Intravenous N-acetylcysteine Research Articles

Cartap Poisoning with Paroxysmal Supraventricular Tachycardia: A Case Report

Cartap, a nereistoxin derivative from the marine annelid Lumbriconeresis heteropoda, is widely used as a pesticide, targeting pests like caterpillars. While the WHO classifies it as moderately hazardous, with a recommended daily intake of 0.05 mg/kg, human toxicity reports are limited. A 34-year-old female was admitted after consuming an unknown poison. She reported epigastric pain, burning sensations, sweating, vomiting, dyspnea, palpitations, and restlessness, compounded by alcohol intake. Initially treated for organophosphate poisoning, her cholinesterase level was 8.91. It was later confirmed she ingested 100 ml of 50% concentration cartap. Treatment included amiodarone for supraventricular tachycardia and intravenous N-acetylcysteine, magnesium sulfate, and midazolam for general tonic clonic seizure. Cartap, toxic through ingestion and skin contact, can cause symptoms such as vomiting, convulsions, and cardiac issues like supraventricular tachycardia. Supportive care is crucial, and awareness of its risks is necessary.

No Significant Beneficial Effects of Intravenous N-Acetylcysteine on Patient Outcome in Non-Paracetamol Acute Liver Failure: A Meta-Analysis of Randomized Controlled Trials.

Acute liver failure is a life-threatening organ dysfunction with systemic organ involvement and is associated with significant mortality and morbidity unless specific management is undertaken. This meta-analysis aimed to assess the effects of intravenous N-acetylcysteine (NAC) on mortality and the length of hospital stay in patients with non-acetaminophen acute liver failure. Two hundred sixty-six studies from four databases were screened, and four randomized control trials were included in the final analysis. Our results could not demonstrate increased overall survival (OR 0.70, 95% CI [0.34, 1.44], p = 0.33) or transplant-free survival (OR 0.90, 95% CI [0.25, 3.28], p = 0.87) in patients treated with intravenous NAC. We observed an increased overall survival in adult patients treated with NAC (OR 0.59, 95% CI [0.35, 0.99], p = 0.05) compared to pediatric patients, but whether this is attributed to the age group or higher intravenous dose administered remains unclear. We did not observe a decreased length of stay in NAC-treated patients (OR -5.70, 95% CI [-12.44, 1.05], p = 0.10). In conclusion, our meta-analysis could not demonstrate any significant benefits on overall and transplant-free patient survival in non-acetaminophen ALF. Future research should also focus on specific etiologies of ALF that may benefit most from the use of NAC.

Toxic epidermal necrolysis in a 37-year-old man with pneumonia: a case report

Apart from allergy, TEN can be caused by infection, such as M. pneumoniae infection. Aim of this case report is to present clinical manifestations of TEN with pneumonia. A 37-year-old man, came to the emergency room with cough and fever since 5 days before hospitalized. The patient received intravenous ceftriaxone (with negative skin test), paracetamol, and n-acetylcysteine. Three days earlier, the patient had gone to primary health center and got paracetamol and n-acetylcysteine. On the first day of treatment, erythematous macules were seen on the anterior and posterior thoracic region, also the patient had sore throat and dysphagia, treated with intravenous dipenhydramine, mefenamic acid, and cetirizine. On the following day, the lesions expanded with multiple bullae on the anterior and posterior thoracic region, and erosion on the labia (BSA 28%). Intravenous methylprednisolone was administered, also Kloderma® and Ikagen® cream, and Kenalog®. Mefenamic acid and paracetamol were discontinued. On the third day of treatment, the lesions expanded (BSA 38%) and the next day, BSA reached 91.5%. The SCORTEN was 1. The patient was referred for treatment at the burn center and IVIg therapy. After the eleventh day of treatment at the referral hospital, the patient was fully recovered. The managements of TEN are stop suspected drugs, wound care, fluid therapy, systemic corticosteroids, and IVIg therapy. Appropriate management of TEN gives complete recovery to patient.

