Oral NAC Research Articles

ORAL N-ACETYL CYSTEINE VERSUS RECTAL INDOMETHACIN FOR PREVENTION OF POST ERCP PANCREATITIS: A MULTICENTER MULTINATIONAL RANDOMIZED CONTROLLED TRIAL.

This multicenter multinational RCT designed to compare the efficacy of suppository indomethacin and NAC for prevention of PEP. During a 6-month period, all of the ERCP cases in seven referral centers were randomly assigned to receive either 1200 mg oral NAC, indomethacin suppository 100 mg, 1200 mg oral NAC plus indomethacin suppository 100 mg or placebo 2 hours before ERCP. The primary outcomes were the rate and severity of any PEP. A total of 432 patients included (41.4% male). They were originally citizens of 6 countries (60.87% Caucasian). They were randomly allocated to receive either NAC (group A, 84 cases), rectal indomethacin (group B, 138 cases), NAC + rectal indomethacin (group C, 115 cases) or placebo (group D, 95 cases). The rate of PEP in groups A, B and C in comparison with placebo were 10.7%, 17.4%, 7.8% vs 20% (P=0.08, 0.614 & 0.01 respectively). The NNT for NAC, indomethacin and NAC + indomethacin was 11, 38 and 8 respectively. Oral NAC is more effective than rectal indomethacin when compared to placebo for prevention of PEP and the combination of NAC and Indomethacin had the lowest incidence of PEP and may have synergistic effect in preventing of PEP (IRCT20201222049798N1; 29/12/2020).

The effect of N-acetylcysteine in patients with non-cystic fibrosis bronchiectasis (NINCFB): study protocol for a multicentre, double-blind, randomised, placebo-controlled trial

BackgroundN-acetylcysteine (NAC), which is specifically involved in airway mucus clearance and antioxidation, is recommended by the treatment guideline for non-cystic fibrosis bronchiectasis (NCFB). However, there is little clinical evidence of its long-term efficacy concerning quality of life (QoL) and exacerbation in patients with NCFB. In addition, the influences of NAC on airway bacterial colonization, chronic inflammation and oxidative stress in NCFB are also unclear.MethodsNINCFB is a prospective, multicentre, double-blind, randomised, placebo-controlled trial that will recruit 119 patients with NCFB and randomly divide them into an NAC group (n = 79) and a control group (n = 40). Participants in the NAC group will receive 600 mg oral NAC twice daily for 52 weeks, while patients in the control group will receive 600 mg placebo twice daily for 52 weeks. The information at baseline will be collected once participants are enrolled. The primary endpoints are the changes in St George’s Respiratory Questionnaire scores and the number of exacerbations in 52 weeks. The secondary endpoints are the 16S rRNA of sputum and the levels of inflammatory factors and oxidative stressors in sputum and serum. Other data related to radiography, lung function tests, number of oral and/or intravenous antibiotic therapies and adverse events (AEs) will also be analysed. Further subgroup analysis distinguished by the severity of disease, severity of lung function, airway bacterial colonization and exacerbation frequency will be performed.DiscussionThe objective of this study is to determine the long-term efficacy of NAC on QoL and exacerbation of NCFB and to explore the effectiveness of NAC for antibiosis, anti-inflammation and antioxidation in NCFB. The study results will provide high-quality clinical proof for the revision and optimization of treatment guidelines and for expert consensus on NCFB treatment.Trial registrationThe trial was registered on the Chinese Clinical Trial Register at April 11, 2020 (chictr.org.cn, ChiCTR2000031817).

A Systematic Review of the Effect of N-Acetylcysteine on Serum Creatinine and Cystatin C Measurements

