Intravenous N-acetylcysteine Research Articles

2322 Liraglutide-Induced Liver Injury With Superimposed Acute Pancreatitis

INTRODUCTION: Liraglutide, commercially known as Victoza is a glucagon-like peptide 1 (GLP-1) receptor agonist that was recently approved for the treatment of diabetes mellitus type 2. Due to its recent arrival in the realm of anti-diabetic medications, the side effects of GLP-1 receptor agonists are not fully established. It is thought that the release of GLP-1 is mediated by sensory neurons located in the intestine and in the liver. This is clinically significant as many of the reported side-effects occur in these sites, namely the liver as was the case with our patient. CASE DESCRIPTION/METHODS: A 64-year-old woman with a medical history of hypertension, diabetes mellitus, hyperlipidemia, and cholecystectomy presented to our emergency department complaining of diffuse abdominal pain for 4 days. The patient denied alcohol consumption, illicit drug use, recent travel or any recent changes in her diet. Laboratory workup included alanine aminotransferase (ALT) of 1359 IU/L, aspartate aminotransferase (AST) of 565 IU/L, alkaline phosphatase (ALP) of 405 IU/L, and lipase of 287 U/L. Physical examination was notable for epigastric tenderness. Of note the patient was seen at our outpatient clinic 6 months at which point she was started on Liraglutide. Liver function tests at that time were within normal limits. Upon hospital admission Liraglutide was held and the patient was promptly started on intravenous fluids and N-acetylcysteine protocol. During her admission markers for viral hepatitis and autoimmune hepatitis were negative. On her third hospital day after discontinuation of Liraglutide the patients symptoms completely resolved and her liver function tests trended down (ALT: 335, AST: 58, ALP: 386). The patient was then discharged home with outpatient follow up scheduled. DISCUSSION: Acute pancreatitis is an established possible complication of liraglutide therapy. The mechanism behind its development is likely attributable to a hypersensitivity or metabolic idiosyncratic reaction. Drug induced liver injury however, is an exceedingly rare complication of liraglutide therapy. Current theories suggest the development of anti-liraglutide antibodies as the main culprit. Liraglutide is a peptide that is 97% homologous with human GLP-1. This is problematic as the development of antibodies against liraglutide may also cross-react with the GLP-1 receptor found on human hepatocytes thus resulting in liver injury. We highlight a rare case of liraglutide induced liver injury with concurrent acute pancreatitis.

A Pilot Randomized Controlled Trial of Intravenous N-acetyl Cysteine in STEMI

A Pilot Randomized Controlled Trial of Intravenous N-acetyl Cysteine in STEMI

Principal results of a randomised open label exploratory, safety and tolerability study with calmangafodipir in patients treated with a 12 h regimen of N-acetylcysteine for paracetamol overdose (POP trial)

BackgroundThe POP Trial was a phase 1, open-label, rising-dose, randomised study that explored the safety and tolerability of calmangafodipir (superoxide dismutase mimetic) co-treatment with n-acetylcysteine (NAC) for paracetamol overdose. MethodsPatients were recruited at the Royal Infirmary of Edinburgh (8th June 2017-10th May 2018). Inclusion criterion: adults within 24 h of a paracetamol overdose that required NAC. Within each of 3 sequential cohorts, participants were randomly assigned, with concealed allocation, to NAC and a single intravenous calmangafodipir dose (n = 6) or NAC alone (n = 2). Calmangafodipir doses were 2, 5, or 10 μmol/kg. Participants, study and clinical teams were not blinded. The primary outcome was safety and tolerability. Secondary outcomes were alanine transaminase (ALT), international normalised ratio (INR), keratin-18, caspase-cleaved keratin-18 (ccK18), microRNA-122, and glutamate dehydrogenase (GLDH). (Clinicaltrials.gov:NCT03177395). FindingsAll 24 participants received their allocated drug doses and were analysed. Primary endpoints: all participants experienced ≥1 adverse event (AE), most commonly gastrointestinal. Patients experiencing ≥1 serious adverse event (SAE): NAC alone, 2/6; NAC + calmangafodipir (2 μmol/kg), 4/6; NAC + calmangafodipir (5 μmol/kg), 2/6; NAC + calmangafodipir (10 μmol/kg), 3/6. No AEs or SAEs were probably or definitely calmangafodipir-related. Secondary safety outcomes demonstrated no differences between groups. With NAC alone, 2/6 had ALT > 100 U/L; with NAC + calmangafodipir, 0/18. No INR difference. Keratin-18 and ccK18 increased in the NAC alone group more than with calmangafodipir (baseline to 20 h fold change, NAC + calmangafodipir (5 μmol/kg) compared to NAC alone: 0.48 (95%CI 0.28–0.83)). microRNA-122 changes were similar to K18, GLDH was frequently undetected. InterpretationCalmangafodipir was tolerated when combined with NAC and may reduce biomarkers of paracetamol toxicity.