Assessing the frequency and types of errors involved in the use of a modified intravenous N-acetylcysteine protocol for acetaminophen overdose.

Acetaminophen overdose is a leading cause of acute liver failure in developing countries. N-acetylcysteine (NAC) is a highly effective antidote for acetaminophen hepatotoxicity, typically initiated in the emergency department. Due to a known high rate of errors with the standard three-bag IV NAC protocol, in 2019, the Ontario Poison Center changed to a modified 3% IV NAC one-bag protocol. This study was undertaken to determine the frequency and types of errors associated with the use of this protocol. Data were gathered via chart review of Ontario Poison Centre electronic medical record cases identified as receiving IV NAC for acetaminophen overdose between August 1 and September 30, 2022. 218 total charts were identified, and 188 were deemed eligible based on inclusion and exclusion criteria. Errors were identified in 25% of charts, consisting of dosing errors in 11.7%, stopping errors in 9.0%, initiation errors in 3.7%, and interruptions in therapy in 3.2%. Dosing errors were the most common type of error (44.4%), with overdoses occurring three times more than underdoses. Errors were identified at 39% of geographic locations in the charts reviewed, with similar frequency in Ontario, Manitoba, and Nunavut. Clinical outcomes were similar in charts with and without errors. The rate of errors identified with this 3% IV NAC one-bag protocol is lower than reported for the standard three-bag protocol, but remains high due to dosing errors. Previously reported issues with prolonged interruptions in therapy with the standard three-bag protocol were low with the current 3% one-bag protocol. Although severe outcomes are rare, IV NAC overdose can be fatal. Identifying local factors in emergency departments that can contribute to administration errors (i.e., dose calculation, pump programming issues) can enhance the safety of this important antidote.

Safety and efficacy of N-acetylcysteine (NAC) as an adjunct to standard treatment in patients with acute ischemic stroke: a randomized controlled pilot trial (NACTLYS)

There is a pressing clinical need for thrombolytic agents that can effectively disaggregate arterial thrombi in acute ischemic stroke without significantly increasing the risk of bleeding. This pilot study aimed to investigate the safety and efficacy of N-acetylcysteine (NAC) as an adjunctive therapy to intravenous recombinant tissue plasminogen activator (rtPA or alteplase). A randomized, open-label, blinded assessor pilot study was conducted. Patients presenting with an acute ischemic stroke within 4.5 h from onset were randomized into two groups: intravenous NAC and rtPA or rtPA alone. Primary outcomes included intracerebral hemorrhage, symptomatic intracerebral hemorrhage, extracranial bleeding, and adverse reactions. Secondary outcomes comprised major neurological improvement assessed by (National Institute of Health Stroke Scale) NIHSS at 24 h, recanalization on first run of angiography in patients who underwent thrombectomy or on repeat vascular imaging at 24 h, modified Rankin scale, and three-month mortality. Forty patients were enrolled, with 21 receiving only rtPA and 19 receiving NAC with rtPA. Baseline characteristics were comparable among groups. No significant differences were observed in adverse events (p = 0.99), intracranial hemorrhage (p = 0.21), symptomatic intracerebral hemorrhage (p = 0.47), or extracranial bleeding (p = 0.21). Median NIHSS at 24 h was significantly lower in the intervention group (p = 0.03). Functional outcomes and three-month mortality were similar between groups (p = 0.85 and p = 0.99 respectively). The co-administration of N-acetylcysteine with alteplase did not significantly alter safety profiles, morbidity, or mortality at 3 months. While no substantial differences were noted, a slightly improved early neurological outcome was observed in the intervention arm. The study's findings were constrained by a small sample size, emphasizing the necessity for future large-scale trials to comprehensively evaluate the safety and efficacy of N-acetylcysteine as a thrombolytic agent in acute ischemic stroke.Trial Registration Clinical Trials Registry India—CTRI/2019/05/019305.

Standardized Hospital Guidelines for Paracetamol Overdose - fewer prescription and drug administration Errors?

