To describe the changes in serum alanine aminotransferase (ALT) levels in nondrinkers receiving acetaminophen for 10 days.Prospective, open-label study.Outpatient clinical research center.Twenty-four healthy volunteers who reported an average alcohol consumption of less than one drink/day for the 30 days preceding study enrollment.Patients were administered acetaminophen 4 g/day for 10 days (study days 1-10).Serum ALT level, total bilirubin level, and international normalized ratio (INR) were measured on study days 0, 4, 7, 9, 11, and 14. Median ALT level increased from 24 U/L on day 0 to 39 U/L on day 7, and remained elevated through day 11 (39 U/L); these increases were statistically significant (p=0.0002). Median ALT level began to trend down by day 14 (35 U/L). Fourteen subjects (58%) had ALT levels above the upper limit of normal; the largest elevation was 3.8 times the upper limit of normal (day 7). No increases in INR or total bilirubin level were noted during the study, and no subject developed symptoms of liver injury (e.g., abdominal pain, jaundice).Daily use of acetaminophen at the maximum dose of 4 g/day for 10 days caused asymptomatic ALT level elevations in subjects who do not consume alcohol. The clinical implication of these elevations remains unclear. Future studies should evaluate ALT changes and their clinical effects when acetaminophen is given for long periods of time.
Liver injury has been reported in children treated with repeated doses of acetaminophen. The objective of this study was to identify and validate reports of liver injury or death in children younger than 6 years who were administered repeated therapeutic doses of acetaminophen. We reviewed US Poison Center data, peer-reviewed literature, US Food and Drug Administration Adverse Event Reports, and US Manufacturer Safety Reports describing adverse effects after acetaminophen administration. Reports that described hepatic abnormalities (description of liver injury or abnormal laboratory testing) or death after acetaminophen administration to children younger than 6 years were included. The identified reports were double abstracted and then reviewed by an expert panel to determine if the hepatic injury was related to acetaminophen and whether the dose of acetaminophen was therapeutic (≤75 mg/kg) or supratherapeutic. Our search yielded 2531 reports of adverse events associated with acetaminophen use. From these cases, we identified 76 cases of hepatic injury and 26 deaths associated with repeated acetaminophen administration. There were 6 cases of hepatic abnormalities and no deaths associated with what our panel determined to be therapeutic doses. A large proportion of cases could not be fully evaluated due to incomplete case reporting. Although we identified numerous examples of liver injury and death after repeated doses of acetaminophen, all the deaths and all but 6 cases of hepatic abnormalities involved doses more than 75 mg/kg per day. This study suggests that the doses of less than 75 mg/kg per day of acetaminophen are safe for children younger than 6 years.
Background: This is the 29th Annual Report of the American Association of Poison Control Centers’ (AAPCC) National Poison Data System (NPDS). As of 1 July 2011, 57 of the nation's poison centers (PCs) uploaded case data automatically to NPDS. The upload interval was 8.43 [6.29, 13.7] (median [25%, 75%]) minutes, creating a near real-time national exposure and information database and surveillance system.Methodology: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Poison center cases with medical outcomes of death were evaluated by a team of 38 medical and clinical toxicologist reviewers using an ordinal scale of 1–6 to assess the Relative Contribution to Fatality (RCF) of the exposure to the death.Results: In 2011, 3,624,063 closed encounters were logged by NPDS: 2,334,004 human exposures, 80,266 animal exposures, 1,203,282 information calls, 6,243 human confirmed nonexposures, and 268 animal confirmed nonexposures. Total encounters showed an 8.3% decline from 2010, while health care facility exposure calls increased by 4.8%. Human exposures with less serious outcomes decreased by 3.4% while those with more serious outcomes (moderate, major or death) increased by 6.8%. All information calls decreased by 17.9% and health care facility (HCF) information calls decreased by 2.9%, Medication identification requests (Drug ID) decreased by 24.1%, and human exposures reported to US poison centers decreased by 2.2%.The top 5 substance classes most frequently involved in all human exposures were analgesics (11.7%), cosmetics/personal care products (8.0%), household cleaning substances (7.0%), sedatives/hypnotics/antipsychotics (6.1%), and foreign bodies/toys/miscellaneous (4.1%). Analgesic exposures as a class increased most rapidly (10,134 calls/year) over the last 11 years. The top 5 most common exposures in children aged 5 years or less were cosmetics/personal care products (14.0%), analgesics (9.9%), household cleaning substances (9.2%), foreign bodies/toys/miscellaneous (6.9%), and topical preparations (6.6%). Drug identification requests comprised 59.5% of all information calls. NPDS documented 2,765 human exposures resulting in death with 1,995 human fatalities judged related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory).Conclusions: These data support the continued value of poison center expertise and need for specialized medical toxicology information to manage the more severe exposures, despite a decrease in calls involving less severe exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national public health resource to collect and monitor US exposure cases and information calls. The continuing mission of NPDS is to provide a nationwide infrastructure for public health surveillance for all types of exposures, public health event identification, resilience response and situational awareness tracking. NPDS is a model system for the nation and global public health.