IntroductionN-acetylcysteine (NAC) is an antioxidant that can regenerate glutathione and is primarily used for acetaminophen overdose. NAC has been tested and used for preventing iatrogenic acute kidney injury or slowing the progression of chronic kidney disease, with mixed results. There are conflicting reports that NAC may artificially lower measured serum creatinine without improving kidney function, potentially by assay interference. Given these mixed results, we conducted a systematic review of the literature to determine whether there is an effect of NAC on kidney function as measured with serum creatinine and cystatin C.MethodsA literature search was conducted to identify all study types reporting a change in serum creatinine after NAC administration. The primary outcome was change in serum creatinine after NAC administration. The secondary outcome was a change in cystatin C after NAC administration. Subgroup analyses were conducted to assess effect of creatinine assay (Jaffe vs. non-Jaffe and intravenous vs. oral).ResultsSix studies with a total of 199 participants were eligible for the systematic review and meta-analysis. There was a small but significant decrease in serum creatinine after NAC administration overall (weighted mean difference [WMD], −2.80 μmol/L [95% confidence interval {CI} −5.6 to 0.0]; P = 0.05). This was greater with non-Jaffe methods (WMD, −3.24 μmol/L [95% CI −6.29 to −0.28]; P = 0.04) than Jaffe (WMD, −0.51 μmol/L [95% CI −7.56 to 6.53]; P = 0.89) and in particular with intravenous (WMD, −31.10 μmol/L [95% CI −58.37 to −3.83]; P = 0.03) compared with oral NAC (WMD, −2.5 μmol/L [95% CI −5.32 to 0.32]; P = 0.08). There was no change in cystatin C after NAC administration.DiscussionNAC causes a decrease in serum creatinine but not in cystatin C, suggesting analytic interference rather than an effect on kidney function. Supporting this, the effect was greater with non-Jaffe methods of creatinine estimation. Future studies of NAC should use the Jaffe method of creatinine estimation when kidney outcomes are being reported. Even in clinical settings, the use of an enzymatic assay when high doses of intravenous NAC are being used may result in underdiagnosis or delayed diagnosis of acute kidney injury.

P0917N-ACETYL CYSTEINE FAILS TO IMPACT ON PLASMA ANTIOXIDANT CAPACITY IN BOTH A PLACEBO CONTROLLED CROSSOVER STUDY AND A PARALLEL GROUP TRIAL OF PATIENTS WITH CKD STAGE III: IMPLICATIONS FOR ITS USE AS A PROPHYLACTIC FOR CONTRAST INDUCED NEPHROPATHY

Abstract This project has been funded by the EU’s INTERREG VA programme, managed by the special EU Programmes Body (SEUPB) Background and Aims N-acetyl-L-cysteine (NAC) has been proposed as a prophylactic for the prevention of contrast induced nephropathy (CIN), a serious, adverse complication following administration of contrast media in patients with diabetes and chronic kidney disease (CKD). However, clinical trial results have failed to demonstrate consistently the beneficial qualities of NAC in this setting. The suggested mechanism by which NAC has been proposed to be effective is via antioxidant activity, but NAC itself appears not to be a powerful antioxidant; intracellular conversion of NAC to glutathione (GSH) is essential for antioxidant effects. We tested the hypothesis that oral or intravenous NAC fails to increase antioxidant activity in the plasma of healthy volunteers or CKD stage III patients undergoing elective coronary angiography. Method 16 healthy volunteers (8 receiving contrast media) and 8 patients with chronic renal failure were recruited to 3 separate groups as a part of a crossover design study. 66 patients with CKD stage III undergoing elective coronary angiography were recruited to a parallel group randomized controlled trial. Each volunteer or patient was randomised to receive NAC (i.v.; 50 mg/kg/hr infusion for 2 h, followed by 20 mg/kg/hr infusion for a further 5 h), or NAC (oral; 1200 mg twice daily, commencing the day before the study visit) or placebo. Participants attended the Clinical Research Facility on three occasions for the crossover groups, but only once in the parallel group trial. Patients were infused with para-aminohippurate (PAH) and inulin to enable measurement of renal function parameters. Plasma and paired buffy coat samples were collected at several time points for 2 hours before contrast infusion and for 6 hours after. Samples were used to measure various clinical parameters, along with intracellular and plasma thiol concentrations and the plasma antioxidant capacity (oxygen radical antioxidant capacity; ORAC). Results Plasma NAC concentrations peaked at 222 µM (healthy volunteers), 354 µM (CKD patients), 271 µM (healthy volunteers receiving contrast) and 348 µM (CKD patients undergoing elective coronary angiography) following infusion of NAC. The corresponding peak concentrations were ∼2 µM following oral NAC across all groups. No comparable increase in the plasma compartment ORAC antioxidant capacity was measured in any of the treatment groups. Equally, contrast infusion itself did not significantly reduce antioxidant capacity in plasma, even in the placebo group. Buffy coat measures showed that there was a significant increase of intracellular GSH in some patients. Also, no clear additional benefit was witnessed by increasing plasma NAC ∼100-fold through infusion of NAC over oral administration. Conclusion NAC fails to influence ORAC antioxidant capacity in the plasma compartment of CKD stage III patients receiving contrast media. Our results question the importance of oxidative stress in contrast-induced nephropathy. Furthermore, the findings fail to demonstrate a direct antioxidant impact of NAC in the plasma compartment and question the antioxidant hypothesis related to contrast-induced nephropathy and NAC.

