Acetaminophen Overdose Research Articles

The Protective Role of Vitamin E on the Liver, Kidney, and Male Reproductive Functions of Paracetamol Overdose in Male Rabbits

The Protective Role of Vitamin E on the Liver, Kidney, and Male Reproductive Functions of Paracetamol Overdose in Male Rabbits

Impact of regulations on paracetamol overdoses between 2018 and 2021: Retrospective monocentric study in a French university hospital

Impact of regulations on paracetamol overdoses between 2018 and 2021: Retrospective monocentric study in a French university hospital

Differentiating Ischemic Hepatitis from Acetaminophen Overdose in Acute Liver Failure: Role of Acetaminophen Adducts-Ischemic Hepatitis vs Acetaminophen Overdose.

Acetaminophen (APAP) hepatotoxicity and ischemic hepatic injury (IH) demonstrate remarkably similar biochemical patterns. Deciding between these two etiologies in the setting of acute liver failure (ALF) can be challenging. We reviewed all cases in the Acute Liver Failure Study Group (ALFSG) registry where these diagnoses were considered, to determine reasons for, and frequency of, difficulties making these diagnoses. We hypothesized that the newly developed APAP-CYS adduct assay could help in discerning the correct diagnosis. Among 3364 patients with ALF or acute liver injury (ALI: INR ≥ 2.0 but without encephalopathy) between 1998 and 2019, 1952 (58%) received a final diagnosis of either APAP (1681) or IH (271). We utilized a review committee of senior hepatologists as well as the APAP-CYS assay (where sera were available), measuring the presence of toxic by-products of APAP injury to optimize adjudication. With these methods, a total of 575 adduct positive APAP cases included 488 recognized APAP, as well as an additional 87 patients previously diagnosed as other etiologies. Nine cases initially attributed to IH were deemed combination APAP-IH injuries. Conversely, 215 of the 280 IH subjects tested for adducts disclosed 173 confirmed as IH with adduct testing below the toxicity threshold, while 9 cases were revised from APAP to the IH-APAP combination phenotype, where both hypotension and APAP likely played a role. Discerning APAP from IH can be difficult-in rare cases, combined injury is observed (18/1952). APAP-CYS testing resulted in revising the diagnosis in 14.6% of cases.

Paracetamol Dosing Errors in People Aged 12 Years and Over: An Analysis of Over 14,000 Cases Reported to an Australian Poisons Information Centre.

Paracetamol dosing errors can cause acute liver injury, with potentially toxic doses only slightly above the therapeutic range. This study aimed to characterise unintentional paracetamol overdose reported to an Australian poisons centre, including time trends, demographics, types of dosing errors, and outcomes. Records regarding paracetamol dosing errors for individuals aged ≥12 years were extracted from the New South Wales Poisons Information Centre database, January 2017 to June 2023. Data from 2021 underwent an in-depth screening of free text case notes to examine: dose, duration, products involved, reasons for ingestion and outcomes including hospitalisation, treatment, liver transplantations and deaths. Where possible, complete outcome data were obtained from medical records of New South Wales hospitalised cases in 2021. There were 14,380 exposures due to paracetamol dosing errors (predominantly self-administered, median age 43 years, 62.6% female), with an average yearly increase of 2.5% (95% CI 1.6-3.8%; p < 0.0001). The in-depth analysis of exposures recorded during 2021 revealed 1899 exposures (median age 46 years, 63.4% female) with 26.8% requiring hospitalisation. Immediate- and modified-release formulations were highly implicated. Multiple paracetamol-containing products were ingested in approximately 20% of exposures. Hospitalised exposures were associated with paracetamol use for dental pain and ingested higher doses for longer durations. Over half of those hospitalised (52%) were treated with the antidote (N-acetylcysteine), and 6% of exposures developed hepatotoxicity. Paracetamol dosing errors continue to occur, with relatively high rates of hospitalisation and liver injury. Many hospitalisations involved use for dental pain. Possible preventative measures include ingredient name prominence and increased education on appropriate dosing.

