Acute Acetaminophen Overdose Research Articles

Patterns of acetaminophen toxicity among patients with low-risk serum concentrations.

In 2012, the Commission on Human Medicines mandated lowering the acetaminophen toxicity nomogram treatment threshold in the UK to 100 µg/ml at 4 h post-ingestion. The present study aim was to evaluate biochemical and liver toxicity patterns in patients who presented with acetaminophen overdose and had low serum acetaminophen concentrations (<150 µg/ml). Patients admitted to the emergency department with a clear history of acute acetaminophen overdose with or without other medication or ethanol were consecutively enrolled into this retrospective cohort study. Patients with serum acetaminophen concentration >150 µg/ml or an unknown ingestion time were excluded. Data were extracted from electronic medical records and are presented as mean ± SD or median (interquartile range). A total of 103 patients were included (median age, 17 [4-21] years) and 80 (78%) were female. The median ingested acetaminophen dose was 5000 (2850-7650) mg. At baseline, the median serum acetaminophen concentration was 42 (4.5-64.8) µg/ml, and median alanine aminotransferase and aspartate aminotransferase levels were 22 (17-28) and 27 (16-45) IU/L, respectively. Twenty patients were treated with acetylcysteine, with none developing adverse reactions. No patient developed hepatotoxicity, including patients with initial multiple product ingestion or other risk factors. Patients presenting with an acute acetaminophen overdose with acetaminophen level <150 µg/ml, including patients with other risk factors, are at low risk of hepatotoxicity.

Two versus Three Infusion Regimens of N-Acetylcysteine for Acetaminophen Overdose.

Acetaminophen overdose is a common clinical condition, often leading to liver toxicity. Current treatments involve the three-infusion N-Acetylcysteine (NAC) regimen (FDA-labeled), which may be complex, time-consuming, and need to be changed. An alternative uses two infusions instead, which offers possible advantages regarding simplicity and administration errors. This study sought to compare the respective efficacies and safety outcomes when treating acute acetaminophen overdose among children and adolescents. At Montreal Children's Hospital, a retrospective study was conducted comparing pre-2003 FDA-labelled three-infusion NAC therapy with a two-infusion regimen. Information was collected regarding patient demographics, NAC administration details, errors, rates of hepatotoxicity, and adverse reactions, and the statistical test Chi-square test was employed to obtain the results. A total of 126 patients met the inclusion criteria. Of these patients, 65 received a two-infusion regimen, and 61 patients received the FDA-labeled regimen. The two-infusion group experienced significantly fewer administration errors (4 errors vs. 23 errors; p < 0.001), while the rates of hepatotoxicity between them were similar. There were no instances of liver transplantation or mortality due to either regimen. Adverse reactions occurred equally frequently between both regimens with no discernible difference-the meantime to administer NAC was 9 h for the two-infusion regimen and 8.5 h for FDA-labeled regimen groups, respectively. Three cases of hepatitis were successfully treated with timely NAC therapy, and no liver transplantation or mortality occurred. Adverse reactions, including anaphylactoid reactions, were observed in both groups but were resolved when temporarily stopped and restarted at a slower infusion rate. The two-infusion NAC regimen proved similar efficacy at protecting liver damage and improving patient outcomes compared to its FDA-labeled three-stage counterpart, with significantly fewer administration errors for this version of NAC treatment, suggesting potential advantages in terms of safety and simplicity. Future research should investigate larger cohorts and more variables to validate these results further and optimize the management of acetaminophen overdose cases; further investigation should focus on dosing strategies, personalized approaches, and long-term patient care in this context.

Biofabricated Palladium Nanoparticle-Decorated Reduced Graphene Oxide Nanocomposite Using the Punica granatum (Pomegranate) Peel Extract: Investigation of Potent In Vivo Hepatoprotective Activity against Acetaminophen-Induced Liver Injury in Wistar Albino Rats.