Effect of N-acetylcysteine on liver and kidney function tests after surgical bypass in obstructive jaundice: A randomized controlled trial

It has been shown that N-acetylcysteine may be useful in correcting postoperative hepatic and renal function in many pathological conditions. The present study aimed to examine the effect of N-acetylcysteine on liver and kidney function tests after surgical bypass in patients with obstructive jaundice. & Materials: A total of 30 patients with obstructive jaundice who were candidates for bypass surgery were enrolled in this randomized clinical trial. In the case group, intravenous N-acetylcysteine (200mg/kg per hour in the first 8h, followed by 100mg/kg per hour for another 16h, the same dose for another 24h) was administered postoperatively. Liver and renal function tests (serum AST, ALT, ALP, GGT, bilirubin, and creatinine) were compared between two groups, as well as duration of hospitalization and ICU stay. Postoperatively, decrease in mean serum AST (p=0.01), ALT (p=0.02), ALP (p=0.01), GGT (p=0.04) and bilirubin (total, p=0.02, direct, p=0.01) levels compared to the preoperative values was significantly more among cases compared to those in controls. Changes in serum creatinine, however, did not differ significantly between two groups (p=0.18). Hospital and ICU stays were also not different between two study groups (p=0.27 and p=0.94 respectively). On the basis of our findings, intravenous N-acetylcysteine in patients with obstructive jaundice could significantly preserve liver function after bypass surgery. Effect of this medication on renal function; however, was not statistically significant. Iranian Registry of Clinical Trial: IRCT2016041016473N7.

Safety and efficacy of adding intravenous N-acetylcysteine to parenteral L-alanyl-L-glutamine in hospitalized patients undergoing surgery of the colon: a randomized controlled trial.

ABSTRACTBACKGROUND: Colon surgery can cause systemic inflammatory response syndrome (SIRS). There is a recent trend towards the use of antioxidant agents in the prevention or alleviation of the severity of postoperative SIRS, but its use is controversial as studies have shown conflicting results.OBJECTIVES: Investigate the efficacy and tolerability of perioperative intravenous administration of N-acetylcysteine (NAC) as an antioxidant and anti-inflammatory agent in patients undergoing colon surgery.DESIGN: Randomized, double-blinded, and controlled clinical trial.SETTING: Surgical critical care unit in Egypt.PATIENTS AND METHODS: Sixty patients who required admission to the ICU following colon surgery were enrolled in the study between July 2015 and October 2016. Eligibility included the need for parenteral nutrition for at least 5 days due to failure of or contraindication to enteral nutrition. Patients were randomly allocated using a computer-generated list to a loading dose of NAC followed by continuous infusion started one hour prior to induction, and continued over 48 hours, or to the control group, who received the same volume of dextrose 5%. Allocation was concealed using opaque, sealed envelopes under pharmacy control. The researcher, the anesthesiologist, the surgeon, and patients were blinded to the treatment allocation.MAIN OUTCOME MEASURES: Clinical and laboratory evaluation for manifestations of SIRS, serum levels of tumor necrosis factor alpha and malondialdehyde, and occurrence of side effects in the study group.SAMPLE SIZE: 60 patients with mean (SD) ages of 56 (15.1) years in the study group (n=30) and 57.7 (12.3) years in the control group (n=30).RESULTS: There was a significant difference in the mean serum level of ALT (22.6 (9.9) U/L in the study group vs. 31.1 (17.8) U/L in the control group, P=.028) after treatment with NAC, but differences between the groups in the serum level of tumor necrosis factor alpha and malondialdehyde after treatment were not significant. Serum levels of malondialdehyde increased in both groups after treatment P<.001. There was no statistically significant difference from baseline or between the groups after treatment in other clinical data and laboratory parameters following NAC administration, and only 6.6% of the patients in the study group experienced mild side effects.CONCLUSIONS: Preoperative administration of NAC is safe, but its efficacy as an antioxidant and anti-inflammatory agent was not statistically significant and requires further investigation in a larger sample.LIMITATIONS: Single-center study, small sample size, and short duration of NAC administration.CLINICAL TRIALS REGISTRY: NCT03589495.CONFLICT OF INTEREST: None.