Introduction: Paracetamol overdose is one of the most common drug overdoses in the UK. The standard treatment is intravenous N-acetylcysteine (NAC) which is usually administered as a 21-hour infusion in UK hospitals. A 12-hour infusion known as the "SNAP" regimen has been implemented in some centres and appears on the TOXBASE database (UK Poisons Information). The availability of two treatment options has caused confusion in our centre resulting in an increased number of prescribing and administration errors. Aims/Objectives: To produce a standardized guideline and prescription chart in two District General Hospital Emergency Departments within the same NHS Trust as part of a Quality Improvement Project (QIP) in an effort to reduce prescribing and administration errors for NAC. Methods: Trust guidelines for Paracetamol overdose were revised using the 12-hour regimen for adults only. A retrospective review of patient notes and electronic discharge summaries was performed prior to and following the implementation of the new guidelines to identify patients that received NAC. The Trust electronic incident reporting system (DATIX) was reviewed for incidents relating to NAC prescription or administration. Results: We had four incidents over three months prior to the introduction of the new guidelines and pre-filled prescription charts. Following the introduction of our new guidelines and prescription charts there were no incidents reported of errors related to NAC. One incident reported was a 16-year-old patient incorrectly receiving the SNAP regimen (without adverse effect) rather than the 21-hour infusion for paediatric patients. Discussion: Use of pre-filled charts reduced the potential human factors in prescription mistakes especially in inaccurate dose calculations and drawing up errors. The charts also prevented confusion between the 21-hour and SNAP NAC Protocols. The standardized guidelines along with the pre-filled charts have reduced the rate of prescription and administration errors of NAC.

Plasmapheresis as an Adjunctive Section Therapy for Yellow Phosphorus Poisoning: A Case Report

Yellow Phosphorus (YP) poisoning is an infrequent, yet severe medical condition characterised by multi-systemic toxicity. The ingestion or inhalation of YP can lead to gastrointestinal irritation, hepatic injury, and Acute Liver Failure (ALF). Plasmapheresis, a therapeutic intervention involving the removal and replacement of plasma components, is a potential adjunctive treatment for YP poisoning. This case report aims to explore the mechanistic rationale, clinical efficacy, and safety considerations of plasmapheresis in the management of this toxicological emergency. Here, a 16-year-old female reported to the Emergency Department (ED), having consumed 1-2 g of Ratol poison at two different times of the day. She came to the hospital on day 4 post-consumption. On admission, the patient was jaundiced and Arterial Blood Gas (ABG) analysis was suggestive of respiratory alkalosis with hypokalemia. Treatment focused on fluid therapy, vitamin K therapy, and N-Acetyl Cysteine (NAC). She developed angioedema and urticaria with no airway compromise, in response to intravenous NAC. A diagnosis of acute liver injury secondary to YP poisoning was made. Close monitoring of liver function and coagulation parameters, and bleeding complications was done. Plasmapheresis was considered as NAC reinitiating was not feasible due to potential anaphylaxis. The patient responded well to the treatment and was discharged on day 7 of hospitalisation.