Acute acetaminophen (APAP) toxicity is a predominant clinical problem, which causes serious liver injury in both humans and experimental animals. This study presents the histological and biochemical factor and antioxidant enzyme level changes induced by an acute acetaminophen overdose in Wistar albino rat livers to elucidate the effective hepatoprotective potential of biofabricated palladium nanoparticle-decorated reduced graphene oxide nanocomposites (rGO/PdNPs-NC) compared to silymarin. After detailed characterization of the hepatoprotective potential of the synthesized rGO/PdNPs-NC, the rats were divided into eight groups (n = 6): control group (normal saline, 1 mL/kg b.w.), silymarin, Punica granatum (pomegranate) peel extract, PdNPs, reduced graphene oxide (rGO-PG), and reduced graphene oxide palladium nanocomposites (rGO/PdNPs-NC, low and high doses) for 7 successive days. The acetaminophen (APAP)-treated group was administered a single dose of acetaminophen (2 g/kg b.w.) on the 8th day. The histopathological results showed that the acetaminophen overdose group exhibited massive intrahepatic hemorrhagic necrosis around the centrilobular region with hepatocytes with vacuolization and swollen cytoplasm found in the liver architecture. This hepatopotential was further assessed by various biochemical parameters such as SGOT, SGPT, ALB, ALP, LDH, direct bilirubin, total bilirubin, and total protein. Also, the antioxidant parameters such as SOD, CAT, MDA, GSH, GRD, and GST were assayed. Rats of groups 7 and 8 showed a significant decrease in SGOT, SGPT, ALP, LDH, direct bilirubin, and total bilirubin (p < 0.001), while a significant increase in the final total protein and ALB as compared to group 2 rats (p < 0.001) was observed. The antioxidant parameters exhibited that rats of groups 7 and 8 showed a significant (p < 0.001) increase in the level of SOD, CAT, GSH, GRD, and GST without affecting the MDA as compared to group 2 rats. Also, the hepatoprotective potential of rGO/PdNPs-NC (low and high doses) was comparable to that of the standard reference drug silymarin. The present study reveals that the rGO/PdNPs-NC possesses significant hepatoprotective activity and acts as an effective and promising curative agent against acetaminophen-induced hepatotoxicity.

Characterization and Quantification of Oxidized High Mobility Group Box 1 Proteoforms Secreted from Hepatocytes by Toxic Levels of Acetaminophen.

The high mobility group box 1 (HMGB1), which is released during acute acetaminophen (APAP) overdose, is thought to mediate a subsequent immune response, particularly hepatic infiltration of macrophages. The redox behavior of HMGB1 and the proteoforms of HMGB1 present in oxidative environments has been the subject of a number of confusing and contradictory studies. Therefore, a stable isotope dilution two-dimensional nanoultrahigh-performance liquid chromatography parallel reaction monitoring/high-resolution mass spectrometry method was developed in order to characterize and quantify oxidative modifications to the cysteine (Cys) residues (Cys-23, Cys-45, and Cys-106) that are present in HMGB1. Disulfide linkages were determined using carbamidoethyl derivatization before and after reduction as well as by direct analysis of disulfide cross-linked peptides. A stable isotope labeled form of HMGB1 was used as an internal standard to correct for sample to sample differences in immunoaffinity precipitation, derivatization, and electrospray ionization. Four discrete HMGB1 proteoforms were found to be released from a hepatocarcinoma cell model of APAP overdose after 24 h. Fully reduced HMGB1 with all three Cys-residues in their free thiol state accounted for 18% of the secreted HMGB1. The proteoform with disulfide between Cys-23 and Cys-45 accounted for 24% of the HMGB1. No evidence was obtained for a disulfide cross-link between Cys-106 and the other two Cys-residues. However, 45% of the HMGB1 formed a cross-link with unidentified intracellular proteins via an intermolecular disulfide bond, and 12% was present as the terminally oxidized cysteic acid. Surprisingly, there was no evidence for the formation of HMGB1 disulfides with GSH or other low molecular weight thiols. Secreted plasma HMGB1 Cys-23/Cys45 disulfide proteoform together with the Cys-106/protein disulfide proteoforms could potentially serve as early biomarkers of hepatoxicity after APAP overdose as well as biomarkers of drug-induced liver injury.