Electrochemical Sensor based on N-Doped Graphite/Aluminum Silicate Nanocomposite Modified Carbon Paste for Simultaneous Detection of Paracetamol and Pamabrom

We have developed an eco-friendly sensor through innovative modification of a carbon paste electrode with nanomaterials. This modification is based on employing a mixture of aluminum silicate and nitrogen-doped graphite nanocomposite (Al2SiO5/NG/CPE), introducing the first electrochemical approach for the voltammetric determination of a combination of paracetamol (PCM) and pamabrom (PAM), which is recognized as an over-the-counter remedy for menstrual cramp relief. N-doped graphite was prepared from graphite and urea using a metal-free soft nitriding method. The morphological characterization of the Al2SiO5/NG nanocomposite was investigated using transmission electron microscopy, energy dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. The experimental conditions were optimized using square wave voltammetry and cyclic voltammetry techniques to explore the impact of scan rate, pH, and concentration. The results exhibited good linearity across a wide concentration range of 0.2 nM–100.0 μM for both drugs. The limits of detection for PCM and PAM were 25 and 24 pM, respectively, while the limits of quantification were 88.3 and 80.0 pM, showing the proposed sensor’s exceptional sensitivity. Furthermore, the proposed sensor was employed to determine the PCM/PAM mixture in bulk powder, pharmaceutical dosage forms, biological fluids, and in the presence of toxic paracetamol metabolites.

Self-poisoning with paracetamol in England: short report of characteristics of individuals and their overdoses according to source of tablets.

Self-poisoning with paracetamol is the most frequently used overdose method in the UK. Psychosocial assessments were conducted by mental health clinicians with 127 consecutive individuals who presented with pure paracetamol overdoses to a large general hospital over 8 months, including asking about the source of the tablets and scoring the patients' acts on the Beck Suicide Intent scale (BSI). Patients were predominantly female (86%) and young (79% aged 12-24 years). Most had used paracetamol which was available in the home (77%). Those who purchased paracetamol for the act took double the number of tablets compared with those who used paracetamol available in the home (37 v. 18), had higher suicidal intent (mean BSI: 11 v. 7) and more often required treatment with N-acetyl cysteine (71% v. 43%). These results highlight the need for safer home storage of paracetamol and consideration of reducing pack size limits on paracetamol that can be purchased.

Is an acute overdose of zolpidem fatal?

Zolpidem, widely prescribed for short-term management of insomnia, is a non-benzodiazepine hypnotic agent. It carries a high potential for abuse and an elevated risk of suicide. Overdose generally results in mild central nervous system depression, though severe outcomes are possible when co-ingested with other CNS depressants. Standard treatments include gastric lavage, flumazenil administration, and intravenous fluids. This case report describes a 66-year-old female admitted after an apparent suicidal ingestion of approximately 200 mg of zolpidem. Upon admission, she was unconscious, with bradypnea and hypotension, scoring 5 on the Glasgow Coma Scale. Gastric lavage and N-acetylcysteine were administered due to elevated liver enzymes suggesting concomitant paracetamol poisoning, which was confirmed by urine tests. Flumazenil temporarily improved her condition, and she was subsequently transferred to the Intensive Care Unit for mechanical ventilation. Her clinical status stabilized, leading to extubation on the second day and transfer to the Psychiatry Unit. This case highlights the critical need for timely intervention and continuous monitoring in zolpidem overdose scenarios, particularly when polypharmacy is involved. In instances of respiratory failure following zolpidem overdose, it is imperative to investigate the potential co-ingestion of additional substances.

Adolescent Acetaminophen and Ibuprofen Self-Poisoning, 2017-2022.

Acetaminophen and ibuprofen are the most common agents involved in adolescent self-poisoning. With increasing suicidality observed during the COVID-19 pandemic, we sought to compare overdose trends, severity, and outcomes for both agents. We performed a retrospective analysis of the National Poison Data System for acetaminophen and ibuprofen single-substance exposures in teenagers 13-19 years of age from 2017-2022. Acetaminophen and ibuprofen overdoses (per 100,000 persons) were plotted by year. Medical outcomes, clinical effects, and therapies were compared to determine if there were differences in overdose severity between the 2 agents. From 2017 to 2022, US poison centers recorded 50,902 single-substance acetaminophen exposures and 41,674 single-substance ibuprofen exposures in teenagers. Cases peaked in 2021 with 40.0 versus 29.1 cases (per 100,000 persons) for acetaminophen and ibuprofen, respectively. Acetaminophen self-poisoning was significantly more likely to result in death (odds ratio, 13.92; 95% confidence interval, 2.18-581.75; P < 0.001) or inpatient admission (odds ratio, 7.38; 95% confidence interval, 7.10-7.66; P < 0.001) compared with ibuprofen. Abdominal pain and vomiting were the most common clinical effects for both agents, and unsurprisingly, acetaminophen was more likely to cause transaminitis and liver dysfunction, whereas ibuprofen was more likely to cause central nervous system depression and metabolic acidosis. For the acetaminophen group, 19 teenagers underwent organ transplantation. Given the increased hospitalization and treatment resources needed for acetaminophen overdoses compared with ibuprofen, it is time to implement acetaminophen packaging policy change to protect US adolescents.