N-Acetylcysteine Prevents Post-embolization Syndrome in Patients with Hepatocellular Carcinoma Following Transarterial Chemoembolization.

Post-embolization syndrome is a common complication after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). N-acetylcysteine (NAC) is known to ameliorate liver damage from several causes. To determine the efficacy of intravenous NAC in the prevention of post-embolization syndrome in HCC patients following TACE. In this study, patients with HCC admitted for TACE were prospectively enrolled. All patients were randomized stratified by Child A or B to receive NAC or placebo. The NAC group received intravenous NAC 24h prior to TACE (150mg/kg/h for 1h followed by 12.5mg/kg/h for 4h, then continuous infusion 6.25mg/h for 48h after the procedure). The placebo group received an infusion of 5% glucose solution until 48h after procedure. The post-embolization syndrome was defined as: T ≥ 38.5 c and serum ALT > 3 times of pretreatment value. In total, 111 HCC patients were enrolled; 57 were randomly assigned to NAC group and 54 to placebo group. The incidence of post-embolization syndrome was lower in NAC group (24.6%) compared to placebo group (48.2%); P = 0.01. On multivariate analysis, receiving IV NAC (P = 0.03) and HCC diameter (P < 0.01) were associated with developing post-embolization syndrome. Post-TACE liver decompensation was documented in 26/111 (23.4%) patients. There was no difference in the incidence of post-TACE liver decompensation between NAC and placebo group. In this study, intravenous NAC administration reduces the incidence of post-embolization syndrome after TACE in patients with HCC. However, it does not prevent post-TACE liver decompensation. This study was registered with Thai Clinical Trial Registry (TCTR20150313002).

A phase 2 trial of N-Acetylcysteine in Biliary atresia after Kasai portoenterostomy.

BackgroundBiliary atresia (BA) is a life-threatening liver disease of infancy, characterized by extrahepatic biliary obstruction, bile retention, and progressive liver injury. The Kasai portoenterostomy (KP) is BA's only nontransplant treatment. Its success is variable and depends on restoration of hepatic bile flow. Many adjunctive therapeutics have been studied to improve outcomes after the KP, but none demonstrate effectiveness. This study tests if N-acetylcysteine (NAC), a precursor to the choleretic glutathione, improves bile flow after KP.MethodsThis report describes the design of an open-label, single center, Phase 2 study to determine the effect of NAC following KP on markers of bile flow and outcomes in BA. The intervention is intravenous NAC (150 mg/kg/day) administered continuously for seven days starting 0–24 h after KP. The primary outcome is normalization of total serum bile acid (TSBA) concentrations within 24 weeks of KP. The secondary objectives are to describe NAC therapy's effect on other clinical parameters followed in BA for 24 months and to report adverse events occurring with therapy. This study follows the “minimax” clinical trial design.DiscussionThis is the first clinical trial to test NAC's effectiveness in improving bile flow after KP in BA. It introduces three important concepts for future BA therapeutic trials: (1) the “minimax” study design, a pertinent design for rare diseases because it detects potential effects quickly with small subject size; (2) the more sensitive bile flow marker, TSBAs, which may correlate with positive long-term outcomes better than traditional bile flow markers such as serum bilirubin; and (3) liver enzyme changes immediately after KP, which can be a guideline for potential drug-induced liver injury in other BA peri-operative adjunctive therapeutic trials.

