the effects of CHMs on acute exacerbation, mortality, the quality of life, 6-minute walking test distance, lung function (total lung capacity, diffusing capacity of the lungs for carbon monoxide, and forced vital capacity), partial pressure of oxygen in blood (PaO2), and safety in patients with IPF. CONCLUSION This review provides clear evidence to assess the effectiveness and safety of CHMs for IPF.
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N-Acetylcysteine for the Treatment of Psychiatric Disorders: A Review of Current Evidence.
Ooi, SL, Green, R, Pak, SC
BioMed research international. 2018;:2469486
Abstract
N-acetylcysteine, a sulphur-containing amino acid for the treatment of paracetamol overdose and chronic obstructive pulmonary disease, is a widely available off-the-shelf oral antioxidant supplement in many countries. With the potential to modulate several neurological pathways, including glutamate dysregulation, oxidative stress, and inflammation that can be beneficial to the brain functions, N-acetylcysteine is being explored as an adjunctive therapy for many psychiatric conditions. This narrative review synthesises and presents the current evidence from systematic reviews, meta-analyses, and latest clinical trials on N-acetylcysteine for addiction and substance abuse, schizophrenia, obsessive-compulsive and related disorders, and mood disorders. Good evidence exists to support the use of N-acetylcysteine as an adjunct treatment to reduce the total and negative symptoms of schizophrenia. N-acetylcysteine also appears to be effective in reducing craving in substance use disorders, especially for the treatment of cocaine and cannabis use among young people, in addition to preventing relapse in already abstinent individuals. Effects of N-acetylcysteine on obsessive-compulsive and related disorders, as well as on mood disorders, remain unclear with mixed reviews, even though promising evidence does exist. Larger and better-designed studies are required to further investigate the clinical effectiveness of N-acetylcysteine in these areas. Oral N-acetylcysteine is safe and well tolerated without any considerable adverse effects. Current evidence supports its use as an adjunctive therapy clinically for psychiatric conditions, administered concomitantly with existing medications, with a recommended dosage between 2000 and 2400 mg/day.
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Efficacy of N-Acetylcysteine in Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis.
Sun, T, Liu, J, Zhao, W
Medicine. 2016;(19):e3629
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Abstract
There are a number of conflicting reports describing the clinical outcomes of using N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis. We have, therefore, performed a meta-analysis to evaluate the efficacy of N-acetylcysteine, compared with control, for the treatment of idiopathic pulmonary fibrosis.Original controlled clinical trials evaluating the efficacy of N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis were included in the analysis. Searches for relevant articles were carried out in July 2014 by 2 independent researchers using PubMed, Embase, Cochrane Central, and Google Scholar. Change in forced vital capacity, change in percentage of predicted vital capacity, change in percentage of predicted carbon monoxide diffusing capacity, changes in 6 minutes walking test distance, rate of adverse events, and rate of death were expressed as outcomes using RevMan 5.0.1.Five trials, with a total of 564 patients, were included in this meta-analysis. The meta-analysis showed that the control group had significant decreases in percentage of predicted vital capacity (standardized mean difference [SMD] = 0.37; 95% confidence interval [CI]: 0.13 to -0.62; P = 0.003) and 6 minutes walking test distance (SMD = 0.25; 95% CI: 0.02-0.48; P = 0.04). There were no statistically significant differences in forced vital capacity (SMD = 0.07; 95% CI: -0.13-0.27; P = 0.52), percentage of predicted carbon monoxide diffusing capacity (SMD = 0.12; 95% CI: -0.06-0.30; P = 0.18), rates of adverse events (odd ratio = 4.50; 95% CI: 0.19-106.41; P = 0.35), or death rates (odd ratio = 1.79; 95% CI: 0.3-5.12; P = 0.28) between the N-acetylcysteine group and the control group.N-Acetylcysteine was found to have a significant effect only on decreases in percentage of predicted vital capacity and 6 minutes walking test distance. N-acetylcysteine showed no beneficial effect on changes in forced vital capacity, changes in predicted carbon monoxide diffusing capacity, rates of adverse events, or death rates.