MiR-106b-5p protects against drug-induced liver injury by targeting vimentin to stimulate liver regeneration.

Understanding the endogenous mechanism of adaptive response to drug-induced liver injury (arDILI) may discover innovative strategies to manage DILI. To gain mechanistic insight into arDILI, we investigated exosomal miRNAs in the adaptive response to toosendanin-induced liver injury (TILI) of mice. Exosomal miR-106b-5p was identified as a specific regulator of arDILI by comprehensive miRNA profiling. Outstandingly, miR-106b-5p agomir treatment alleviated TILI and other DILI by inhibiting apoptosis and promoting hepatocyte proliferation. Conversely, antagomir treatments had opposite effects, indicating that miR-106b-5p protects mice from liver injury. Injured hepatocytes released miR-106b-5p-enriched exosomes taken up by surrounding hepatocytes. Vim (encodes vimentin) was identified as an important target of miR-106b-5p by dual luciferase reporter and siRNA assays. Furthermore, single-cell RNA-sequencing analysis of toosendanin-injured mouse liver revealed a cluster of Vim + hepatocytes; nonetheless declined following miR-106b-5p cotreatment. More importantly, Vim knockout protected mice from acetaminophen poisoning and TILI. In the clinic, serum miR-106b-5p expression levels correlated with the severity of DILI. Indeed, liver biopsies of clinical cases exposed to different DILI causing drugs revealed marked vimentin expression among harmed hepatocytes, confirming clinical relevance. Together, we report mechanisms of arDILI whereby miR-106b-5p safeguards restorative tissue repair by targeting vimentin.

The Possible Protective Role of N-acetylcysteine against Testicular Toxicity Induced by Paracetamol Overdose in Adult Male Rats

Many substances, even medicines with proven therapeutic benefits, can harm cells by metabolically activating them into extremely reactive substances. Paracetamol is one of the most widely used over-the-counter analgesics. This study examines the harmful effects of paracetamol on the lipid peroxidation process in testes homogenates as well as enzymatic and non-enzymatic antioxidant activities. Also, examine the effects on male hormones and sperm count. The study also assesses if N-acetylcysteine protects against testicular damage induced by paracetamol excess. Forty mature male albino rats were created. Group 1 as a control, Group 2 paracetamol (650 mg/kg), Group 3 NAC (150 mg/kg), and Group 4 both paracetamol and NAC. Samples of blood and testicles were taken after 15 days to measure sperm and testicular biochemistry. Testicular tissues had considerably higher amounts of MDA and H2O2. SOD, GSH, and CAT levels significantly decreased. FSH and LH rise. On the other hand, testosterone levels decrease following paracetamol exposure. The administration of NAC generated changes in testosterone levels, FSH, LH, and antioxidant enzymes. The sperm morphology showed an increase in abnormalities but a significant decrease in motility and count. NAC effectively lowers the toxicity of paracetamol to the testicles while restoring biomarkers associated with normal testicular function.

Evaluation of Serum Acetaminophen Concentration Utility for Closure of Patent Ductus Arteriosus.