Mo1422 – Clinical Benefit of Intravenous N-Acetylcysteine in Patients with Ischemic Hepatopathy

Mo1422 – Clinical Benefit of Intravenous N-Acetylcysteine in Patients with Ischemic Hepatopathy

Clinical practice guidelines for the provision of renal service in Hong Kong: General Nephrology.

Clinical practice guidelines for the provision of renal service in Hong Kong: General Nephrology.

Intravenous N-acetylcysteine versus intravenous theophylline in the prevention of contrast-induced nephropathy in critically ill patients: a prospective randomized clinical trial

Aim Despite the use of several agents for prophylactic agents, contrast-induced nephropathy (CIN) remains a crucial clinical problem. The aim was to compare the efficacy of intravenous N-acetylcysteine (NAC) and intravenous theophylline in the prevention of CIN in critically ill patients. Patients and methods A total of 90 patients were admitted to the ICU with at least one risk factor for CIN and randomly divided into three groups. All patients received the regular management of renal protection with good hydration, to maintain adequate intravenous volume expansion with isotonic crystalloids (normal saline: 1–1.5 ml/kg/h) 3–12 h before the procedure, and it was continued for 6–24 h afterward. In the first group, patients received 6 mg theophylline intravenously over 30 min as a loading dose, followed by a maintenance dose of 0.5 mg/kg/h intravenously, to be started after the loading dose (group T). In the second group, patients received the full course of treatment with NAC (group A), which comprised three consecutive intravenous infusions: first infusion as initial loading dose of 150 mg/kg body weight infused in 200 ml over 1 h, followed by the second infusion of 50 mg/kg in 500 ml over the next 4 h, followed by the third infusion of 100 mg/kg in 1 l over the next 16 h (to be completed on the day of the examination). Control group: in this group, 30 patients received no additional drug before administration of radiocontrast medium. They only received the regular management of renal protection with good hydration. Results Despite the inclusion of ICU patients at high risk for CIN, we found a significant lower incidence of CIN and a lower incidence of patients requiring dialysis among patients under prophylaxis of intravenous NAC and intravenous aminophylline, as creatinine concentration was elevated by 25% in only four patients in the NAC group and only in three patients in the aminophylline group, and the incidence of CIN and patients requiring dialysis were significantly lower (P Conclusion We concluded that the administration of intravenous NAC or intravenous theophylline around the time of contrast administration prevents renal injury in equal efficacy compared with patients receiving no additional drugs at the time of contrast administration as regards incidence of nephropathy and incidence of dialysis among study patients.

Effect of Intravenous and Oral N-Acetylcysteine Treatment in a Patient with Sickle Cell Disease at Disease Baseline