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Treatment of idiopathic pulmonary fibrosis: a network meta-analysis.
Rochwerg, B, Neupane, B, Zhang, Y, Garcia, CC, Raghu, G, Richeldi, L, Brozek, J, Beyene, J, Schünemann, H
BMC medicine. 2016;:18
Abstract
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with high morbidity and mortality. Effective treatments for IPF are limited. Several recent studies have investigated novel therapeutic agents for IPF, but very few have addressed their comparative benefits and harms. METHODS We performed a Bayesian network meta-analysis (NMA) to assess the effects of different treatments for IPF on mortality and serious adverse events (SAEs). We searched MEDLINE and EMBASE for randomized controlled trials (RCTs) up to August 2015. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach served to assess the certainty in the evidence of direct and indirect estimates. We calculated the surface under the cumulative ranking curve (SUCRA) for each treatment. We included parallel group RCTs, including factorial designs, but excluded quasi-randomized and cross-over trials. Studies were only included if they involved adult (≥18 years of age) patients with IPF as defined by the 2011 criteria and examined one of the 10 interventions of interest (ambrisentan, bosentan, imatinib, macitentan, N-acetylcysteine, nintedanib, pirfenidone, sildenafil, prednisone/azathioprine/N-acetylcysteine triple therapy, and vitamin K antagonist). RESULTS A total of 19 RCTs (5,694 patients) comparing 10 different interventions with placebo and an average follow-up period of 1 year fulfilled the inclusion criteria. SUCRA analysis suggests nintedanib, pirfenidone, and sildenafil are the three treatments with the highest probability of reducing mortality in IPF. Indirect comparison showed no significant difference in mortality between pirfenidone and nintedanib (NMA OR, 1.05; 95% CrI, 0.45-2.78, moderate certainty of evidence), pirenidone and sildenafil (NMA OR, 2.26; 95% CrI, 0.44-13.17, low certainty of evidence), or nintedanib and sildenafil (NMA OR 2.40; 95% CrI, 0.47-14.66, low certainty of evidence). Sildenafil, pirfenidone, and nintedanib were ranked second, fourth, and sixth out of 10 for SAEs. CONCLUSION In the absence of direct comparisons between treatment interventions, this NMA suggests that treatment with nintedanib, pirfenidone, and sildenafil extends survival in patients with IPF. The SAEs of these agents are similar to the other interventions and include mostly dermatologic and gastrointestinal manifestations. Head-to-head comparisons need to confirm these findings.
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Comparing new treatments for idiopathic pulmonary fibrosis--a network meta-analysis.
Loveman, E, Copley, VR, Scott, DA, Colquitt, JL, Clegg, AJ, O'Reilly, KM
BMC pulmonary medicine. 2015;:37
Abstract
BACKGROUND The treatment landscape for idiopathic pulmonary fibrosis, a devastating lung disease, is changing. To investigate the effectiveness of treatments for idiopathic pulmonary fibrosis we undertook a systematic review, network meta-analysis and indirect comparison. METHODS We searched MEDLINE, EMBASE and The Cochrane library for relevant studies. Randomised controlled trials of pirfenidone, nintedanib or N-acetylcysteine were eligible. Predefined processes for selecting references, extracting data and assessing study quality were applied. Our network meta-analysis of published data used a fixed effect model. For forced vital capacity measures a standardised mean difference approach was used and converted to odds ratios for interpretation. RESULTS Of 1076 references, 67 were retrieved and 11 studies included. Studies were of reasonable size, populations were similar, and the overall quality was good. Only two treatments, pirfenidone (odds ratio 0.62, 95% credible interval 0.52, 0.74) and nintedanib (0.41, 95% credible interval 0.34, 0.51) produced a statistically significant slowing in the rate of forced vital capacity decline compared with placebo. In an indirect comparison, results indicate that nintedanib is statistically significantly better than pirfenidone in slowing forced vital capacity decline (odds ratio 0.67, 95% credible interval 0.51, 0.88). Results were stable in scenario analysis and random effects models. Indirect comparisons of mortality were not statistically significant between nintedanib and pirfenidone. CONCLUSIONS Two treatments show beneficial effects and when compared indirectly nintedanib appears to have superior benefit on forced vital capacity. Limitations to indirect comparisons should be considered when interpreting these results, however, our findings can be useful to inform treatment decisions.