Randomized controlled trial of N-acetylcysteine therapy for RYR1-related myopathies.

ObjectiveTo investigate the efficacy of N-acetylcysteine (NAC) for decreasing elevated oxidative stress and increasing physical endurance in individuals with ryanodine receptor 1-related myopathies (RYR1-RM).MethodsIn this 6-month natural history assessment (n = 37) followed by a randomized, double-blinded, placebo-controlled trial, 33 eligible participants were block-randomized (1:1) to receive NAC (n = 16) or placebo (n = 17), orally for 6 months (adult dose 2,700 mg/d; pediatric dose 30 mg/kg/d). The primary endpoint was urine 15-F2t isoprostane concentration and the clinically meaningful co-primary endpoint was 6-minute walk test (6MWT) distance.ResultsWhen compared to the general population, participants had elevated baseline 15-F2t isoprostane concentrations and most had a decreased 6MWT distance (mean ± SD 3.2 ± 1.5 vs 1.1 ± 1.7 ng/mg creatinine and 468 ± 134 vs 600 ± 58 m, respectively, both p < 0.001). 15-F2t isoprostane concentration and 6MWT distance did not change over the 6-month natural history assessment (p = 0.98 and p = 0.61, respectively). NAC treatment did not improve 15-F2t isoprostane concentration (least squares means difference 0.1 [95% confidence interval [CI] −1.4 to 1.6] ng/mg creatinine, p = 0.88) or 6MWT distance (least squares means difference 24 [95% CI −5.5 to 53.4] m, p = 0.11). NAC was safe and well-tolerated at the doses administered in this study.ConclusionIn ambulatory RYR1-RM–affected individuals, we observed stable disease course, and corroborated preclinical reports of elevated oxidative stress and decreased physical endurance. NAC treatment did not decrease elevated oxidative stress, as measured by 15-F2t isoprostane.Classification of evidenceThis study provides Class I evidence that, for people with RYR1-RM, treatment with oral NAC does not decrease oxidative stress as measured by 15-F2t isoprostane.Clinicaltrials.gov identifierNCT02362425.

1443. N-Acetyl Cysteine Coadministration in Prevention of Amphotericin--Induced Electrolytes Imbalances in Children

BackgroundAmphotericin B (AmB) can cause electrolyte abnormalities, including hypokalemia, hypomagnesemia, hypernatremia, and metabolic acidosis; and most important, acute renal failure.MethodsWe conducted a randomized prospective cohort study from March 2012 to February 2018 at Hacettepe University Ihsan Doğramacı Children Hospital to children receiving AmB.ResultsA total of 87 patients including 37 patients with NAC and 50 patients without NAC received liposomal amphotericin B during the study period.Serum creatinine, blood urea nitrogen, phosphorus were not different statistically in both groups during the study period. Serum sodium, potassium, calcium, phosphorus, magnesium values taken on third day of AmB treatment were not statistically different in both groups. Mean serum magnesium value was higher in NAC received group on the seventh day of AmB treatment; 1.97 ± 0.33 and 1.69 ± 0.46, respectively, it was statistically significant (P = 0.025). Mean serum magnesium value was also statistically significantly higher in NAC received group on the 14th day of treatment; 1.93 ± 0.20 and 1.72 ± 0.247, respectively, in both groups (P = 0.01). Mean serum sodium values on the 14th day of AmB treatment were also statistically different between 2 groups; 136.7 ± 3.7 and 140.04 ± 5.1, respectively (P = 0.005). Serum sodium values on the 14th day of AmB treatment was in more normal limits in NAC received group. Serum alanine aminotransferase level was significantly lower in NAC received group (P = 0.02). Serum aspartate aminotransferase level was significantly lower in NAC received group (P = 0.007). Nineteen of 37 (51.4%) patients who received NAC concomitantly with AmB and 44 of 50 patients (88%) who received AmB without NAC supplemented with potassium due to hypokalemia (P < 0.001). Two of NAC received 37 patients (5.4%) and 10 of NAC not received 50 patients (20%) died. Mortality was found 2.3 times more in NAC not-received group.ConclusionCo-treatment with oral NAC once daily in children during AmB treatment course was significantly effective in preventing or ameliorating different features of its nephrotoxicity including hypokalemia, hypomagnesemia, and renal potassium as well as magnesium wasting Disclosures All authors: No reported disclosures.