Background: We previously showed that patients with sickle cell disease (SCD) have elevated levels of von Willebrand factor (VWF) with high adhesive activity and the level of total active VWF correlated with hemolysis at disease baseline. These findings suggest that VWF plays a role in the pathophysiology of SCD [Chen et al, Blood. 2011; 117:3680‐3]. We also showed that N-acetylcysteine (NAC), a mucolytic and antioxidant drug, can reduce the level of large VWF multimers and platelet adhesion in human plasma in vitro and in mice in vivo [Chen et al, JCI, 2011, 121:522]. Based on these findings, we hypothesized that administration of NAC in SCD patients might reduce VWF multimers in vivo and reduce oxidative stress by scavenging reactive oxygen species (ROS). We started a pilot study to evaluate the effects of intravenous (IV) and oral NAC administration in SCD patients at disease baseline (NCT01800526). In this report, we administered NAC to one patient by IV and orally and compared the effect on biomarkers by the two routes of NAC administration.Patient and protocol: The subject is a 51-year-old male with SS genotype, a history of leg ulcers and acute chest syndrome, and who was not taking hydroxyurea at the time of the study. NAC was infused at a low dose (150 mg/kg over 8 hours) and infusion was repeated at high dose (300 mg/kg over 8 hrs) after 4 weeks. Blood samples were collected before (0), during (4 hr) and after the NAC infusions (8, 24 and 72 hr). Five months after the high dose IV infusion, during which parameters returned to baseline levels, oral NAC was administered for 4 weeks at 2.4g/day. Weekly blood samples were collected four weeks before the start of oral NAC, during oral NAC, and one week after oral NAC administration. We measured RBC parameters and RBC fragments, dense cells and percentage of platelet-monocyte complexes (PMC) by flow cytometry. We also analyzed VWF antigen, VWF multimers, ADAMTS13 antigen and activity levels in plasma. We also measured total, oxidized and reduced forms of NAC, cysteine and glutathione levels in plasma and whole blood by mass spectrometry.Results: 1) The subject did not experience adverse side effect during and after the treatment period. 2) RBC, hemoglobin and hematocrit levels did not significantly change with either IV or oral NAC treatment. Oral and IV NAC decreased dense cell and RBC fragments. NAC reduced the number of dense cells 13% during low dose IV, 79% during high dose IV and 73% with the oral administration. Compared to baseline, RBC fragments decreased 40% during low dose IV, 28% during high dose IV, and 27% with the oral NAC treatment. 3) NAC reduced formation of PMC from 71% to 24% (low dose IV), from 72% to 35% (high dose IV), and from 62% to 27% (oral). 4) VWF multimer size significantly decreased during low and high dose NAC infusions but did not change with oral NAC administration. VWF antigen and ADAMTS13 activity levels did not change with either routes of NAC administration. 5) The concentration of NAC in whole blood increased during treatments: elevated to 0.5 mM and 1 mM at the end of low- and high-dose IV infusions, respectively. At the conclusion of oral administration, the NAC concentration was 4 µM. Total glutathione concentrations in whole blood did not change significantly during and after NAC treatment at either dose or by either route. Free Cys concentrations in plasma increased compared to respective baseline levels 10-fold for low dose infusion (from 10 µM to 101 µM), 20-fold for high dose infusion (from 9 µM to 200 µM), but the level did not change significantly for oral administration (from 5 µM to 7 µM). Protein-bound Cys levels in plasma as markers of oxidative stress were significantly decreased with low- and high-dose IV infusion. However, the level did not change significantly with oral NAC administration.Summary: Both IV and oral administration of NAC were safe and well tolerated in the patient with SCD. Both IV and oral administration reduced the number of dense cells, RBC fragmentation, and formation of PMCs. IV, but not oral NAC, reduced VWF multimer size. These finding suggest that IV administration resulted in higher concentration and had more biologic effects; however both approaches may have a role in treatment of patients with SCD. DisclosuresKonkle:Sangamo: Research Funding; Gilead: Consultancy; Shire: Research Funding; Genentech: Consultancy; CSL Behring: Consultancy; Bioverativ: Research Funding; BioMarin: Consultancy; Spark: Consultancy, Research Funding; Pfizer: Research Funding.

Treatment of hepatic veno-occlusive disease in children with N-acetylcysteine.

In our institution, hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) has been treated with N-acetylcysteine (NAC) since 2008-a loading dose of 150mg/kg, followed by 12 doses of 70mg/kg 6 hourly. Nine children were diagnosed with hepatic VOD/SOS. Hepatic VOD/SOS occurred in seven children after stem cell transplantation and two were receiving chemotherapy for Wilms tumor. Their clinical severity was classified as moderate in two and severe in seven by the European Society for Blood and Marrow Transplantation criteria. All children recovered and were discharged from 4 to 16days after diagnosis. No side effects were observed. Intravenous NAC is an effective treatment for hepatic VOD/SOS.

BET 1: In paracetamol overdose, is oral N-acetylcysteine as effective as intravenous N-acetylcysteine?

A short-cut review was carried out to establish whether oral N-acetylcysteine is as effective as intravenous N-acetylcysteine in the management of paracetamol overdose. Seven studies were directly relevant to the...