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Efficacy of N-acetylcysteine in preventing atrial fibrillation after cardiac surgery: a meta-analysis of published randomized controlled trials.
Liu, XH, Xu, CY, Fan, GH
BMC cardiovascular disorders. 2014;:52
Abstract
BACKGROUND Atrial fibrillation is a common complication after cardiac surgery. The aim of this study is to evaluate whether N-acetylcysteine (NAC) could prevent postoperative atrial fibrillation (POAF). METHODS PubMed, Embase and Cochrane Center Register of Controlled Trials were searched from the date of their inception to 1 July 2013 for relevant randomized controlled trials (RCTs), in which NAC was compared with controls for adult patients undergoing cardiac surgery. Outcome measures comprised the incidence of POAF, all-cause mortality, length of intensive care unit (ICU) stay, hospital length of stay, and the incidence of cerebrovascular events. The meta-analysis was performed with the fixed-effect model or random-effect model according to the heterogeneity. RESULTS We retrieved ten studies enrolling a total of 1026 patients. Prophylactic NAC reduced the incidence of POAF (OR 0.56; 95% CI 0.40 to 0.77; P < 0.001) and all-cause mortality (OR 0.40; 95% CI 0.17 to 0.93; P = 0.03) compared with controls, but failed to reduce the stay in ICU and overall stay in hospital. No difference in the incidence of cerebrovascular events was observed. CONCLUSIONS Prophylactic use of NAC could reduce the incidence of POAF and all-cause mortality in adult patients undergoing cardiac surgery. However, larger RCTs evaluating these and other postoperative complication endpoints are needed.
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Measures used to treat contrast-induced nephropathy: overview of reviews.
Kwok, CS, Pang, CL, Yeong, JK, Loke, YK
The British journal of radiology. 2013;(1021):20120272
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OBJECTIVES Despite many interventions that have been tried, controversy remains regarding the efficacy of interventions for contrast-induced nephropathy (CIN), so we aimed to evaluate the best evidence from recent meta-analyses. METHODS We searched MEDLINE, EMBASE and the Cochrane library for interventions which have been used for CIN. We included only the most recent meta-analysis of each intervention. We extracted data on the methodology, quality and results of each meta-analysis. We performed narrative synthesis and adjusted indirect comparison of interventions that were shown to be statistically significant compared with a placebo. RESULTS We included 7 systematic reviews and meta-analyses involving 9 different interventions for CIN, with a total of 15 976 participants. A significantly decreased risk of CIN was reported in meta-analysis of the following interventions: N-acetylcysteine [odds ratio (OR) 0.65, 95% confidence interval (CI) 0.48-0.88, I(2)=64%], theophylline [relative risk (RR) 0.48, 95% CI 0.26-0.89, I(2)=44%], statins (RR 0.51, 95% CI 0.34-0.77, I(2)=0%) and sodium bicarbonate (RR 0.62, 95% CI 0.45-0.86, I(2)=49%). Furosemide was shown to increase the risk of CIN (RR 3.27, 95% CI 1.48-7.26, I(2)=0%). Other interventions such as renal replacement therapy, angiotensin-converting enzyme inhibitors, dopamine and fenoldapam failed to show any significant difference from the control group. CONCLUSION Although there is some evidence to suggest that N-acetylcysteine, theophylline, sodium bicarbonate and statins may reduce incidence of CIN, limitations in the study quality and heterogeneity preclude any firm recommendations. ADVANCES IN KNOWLEDGE N-acetylcysteine, theophylline, sodium bicarbonate and statins show some promise as potentially efficacious agents for preventing CIN, but more high-quality studies are needed before they can be recommended for use in routine practice.
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Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis.