N-Acetyl cysteine does not improve repeated intense endurance cycling performance of well-trained cyclists

To evaluate the effect of antioxidant supplementation on intense endurance exercise performance and the physiologic exercise response acutely and in early recovery. Well-trained cyclists (n = 11, peak VO2: 69 ± 7ml/min/kg) completed two identical standardized 20-min warm-up periods (WU-1 and WU-2) prior to two performance tests (PT) with a duration of ~ 4min representing a qualifying (PT-1) and final race (PT-2) on the same day separated by 90min. Subjects were supplemented orally with placebo (PLA) and N-acetyl cysteine (NAC; 20mg/kg) before exercise in a double-blinded crossover design. Mean power during PT-1 did not differ (P = 0.39) between PLA (400 ± 44W) and NAC (401 ± 44W) as was the case during PT-2 with similar performance (P = 0.74) between PLA (401 ± 43W) and NAC (400 ± 42W). Subjective "readiness" was lowered by prior exhaustive exercise from PT-1 to PT-2 (P = 0.012) in both PLA and NAC. Plasma total antioxidant capacity was not affected by supplementation and prior exhaustive exercise (respective main effects: P = 0.83 and P = 0.19) which also was observed for peak VO2 at ~ 5L/min (P = 0.84 and P = 0.30). In WU-1 and WU-2, both cycling economy at ~ 20% (P = 0.10 and P = 0.21) and plasma potassium at ~ 5mmol/L (P = 0.46 and P = 0.26) were unaffected by supplementation and prior exercise. Athletes executing maximal efforts of a ~ 4-min duration twice daily, as seen in track cycling, appear to gain no benefit from oral NAC supplementation on acute and subsequent performance following short-term recovery. Moreover, well-trained cyclists exhibit rapid recovery from a single bout of intense endurance cycling.

Prophylactic oral NAC reduced poor hematopoietic reconstitution by improving endothelial cells after haploidentical transplantation

AbstractPoor graft function (PGF) and prolonged isolated thrombocytopenia (PT) remain life-threatening complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Endothelial cells (ECs) play a crucial role in regulating hematopoiesis in the bone marrow (BM) microenvironment. However, whether the impaired BM ECs are responsible for defective hematopoiesis in PGF and PT patients requires clarification, and clinical management is challenging. Two prospective clinical trials were included in the current study. In the first trial (N = 68), PGF and PT patients demonstrated defective BM ECs pre-HSCT and impaired BM EC dynamic reconstitution at early time points post-HSCT, which was positively correlated with reactive oxygen species (ROS) levels. Receiver operating characteristic curves showed that BM EC < 0.1% pre-HSCT could identify high-risk patients with PGF and PT. The second trial enrolled patients (N = 35) with EC < 0.1% who accepted oral N-acetyl-l-cysteine (NAC; 400 mg 3 times per day) from −14 days pre-HSCT to +2 months post-HSCT continuously, whereas the remaining EC ≥ 0.1% patients (N = 39) received allo-HSCT only. Prophylactic NAC intervention was safe and effective in preventing the occurrence of PGF and PT in EC < 0.1% patients by promoting the dynamic reconstitution of BM ECs and CD34+ cells, along with reducing their ROS levels, which was further confirmed by in situ BM trephine biopsy analyses. These findings suggest that the impaired BM ECs pre-HSCT are responsible for the defective hematopoiesis in PGF and PT patients. Therefore, improvement of BM ECs through prophylactic NAC intervention may be a promising therapeutic approach to promote hematopoietic reconstitution post-HSCT. This trial was registered at www.clinicaltrials.gov as #NCT03236220 and #NCT02978274.