Sensitivity of dose-estimations for acute acetaminophen overdose in predicting hepatotoxicity risk using the Rumack-Matthew Nomogram.

Timely assessment of acetaminophen concentration in overdose situations is not always available in resource‐poor settings. The 150 mg/kg dose‐estimate for acetaminophen is widely considered as criterion for acetaminophen overdose. Its sensitivity and specificity when compared to the 150 mg/L treatment line on the Rumack‐Matthew Nomogram (150‐treatment line) has rarely been evaluated. This is a retrospective chart review of acute acetaminophen overdose patients. We evaluated the sensitivity and specificity of the 150, 200 mg/kg and 8‐ and 10‐g dose‐estimates by plotting the serum acetaminophen levels and using 150‐treatment line on the Nomogram as the treatment cut‐off. A comparison of medical care costs was performed. We enrolled 784 cases for analysis. Median (IQR) age was 23 (20–28) years (81.9% female). There were 545 cases (69.5%) where the estimated ingested acetaminophen dose were ≥150 mg/kg and 406 cases (51.8%) with concentrations ≥150‐treatment line. Hepatotoxicity and acute liver injury (ALI) occurred in 7.3% and 23.9%, respectively. The sensitivity and specificity of 150 mg/kg dose‐estimate for the 150‐treatment line were 92.6% (95% CI 89.6, 94.8) and 55.3% (95% CI 50.3, 60.2). Among patients with dose‐estimate below150 mg/kg, none developed hepatotoxicity and 17 (7.1%) develop ALI. The administration of activated charcoal significantly decreased the risk of being above the 150‐treatment line by half. In resource‐poor setings, the use of 150 mg/kg dose‐estimate as a stand‐alone criteria for initiation of N‐acetylcysteine therapy is satisfactory, especially when combined with decontamination with activated charcoal and follow up of aminotransferase at 24 h.

Macrophage migration inhibitory factor as a potential biomarker in acetaminophen overdose: a pilot study

Acetaminophen overdose is a leading cause of liver failure in the United States. Macrophage migration inhibitory factor (MIF) is a cytokine that is released early and promotes acetaminophen toxicity in preclinical models. This cytokine could prove a useful biomarker in emergency department (ED) patients immediately following an acute acetaminophen overdose. We selected a convenience sample of thirteen patients from a prospective consecutive cohort of ED patients with suspected acute overdose. Research associates collected waste specimens for MIF analysis that remained after use for clinical care. Our team compared patients with confirmed acetaminophen overdose (n = 9) to patients without acetaminophen exposure or liver injury (n = 3) and a patient with liver injury in the absence of detectable acetaminophen (n = 1). In our acetaminophen group, all nine patients had measurable acetaminophen concentrations. Median MIF serum concentrations were 16.08 ng/mL (In this pilot study, MIF was feasible to measure in specimens from an ED drug overdose cohort, and was significantly elevated in the acetaminophen group compared to non-acetaminophen controls without liver injury.

Decision tree outcome prediction of acute acetaminophen exposure in the United States: A study of 30,000 cases from the National Poison Data System.

Acetaminophen is one of the most commonly used analgesic drugs in the United States. However, the outcomes of acute acetaminophen overdose might be very serious in some cases. Therefore, prediction of the outcomes of acute acetaminophen exposure is crucial. This study is a 6-year retrospective cohort study using National Poison Data System (NPDS) data. A decision tree algorithm was used to determine the risk predictors of acetaminophen exposure. The decision tree model had an accuracy of 0.839, an accuracy of 0.836, a recall of 0.72, a specificity of 0.86 and an F1_score of 0.76 for the test group and an accuracy of 0.848, a recall of 0.85, a recall of 0.74, a specificity of 0.87 and an F1_score of 0.78 for the training group. Our results showed that elevated serum levels of liver enzymes, other liver function test abnormality, anorexia, acidosis, electrolyte abnormality, increased bilirubin, coagulopathy, abdominal pain, coma, increased anion gap, tachycardia and hypotension were the most important factors in determining the outcome of acute acetaminophen exposure. Therefore, the decision tree model is a reliable approach in determining the prognosis of acetaminophen exposure cases and can be used in an emergency room or during hospitalization.