FRI646 Dulaglutide-induced Acute Liver Injury - A Case Report

Abstract Disclosure: M. Shahid: None. A. Hamza: None. D. Vather-Wu: None. S. Sultan: None. P. Nabizadeh: None. Introduction: Drug-induced liver injury (DILI) accounts for almost 10% of all cases of acute hepatitis and can occur within days to months of initiation of a medication. Outcomes can vary from spontaneous resolution on discontinuation of the offending agent to fulminant hepatic failure requiring transplant or even death. Dulaglutide is a GLP-1 receptor agonist that augments glucose-dependent insulin secretion and slows gastric emptying. It is a weekly injectable medication for management of type 2 diabetes mellitus (T2DM). Commonly reported side effects include nausea, vomiting, appetite suppression, and diarrhea or constipation. To date, there have been less than five published case reports of Dulaglutide-induced acute liver injury (ALI). Hereby, we present a case of Dulaglutide-induced ALI with coagulopathy that resolved with the use of N-acetylcysteine (NAC), steroids, and cessation of the medication. Clinical Case: A 38-year-old female with past medical history of T2DM, hypertension, dyslipidemia, and hypothyroidism presented with complaints of nausea, vomiting and epigastric discomfort for 5 days. She reported having malaise and lethargy for a month since she was started on Dulaglutide for management of her T2DM. Her physical examination was unremarkable. The laboratory workup showed AST >6000 U/L, ALT >3300 U/L, ALP 231 U/L, total bilirubin 3.3 mg/dL, direct bilirubin 2.3 mg/dL, indirect bilirubin 1.0 mg/dL, PT 40.3 seconds, INR 3.36 and negative toxicology screening. She was started empirically on intravenous NAC and methylprednisolone, and was followed by serial biochemical measurements. Further workup revealed no evidence of acute viral hepatitis, autoimmune hepatitis, metabolic (alpha-1-antitrypsin deficiency, Wilson disease, hemochromatosis) or alcohol-related ALI. There were no clinical or imaging findings suggestive of ischemic hepatopathy, venous outflow obstruction or biliary obstruction. After ruling out other causes, the ALI was attributed to Dulaglutide use. AST and ALT improved significantly within 7 days and subsequently normalized within 3-4 weeks. Hepatic synthetic function also normalized within 2 weeks without any sequelae. Conclusion: This report highlights the need for awareness regarding potential but not insignificant risk of dulaglutide as cause of DILI. Extensive testing for other causes of ALI was negative and Dulaglutide-induced ALI was the most likely etiology in our case. Given limited data on hepatotoxicity induced by GLP-1 receptor agonists, further research is needed to ascertain this potentially fatal adverse reaction. We hope to contribute to the current medical literature. Presentation: Friday, June 16, 2023

S1599 Intravenous N-Acetylcysteine and Oral Misoprostol in Combination May Be Effective in Treating Hepatorenal Syndrome

S1599 Intravenous N-Acetylcysteine and Oral Misoprostol in Combination May Be Effective in Treating Hepatorenal Syndrome

A Case of Acute Aluminium Phosphide Poisoning With ST Segment Elevation ECG Changes

AlP poisoning has elevated mortality rates because of cardiovascular involvement. Patient survival can be increased by prompt supportive care. In this study, we evaluated a case of aluminium phosphide intentional poisoning in an adult patient. The patient had toxic myocarditis and developed ST elevation on ECG during hospital course, raised troponins and global hypokinesia on echocardiogram. The patient was managed by trimetazidine, intravenous magnesium sulphate, n-acetylcysteine and inotropes. Follow-up echocardiogram, three months later was normal. Keywords: Pesticide, Aluminium phosphide, Cardiotoxicity.

Single cell RNA-sequencing analysis reveals that N-acetylcysteine partially reverses hepatic immune dysfunction in biliary atresia

Our previous study indicated that CD177+ neutrophil activation has a vital role in the pathogenesis of biliary atresia (BA), which is partially ameliorated by N-acetylcysteine (NAC) treatment. Here, we evaluated the clinical efficacy of NAC treatment and profiled liver-resident immune cells via single cell RNA-sequencing (scRNA-seq) analysis to provide a comprehensive immune landscape of NAC-derived immune regulation. A pilot clinical study was conducted to evaluate the potential effects of intravenous NAC treatment on infants with BA, and a 3-month follow-up was carried out to assess treatment efficacy. scRNA-seq analysis of liver CD45+ immune cells in the control (n= 4), BA (n= 6), and BA+ NAC (n= 6) groups was performed and the effects on innate cells, including neutrophil and monocyte-macrophage subsets, and lymphoid cells were evaluated. Intravenous NAC treatment demonstrated beneficial efficacy for infants with BA by improving bilirubin metabolism and bile acid flow. Two hepatic neutrophil subsets of innate cells were identified by scRNA-seq analysis. NAC treatment suppressed oxidative phosphorylation and reactive oxygen species production in immature neutrophils, which were transcriptionally and functionally similar to CD177+ neutrophils. We also observed the suppression of hepatic monocyte-mediated inflammation, decreased levels of oxidative phosphorylation, and M1 polarisation in Kupffer-like macrophages by NAC. In lymphoid cells, enhancement of humoral immune responses and attenuation of cellular immune responses were observed after NAC treatment. Moreover, cell-cell interaction analysis showed that innate/adaptive proinflammatory responses were downregulated by NAC. Our clinical and scRNA-seq data demonstrated that intravenous NAC treatment partially reversed liver immune dysfunction, alleviated the proinflammatory responses in BA by targeting innate cells, and exhibited beneficial clinical efficacy. BA is a serious liver disease that affects newborns and has no effective drug treatment. In this study, scRNA-seq showed that NAC treatment can partially reverse the immune dysfunction of neutrophil extracellular trap-releasing CD177+ neutrophils and Kupffer cells, and lower the inflammatory responses of other innate immune cells in BA. In consequence, intravenous NAC treatment improved the clinical outcomes of patients with BA in term of bilirubin metabolism.

