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N-Acetylcysteine's Role in Sepsis and Potential Benefit in Patients With Microcirculatory Derangements.
Chertoff, J
Journal of intensive care medicine. 2018;(2):87-96
Abstract
OBJECTIVE To review the data surrounding the utility of N-acetylcysteine (NAC) in sepsis and identify areas needed for additional research. DATA SOURCES A review of articles describing the mechanisms of action and clinical use of NAC in sepsis. SUMMARY OF REVIEW Despite many advances in critical care medicine, still as many as 50% of patients with septic shock die. Treatments thus far have focused on resuscitation and restoration of macrocirculatory targets in the early phases of sepsis, with less focus on microcirculatory dysfunction. N-acetylcysteine, due to its anti-inflammatory and antioxidative properties, has been readily investigated in sepsis and has yielded largely incongruous and disappointing results. In addition to its known anti-inflammatory and antioxidative roles, one underappreciated property of NAC is its ability to vasodilate the microcirculation and improve locoregional blood flow. Some investigators have sought to capitalize on this mechanism with promising results, as evidenced by microcirculatory vasodilation, improvements in regional blood flow and oxygen delivery, and reductions in lactic acidosis, organ failure, and mortality. CONCLUSION In addition to its antioxidant and anti-inflammatory properties, N-acetylcysteine possesses vasodilatory properties that could benefit the microcirculation in sepsis. It is imperative that we investigate these properties to uncover NAC's full potential for benefit in sepsis.
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Comparative efficacy of pharmacological interventions for contrast-induced nephropathy prevention after coronary angiography: a network meta-analysis from randomized trials.
Ma, WQ, Zhao, Y, Wang, Y, Han, XQ, Zhu, Y, Liu, NF
International urology and nephrology. 2018;(6):1085-1095
Abstract
BACKGROUND Contrast-induced nephropathy (CIN) is the major complication related to contrast media administration in patients after coronary angiography (CAG). However, inconsistent results have been published in the literature regarding the effects of pharmacological drugs on CIN prevention. We conducted a network meta-analysis to evaluate the relative efficacy of pharmacological interventions for the prevention of CIN. METHODS We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to July 2017. We included any randomized controlled trials of eleven pharmacological interventions that reported the prevention of CIN. RESULTS We identified 3850 records through database searches, of which 107 studies comprising 21,450 participants were finally identified. Compared with intravenous saline, intravenous saline plus pharmacological drugs including statin [relative risk (RR) 0.57; 95% credibility interval (CrI) 0.39 to 0.83], N-acetylcysteine (NAC) (RR 0.84; 95% CrI, 0.71 to 0.98), vitamin and its analogues (RR 0.66; 95% CrI 0.45 to 0.97), brain natriuretic peptide (BNP) and its analogues (RR 0.46; 95% CrI 0.30 to 0.70), prostaglandin analogues (RR 0.37; 95% CrI 0.18 to 0.76), NAC plus sodium bicarbonate (SB) (RR 0.60; 95% CrI 0.39 to 0.90), and statin plus NAC (RR 0.39; 95% CrI 0.21 to 0.70), have helped to reduce the incidence of CIN in patients after CAG. The top four ranked treatments were statin plus NAC, BNP and its analogues, statin, and vitamin and its analogues, respectively. NAC plus intravenous saline was associated with lower incidence of short-term all-cause mortality than intravenous saline alone (RR 0.62; 95% CI, 0.40 to 0.96; P = 0.03). However, no evidence indicated that any of the pharmacological drugs were associated with a reduced requirement for dialysis and major adverse cardiac and cerebrovascular events (MACCE). CONCLUSIONS Statin plus NAC plus intravenous saline seems to be the most effective treatment for the prevention of CIN in patients after CAG. NAC plus intravenous saline may have a protective role against short-term all-cause mortality. However, none of these drugs has effectively decreased the requirement for dialysis and MACCE.
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Efficacy of N-Acetylcysteine in Preventing Acute Kidney Injury After Cardiac Surgery: A Meta-Analysis Study.