Tam, J, Nash, EF, Ratjen, F, Tullis, E, Stephenson, A
The Cochrane database of systematic reviews. 2013;(7):CD007168
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BACKGROUND Cystic fibrosis is an inherited condition resulting in thickened, sticky respiratory secretions. Respiratory failure, due to recurrent pulmonary infection and inflammation, is the most common cause of mortality. Muco-active therapies (e.g. dornase alfa and nebulized hypertonic saline) may decrease sputum viscosity, increase airway clearance of sputum, reduce infection and inflammation and improve lung function. Thiol derivatives, either oral or nebulized, have shown benefit in other respiratory diseases. Their mode of action is likely to differ according to the route of administration. There are several thiol derivatives, and it is unclear which of these may be beneficial in cystic fibrosis. OBJECTIVES To evaluate the efficacy and safety of nebulized and oral thiol derivatives in people with cystic fibrosis. SEARCH METHODS We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, hand searches of relevant journals, abstract books and conference proceedings.Most recent search: 13 June 2013.We also conducted a PubMed search on 26 February 2013 for relevant published articles. SELECTION CRITERIA Randomized and quasi-randomized controlled trials comparing nebulized or oral thiol derivatives to placebo or another thiol derivative in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS The authors independently assessed trials for inclusion, analysed risk of bias and extracted data. MAIN RESULTS Searches identified 23 trials; nine trials (255 participants) are included, of these seven trials are more than 10 years old. Three trials of nebulized thiol derivatives were identified (one compared 20% N-acetylcysteine to 2% N-acetylcysteine; another compared sodium-2-mercaptoethane sulphonate to 7% hypertonic saline; and another compared glutathione to 4% hypertonic saline). Although generally well-tolerated with no significant adverse effects, there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments.Six trials of oral thiol derivatives were identified. Three trials compared N-acetylcysteine to placebo; one compared N-acetylcysteine, ambroxol and placebo; one compared carbocysteine to ambroxol; and one compared low and high-dose N-acetylcysteine. Oral thiol derivatives were generally well-tolerated with no significant adverse effects, however there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments. AUTHORS' CONCLUSIONS We found no evidence to recommend the use of either nebulized or oral thiol derivatives in people with cystic fibrosis. There are very few good quality trials investigating the effect of these medications in cystic fibrosis, and further research is required to investigate the potential role of these medications in improving the outcomes of people with cystic fibrosis.
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N-Acetylcysteine supplementation for the prevention of atrial fibrillation after cardiac surgery: a meta-analysis of eight randomized controlled trials.
Gu, WJ, Wu, ZJ, Wang, PF, Aung, LH, Yin, RX
BMC cardiovascular disorders. 2012;:10
Abstract
BACKGROUND Atrial fibrillation is the most common type of arrhythmia after cardiac surgery. An increasing body of evidence demonstrates that oxidative stress plays a pivotal role in the pathophysiology of atrial fibrillation. N-acetylcysteine (NAC) is a free radical scavenger, and may attenuate this pathophysiologic response and reduce the incidence of postoperative AF (POAF). However, it is unclear whether NAC could effectively prevent POAF. Therefore, this meta-analysis aims to assess the efficacy of NAC supplementation on the prevention of POAF. METHODS Medline and Embase were systematically reviewed for studies published up to November 2011, in which NAC was compared with controls for adult patients undergoing cardiac surgery. Outcome measures comprised the incidence of POAF and hospital length of stay (LOS). The meta-analysis was performed with the fixed-effect model or random-effect model according to the heterogeneity. RESULTS Eight randomized trials incorporating 578 patients provided the best evidence and were included in this meta-analysis. NAC supplementation significantly reduced the incidence of POAF (OR 0.62, 95% CI 0.41 to 0.93; P = 0.021) compared with controls, but had no effect on LOS (WMD -0.07, 95% CI -0.42 to 0.28; P = 0.703). CONCLUSIONS The prophylactic NAC supplementation may effectively reduce the incidence of POAF. However, the overall quality of current studies is poor and further research should focus on adequately powered randomized controlled trials with POAF incidence as a primary outcome measure.