Can acetylcysteine ameliorate cisplatin-induced toxicities and oxidative stress without decreasing antitumor efficacy? A randomized, double-blind, placebo-controlled trial involving patients with head and neck cancer.

The protective antioxidant activity of acetylcysteine (NAC) against toxicity due to cisplatin has been reported in experimental models; however, its efficacy in patients has not been elucidated. The aim of this study was to investigate the possible protective effect of NAC on cisplatin‐induced toxicity and the effect of NAC on clinical response and oxidative stress in patients treated for head and neck cancer. This was a randomized, double‐blind, placebo‐controlled trial conducted in patients receiving high‐dose cisplatin chemotherapy concomitant to radiotherapy. Patients were randomly assigned to groups and received: (a) 600 mg NAC syrup, orally once daily at night for 7 consecutive days or (b) placebo, administered similarly to NAC. Nephro‐, oto‐, hepato‐, myelo‐, and gastrointestinal toxicities, clinical responses, and plasma and cellular markers of oxidative stress were evaluated. Fifty‐seven patients were included (n = 28, NAC arm; and n = 29, placebo arm). A high prevalence of most types of toxicities was observed after cisplatin chemotherapy; however, the parameters were similar between the two groups. There was a predominance of partial response to treatment. In the cellular and plasmatic oxidative stress analyses, minor differences were observed. Overall, there was no statistically significant difference between the groups for all outcomes. These findings show that low‐dose oral NAC does not protect patients with head and neck cancer from cisplatin‐induced toxicities and oxidative stress. The antitumor efficacy of cisplatin was apparently not impaired by NAC.

Acute Effect of Oral N-Acetylcysteine on Muscle Soreness and Exercise Performance in Semi-Elite Rugby Players

ABSTRACTN-acetylcysteine (NAC) supplementation may enhance performance and reduce soreness from acute, repeated-sprint, high-intensity exercise. Our aim was to investigate whether semi-elite rugby union athletes may benefit. In a randomized block design, 17 semi-elite male rugby players were assigned to receive either 1 g oral NAC (n = 8) or placebo (n = 9) for six days. The mean percentage effect of NAC on exercise performance was assessed through completion of a broken bronco exercise test on days 5 and 6 of supplementation. Players self-reported muscle soreness and tolerability to supplements using a modified Muscle Pain and Treatment Satisfaction Questionnaire throughout the supplement duration. NAC produced a likely beneficial performance effect on maximum shuttle sprint time (2.4%; 90% confidence limit ± 4.8%) but was unclear on total time during back-to-back broken bronco tests compared to placebo. NAC had a likely protective effect on subjective muscle soreness during days 1–4 of supplementation (−19% ± 27%) but a very likely harmful effect on days 5 and 6 of supplementation (71% ± 59%). Daily supplementation with 1 g of oral NAC for six days produced no adverse side effects, reduced muscle soreness after one bout of damaging exercise, but increased soreness following the second bout. The performance effects were generally unclear apart from maximal sprint time.

Oral N-Acetyl Cysteine Lowered IL 6 Level Among Stage V Chronic Kidney Disease Patients on Continuous Ambulatory Peritoneal Dialysis (CAPD)

Background. IL 6 level is increased in stage V CKD patients on CAPD. N-Acetyl Cysteine is a compound containing thiol with antioxidant and anti-inflammatory effects. Objective. To examine the effect of oral NAC on IL 6 level in stage V CKD patients on CAPD. Method. An experimental research with Randomized Double Blind Control Trial, involving 30 CKD patients on CAPD in Dr Moewardi Hospital. They were divided into control group/placebo (15 patients) and oral NAS treatment group (15 patients). IL 6 level was measured before and after 8 weeks of treatment. Result. Level of IL 6 before and after treatment in control group were (8.13 + 7.62 vs 11.16 + 8.32 , p= 0,001), significantly (p<0,001). Level of IL 6 before and after treatment in treatment group were (9.72 + 7.29 vs 6.09 + 3.82, p = 0,002); lowered significantly (p<0,05). Conclusion. Oral NAC lowered the level of IL 6 in stage V CKD patients on CAPD.