N-Acetylcysteine Improves Renal Function and Reduces Tissue Malondialdehyde Levels in Glycerol-Induced Acute Kidney Injury

Introduction: The etiology of myoglobinuric acute kidney injury involves oxidative injury brought on by the Fenton reaction and myoglobin redox cycle. Renal tubules may be harmed, and lipid peroxidation compounds with vasoconstrictor characteristics may be produced. N-acetylcysteine (NAC) is an antioxidant shown to improve renal microcirculation and have protective effects in various models of renal damage. The aim of the study was to demonstrate the protective impact of NAC in glycerol-induced rats by measuring tissue malondialdehyde (MDA) level and renal function test (RFT), and to determine the correlation between the protective effect and NAC dose.Methods: This study measured tissue malondialdehyde (MDA) and renal function to examine any protective effect of NAC in a glycerol-induced rat model and to determine whether the effect was dose-related. Five groups of male Wistar rats were used: 1) saline control group, (2) glycerol (50%, 8mL/kg, i.m) plus saline i.v group, 3) glycerol plus NAC (100 mg/kg)-treated group, 4) glycerol plus NAC (200 mg/kg)-treated group, 5) glycerol plus NAC (400 mg/kg)-treated group. At 24 hrs, after glycerol injection, rats were sacrificed, cardiac blood was taken for renal function measurement, and renal tissues were removed for thiobarbituric acid MDA level assessment.Results: Our study revealed that glycerol administration significantly amplified renal tissue MDA, serum creatinine, and BUN (blood urea nitrogen) levels. However, NAC administration dampened the MDA increment and renal function deterioration (p<0.05). Moreover, tissue MDA, BUN, and serum creatinine levels were significantly correlated to NAC dose (r=0.485; r=0.491; rs=0.544, respectively; all p<0.05), indicating that NAC protection declines by dose increments.Conclusion: In this glycerol-induced acute kidney injury rat model, the administration of intravenous NAC 100 mg/kg reduced lipid peroxidation and improved renal function. Nevertheless, the protective effect was diminished in higher doses.

Efficiency of exogenous surfactant combined with intravenous N-acetylcysteine in two-hit rodent model of ARDS

Accumulation of reactive oxygen species during hyperoxia together with secondary bacteria-induced inflammation leads to lung damage in ventilated critically ill patients. Antioxidant N-acetylcysteine (NAC) in combination with surfactant may improve lung function. We compared the efficacy of NAC combined with surfactant in the double-hit model of lung injury. Bacterial lipopolysaccharide (LPS) instilled intratracheally and hyperoxia were used to induce lung injury in Wistar rats. Animals were mechanically ventilated and treated intravenously with NAC alone or in combination with intratracheal surfactant (poractant alfa; PSUR+NAC). Control received saline. Lung functions, inflammatory markers, oxidative damage, total white blood cell (WBC) count and lung oedema were evaluated during 4 hrs. Administration of NAC increased total antioxidant capacity (TAC) and decreased IL-6. This effect was potentiated by the combined administration of surfactant and NAC. In addition, PSUR+NAC reduced the levels of TNFα, IL-1ß, and TAC compared to NAC only and improved lung injury score. The combination of exogenous surfactant with NAC suppresses lung inflammation and oxidative stress in the experimental double-hit model of lung injury.