Acetaminophen for patent ductus arteriosus (PDA) closure has gained popularity over the last decade; however, therapeutic drug monitoring for this indication remains uncertain. The exact timing and goal trough serum acetaminophen concentration ranges are not well defined. The purpose of our study is to evaluate the impact of therapeutic drug monitoring on both PDA closure rates and identify real-world risk of hepatotoxicity. Retrospective single-center chart review of neonates admitted to the neonatal intensive care unit (NICU) between April 2016 and August 2022 with at least 1 serum acetaminophen concentration to monitor for PDA closure. Acetaminophen was initiated at 15 mg/kg administered intravenously every 6 hours and a trough serum concentration was obtained prior to the sixth or seventh dose. PDA closure was confirmed radiographically with corresponding provider documentation. Associations of efficacy to closure were -analyzed using descriptive statistics. Thirty-eight neonates were included in the analysis, of which 18 (47%) achieved PDA closure. First serum acetaminophen trough concentration was obtained before the seventh dose [IQR, 6-8] and ranged from undetectable (< 5 mg/L) to 30.8 mg/L. Subgroup analysis of first concentrations revealed therapeutic trough, defined as 10 to 20 mg/L, did not correlate to PDA closure (no closure median concentration = 14.7 [IQR, 13-15.6] vs closure median concentration = 15.4 [IQR, 11.4-18.5], p = 0.42), or duration of treatment. No neonate experienced acetaminophen-associated toxicity. PDA closure did not correlate to serum acetaminophen trough concentration. The regimen of 15 mg/kg every 6 hours appears safe as no neonate experienced acetaminophen toxicity or discontinued treatment early.

Effect of ferroptosis inhibitors in a murine model of acetaminophen-induced liver injury.

Liver injury caused by acetaminophen (APAP) overdose is the leading cause of acute liver failure in western countries. The mode of APAP-induced cell death has been controversially discussed with ferroptosis emerging as a more recent hypothesis. Ferroptosis is characterized by ferrous iron-catalyzed lipid peroxidation (LPO) causing cell death, which can be prevented by the lipophilic antioxidants ferrostatin-1 and UAMC-3203. To assess the efficacy of these ferroptosis inhibitors, we used two murine models of APAP hepatotoxicity, APAP overdose alone or in combination with FeSO4 in fasted male C57BL/6J mice. APAP triggered severe liver injury in the absence of LPO measured as hepatic malondialdehyde (MDA) levels. In contrast, ferrous iron co-treatment aggravated APAP-induced liver injury and caused extensive LPO. Standard doses of ferrostatin-1 did not affect MDA levels or the injury in both models. In contrast, UAMC-3203 partially protected in both models and reduced LPO in the presence of ferrous iron. However, UAMC-3203 attenuated the translocation of phospho-JNK through downregulation of the mitochondrial anchor protein Sab resulting in reduced mitochondrial dysfunction and liver injury. Thus, APAP toxicity does not involve ferroptosis under normal conditions. The lack of effects of ferroptosis inhibitors in the pathophysiology indicates that ferroptosis signaling pathways are not relevant therapeutic targets.

Empagliflozin impact on experimentally induced acetaminophen toxicity: Imprint of mitochondrial dynamics, biogenesis, and cGAS/STING signal in amending liver insult.

Acetaminophen (APAP) is one of the most clinically relevant medications associated with acute liver damage. A prolific deal of research validated the hepatoprotective effect of empagliflozin (EMPA); however, its effect on APAP-induced hepatotoxicity has still not been investigated. In this study, the prospective hepatoprotective impact of EMPA against APAP-induced hepatotoxicity was investigated. Twenty-eight Balb-C mice were assigned to four groups: control, APAP, EMPA10/APAP, and EMPA25/APAP. At the end of the experiment, serum hepatotoxicity biomarkers, MDA level, and GSH content were estimated. Hepatic mitofusin-2 (MFN2), optic atrophy 1 (OPA1), dynamin-related protein 1 (Drp1), and mitochondrial fission 1 protein (FIS1) were immunoassayed. PGC-1α, cGAS, and STING mRNA expression were assessed by real-time PCR. Histopathological changes and immunohistochemistry of INF-β, p-NF-κB, and iNOS were evaluated. APAP treatment caused significant hepatic functional impairment and increased hepatic MDA levels, as well as a concomitant decrease in GSH content. Marked elevation in Drp1 and FIS1 levels, INF-ß, p-NF-κB, and iNOS immunoreactivity, and reduction in MFN2 and OPA1 levels in the APAP-injected group, PGC-1α downregulation, and high expression of cGAS and STING were also documented. EMPA effectively ameliorated APAP-generated structural and functional changes in the liver, restored redox homeostasis and mitochondrial dynamics balance, and enhanced mitochondrial biogenesis, remarkably diminished hepatic expression of cGAS and STING, and elicited a reduction in hepatic inflammation. Moreover, the computational modeling data support the interaction of APAP with antioxidant system-related proteins as well as the interactions of EMPA against Drp1, cGAS, IKKA, and iNOS proteins. Our findings demonstrated for the first time that EMPA has an ameliorative impact against APAP-induced hepatotoxicity in mice via modulation of mitochondrial dynamics, biogenesis, and cGAS/STING-dependent inflammation. Thus, this study concluded that EMPA could be a promising therapeutic modality for acute liver toxicity.