N-acetyl Cysteine Therapy as Adjunctive Therapy for Treatment of Acute Hepatitis A

Background and study aim: Hepatitis A is an acute, usually mild and self-limiting disease affecting the liver. We aim to assess the effect of oral N-acetyl cysteine compared with placebo on length of hospital stay in adult patients who were admitted to the hospital with acute hepatitis A which might cause earlier resolution of hepatitis. Subjects and Methods: 40 patients were diagnosed as acute hepatitis A and classified into two groups, the first one involved 20 patients who received oral N-acetyl cysteine and supportive treatment, and the second one involved also 20 patients but they received placebo and supportive treatment. We measured complete blood count (CBC), kidney profile (KP), liver function test (LFT), blood glucose, C-reactive protein (CRP) and coagulation profiles on the day of presentation, and every other day till the day of discharge from the hospital. Serological tests were done for HAV Immunoglobulin M (IgM), HEV IgM, HBsAg, HBcIgM, antibody to Hepatitis C virus. Results: The mean length of hospital stay in the NAC group was 13.2 days compared with 14.3 days in the placebo group. Length of hospital stay differed significantly between groups. The mean time of reliving symptoms at presentation was 3.6 days in the NAC group and 4.4 days in the placebo group. The mean time of reliving symptoms at presentation was significantly lower in NAC group than in placebo group. Conclusion: use of oral NAC as adjunctive therapy for treatment of acute hepatitis A was safe in these patients and was associated with a shorter length of patient stay in the hospital.

N-acetylcysteine in COPD: why, how, and when?

Oxidants have long been recognized to have an important role in the pathogenesis of COPD, and in this cigarette smoke has a strong responsibility, because it generates a conspicuous amount of oxidant radicals able to modify the structure of the respiratory tract and to enhance several mechanisms that sustain lung inflammation in COPD. In fact, oxidative stress is highly increased in COPD and natural antioxidant capacities, mainly afforded by reduced glutathione, are often overcome. Thus an exogenous supplementation of antioxidant compounds is mandatory to at least partially counteract the oxidative stress. For this purpose N-acetylcysteine has great potentialities due to its capacity of directly contrasting oxidants with its free thiols, and to the possibility it has of acting as donor of cysteine precursors aimed at glutathione restoration. Many studies in vitro and in vivo have already demonstrated the antioxidant capacity of NAC. Many clinical studies have long been performed to explore the efficacy of NAC in COPD with altern results, especially when the drug was used at very low dosage and/or for a short period of time. More recently, several trials have been conducted to verify the appropriateness of using high-dose NAC in COPD, above all to decrease the exacerbations rate. The results have been encouraging, even if some of the data come from the most widely sized trials that have been conducted in Chinese populations. Although other evidence should be necessary to confirm the results in other populations of patients, high-dose oral NAC nevertheless offers interesting perspectives as add-on therapy for COPD patients.

N-acetylcysteine in COPD: why, how, and when?

Oxidants have long been recognized to have an important role in the pathogenesis of COPD, and in this cigarette smoke has a strong responsibility, because it generates a conspicuous amount of oxidant radicals able to modify the structure of the respiratory tract and to enhance several mechanisms that sustain lung inflammation in COPD. In fact, oxidative stress is highly increased in COPD and natural antioxidant capacities, mainly afforded by reduced glutathione, are often overcome. Thus an exogenous supplementation of antioxidant compounds is mandatory to at least partially counteract the oxidative stress. For this purpose N-acetylcysteine has great potentialities due to its capacity of directly contrasting oxidants with its free thiols, and to the possibility it has of acting as donor of cysteine precursors aimed at glutathione restoration. Many studies in vitro and in vivo have already demonstrated the antioxidant capacity of NAC. Many clinical studies have long been performed to explore the efficacy of NAC in COPD with altern results, especially when the drug was used at very low dosage and/or for a short period of time. More recently, several trials have been conducted to verify the appropriateness of using high-dose NAC in COPD, above all to decrease the exacerbations rate. The results have been encouraging, even if some of the data come from the most widely sized trials that have been conducted in Chinese populations. Although other evidence should be necessary to confirm the results in other populations of patients, high-dose oral NAC nevertheless offers interesting perspectives as add-on therapy for COPD patients.