EE452 The Economic Impact on the Introduction of the Antidote N-Acetylcysteine in the Management of Acute Paracetamol Intoxication in Algeria

N-acetylcysteine (NAC) is the specific antidote treatment of paracetamol intoxications, which aims to prevent the complications related to them. The objective is to highlight the economic impact of using intravenous NAC versus oral NAC in the therapeutic protocol of paracetamol intoxications in Algeria.

Response to Intravenous N-Acetylcysteine Supplementation in Critically Ill Patients with COVID-19

Administering N-acetylcysteine (NAC) could counteract the effect of free radicals, improving the clinical evolution of patients admitted to the Intensive Care Unit (ICU). This study aimed to investigate the clinical and biochemical effects of administering NAC to critically ill patients with COVID-19. A randomized controlled clinical trial was conducted on ICU patients (n = 140) with COVID-19 and divided into two groups: patients treated with NAC (NAC-treated group) and patients without NAC treatment (control group). NAC was administered as a continuous infusion with a loading dose and a maintenance dose during the study period (from admission until the third day of ICU stay). NAC-treated patients showed higher PaO2/FiO2 (p ≤ 0.014) after 3 days in ICU than their control group counterparts. Moreover, C-reactive protein (p ≤ 0.001), D-dimer (p ≤ 0.042), and lactate dehydrogenase (p ≤ 0.001) levels decreased on the third day in NAC-treated patients. Glutathione concentrations decreased in both NAC-treated (p ≤ 0.004) and control (p ≤ 0.047) groups after 3 days in ICU; whereas glutathione peroxidase did not change during the ICU stay. The administration of NAC manages to improve the clinical and analytical response of seriously ill patients with COVID-19 compared to the control group. NAC is able to stop the decrease in glutathione concentrations.

Effect of a pharmacist-based toxicology consult service on appropriate use of intravenous N-acetylcysteine for acetaminophen toxicity: A retrospective cohort study.

Incorporating clinical pharmacists on the medical team has been associated with fewer medication errors and increased error interception. Due to the logistical complexities of the intravenous (IV) N-acetylcysteine (NAC) regimen for acetaminophen toxicity, many opportunities for medication errors exist. A pharmacist-based toxicology consultation service was implemented at our institution, allowing pharmacists to formally aid in the management of toxicology patients throughout their hospital admission, including those with acetaminophen toxicity. The purpose of this study was to evaluate the effect of a house-wide pharmacist-based toxicology consult service on errors associated with IV NAC treatment for patients admitted with acetaminophen toxicity. A retrospective, pre-post cohort study was conducted on patients who received IV NAC for acetaminophen toxicity. The intervention evaluated was the implementation of a pharmacist-based toxicology consult service, known as the pharmacy toxicology team. The primary end point was the incidence of an error associated with IV NAC. An error was defined as the composite of inappropriate dose, administration rate, initiation, continuation, or discontinuation. Eighty-four patients were included; 30 patients in the pregroup, and 54 patients in the postgroup. Fewer patients experienced an error in the postgroup compared to the pregroup (30% vs 63%, P = 0.003). The implementation of this unique pharmacist-based toxicology consult service was associated with fewer patients experiencing an error related to IV NAC therapy for acetaminophen toxicity. Application of this data may aid in the justification for development of clinical pharmacist-based toxicology consult services at other institutions.

Dynamic thiol–disulphide homeostasis as a biomarker for predicting the development of contrast medium-associated acute kidney injury in the endovascular treatment of peripheral arterial disease: should intravenous N-acetylcysteine be given before the procedure?