Should high-dose N-acetylcysteine be given in cases of massive paracetamol overdoses: A narrative review.

N-acetylcysteine (NAC) is regarded as an effective treatment of paracetamol overdoses. However, in cases of "massive" paracetamol overdoses, recent studies indicate that patients may not be sufficiently treated with the standard dose of NAC (300 mg/kg over 20-21 h). The subject is further complicated because "massive overdoses" and "high-risk" are defined differently; some studies use the ingested amount (e.g., >40 g), and some studies use blood concentrations of paracetamol and transaminases. This narrative review investigates whether high-dose NAC significantly decreases the risk of hepatotoxicity in patients with massive paracetamol overdoses. Three observational studies were analysed; one study with 373 patients found no significant difference (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 0.49-3.29). One study with 79 patients found a significant difference (OR: 0.27, 95% CI: 0.08-0.94). The third study with 89 patients found a significant difference in hepatoxicity between the groups (p= 0.043). There are no solid evidence to support that treatment with high-dose NAC significantly reduces the rate of hepatotoxicity in patients presenting with massive paracetamol overdoses. Differences in inclusion criteria in the included studies make the studies incomparable. This paper shows that standardized inclusion is needed to determine whether a high-dose NAC regimen should be included in clinical practice.

Association of Acetaminophen (Paracetamol) Use With Severity and Outcomes in Patients With Viral Hepatitis-Associated Acute Liver Failure.

Acute viral hepatitis (AVH) comprises 11% of acute liver failure (ALF) in North America while acetaminophen (APAP) toxicity represents 46%. The use of APAP to treat prodromal hepatitis symptoms is common. It is unknown if concurrent APAP use impacts liver injury in AVH-induced ALF. In this prospective, multicenter cohort study, 356 patients meeting criteria for AVH including hepatitis A, B, Epstein-Barr virus, and herpes simplex virus, all leading to ALF (hepatic encephalopathy after acute illness, international normalized ratio ≥1.5), or acute liver injury (acute liver injury, international normalized ratio >2.0, no hepatic encephalopathy) were reviewed for evidence of APAP use: APAP ingestion history or measurement of serum APAP level or APAP-CYS adducts, a specific biomarker released into blood with APAP injury. Patients were grouped by APAP exposure level, from high (measurable APAP levels or toxic APAP-CYS), medium (therapeutic APAP-CYS), low (history of APAP ingestion only and/or barely detectable APAP-CYS), or no exposure recorded. Two hundred five of 356 patients (57.5%) with AVH-ALF had evidence of APAP use: 87 out of 356 (24%) demonstrated high or medium exposures. The aminotransferase and bilirubin levels of high/medium group resembled a mixed APAP-viral injury. Mortality was the highest (51.6%, 21.4%, 28.8%, and 30.5%), and transplant-free survival was the lowest (22.6%, 44.6%, 41.5%, and 40.4%) in the high exposure group compared with medium, low, and no exposure groups. However, the specific comparisons of mortality and transplant-free survival between the high exposure and no exposure groups were not statistically different even after adjusting for baseline patient characteristics differences. APAP use in AVH-ALF is common and may negatively impact outcomes compared with little or no APAP exposure. Prospective studies of the safest and effective dose of APAP to use in patients with AVH are needed.