Fewer adverse effects associated with a modified two-bag intravenous acetylcysteine protocol compared to traditional three-bag regimen in paracetamol overdose

Context: The intravenous (IV) N-acetylcysteine (NAC) regimen used worldwide in paracetamol overdose is complex with three separate weight-based doses and is associated with a high incidence of adverse events including non-allergic anaphylactoid reactions (NAARs). In 2012, Denmark adopted the two-bag IV NAC regimen which combined the first two infusions of the three-bag regimen and kept the third infusion unchanged. We compared the safety and efficacy of the two-bag IV NAC regimen with the traditional Danish three-bag regimen.Methods: A medical chart review was conducted in three Danish medical centers from January 2012 through December 2014. Safety and efficacy data were compared for patients who received the traditional infusion protocol in Denmark or the 20-h two-bag IV regimen.Results: Four hundred and ninety-three cases received the two-bag regimen and 274 received the three-bag regimen. The overall incidence of NAARs was 9% with all being mild to moderate in intensity. Fewer subjects in the two-bag group (4%) developed NAARs compared to 17% in the three-bag group (p < .001). Overall, 31 patients (4%) developed hepatotoxicity. There was no apparent difference in hepatotoxicity rates between the groups and no deaths or liver transplants. Patients receiving the two-bag regimen had fewer interruptions or delays (5%) compared to the three-bag regimen cohort (12%). Overall, there were very few medication errors reported (1%).Conclusions: The incidence of NAARs was lower in patients receiving acetylcysteine in a two-bag regimen compared to the traditional Danish three-bag regimen without an apparent reduction in efficacy.

Correction to: Anaphylactoid Reactions to Intravenous N-Acetylcysteine during Treatment for Acetaminophen Poisoning.

The original article has been corrected. Table 4 in PDF version of this article has been corrected since the original publication of the article because the first column of numbers (under the heading "Female") in the original PDF version was typeset poorly.

Anaphylactoid Reactions to Intravenous N-Acetylcysteine during Treatment for Acetaminophen Poisoning.

Anaphylactoid reactions to intravenous (IV) N-acetylcysteine (NAC) are well-recognized adverse events during treatment for acetaminophen (APAP) poisoning. Uncertainty exists regarding their incidence, severity, risk factors, and management. We sought to determine the incidence, risk factors, and treatment of anaphylactoid reactions to IV NAC in a large, national cohort of patients admitted to hospital for acetaminophen overdose. This retrospective medical record review included all patients initiated on the 21-h IV NAC protocol for acetaminophen poisoning in 34 Canadian hospitals between February 1980 and November 2005. The primary outcome was any anaphylactoid reaction, defined as cutaneous (urticaria, pruritus, angioedema) or systemic (hypotension, respiratory symptoms). We examined the incidence, severity and timing of these reactions, and their association with patient and overdose characteristics using multivariable analysis. An anaphylactoid reaction was documented in 528 (8.2%) of 6455 treatment courses, of which 398 (75.4%) were cutaneous. Five hundred four (95.4%) reactions occurred during the first 5 h. Of 403 patients administered any medication for these reactions, 371 (92%) received an antihistamine. Being female (adjusted OR 1.24 [95%CI 1.08, 1.42]) and having taken a single, acute overdose (1.24 [95%CI 1.10, 1.39]) were each associated with more severe reactions, whereas higher serum APAP concentrations were associated with fewer reactions (0.79 [95%CI 0.68, 0.92]). Anaphylactoid reactions to the 21-h IV NAC protocol were uncommon and involved primarily cutaneous symptoms. While the protective effects of higher APAP concentrations are of interest in understanding the pathophysiology, none of the associations identified are strong enough to substantially alter the threshold for NAC initiation.

Efficacy of Granulocyte Colony-Stimulating Factor and N-Acetylcysteine Therapies in Patients With Severe Alcoholic Hepatitis

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. 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 day90. 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. 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.

Protection from Reperfusion Injury with Intracoronary N-Acetylcysteine in Patients with STEMI Undergoing Primary Percutaneous Coronary Intervention in a Cardiac Tertiary Center