A Basis for the Decision to Rule in or out Acetaminophen Toxicity: Assessment of the Serum Level Within 4 Hours Post Overdose

Background: Acetaminophen is a popular antipyretic and analgesic medication worldwide; however, its therapeutic window is narrow, which may lead to overdose or toxicity. This study was conducted to assess the correlation between the serum acetaminophen levels before and 4 hours after the acute toxicity with this drug. The objective of this study was to test the validity of the serum level to arrive at a clinical decision on the toxicity with acetaminophen. Methods: This cross-sectional study was performed on patients hospitalized and treated with a diagnosis of acute acetaminophen overdose during one year (Sept. 2018 to Sept. 2019) at the Toxicology Department of Imam Reza Hospital, Mashhad, Iran. Patients were analyzed for demographics, time of ingestion, their first and second serum acetaminophen concentrations. Results: A total of 204 patients (106 male &amp; 98 female) were included in this study. The average dose of acetaminophen ingestion by these patients was 14.5±3.50 g and all patients were treated successfully with N-Acetyl-Cysteine (NAC). The variables of age (P=0.293), serum acetaminophen levels at 1-2 h (P=0.679), and at 2-3 h (P=0.126) did not have significant relationships with the serum acetaminophen level on the fourth hour. However, the serum acetaminophen levels tested between 3-4 h and acetaminophen intoxication dosage had significant relationships with the acetaminophen level on the fourth hour. Conclusion: In patients with acute acetaminophen toxicity, the data on the serum levels obtained before a 4-hour timepoint from the ingestion were not useful to decide on the need for the rescue treatment with N-acetyl-cysteine.

Point-of-Care Testing and N-Acetylcysteine for Acute Acetaminophen Overdose

&#x0D; Evidence on the clinical utility and cost-effectiveness of point-of-care devices could not be identified.&#x0D; Two evidence-based guidelines recommend a 2-bag regimen of N-acetylcysteine, consisting of both a loading dose and maintenance dose, administered by IV for patients with acute acetaminophen overdose.&#x0D;

Laboratory analysis of acute acetaminophen overdose patients in Emergency Medical Centers: including analysis of one toxicological laboratory data

Purpose: Acetaminophen (APAP) is a widely available drug responsible for a large part of drug-induced hepatotoxicity in developed countries. Although acetaminophen overdose cases in Korea are being continuously reported, there are no reports related to the level of this drug in the patient's blood or of laboratory analysis at emergency departments (ED). This study sought to analyze the acetaminophen overdose cases at a toxicological laboratory and to survey APAP analysis services offered at select EDs. Methods: We analyzed the demographic and analytic data at a toxicological laboratory run by the National Emergency Medical Center (NMC) in 2019-2020. We surveyed the APAP laboratory service in the 38 regional emergency medical centers (EMCs) and 68 local EMCs near the toxicological laboratory. Results: We studied 175 acute poisoning cases (112 women) with positive blood APAP results (mean age 47.0±24.1 years). Suicide attempts comprised 40.0% of the cases and 30.3% APAP overdose events. In the univariate analysis, we observed that patients were significantly younger, with fewer underlying medical diseases. There were a higher number of APAP overdose events, more favorable initial mental status, more toxic quantity intake in the above treatment line group (p&lt;0.05), In multivariate analysis, the toxic amount intake was significantly more frequent in the above treatment line group (p&lt;0.01). Hospital APAP analysis services were available in six EMCs (3/38 regional and 3/68 local). The hospital blood APAP level reporting intervals were shorter than outside-hospital laboratory services (p&lt;0.01, regional 7.0±3.0 vs. 40.6±27.5, local 5.3±3.1 vs. 57.9±45.1 hours). The NMC toxicological laboratory reporting interval was shorter than the other outside-hospital laboratories (p&lt;0.01, regional 5.7±0.6 vs. 50.2±22.7 local 7.5±3.0 vs. 70.5±41.5 hours). Conclusion: Over the treatment line group, toxic amount intake was significantly more frequent. Only six of 106 EMCs have their own APAP analysis service in their hospitals.