Mei, M, Zhao, HW, Pan, QG, Pu, YM, Tang, MZ, Shen, BB
Journal of investigative surgery : the official journal of the Academy of Surgical Research. 2018;(1):14-23
Abstract
PURPOSE To evaluate whether perioperative N-acetylcysteine (NAC) administration reduces the risk of cardiac surgery associated acute kidney injury (CSA-AKI). MATERIALS AND METHODS A systematic literature review (Medline, PubMed, Cochrane, Biomedical central, Google Scholar) identified 10 studies (1391 patients; 695 NAC and 696 placebo) that compared the efficacy and adverse effects of perioperative NAC administration for CSA-AKI prevention in adults undergoing elective cardiac surgery. Meta-analysis was performed using Comprehensive Meta-Analysis statistical software. RESULTS Patients in the NAC-treated and placebo groups had similar rate of CSA-AKI occurrence, change in creatinine levels, as well as the in-hospital mortality rate (RR = 0.841, 95% CI = 0.691 to 1.023, p = 0.083; pooled difference in means = -0.328, 95% CI = -0.712 to 0.056, p = 0.094; RR = 0.741, 95% CI = 0.388 to 1.418, p = 0.366, respectively). CONCLUSIONS Our study does not support perioperative NAC administration as a mean to reduce the risk of CSA-AKI.
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Evaluating the Effect of Oral N-acetylcysteine as an Adjuvant Treatment on Clinical Outcomes of Patients with Rheumatoid Arthritis: A Randomized, Double Blind Clinical Trial.
Batooei, M, Tahamoli-Roudsari, A, Basiri, Z, Yasrebifar, F, Shahdoust, M, Eshraghi, A, Mehrpooya, M, Ataei, S
Reviews on recent clinical trials. 2018;(2):132-138
Abstract
OBJECTIVE Oxidative stress and Overproduction of pro-inflammatory cytokines are contributed in Rheumatoid Arthritis (RA) pathogenesis. N-acetylcysteine (NAC) is an antioxidant and antiinflammatory agent which demonstrated analgesic effects in some studies. This study is designed to assess the effects of oral NAC as an adjuvant therapy on the clinical outcomes of patients with active RA. METHODS In this randomized clinical trial, 51 RA patients with active RA were studied in 2 groups: NAC group (27 patients) received standard treatment of RA and 600 mg NAC twice a day for 12 weeks, and placebo group (24 patients) received the standard treatment of RA and placebo. Disease activity score (DAS28) was used to assess the activity of RA, Visual Analog Scale (VAS) for the severity of pain, Health Assessment Questionnaire (HAQ) for the patients' physical performance, and Global Health (GH) parameter for the patients' assessment of their disease activity. The number of tender and swollen joints and Erythrocyte Sedimentation Rate (ESR) were also determined for each patient. Data were analyzed using SPSS version 16.0 (Chicago, IL, USA). RESULTS After 12 weeks of intervention, there were no significant differences between two groups in DAS28 score and ESR (P values were 0.4 and 0.6, respectively). However, GH, VAS, and HAQ scores were improved significantly in the NAC group compared to the placebo group. CONCLUSION Our findings indicate that oral administration of NAC may be associated with improving health status in RA patients and considered as an adjuvant therapy in these patients. Further studies with larger sample size, longer study duration and higher doses of NAC are needed to confirm the effects of oral NAC in RA patients.
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Efficacy of Granulocyte Colony-Stimulating Factor and N-Acetylcysteine Therapies in Patients With Severe Alcoholic Hepatitis.