CHARACTERISTICS OF IMMUNOREACTIVITY IN THE RAT UNDER CONDITIONS OF TOXIC INJURY WITH ACETAMINOPHEN

The aim of this work was to to determine the integral leukocyte indices in animals with toxic damage by acetaminophen on the background of protein deficiency. The study was conducted on 4 groups of animals: Group I - control animals (K); II – rats kept on a low-protein diet (LPD); ІІІ – animals with acetaminophen-induced liver injury receiving complete ration (AII); IV – animals with acetaminophen-induced liver injury that were previously maintained on semi-synthetic low-protein ration (LPD/AII). Preparation of blood smears, their fixation and staining was carried out by the generally accepted method. The ratio of different types of leukocytes in stained blood smears was calculated using a standard method using a leukocyte counter and a microscope (eyepiece × 10, objective × 100). Standard formulas were used to calculate integral hematological indices. It was established that the supply of protein in the diet is critical for the functioning of the immune system under conditions of acetaminophen intoxication, since under these conditions there is a change in leukocyte indices, in particular, the index of immunoreactivity, the index of leukocyte shift, the index of the ratio of neutrophils and lymphocytes, the index of the reactive response of neutrophils, which indicates the intensification of inflammatory processes in the body and the formation of defects in the cellular link of immunity, disruption of the mechanisms of the specific immune response and the formation of a state of endotoxicosis. The obtained results can be used to develop approaches to the early diagnosis of impaired immunoreactivity in animals with toxic damage by acetaminophen against the background of dietary protein deficiency, while the studied integral hematological indicators can be used as additional early diagnostic markers of impaired immunoreactivity and endotoxicosis. Key words: acetaminophen, dietary protein deficiency, leukocytes, immunoreactivity indices

AGE-DEPENDENCE OF BIOCHEMICAL MANIFESTATIONS OF HEPATOTOXICINJURY IN RAT EXPOSED TO XENOBIOTICS OF VARIOUS GENESIS

Currently, the problem of liver diseases against the backdrop of the toxic effects of medicinal and industrial (herbicides) xenobiotics on the body is becoming increasingly relevant. The activation of compensatory mechanisms in response to the action of toxic agents –acetaminophen and/or diquat is closely related to age-specific features. Heightened focus on acetaminophen-induced injury is linked to the widespread use of this medication as an analgesic and antipyretic during pandemics of infectious and inflammatory diseases, especially under the conditions of warfare in Ukraine. In return, the widespread use of the herbicide diquat is accompanied by an increase in the registration of cases of diquat -induced acute poisoning. The aim of study was to evaluation the biochemical parameters of the functional state of the liver of different-aged rats under conditions of acetaminophen-and diquat-induced toxic injury. Animals were divided into three age groups: adolescent (60 days), reproductive (150 days), and mature age rats (360 days). Acute toxic injury by acetaminophen was modeled by its oral administration through gastric intubation at a daily dose of 1250 mg/kg of the animal's body weight during the last 2 days of the experiment. Acute toxic damage by diquat was modeled by a single intragastric administration using a probe at a dose of 115.5 mg/kg of the animal's body weight. The functional state of the liver was assessed on an automatic biochemical analyzer NTI Biochem FC-120.Acetaminophen intoxication led to an increase in the absolute liver mass indicator, organ index, changes in the macroscopic structure of the organ, increased serum activities of ALT and AST, total LDH, and a decrease in the De Ritis ratio amidst increased activities of ALP, GGT, and levels of total and indirect bilirubin in all age groups compared to the control. The most significant changes were observed in mature age animals (increase in ALT activity by 76%, AST by 56%, ALP by 51%, GGT by 51%, and a decrease in the De Ritis ratio by 47%). Under conditionsof diquat-induced toxic injury, a slightly different trend and degree in manifestation of established changes are observed. A more pronounced hepatotoxic effect was registered in adolescent animals, manifested by the maximum increase in absolute liver mass by 26%, ALT activity by 71%, AST by 47%, ALP by 50%, Bili-T level by 69%. No statistically significant differences compared to the control and APAP-induced injury in the activity of total LDH and GGT upon administration of toxic doses of the herbicide diquat regardless of age category were observed.Based on the experimental results, an age-related multidirectionality in the adverse effects of the medicinal xenobiotic acetaminophen and the industrial xenobiotic diquat on indicators of the morpho-functional state of the liver is observed. The most sensitive age group of animals to toxic injury by acetaminophen are rats of 360 days of age, while for diquat –60 days of age

Safety and Efficacy of N-Acetylcysteine as an Adjuvant Therapy in Critically Ill COVID-19 Patients