Objectives: To describe a case of fat embolus syndrome with lipoid pneumonia resulting from intravenous infusion of lipid and to illustrate the potential for accidental intravenous administration of vegetable oil-based progesterone preparations in the treatment of oncology patients. Case Report: A patient with recurrent ovarian carcinoma accidentally received approximately 20 mL (0.29mL/kg) of a peanut oil-based methylprogesterone product intravenously via infusion pump over 24 hours. The patient developed a lipoid pneumonia with dyspnea, cough, hypoxia, radiographic infiltrates, and a pleural effusion. She was hospitalized for 4 days, and signs and symptoms resolved over 2 weeks following steroids and supportive care. Discussion: Experience with accidental or intentional intravenous lipid overdose in humans is limited. Typical findings of fat embolus syndrome are similar to lipid aspiration, with respiratory distress, hypoxia, and pulmonary infiltrates. In contrast to aspiration, however, fat embolus syndrome results in lipogranulomas surrounding blood vessels, rather than air passages, and potentially produces cerebrovascular, accident-like symptoms. Management of fat embolus syndrome is similar to that for lipid aspiration. However, as seen in this case, fat embolus syndrome typically resolves over several weeks as opposed to the 3-month to 1-year period seen with aspiration lipoid pneumonias. Conclusions: Accidental intravenous infusion of vegetable oil-based products is a potential complication of the increased use of intravenous progesterones.
Background Drug induced liver injury (DILI) remains a prominent global issue and acetaminophen (APAP) overdose represents a common cause of hepatic injury and DILI. Transient alanine aminotransferase (ALT) elevations have been documented while adhering to recommended daily dosing. However, no metabolites have been identified in pre-treatment samples predicting which patients will develop these transient increases.Methods This was a secondary analysis of samples collected from a parent study describing the course of ALT levels in subjects receiving therapeutic APAP dosing. Two hundred and four subjects recruited from Denver, Colorado received 4 g APAP/daily for at least 16 days. Subjects were grouped by ALT at any monitored time point above 60 units/L (n = 25) vs. no increase (n = 179). Serum samples from days 0, 7, 16, and 31 were run on ultra-high performance liquid chromatography mass spectrometry. We report the metabolomic results of samples analyzed prior to APAP administration and over time. Significant changes in metabolite and demographic variable expressions were explored using t-tests with false discovery rate correction, chi square, and partial least squares discriminant analyses.Results Within pre-treatment day 0 samples, allantoate and ornithine were significantly elevated in subjects of the ALT elevation group (p = .032). Baseline ALT (p = .011) and alkaline phosphatase (p = .006) were also significant. These metabolites were significant independent of race, ethnicity, gender, or BMI.Conclusions Allantoate and ornithine are directly involved in pathways related to nitrogen release and urea production. Further investigation into alterations in the glutathione metabolism and urea cycle pathways may lead to a greater understanding of the mechanisms associated with hepatic adaptation for a variety of pharmaceuticals.
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