Evidence suggests that oxidative stress plays a principal role in myocardial damage following ischemia/reperfusion events. Recent studies have shown that the antioxidant properties of N-acetylcysteine (NAC) may have cardioprotective effects in high doses, but-to the best of our knowledge-few studies have assessed this. Our objective was to investigate the impact of high-dose NAC on ischemia/reperfusion injury. We conducted a randomized double-blind placebo-controlled trial in which 100 consecutive patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) were randomly assigned to the case group (high-dose NAC 100mg/kg bolus followed by intracoronary NAC 480mg during PCI then intravenous NAC 10mg/kg for 12h) or the control group (5% dextrose). We measured differences in peak creatine kinase-myocardial band (CK-MB) concentration, highly sensitive troponin T (hs-TnT), thrombolysis in myocardial infarction (TIMI) flow, myocardial blush grade (MBG), and corrected thrombolysis in myocardial infarction frame count (cTFC). The peak CK-MB level was comparable between the two groups (P=0.327), but patients receiving high-dose NAC demonstrated a significantly larger reduction in hs-TnT (P=0.02). In total, 94% of the NAC group achieved TIMI flow grade 3 versus 80% of the control group (P=0.03). No significant differences were observed between the two groups in terms of changes in the cTFC and MBG. In this study, NAC improved myocardial reperfusion markers and coronary blood flow, as revealed by differences in peak hs-TnT and TIMI flow grade 3 levels, respectively. Further studies with large samples are warranted to elucidate the role of NAC in this population. ClinicalTrials.gov identifier: NCT01741207, and the Iranian Registry of Clinical Trials (IRCT; http://irct.ir ) registration number: IRCT201301048698N8.

Modified two step N-acetylcysteine dosing regimen for the treatment of acetaminophen overdose a safe alternative

Intravenous N-acetylcysteine (IV NAC) is currently the approved treatment for acetaminophen (APAP) overdose with a three-step regimen totaling 300 mg/kg over 21 hours. Due to the complexity of this regimen, some institutions have used simplified, off-label regimens to mitigate dosing errors, adverse effects and shorten treatment durations. This article describes a modified two-step IV NAC regimen 510 mg/kg over 25 hours. We performed a retrospective analysis of outcomes in APAP overdose treated with a modified two-step IV NAC regimen between January 1, 2009 and April 30, 2014. We identified patients using medication charges. We included 79 patients in the analysis whom received IV NAC for APAP overdose. We found no documentation of adverse events during infusions. The median time from ingestion to initiation of treatment was 7.5 hours (interquartile range 5, 12 hours) and the median duration of therapy was 32 hours (interquartile range 25, 49 hours). A modified two-step regimen (510 mg/kg over 25 hours), which provides almost twice the dose of the recommended FDA approved dose of 300 mg/kg over 21 hours, may be a less complex and safer alternative to the traditional regimen.

Intravenous N-acetylcysteine for the PRevention Of Contrast-induced nephropathy - a prospective, single-center, randomized, placebo-controlled trial. The INPROC trial.

IntroductionContrast-induced nephropathy (CIN) is a common clinical problem that is growing in importance as an increasing number of tests and procedures which utilize contrast media (CM) are performed.AimTo evaluate the efficacy of intravenous N-acetylcysteine (NAC) for prevention of CIN after diagnostic and/or interventional procedures requiring CM administration.Material and methodsIn a prospective, single-center, randomized, placebo-controlled trial the preventive effects of N-acetylcysteine were evaluated in 222 patients undergoing elective angiography and/or angioplasty. Patients were randomly assigned to receive either NAC or placebo. All patients received intravenous hydration with normal saline before and after catheterization. Serum creatinine (SCr) and estimated glomerular filtration rate were assessed at baseline, at 48–72 h and 10–15 days after CM administration. Contrast-induced nephropathy was defined as an increase in SCr of at least 44 µmol/l (0.5 mg/dl) or an increase of ≥ 25% of the baseline value 48–72 h after CM administration.ResultsContrast-induced nephropathy occurred in 30 of 222 patients (13.5%): 9 of 108 patients in NAC (8.3%) and 21 of 114 patients in the control group (18.4%; p = 0.0281). The multivariate Cox analysis revealed that elevated SCr at 10–15 days (HR = 2.69; p = 0.018) and baseline SCr level (HR = 1.009; p = 0.015) were independent prognostic variables for adverse events during follow-up.ConclusionsOur findings suggest that intravenous NAC along with intravenous hydration may help prevent declining renal function after CM exposure. Elevated SCr level 10–15 days after CM administration was associated with increased risk of adverse events in long-term observation, while elevated SCr within 72 h was not. Measuring SCr at least 10 days after exposure to CM may provide a better outcome measure.