Abstract Background COVID-19 may cause pneumonia, acute respiratory distress syndrome, cardiovascular alterations, and multiple organ failure, which have been ascribed to a cytokinestorm, a systemic inflammatory response, and an attack by the immune system. Moreover, an oxidative stress imbalance has been demonstrated to occur in COVID- 19 patients. N- Acetyl-L-cysteine (NAC) is a precursor of reduced glutathione (GSH). Aim of the Work we retrospectively will investigate safety and efficacy of NAC dose given in paracetamol toxicity as an adjuvant therapy in critically ill COVID-19 patients with acute respiratory distress and determine whether NAC in high doses can avoid respiratory failure in patients with COVID-19. Patients and Methods This was a retrospective observational study in which all cases were collected from ICU of Ain shams university hospitals during COVID-19 outbreak. All data were extracted from clinical records. All patients initially admitted to ICU with SPO2 less than 94 % were included between December 2020 to February 2022. Exclusion Criteria included Need for immediate mechanical ventilation on admission, known allergy or hypersensitivity to NAC, end stage renal and liver diseases, heart failure and pregnancy. All patients with severe COVID-19 (confirmed or suspected received standard care, according to the institutional protocol. Results Patients were randomized into two equal groups (number (n)=40 each) as the N1(NAC) group who was given intravenously, initially 150 mg/kg in 200 mL of 0.9% NaCL for 60 minutes (first bag), followed by 50 mg/kg in 500 mL of 0.9% NaCL for 4 hours (second bag), and then 100 mg/kg in 1000 mL of 0.9%NaCL for 16 hours (third bag) and N2(Non NAC) group who received intravenously N-acetylcysteine (NAC) 600mg /12hr and The primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to the intensive care unit (ICU), time in ICU, and mortality. There were no statistically significant differences between the two groups (p &amp;gt; 0.05) The effect of NAC on mechanical ventilations, mortality, ICU stays, and hospital stays is a matter of controverse in ARDS patients. We found that intravenous high dose of NAC did not improve oxygenation, mortality rate and did not reduce the requirement for mechanical ventilation when administered for COVID 19 patients with ARDS. Also, the duration of ICU and hospital stays were relatively prolonged in the NAC-treated patients. These might be due to prolonged survival time with NAC-treated patients, but not to be detected with the small single centered trial.. Conclusion Use of high doses of NAC administration can not affect the need of mechanical ventilation, rate of mortality, the need, duration of ICU admission and hospital stays for patients with severe COVID-19.

Paracetamol overdose causing acute kidney injury without hepatotoxicity: a case report

BackgroundParacetamol is a widely used analgesic and antipyretic. Paracetamol-induced hepatotoxicity is well known, but nephrotoxicity without hepatotoxicity is rarely seen.Case presentationWe present a case of acute kidney injury without hepatotoxicity in paracetamol overdose. A 15-year-old girl was admitted 48 h after she had taken 10 g of paracetamol. She was complaining of abdominal pain and vomiting. Her blood level of creatinine was 1.20 mg/dL on admission, with a peak at 3.67 mg/dL 3 days later. The liver blood tests and blood paracetamol level were negative. She did not receive N-acetyl cysteine and was treated with intravenous fluid (crystalloid). The ultrasonography of the kidneys was normal. Her renal function returned almost to baseline 7 days after admission. It was concluded that the diagnosis was an acute kidney injury caused by acute tubular necrosis due to paracetamol overdose.ConclusionThis case shows that nephrotoxicity can occur without hepatotoxicity in paracetamol overdose.

Perioperative N-acetylcysteine: evidence and indications.

Nonopioid analgesics serve to improve analgesia and limit side effects and risks of perioperative opioids. N-acetylcysteine (NAC), the primary treatment of acetaminophen toxicity, may have perioperative indications, including analgesia. NAC impacts glutathione synthesis, oxidant scavenging, glutamate receptor modulationand neuroinflammation. Potential perioperative benefits include arrhythmia prevention after cardiac surgery, decreased contrast-induced nephropathy, improved post-transplant liver functionand superior pulmonary outcomes with general anesthesia. NAC may improve perioperative analgesia, with some studies displaying a reduction in postoperative opioid use. NAC is generally well tolerated with an established safety profile. NAC administration may predispose to gastrointestinal effects, while parenteral administration may carry a risk of anaphylactoid reactions, including bronchospasm. Larger randomized trials may clarify the impact of NAC on perioperative analgesic outcomes.