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.

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

PURPOSE: 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. METHODS: 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 ≥5.0 mM-hour. Data were analyzed using multinomial logistic regressions, odds ratio (OR), stratified OR, and 95% confidence interval (CI). RESULTS: 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. CONCLUSION: We conclude that being overweight or obese is an independent risk factor of ALI in acute acetaminophen overdoses.

Transfer of Methamphetamine (MA) into Breast Milk and Urine of Postpartum Women who Smoked MA Tablets during Pregnancy: Implications for Initiation of Breastfeeding.

BACKGROUND: Methamphetamine (MA) use by pregnant women remains a growing problem in South East Asia. After delivery, a negative maternal urine MA assay is assumed to reflect the absence of MA in breast milk and marks breastfeeding initiation. To date, no data exist that describe the relationship between the peripartum and postpartum transfer of MA into breast milk and its urinary excretion in women, following recreational use by smoking. OBJECTIVE: This study aimed to determine the pharmacokinetic of smoked MA in breast milk and its relationship to urinary MA excretion in postpartum women who tested positive for MA before delivery. METHODS: Timed urine and breast milk samples of 33 women who had positive urine drug screens for MA prior to delivery were analyzed for MA using Acquity Ultra Performance Liquid Chromatography (Waters, Milford, Massachusetts, USA) with the ACQUITY UPLC Photodiode Array Detector (Waters). Those participants with 4 or more timed breast milk samples were included for pharmacokinetic calculation using log-linear trapezoidal rule. RESULTS: Pharmacokinetic data from 2 women were analyzed. The half-life values for MA in the breast milk were 11.3 and 40.3 hours. The absolute infant doses were 21.3 and 51.7 µg/kg/day. Methamphetamine disappears from breast milk approximately 1 day before the maternal urine MA becomes negative. CONCLUSION: Smoked MA shows a similar breast milk pharmacokinetic pattern to previously reported intravenous MA. Breastfeeding can be safely initiated in mothers whose urine MA screen has turned negative for ≥ 24 hours. However, concurrent maternal substance use treatment and screening is necessary for continued promotion of lactation.

Acetaminophen Psi Nomogram: a sensitive and specific clinical tool to predict hepatotoxicity secondary to acute acetaminophen overdose.

BACKGROUND: Acetaminophen Psi Parameter (APP) is a composite of acetaminophen (paracetamol) level and lag time before N-acetylcysteine (NAC) therapy. The APP is a significant predictor of hepatotoxicity secondary to acute acetaminophen overdose. Acetaminophen Psi Nomogram (APN) was invented as a graphic analog of the APP for use in predicting individual patient's risk of hepatotoxicity. Clinical accuracy of the APN has never been validated OBJECTIVE: The authors are reporting the validity of APN in predicting hepatotoxicity secondary to acute acetaminophen overdose at Siriraj Hospital. MATERIAL AND METHOD: This present study is a retrospective review of medical records of patients with acute acetaminophen overdose at Siriraj Hospital between January 2004 and June 2009. Each case was classified by APN into an appropriate risk group. The outcome of interest was hepatotoxicity. The validity of the APN is reported as sensitivity and specificity. Secondary outcomes include serum acetaminophen concentrations, delay to NAC therapy, and APP for each APN's risk group. RESULTS: One hundred and sixty-one patients were enrolled Higher APN risk classifications are associated with a trend towards higher acetaminophen levels, longer delayed to NAC initiation, and larger APP. Twenty five patients (15.5%) developed hepatotoxicity. The number of patients who were above the APN's risk lines, 1% and 50% were 88 (54.7%) and 17 (10.6%), respectively, with corresponding sensitivities of 100.0% (95% CI 186.6, 100.0) and 40.0% (95% C121.2, 61.3). APN's risk lines 50% had specificity of 94.9% (95% CI 89.7, 97.9). CONCLUSION: Acetaminophen Psi Nomogram is a sensitive and specific tool for prediction of hepatotoxicity secondary to acute acetaminophen overdose. By application of the APN, a significant proportion of patients may not require either further follow-up after the completion of NAC therapy or prolongation of NAC therapy. Patients in high APN's risk ranges may be treated and monitored more intensively with confidence.