Singh, V, Keisham, A, Bhalla, A, Sharma, N, Agarwal, R, Sharma, R, Singh, A
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2018;(10):1650-1656.e2
Abstract
BACKGROUND & AIMS Patients with alcoholic hepatitis (AH) have high mortality, so new therapies are needed. Administration of granulocyte colony stimulating factor (G-CSF) increases survival times of patients with AH. It is not known whether addition of N-acetyl cysteine (NAC) to G-CSF could further increase survival time. We performed a randomized controlled pilot study to compare the efficacy of standard medical therapy with pentoxifylline to treatment with a combination of G-CSF and standard medical therapy as well as to the combination of NAC, G-CSF, and standard medical therapy in patients with severe AH. METHODS We performed an open-label, single-center study of 57 patients with severe AH admitted to a Liver Intensive Care unit in India from October 2014 through March 2017. Patients were randomly assigned to groups that received standard medical therapy (with pentoxifylline) plus G-CSF for 5 days (G-CSF group; n = 18), standard medical therapy plus G-CSF and intravenous NAC for 5 days (combination group; n = 19), or standard medical therapy alone (n = 20). Clinical data and blood samples were collected at baseline; on day 6; and 1, 2, and 3 months after the study began. CD34+ cells were measured in blood samples collected on days 0 and 6. The primary outcome was proportion of patients surviving for 90 days. Secondary outcomes were mobilization of CD34+ cells at day 6, as well as Child Turcotte Pugh, model for end-stage liver disease, and modified discriminant function scores until day 90. RESULTS Significantly higher proportions of patients in the G-CSF group (16/18) and the combination group (13/19) survived for 90 days than in the standard medical therapy group (6/20) (P = .0001 for G-CSF group and P = .037 and combination group). The GGSF and combination groups each had increased numbers of CD34+ cells from baseline until day 6, compared with the standard medical therapy group. The G-CSF group (but not the combination group) had significantly larger median reductions in modified discriminant function scores at study months 1 (reduction of 60.36%), 2 (reduction of 75.36%), and 3 (reduction of 88.73%) vs the standard medical therapy group (P = .02; P = .05; and P = .00, respectively). The G-CSF group had a significantly larger median reduction in model for end-stage liver disease score at 3 months (reduction of 55.77%; P = .01), but not in Child Turcotte Pugh score, compared with the standard medical therapy group. All groups had similar numbers of complications. CONCLUSION In a pilot randomized controlled trial, we found administration of G-CSF to improve liver function and increase survival times in patients with severe AH, compared with standard therapy. We found no evidence for benefit of adding NAC to G-CSF. These findings require confirmation in larger trials. ClincialTrials.gov, number: NCT02971306.
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Lessons learned from the PRESERVE trial.
Partovi, S, Trischman, T, Kang, PS
The British journal of radiology. 2018;(1087):20180092
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Abstract
The recently published Prevention of Serious Adverse Events Following Angiography (PRESERVE) trial is presently the largest and most comprehensive clinical trial comparing commonly applied strategies for prevention of iodinated contrast-induced acute kidney injury in high-risk patients. The fundamental conclusion of the PRESERVE trial is that oral acetylcysteine and i.v. sodium bicarbonate are not superior to simple i.v. hydration with isotonic saline for the prevention of contrast-induced renal sequelae. In this commentary, we discuss the results in the context of selected past major trials, and provide insights into the strengths and potential weaknesses of the PRESERVE trial. In the future, developing individualized preventive approaches to avoid contrast-induced acute kidney injury for different patient populations is recommended.
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Long-Term Protective Effect of N-Acetylcysteine against Amikacin-Induced Ototoxicity in End-Stage Renal Disease: A Randomized Trial.
Vural, A, Koçyiğit, İ, Şan, F, Eroğlu, E, Ketenci, İ, Ünal, A, Tokgöz, B, Ünlü, Y
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 2018;(1):57-62
Abstract
BACKGROUND The aim of the study is to evaluate the long-term protective effect of N-acetylcysteine (NAC), an antioxidant agent, against aminoglycoside (AG)-induced ototoxicity. METHODS A total of 40 patients receiving continuous ambulatory peritoneal dialysis (CAPD) and having their first peritonitis attacks and planned to be treated with AGs were enrolled in the study. They were randomized into 2 groups: 1 group received additional NAC and the other did not. All patients underwent hearing tests with pure tone audiometry (PTA) after the diagnosis, at 1 month and 12 months and at the same time the tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured. RESULTS Patients taking NAC had better hearing test results in both ears at 1 month except 2,000 Hz for the left ear, which wasn't significantly different between the 2 groups. Although patients taking NAC had generally better PTA results at 12 months, differences between the 2 groups were not statistically significant. Baseline IL-6 level was significantly higher in the NAC group than the control group. Both TNF-α and IL-6 levels at 1 month were significantly lower in the NAC group than in the control group. On the other hand, there was no significant difference between the 2 groups in terms of TNF-α and IL-6 levels at 12 months. CONCLUSIONS The results of the current study showed that NAC, a potent anti-inflamatory drug, may be otoprotective, but that the effect is not long-lasting.
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Modern Management of Acute Liver Failure.