To determine the predictive ability of serum thiol-disulphide levels for contrast medium-associated acute kidney injury (CA-AKI) after endovascular treatment (EVT) of peripheral arterial disease (PAD) and evaluate the efficacy of intravenous N-acetylcysteine (NAC) in preventing CA-AKI. This double-blind, randomised controlled study included 85 consecutive adult patients who underwent EVT for PAD. Patients were divided into NAC negative (NAC-) and positive (NAC+) groups. While the NAC- group received only 500 ml saline, the NAC+group received 500 ml saline plus intravenous 600 mg NAC before the procedure. Intra- and intergroup patient characteristics, procedural details, preoperative thiol-disulphide levels, and ischaemia-modified albumin (IMA) levels were recorded. There was a significant difference between NAC- and NAC+groups regarding native thiol, total thiol, disulphide/native thiol ratio (D/NT), and disulphide/total thiol ratio (D/TT). There was also a significant difference between the NAC- (33.3%) and NAC+ (13%) groups in CA-AKI development. Logistic regression analysis showed that the D/TT (OR 2.463) and D/NT (OR 2.121) were the most influential parameters for CA-AKI development. In the receiver operating characteristic (ROC) curve analysis, the sensitivity of native thiol to detect the development of CA-AKI was 89.1%. The negative predictive values of native thiol and total thiol were 95.6% and 94.1%, respectively. The serum thiol-disulphide level can be used as a biomarker to detect CA-AKI development and reveal patients with a low risk for CA-AKI development before EVT of PAD. Furthermore, thiol-disulphide levels allow for the indirect quantitative monitoring of NAC. Preprocedural intravenous NAC administration significantly inhibits CA-AKI development.

Efficacy of dexamethasone and N-acetylcysteine combination in preventing post-embolization syndrome after transarterial chemoembolization in hepatocellular carcinoma

Conventional transarterial chemoembolization (cTACE) is the current standard treatment for intermediate-stage hepatocellular carcinoma (HCC). Post-embolization syndrome (PES) is complex clinical syndrome that presents as fever, abdominal pain, nausea, and vomiting. Either dexamethasone (DEXA) or N-acetylcysteine (NAC) is used to prevent PES; however, the synergistic effect of their combined therapy for preventing PES and liver decompensation has not been determined. To evaluate the efficacy of DEXA and NAC combination in preventing PES and liver decompensation after cTACE. Patients with Barcelona Clinic Liver Cancer stage A or B HCC who were scheduled for TACE were prospectively enrolled. All patients were randomly stratified to receive NAC and DEXA or placebo. The dual therapy (NAC + DEXA) group received intravenous administration of 10 mg DEXA every 12 h, NAC 24 h prior to cTACE (150 mg/kg/h for 1 h followed by 12.5 mg/kg/h for 4 h), and a continuous infusion of 6.25 mg/h NAC plus 4 mg DEXA every 12 h for 48 h after cTACE. The placebo group received an infusion of 5% glucose solution until 48 h after procedure. PES was defined by South West Oncology Group toxicity code grading of more than 2 that was calculated using incidence of fever, nausea, vomiting, and pain. One-hundred patients were enrolled with 50 patients in each group. Incidence of PES was significantly lower in the NAC + DEXA group compared with in the placebo group (6% vs 80%; P < 0.001). Multivariate analysis showed that the dual treatment is a protective strategic therapy against PES development [odds ratio (OR) = 0.04; 95% confidence interval (CI): 0.01-0.20; P < 0.001). Seven (14%) patients in the placebo group, but none in the NAC + DEXA group, developed post-TACE liver decompensation. A dynamic change in Albumin-Bilirubin score of more than 0.5 point was found to be a risk factor for post-TACE liver decompensation (OR = 42.77; 95%CI: 1.01-1810; P = 0.049). Intravenous NAC + DEXA administration ameliorated the occurrence of PES event after cTACE in patients with intermediate-stage HCC.