Cell-permeable succinate prodrugs rescue mitochondrial respiration in cellular models of acute acetaminophen overdose.

Acetaminophen is one of the most common over-the-counter pain medications used worldwide and is considered safe at therapeutic dose. However, intentional and unintentional overdose accounts for up to 70% of acute liver failure cases in the western world. Extensive research has demonstrated that the induction of oxidative stress and mitochondrial dysfunction are central to the development of acetaminophen-induced liver injury. Despite the insight gained on the mechanism of acetaminophen toxicity, there still is only one clinically approved pharmacological treatment option, N-acetylcysteine. N-acetylcysteine increases the cell's antioxidant defense and protects liver cells from further acetaminophen-induced oxidative damage. Because it primarily protects healthy liver cells rather than rescuing the already injured cells alternative treatment strategies that target the latter cell population are warranted. In this study, we investigated mitochondria as therapeutic target for the development of novel treatment strategies for acetaminophen-induced liver injury. Characterization of the mitochondrial toxicity due to acute acetaminophen overdose in vitro in human cells using detailed respirometric analysis revealed that complex I-linked (NADH-dependent) but not complex II-linked (succinate-dependent) mitochondrial respiration is inhibited by acetaminophen. Treatment with a novel cell-permeable succinate prodrug rescues acetaminophen-induced impaired mitochondrial respiration. This suggests cell-permeable succinate prodrugs as a potential alternative treatment strategy to counteract acetaminophen-induced liver injury.

5-Oxoproline concentrations in acute acetaminophen overdose

Introduction: Several reports describe high anion gap metabolic acidosis with 5-oxoproline (5-OP) after acetaminophen exposure, including therapeutic use of acetaminophen. The mechanism may involve disordered glutathione metabolism. It is unknown whether acute acetaminophen overdose consistently causes elevations in 5-oxoproline concentration.Methods: We enrolled 23 consecutive adult and adolescent patients with measureable plasma APAP after acute APAP overdose. We used plasma left over in the laboratory after blood tests obtained in clinical care of the patients. We measured plasma [5-OP] by GC/MS. We compared the [5-OP] to laboratory results obtained in the care of these patients to search for correlations. The study had IRB approval.Results: Eighteen patients had non-detectable or normal (<100 μmol/L) 5-oxoproline concentrations. Six more patients had concentrations between 100 μmol/L and 300 μmol/L. There was no significant correlation of 5-OP with APAP, AST, ALT, creatinine, anion gap, INR, or total bilirubin.Discussion: Limitations of the study include small sample size and treatment with IV N-acetylcysteine for all patients with APAP concentrations above the 150 line of the Rumack Matthew nomogram or with hepatotoxicity. We believe that inherited enzyme deficiencies more likely explain cases of 5-oxoprolinemia.Conclusion: Acetaminophen overdose generally results in normal 5-oxoproline concentrations with some patients having slightly elevated 5-oxoproline concentrations.