Khan, R, Koppe, S
Gastroenterology clinics of North America. 2018;(2):313-326
Abstract
Acute liver failure is a rare but life-threatening disease that can lead to progressive encephalopathy, intracranial hypertension, and multiorgan failure. In the developed world, the most common cause remains acetaminophen overdose, but there are still many cases in which there is acute liver failure of unknown etiology. The mainstay of acute liver failure management remains supportive care in the critical care setting. If supportive treatment does not stabilize the disease process, the patient may require emergent liver transplantation. This article summarizes the current management of acute liver failure.
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The effect of N-acetylcysteine and working memory training on cocaine use, craving and inhibition in regular cocaine users: correspondence of lab assessments and Ecological Momentary Assessment.
Schulte, MHJ, Wiers, RW, Boendermaker, WJ, Goudriaan, AE, van den Brink, W, van Deursen, DS, Friese, M, Brede, E, Waters, AJ
Addictive behaviors. 2018;:24-31
Abstract
INTRODUCTION Effective treatment for cocaine use disorder should dampen hypersensitive cue-induced motivational processes and/or strengthen executive control. Using a randomized, double-blind, placebo-controlled intervention, the primary aim of this study was to investigate the effect of N-Acetylcysteine (NAC) and working memory (WM)-training to reduce cocaine use and craving and to improve inhibition assessed in the laboratory and during Ecological Momentary Assessment (EMA). The second aim was to examine correspondence between laboratory and EMA data. METHODS Twenty-four of 38 cocaine-using men completed a 25-day intervention with 2400mg/day NAC or placebo and WM-training as well as two lab-visits assessing cocaine use, craving and inhibition (Stop Signal task). Additionally, cocaine use, craving and cognition (Stroop task) were assessed using EMA during treatment, with 26 participants completing 819 assessments. RESULTS Cocaine problems according to the Drug Use Disorder Identification Test (DUDIT) decreased more after NAC than after placebo, and the proportion of cocaine-positive urines at lab-visit 2 was lower in the NAC group. No NAC effects were found on craving. For cocaine use and craving, results from the lab data were generally similar to EMA results. NAC also showed some effects on cognitive control: improved inhibition assessed with the Stop Signal task in the lab, and decreased classic Stroop performance during EMA. There were no significant effects of number of completed WM-training sessions. CONCLUSIONS Overall this study revealed mixed findings regarding the treatment of cocaine use disorders with NAC and WM-training. The effect of NAC on inhibition should be further investigated.
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The role of depressive symptoms in treatment of adolescent cannabis use disorder with N-Acetylcysteine.
Tomko, RL, Gilmore, AK, Gray, KM
Addictive behaviors. 2018;:26-30
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Abstract
Relative to adults, adolescents are at greater risk of developing a cannabis use disorder (CUD) and risk may be exacerbated by co-occurring depressive symptoms. N-Acetylcysteine (NAC), an over-the-counter antioxidant, is thought to normalize glutamate transmission. Oxidative stress and glutamate transmission are disrupted in both depression and CUD. Thus, NAC may be particularly effective at promoting cannabis abstinence among adolescents with elevated depressive symptoms. Secondary analyses were conducted using a sub-sample of adolescents with CUD (N = 74) who participated in an 8-week randomized placebo-controlled clinical trial examining the efficacy of NAC for cannabis cessation. It was hypothesized that NAC would reduce severity of depressive symptoms, and that decreases depressive symptom severity would mediate decreases in positive weekly urine cannabinoid tests (11-nor-9-carboxy-Δ9-tetrahydrocannabinol). Additionally, it was expected that adolescents with greater severity of baseline depressive symptoms would be more likely to become abstinent when assigned NAC relative to placebo. Results from linear mixed models and generalized estimating equations did not suggest that NAC reduced severity of depressive symptoms, and the hypothesis that NAC's effect on cannabis cessation would be mediated by reduced depressive symptoms was not supported. However, an interaction between treatment condition and baseline severity of depressive symptoms as a predictor of weekly urine cannabinoid tests was significant, suggesting that NAC was more effective at promoting abstinence among adolescents with heightened baseline depressive symptoms. These secondary findings, though preliminary, suggest a need for further examination of the role of depressive symptoms in treatment of adolescent CUD with NAC.