Efficacy of N-acetyl Cysteine in Severe COVID-19 Patients: A Randomized Controlled Phase III Clinical Trial

Background: Today, various drugs have been investigated as the primary or complementary treatment for coronavirus disease 2019 (COVID-19). N-acetylcysteine (NAC) has been used as a mucolytic in pulmonary diseases. This drug apparently contributes to the retrieval of the intracellular antioxidant system. Objectives: This study aimed to determine the efficacy of NAC in severe COVID-19 patients admitted to the intensive care unit (ICU). Methods: This single-blinded randomized controlled phase III clinical trial included 40 patients with confirmed COVID-19 (based on polymerase chain reaction) admitted to the Shahid Mohammadi Hospital’s ICU, Bandar Abbas, Iran, in 2020. All cases had severe COVID-19. They were allocated randomly to two equal groups. Patients in the control group received standard drug therapy based on the treatment protocol of the national COVID-19 committee, while those in the NAC group received a single dose of intravenous NAC (300 mg/kg) upon admission to the ICU in addition to standard drug treatment. Clinical status and laboratory tests were done on admission to the ICU and then 14 days later or at discharge without knowing the patient grouping. Results: The two groups were comparable regarding age, gender, and other baseline laboratory and clinical parameters. At the final evaluation, respiratory rate (21.25 ± 4.67 vs. 27.37 ± 6.99 /min) and D-dimer (186.37 ± 410.23 vs. 1339.04 ± 2183.87 ng/mL) were significantly lower in the NAC group (P = 0.004 and P = 0.030, respectively). Also, a lower percentage of patients in the NAC group had lactate dehydrogenase (LDH) ≤ 245 U/L (0% vs. 25%, P = 0.047). Although the length of ward and ICU stay was shorter in the NAC group than in controls, the difference was statistically insignificant (P = 0.598 and P = 0.629, respectively). Mortality, on the other hand, was 75% in the control group and 50% in the NAC group, with no statistically significant difference (P = 0.102). Concerning the change in the study parameters, only the decrease in diastolic blood pressure (DBP) was significantly higher with NAC (P = 0.042). The intubation and mechanical ventilation rates were higher, while oxygen with mask and nasal oxygen rates were lower with NAC, but the difference was statistically insignificant. Conclusions: Based on the current research, NAC is related to a significant decrease in RR, D-dimer, and DBP in severe COVID-19. Also, LDH was significantly lower in the NAC group than in the controls. More research with larger sample sizes is needed to validate the current study results.

„Vanishing bile duct syndróm“ ako prejav poliekového poškodenia pečene u pacienta po polytraume

Summary: Vanishing bile duct syndrome is a type of drug-induced cholestatic liver injury that occurs when the body is exposed to drugs or other foreign substances. We hospitalized a 44-year-old, so far healthy, male with gradually developing painless icterus and pruritus of the whole body after severe polytrauma. The patient had previously undergone a complex treatment (antibio tics, antifungals, parenteral nutrition, LMWH). Laboratory tests revealed a several-fold elevation of total and conjugated bilirubin with a 3-fold increase in ALP levels, no signifi cant elevation of transaminases, a decrease in prothrombin time and IgG4 antibody positivity. An MRCP scan was performed revealing irregular intrahepatic bile ducts, a dilated common bile duct and characteristics of primary or secondary sclerosing cholangitis. Further examinations ruled out infectious, metabolic, toxic and oncological causes of hepatopathy. A liver bio psy ruled out both autoimmune hepatitis and IgG4 hepatopathy and displayed images of “vanishing bile duct syndrome” in drug-induced liver injury (DILI). Empirical treatment with high-dose intravenous N-acetylcysteine and other hepatoprotective agents led to a gradual decrease of bilirubin, normalization of coagulation parameters and remission of icterus and clinical complaints. This case report points to a cholestatic type of drug-induced liver injury with histologically confi rmed vanishing bile duct syndrome and the need to think of DILI as one of the causes of the otherwise unexplained hepatopathy. Key words: cholangitis – DILI – hepatopathy – IgG4 – vanishing bile duct syndrome