Changing nomogram risk zone classification with serial testing after acute acetaminophen overdose: a retrospective database analysis

Context: The Rumack–Matthew nomogram stratifies patients into discrete risk zones following acetaminophen (APAP) overdose. Treatment decisions have traditionally been based on the initial risk zone. “Line-crossing” between zones occurs and is poorly understood. The study objective was to characterize line-crossing behavior in acute APAP overdose patients, especially moving from below to above the nomogram treatment threshold.Methods and materials: The study was a secondary analysis of the Canadian Acetaminophen Overdose Study (CAOS) database, a large medical record review of patients hospitalized in eight large Canadian cities (1980–2005) following APAP poisoning. Population consisted of acute APAP overdose patients with at least two serum concentrations performed during hospitalization. Using ordinal logistic regression, we studied the effects of patient demographics, ingestion size/timing, APAP concentrations, time to N-acetylcysteine (NAC), and co-ingestants on a three-level dependent variable: patients whose risk increased two or more zones, those remaining in the same or adjacent zone, and those whose risk fell by two or more zones.Results: Of the 3201 eligible hospitalizations with 7705 APAP concentrations, half (1679, 52.5%) crossed at least one zone (up or down) within 24 h of acute ingestion, including 190 (5.9%), who crossed at least two lines into a higher risk zone, and 516 (16.1%) at least two lines into a lower risk zone. Of the 1251 patients initially below the nomogram treatment line of 150 μg/mL, 131 (10.8%) patients crossed above this line. Being older, male, and co-ingesting opioids, antimuscarinics, or NSAIDs were independently associated with line-crossing.Conclusions: Patients commonly crossed nomogram risk zones, including from below to above the current treatment threshold. These findings support recommendations for serial APAP testing until the individual risk of hepatic injury is clearly established.

Acute acetaminophene-induced hepatotoxicity and nephrotoxicity; therapeutic effect of dexmedetomidine

Acute acetaminophen (APAP) overdose has been shown to cause toxicity and the primary treatment medication is N-acetylcysteine (NAC). Dexmedetomidine (DEX) is a sedative drug with known antioxidant properties. We researched whether DEX has an injury-reducing effect on toxicity. Rats were divided into: Group I (control), Group II (APAP) Group III (NAC) Group IV (DEX) and Group V (NAC+DEX). Histopathologic investigations of tissues were performed and glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA), myeloperoxidase (MPO) and beta trace protein (PGD2S) levels were studied in blood samples. DEX administration for hepatotoxicity and nephrotoxicity induced with APAP, caused a significant reduction in oxidative injury markers like MDA and MPO, a significant increase in GSH-Px level and a significant degree of amelioration in liver histopathologic scores. DEX administration for APAP toxicity causes a reduction in oxidative injury biomarkers, increased antioxidant biomarker levels and significant reduction in liver histopathologic scores. The beneficial effect of DEX use for detection of toxicity induced by acute APAP overdose, was shown in this study for the first time (Tab. 5, Fig. 2, Ref. 41).

Evaluation of Cut-off Values in Acute Acetaminophen Intoxication Following the Revised Guideline of the United Kingdom

Purpose: In 2012, a revised guideline for acute acetaminophen overdose was proposed in the UK, recommending that the treatment threshold should be lowered to 100 mcg/ml at 4 hours after ingestion without risk stratification of hepatotoxicity. However, the poison centers in some developing countries do not have laboratory resources to provide serum drug levels in time. The primary aim of the study is to evaluate the cut-off value of reported dose per kilogram to determine when N-acetylcysteine treatment is warranted under the revised guideline. Methods: Data were collected retrospectively from the toxicology registry of an urban emergency medical center between 1st January 2010 and 30th June 2017. Inclusion criteria were single acute overdose of more than 75 mg/kg in 15 hours from ingestion and over 14 years of age. Subgroups were created by 25 mg/kg increments of reported dose, then sensitivity, specificity, positive predictive value and negative predictive value were calculated for the cut-off values of 100 mg/kg, 125 mg/kg, 150 mg/kg and 175 mg/kg for toxic serum level over '100-treatment line'. Results: A total of 99 patients were enrolled in the study; 24 patients showed toxic serum levels (24.2%). Zero of 17 patients with an ingestion dose under 100 mg/kg showed toxic level (0%), and 0 of 15 under 125 mg/kg (0%), 2 of 14 under 150 mg/kg (14.3%), and 4 of 12 under 175 mg/kg (33.3%) had toxic levels. The higher the ingested dose per kilogram of weight, the higher the frequency of the toxic serum concentration on the first test (${chi}^2$ test for trend, ${chi}^2=22.66$, p-value&lt;0.001) and the sensitivity of each value was 100%, 100%, 92% and 76%. Conclusion: In acute single acetaminophen intoxication, the ingestion dose of 100 mg/kg of weight will be useful in determining the need for the N-acetylcysteine antidote in the indigent laboratory environment.