Comparison of combination therapy of high-dose oral N-acetylcysteine and intravenous sodium bicarbonate hydration with individual therapies in the reduction of Contrast-induced Nephropathy during Cardiac Catheterisation and Percutaneous Coronary Intervention (CONTRAST): A multi-centre, randomised, controlled trial

IntroductionN-acetylcysteine (NAC) and sodium bicarbonate (SOB) therapies may prevent contrast-induced nephropathy (CIN). However, the efficacy of using combination over individual therapies was not established, and there was no large randomised study comparing abbreviated SOB therapy with conventional sustained saline pre-hydration with oral NAC. MethodsIn a multi-centre, open-label, randomised, controlled trial (NCT00497328), we prospectively enrolled 548 patients with at least moderate renal impairment undergoing cardiac catheterisation with or without percutaneous coronary intervention. Patients were randomly assigned to 3 groups: 1) NAC: 154mEq/L sustained sodium chloride regime (1mL/kg/h 12h before, during and 6h after the procedure) with oral NAC at 1.2g bid for 3days (n=185); 2) SOB: 154mEq/L abbreviated SOB regime at 3mL/kg/h 1h before the procedure, and 1mL/kg/h during and 6h after the procedure (n=182); and 3) COM: combination of abbreviated SOB regime and oral NAC (n=181). The primary end point was incidence of CIN. The secondary end points were rise in serum creatinine, hospitalisation duration, haemodialysis, morbidity and mortality within 30days. ResultsThe 3 groups had similar baseline characteristics: age 68±10years, 76% male, 48% diabetic and baseline glomerular filtration rate (GFR) 47.7±13.0mL/min. There were 41 (8.8%) patients with GFR<30. The CIN incidences were NAC 6.5%, SOB 12.8% and COM 10.6%. The COM regimen was not superior to either the NAC (relative risk (RR)=1.61, 95% confidence interval (CI): 0.76 to 3.45, p=0.225) or SOB (RR=0.83, 95% CI: 0.44 to 1.56, p=0.593) regimens. The CIN incidence was lower in the NAC group than the SOB group (adjusted odds ratio (OR)=0.40, 95% CI: 0.17 to 0.92; p=0.032). Multivariate analysis showed contrast volume (OR=1.99, 95% CI: 1.33 to 2.96, p<0.001 per 100mL), female (OR=2.47, 95% CI: 1.22 to 5.00, p=0.012) and diabetes (OR=2.03, 95% CI: 1.03 to 3.99, p=0.041) were independent risk predictors. There were no differences in the secondary outcomes among the 3 groups. ConclusionThe combination regimen was not superior to individual regimens in preventing CIN in patients with baseline renal impairment. There was a trend suggesting that the 12-hour sustained sodium chloride pre-hydration regimen was more protective than the 1-hour abbreviated SOB regimen.

Effect of oral N-acetyl cysteine supplementation in type 2 diabetic patients on intracellular glutathione content and innate immune responses to Burkholderia pseudomallei

Type 2 diabetic patients have increased susceptibility to melioidosis, an infectious disease caused by Burkholderia pseudomallei. We had previously shown that peripheral blood mononuclear cells (PBMCs) from diabetic patients with poor glycemic control had a defective IL-12 and IFNγ response to B. pseudomallei infection, resulting in poor intracellular bacterial control. The impaired IL-12 response was due to glutathione (GSH) deficiency characterized by a low reduced to oxidized glutathione ratio (GSH ratio) and could be restored by the addition of reduced GSH to the infected cells. Our goal is to determine whether N-acetyl cysteine (NAC, a GSH pro-drug) supplementation in diabetic patients could improve their immune control of B. pseudomallei. Type 2 diabetic patients with poor glycemic control were given oral supplementation of NAC for six weeks at 1200 mg daily. Their PBMCs and subsets of immune cells showed a significant increase in free GSH concentration. However, the GSH ratio, IL-12 and IFNγ production, and intracellular bacterial killing upon ex-vivo infection did not improve. Thus, oral NAC supplementation in diabetic patients is sufficient to increase intracellular GSH content in blood cells. However, modulating the free GSH content is not sufficient to improve infection outcome as it is the GSH ratio that regulates the IL-12 response in monocytes.

