ABSTRACT
BACKGROUND: Recent recognition of "massive" acetaminophen (APAP) overdoses has led to the question of whether standard dosing of N-acetylcysteine (NAC) is adequate to prevent hepatoxicity in these patients. The primary aim of this study was to evaluate the clinical outcome for patients with massive APAP overdose who received standard intravenous NAC dosing of 300 mg/kg over 21 h. METHODS: This was a single-center retrospective cohort study conducted by chart review of APAP overdoses reported to a regional poison center from 1 January 2010 to 31 December 2019. Massive APAP overdose was defined by single, acute overdose resulting in an APAP concentration exceeding 300 mcg/mL at 4 h post-ingestion. Standard univariate statistical analysis was conducted to describe the cohort, and a multivariate logistic model was utilized to calculate adjusted odds ratios for risk of hepatoxicity. RESULTS: 1425 cases of APAP overdose were reviewed. 104 cases met the inclusion criteria of massive APAP overdose. Overall, 79 cases (76%) had no acute liver injury or hepatotoxicity, and 25 (24%) developed hepatoxicity. Nine percent (n = 4) of cases receiving NAC within 8 h developed hepatotoxicity. Crude odds for hepatoxicity was 5.5-fold higher for cases who received NAC after 8 h. CONCLUSIONS: Standard NAC dosing received within 8 h prevented hepatoxicity in 91% (n = 40) of cases in our series of massive APAP overdoses. Additional data is needed to determine the clinical outcomes of massive APAP overdose using current intravenous NAC dosing.
Subject(s)
Acetaminophen/poisoning , Acetylcysteine/administration & dosage , Analgesics, Non-Narcotic/poisoning , Antidotes/administration & dosage , Chemical and Drug Induced Liver Injury/prevention & control , Drug Overdose/drug therapy , Adolescent , Adult , Chemical and Drug Induced Liver Injury/diagnosis , Chemical and Drug Induced Liver Injury/etiology , Drug Administration Schedule , Drug Overdose/diagnosis , Female , Humans , Infusions, Intravenous , Male , Poison Control Centers , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Young AdultABSTRACT
We present a case of 4-bromo-2,5-dimethoxy-N-[(2-methoxyphenyl)methyl]-benzeneethanamine (25B-NBOMe), an N-benzyl phenethylamines derivative, intoxication and a high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method for detection and quantification of 25B-NBOMe. A 19-year-old male was found unresponsive with generalized grand mal seizure activity. On the second day of hospitalization, a friend admitted that the patient used 'some unknown drug' called 25B. Serum and urine collected were sent to the Virginia Commonwealth University Medical Center Toxicology Laboratory for analysis. An HPLC-MS/MS method for the identification and quantification of 25B-NBOMe using 2-(2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine (25H-NBOMe) as the internal standard (ISTD) was developed. As this is a novel, single-case presentation, an assay validation was performed prior to testing to ensure the reliability of the analytical results. The serum and urine specimens were determined to contain 180 pg/ml and1900 pg/ml of 25B-NBOMe, respectively.
Subject(s)
Anisoles/blood , Anisoles/urine , Designer Drugs/pharmacokinetics , Phenethylamines/blood , Phenethylamines/urine , Substance Abuse Detection/methods , Adult , Anisoles/toxicity , Chromatography, Liquid/methods , Designer Drugs/toxicity , Humans , Male , Phenethylamines/toxicity , Reproducibility of Results , Tandem Mass Spectrometry/methods , Young AdultABSTRACT
BACKGROUND: Acute poisoning with organophosphate compounds can cause chronic neuropsychological disabilities not prevented by standard antidotes of atropine and pralidoxime. We determine the efficacy of naltrexone in preventing delayed encephalopathy after poisoning with the sarin analogue diisofluorophosphate (DFP) in rats. METHODS: A randomized controlled experiment was conducted. Rats were randomly assigned to receive a single intraperitoneal (IP) injection of 5 mg/kg DFP (n = 12) or vehicle control (isopropyl alcohol, n = 5). Rats were observed for cholinesterase toxicity and treated with IP atropine (2 mg/kg) and pralidoxime (25 mg/kg) as needed. After resolution of acute toxicity, rats injected with DFP were again randomized to receive daily injections of naltrexone (5 mg/kg per day) or saline (vehicle control). Control animals also received daily injections of saline. For 4 weeks after acute poisoning, rats underwent neurologic testing with the Morris Water Maze for assessment of spatial learning and reference memory. Comparisons on each test day were made across groups using analysis of variance followed by Fisher's least significant difference. Comparisons of changes in performance between first and last test day within each group were made using a paired t test. Significance was determined at P < .05. RESULTS: All rats receiving DFP developed toxicity requiring rescue. Spatial learning was significantly worse in the DFP-only group compared with the naltrexone-treated and control groups at day 10 (P = .0078), day 13 (P = .01), day 24 (P = .034), and day 31 (P = .03). No significant differences in reference memory were detected at any time point. CONCLUSION: Naltrexone protected against impairment of spatial learning from acute poisoning with DFP in rats.