The Effects of Chronic Iron Overload in Rats with Acute Acetaminophen Overdose.

Rats are resistant to acetaminophen (APAP) hepatotoxicity. In this study, we evaluated whether by augmentation of the hepatic oxidative stress, through the induction of hepatic iron overload (IO), it will be feasible to overcome the resistance of rats to the toxic effects of APAP. Rats with no or increased hepatic IO. Providing iron by diet induced hepatocellular IO, while parenteral iron administration induced combined hepatocellular and sinusoidal cell IO. APAP administration to rats with no IO caused an increase in hepatic oxidative stress and a decrease in the hepatic antioxidative markers but no hepatic cell damage. APAP administration to rats with hepatocellular IO further amplified the hepatic oxidative stress but induced only hepatocyte feathery degeneration without any increase in serum aminotransaminases. APAP administration to rats with combined hepatocellular and sinusoidal cell IO caused an unexpected decrease in hepatic oxidative stress and increase in the hepatic antioxidative markers and no hepatic cell damage. No hepatic expression of activated c-jun-N-terminal kinase was detected in any of the rats. The hepatic distribution of iron may affect its oxidative/antioxidative milieu. Augmentation of hepatic oxidative stress did not increase the rats' vulnerability to APAP.

Evaluation of the children with acute acetaminophen overdose and intravenous N-acetylcysteine treatment.

Objective:To evaluate the demographic and clinical features associated with acetaminophen overdose and to identify the clinical use of IV (intravenous) N- Acetylcysteine (NAC) treatment in children.Methods:This prospective study was conducted in Kanuni Sultan Suleyman Training and Research Hospital between August 2016 and August 2017. A total of 59 patients with overdose acetaminophen ingestion were included in this study. The toxic dose for acute acetaminophen intake was defined as greater than 150 mg/kg. Rumack-Matthew nomogram was used to evaluate the risk of acute intoxication and to determine the decision of using antidote.Results:The mean age of the patients was 8.5±6.4 y and 34 of them (58%) were female. The mean time from ingestion to admission was 4.3±4.7 h. The mean ingested acetaminophen dose was 142.1±80 mg/kg. Twenty four patients (41%) received NAC and there were significant differences in terms of acetaminophen dose, creatinine and INR between antidote and decontamination therapy groups at admission time (p= 0.00, p= 0.03, p= 0.02, respectively). The complication due to antidote therapy was observed in only 1 patient.Conclusions:This study confirms that the side effects due to IV NAC therapy are uncommon and it is generally well tolerated in children.

Being overweight or obese as a risk factor for acute liver injury secondary to acute acetaminophen overdose.

Increased incidences of hepatotoxicity have been observed in obese patients with acute acetaminophen overdose. We evaluate whether the status of being overweight or obese is associated with increase in the development of hepatotoxicity and acute liver injury (ALI) in patients with acute acetaminophen overdose. This was a retrospective cohort study comparing the risk of hepatotoxicity and ALI between overweight or obese patients (body mass index [BMI]≥25) and normal BMI patients (BMI≤24.9) presenting with acute acetaminophen overdose at Siriraj Hospital during January 2004 to June 2012. All patients were treated with intravenous N-acetylcysteine. Psi parameters were calculated. High psi was defined as psi of ≥5.0mM-hour. Data were analyzed using multinomial logistic regressions, odds ratio (OR), stratified OR, and 95% confidence interval (CI). There were 197 patients who fulfilled the criteria for analysis, 35 (17.8%) were obese, 24 (12.2%) were overweight, and 138 (70%) were normal BMI cases. Hepatotoxicity and ALI developed in 25 (12.7%) and 40 (20.3%) cases, respectively. Multinomial logistic regression revealed that the overweight-obesity status and log10 (psi value) were significant risk factors of ALI, with OR (95% CI) of 2.68 (1.21-5.95) and 1.74 (1.27-2.38), respectively, while only log10 (psi) was a significant risk factor of hepatotoxicity with OR (95% CI) 378.51 (39.49-3627.99). From stratification, overweight-obesity had significant odds ratios for ALI in strata with low acetaminophen concentration, early initiation of N-acetylcysteine and low psi. We conclude that being overweight or obese is an independent risk factor of ALI in acute acetaminophen overdoses.