Study on Effectiveness of Low Dose Theophylline as Add-on to Inhaled Corticosteroid for Patients with Sulfur Mustard Induced Bronchiolitis

Background: Theophylline may reverse steroid resistance and decrease inflammation in patients with chronic pulmonary disease and sulfur mustard (SM) induced bronchiolitis. This study was designed to assess the effects of low-dose theophylline on improvement of pulmonary function tests (PFTs) of SM exposed patients. Methods: In this comparative observational study, a group of SM-exposed victims during the Iraq-Iran war who were treated with oral slow releasing (SR) theophylline, salmetrol, fluxitide, omeprazole and NAC (study group) were compared to a group of age and gender matched SM-exposed patients who received same medications except oral SR theophylline (historical control group). PFTs were measured at the beginning of the study and after 8 weeks of the treatment. Results: In total, 33 subjects in the study group and 27 subjects in the control group were studied. Mean (SD) age of all subjects was 51 (14.1) years. In the study group, on the 8th week post-treatment, PFTs decreased, though the differences of tests between before and after treatment were not significant. In the control group, all the tests decreased in the same period and these reductions were not also significant. However, the changes in PFTs were significantly different between the two groups. The results of most PFTs in the controls decreased in greater extents compared to theophylline treated patients. This shows that despite theophylline was unable to improve the patients; it was partially able to decelerate the reductions in PFTs. Conclusion: Theophylline may not improve PFTs of SM exposed patients but it may decelerate the progress of the underlying respiratory disease. Further studies in this setting with higher doses of theophylline and longer term of evaluation are needed to better understand the pathophysiological mechanism of SM induced bronchiolitis and the effectiveness of the treatment with theophylline.

PROTECTION OF N-ACETYLCYSTEINE FOR PATIENTS WITH CONTRAST INDUCED NEPHROPATHY AFTER PERCUTANEOUS CORONARY INTERVENTION TREATMENT

ObjectivesThis paper aims to explore whether there is a preventive and protective effect of N-acetylcysteine for patients with contrast induced nephropathy after percutaneous coronary intervention treatment.MethodsWe divided the 230 patients,...

The Clinical Management of Acetaminophen Poisoning in a Community Hospital System: Factors Associated with Hospital Length of Stay

Acetaminophen (APAP) overdose is the most common pharmaceutical poisoning. The objective of this study was to examine the management of patients admitted for treatment of APAP overdose. Factors impacting hospital length of stay (LOS) were of particular interest. This was a retrospective cohort study of patients admitted to Kaiser Permanente Northern California hospitals for APAP overdose from July 2003 through December 2007. Medical records were abstracted for patient demographic data, key factors of overdose, California Poison Control System (CPCS) contact, data regarding hospital course, transfer for liver transplantation, and death. Four hundred thirty-five patients were included. The mean hospital LOS was 66.5 h (95% CI 62.1, 71.0). Four patients (0.9%) died. Eight patients (1.8%) were transferred for liver transplantation, but all of these patients later recovered without transplant. Of 289 cases eligible for placement on the Rumack-Matthew nomogram (acute ingestion with known time of ingestion <24 h and normal liver enzymes), 161 (55.7%) had APAP levels above the "200" line and 77 (26.6%) fell below the "150" line. CPCS was contacted in 295 cases (67.8%). Mean LOS in cases with CPCS consultation was 61.9 h (95% CI 57.2, 66.5 h) versus 76.3 h (95% CI 66.6, 86.0 h) in those without. LOS in cases treated with IV NAC was 67.1 h (95% CI 57.7, 76.5 h) versus 66.4 h (95% CI 61.2, 71.5 h) in cases treated with oral NAC. Many patients admitted for APAP overdose had serum APAP levels below the minimum toxicity level. Use of IV NAC did not impact hospital LOS. CPCS consultation appeared to decrease mean hospital LOS.

Hepatic derangement following N-Acetylcysteine enemas in an infant with cystic fibrosis

We discuss an infant with MI secondary to cystic fibrosis, who was managed surgically by a double barrel ileostomy for mid - small bowel atresia and developed severe faecal impaction in the post - operative period. The faecal impaction was treated successfully with oral NAC and 0.2% NAC contrast enemas. The patient's liver function tests revealed a dramatic increase in transaminases and bilirubin contemporaneous with the administration of the enemas. The levels showed a spontaneous improvement after discontinuation. This is only the second reported case of hepatotoxicity secondary to NAC enemas in the literature. While our experience offers modest support for the use of NAC, its efficacy is not yet proven and paediatric surgeons using NAC in the enema form need to closely monitor liver function contemporaneous with this agent's administration and adjust their treatment accordingly.