Evaluation of Prothrombin Time in Acute Acetaminophen Overdose treated by N-acetylcysteine

Background: Acetaminophen (N-Acetyl-p aminophenol; APAP) is one of the most common types of analgesics. It is also the most common xneobitic reported to poison centers. This study investigates if therapeutic doses of NAC can falsely increase coagulation tests, prothrombin time (PT) and bleeding time (BT). ​​ Methods: Thirty-six APAP poisoned patients whose acetaminophen serum concentration were in toxic zone in the Rummak-Matheiw graph were treated by NAC according to standard intravenous 21 hours protocol. Prothrombin time (PT) and bleeding time (BT) in all cases were measured before the start of the NAC and at the 8th and 16th hour of the treatment. Results: The mean age of the cases was 21.5 ± 5.12 years old. Among them, 31 cases (86%) were female. The mean dose of ingested APAP was 9.6 ±2.0 grams (7.8 – 16.1 g). Mean of SLA was 196.0±37.7. The means of BT were nor significantly different at all evolution times (2.6±0.64, 2.6±0.62 and 2.6± 0.6. The means of PT rose at 16th hour of NAC treatment in as compared 8th hour (16.1± 1.1 s 12.3±0.6 s, respectively) (P <0.001). Conclusion: With specific reference to our study results, a low level of rising PT resulting from an NAC treatment is not a reliable indicator of liver damage. Further investigation on the effect of NAC on clotting factors is recommended.

Outcomes of Patients With Premature Discontinuation of the 21-h Intravenous N-Acetylcysteine Protocol After Acute Acetaminophen Overdose

BackgroundThe minimum recommended treatment duration for i.v. N-acetylcysteine (NAC) after an acute, single acetaminophen (APAP) overdose is 21 h. Some have questioned whether shorter courses may be sufficient in carefully selected cases. ObjectiveWe sought to describe the incidence of hepatotoxicity in a cohort of acute APAP overdose patients who received <21 h of i.v. NAC for any reason. MethodsWe performed a secondary analysis of a large multicenter retrospective cohort of patients hospitalized for APAP poisoning. We selected patients with a potentially toxic serum APAP concentration measured between 4 and 24 h post ingestion, in whom i.v. NAC was initiated but discontinued before completing the full 21-h course. We further characterized outcomes in these patients as a function of two novel risk-prediction tools, the psi (ψ) parameter and APAP × aminotransferase (AT) product. The ψ parameter is an estimate of the cellular burden of injury based on the area under the concentration-time curve before treatment, and calculated with respect to the APAP concentration and time to initiation of NAC. ResultsFifty-nine patients met inclusion criteria. Intravenous NAC was initiated a median of 11.3 h post ingestion and administered for a median of 11.0 h. Hepatotoxicity (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] > 1,000 IU/L) occurred in one patient (1.7%; 95% confidence interval 0.04–9.1), and eight additional patients developed hepatic injury (AST or ALT > 100 IU/L). No fatalities occurred. A multiplication product of APAP and AT (APAP × AT) that falls below 10,000 μmol/L/IU-L, or pretreatment ψ < 5 mmol/L-h suggested a low risk of hepatic injury. ConclusionsIn this retrospective analysis of patients treated with < 21 h of i.v. NAC for acute APAP overdose, the incidence of hepatotoxicity and coagulopathy was low, despite delays to NAC treatment.