The administration of N-acetylcysteine causes a decrease in prothrombin time in patients with paracetamol overdose but without evidence of liver impairment

Lucena, M. Isabel; López-Torres, Enrique; Verge, Carmen; Andrade, Raúl J.; Puche, M.; Seoane, Jorge García; Cuesta, Felipe Sánchez de la

doi:10.1097/00042737-200501000-00012

Cited by 16 publications

(10 citation statements)

References 10 publications

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“…We found that the INR does not undertreat anyone, but is the worst biomarker for overtreatment. Furthermore, NAC acts to prolong the INR (Jepsen and Hansen 1994), and the INR can be increased in patients with APAP overdose without hepatotoxicity after NAC treatment (Schmidt et al, 2002;Lucena et al, 2005).…”

Section: Nac Treatment Analysis Using a Systems Model Of The Liver 537mentioning

confidence: 99%

An Analysis of N-Acetylcysteine Treatment for Acetaminophen Overdose Using a Systems Model of Drug-Induced Liver Injury

Woodhead

Howell²,

Yang³

et al. 2012

The Journal of Pharmacology and Experimental Therapeutics

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N-acetylcysteine (NAC) is the treatment of choice for acetaminophen poisoning; standard 72-h oral or 21-h intravenous protocols are most frequently used. There is controversy regarding which protocol is optimal and whether the full treatment course is always necessary. It would be challenging to address these questions in a clinical trial. We used DILIsym, a mechanistic simulation of drug-induced liver injury, to investigate optimal NAC treatment after a single acetaminophen overdose for an average patient and a sample population (n ϭ 957). For patients presenting within 24 h of ingestion, we found that the oral NAC protocol preserves more hepatocytes than the 21-h intravenous protocol. In various modeled scenarios, we found that the 21-h NAC infusion is often too short, whereas the full 72-h oral course is often unnecessary. We found that there is generally a good correlation between the time taken to reach peak serum alanine aminotransferase (ALT) and the time taken to clear N-acetyl-p-benzoquinone imine (NAPQI) from the liver. We also found that the most frequently used treatment nomograms underestimate the risk for patients presenting within 8 h of overdose ingestion. V max for acetaminophen bioactivation to NAPQI was the most important variable in the model in determining interpatient differences in susceptibility. In conclusion, DILIsym predicts that the oral NAC treatment protocol, or an intravenous protocol with identical dosing, is superior to the 21-h intravenous protocol and ALT is the optimal available biomarker for discontinuation of the therapy. The modeling also suggests that modification of the current treatment nomograms should be considered.

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Section: Nac Treatment Analysis Using a Systems Model Of The Liver 537mentioning

confidence: 99%

An Analysis of N-Acetylcysteine Treatment for Acetaminophen Overdose Using a Systems Model of Drug-Induced Liver Injury

Woodhead

Howell²,

Yang³

et al. 2012

The Journal of Pharmacology and Experimental Therapeutics

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“…Two studies have evaluated PT after acetaminophen toxicity in the absence of hepatic failure, reporting a decrease in prothrombin index (equivalent to an increase in PT) in patients given IV NAC without any evidence of liver injury. 6,7 However, these studies were retrospective, observational, and complicated by the presence of supratherapeutic doses of acetaminophen. Jepsen and Hansen 17 investigated the influence of NAC on PT in six healthy subjects both in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…4,5 However, there has been evidence to suggest that the use of IV NAC itself may be responsible for the prolongation of PT. [6][7][8] In the setting of acetaminophen overdose, accurate PT measurements are clinically important in many ways. PT is a marker of the severity of liver injury and is often measured serially when evaluating a patient in fulminant hepatic failure.…”

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confidence: 99%

The In Vitro Effect of N-Acetylcysteine on Prothrombin Time in Plasma Samples From Healthy Subjects

Pizon

Jang²,

Wang³

2011

Academic Emergency Medicine

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Objectives: In the treatment of acetaminophen toxicity, clinicians believe that N-acetylcysteine (NAC) artificially elevates prothrombin time (PT), potentially obscuring signs of liver damage. However, the effect of NAC on human blood coagulation remains unverified. The purpose of this study was to evaluate the effect of NAC on PT prolongation in human plasma. Methods:The authors obtained blood samples from 33 volunteer subjects. The blood plasma samples were divided into four 1-mL aliquots. The first aliquot was used as a control. To three additional aliquots, varying amounts of NAC were added, maintaining constant volume with a maximum dilution of 0.5%. The four concentrations of NAC (control, 250, 500, or 1,000 mg ⁄ L) were incubated at 37°C for 1 hour, and PT was measured. PT values were compared using fixed effects regression.Results: Mean (± standard deviation [SD]) PT values for the control, 100, 500, and 1,000 mg ⁄ L NAC values were 13.9 (±1.01), 14.2 (±1.08), 15.5 (±1.21), and 17.4 (±1.72) seconds, respectively. At the 1,000 mg ⁄ L concentration, two PTs exceeded 22 seconds, and half exceeded 17 seconds. PT increased with NAC concentrations (fixed effects regression p < 0.001) in a dose-dependent manner.Conclusions: In this in vitro human model, NAC had a dose-dependent effect on PT.

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“…Dextropropoxyphene measurement is not a routine analysis but plasma concentration of paracetamol can be used to estimate ingested dextropropoxyphene dose (4). Toxic plasma concentrations usually reported in the literature range 1-2 μg/ml for propoxyphene whereas lethal concentrations range from 0.74 to17 μg/ml (8)(9)(10). Concomitant ingestion of alcohol increases toxic effects and the risk of death (11), while addiction to opiates or chronic ingestion of dextropropoxyphene gives a better tolerance to high dose of dextropropoxyphene acute intake.…”

Section: Discussionmentioning

confidence: 99%

Voluntary Ingestion of Dextropropoxyphene-Paracetamol: A Severe Two-Step Intoxication Not to Be Underestimated

Nisse¹,

Humbert

Flahaut

et al. 2010

Acta Clinica Belgica

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Dextropropoxyphene overdose is known to cause widening of the QRS complex on electrocardiogram. We report a case of a 18 years old woman who ingested 36 g paracetamol and 2,1 g dextropropoxyphene in suicide attempt. She developed seizures, wide QRS complex and cardiac arrest. The routine blood screening for different psychotropic drugs, opiates and alcohol turned out to be negative. The propoxyphene and paracetamol high concentrations determined in plasma were respectively 4.321 μg/ml at 3.5 hours (lethal value > 2 μg/ml) and 588 μg/ml at 5.0 hours (toxic value > 168 μg/ml). Cardiac arrest consecutive to the toxic effects of dextropropoxyphene on respiratory and cardiac functions usually occurs within one hour after ingestion and before patient reaches hospital.

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The administration of N-acetylcysteine causes a decrease in prothrombin time in patients with paracetamol overdose but without evidence of liver impairment

Cited by 16 publications

References 10 publications

An Analysis of N-Acetylcysteine Treatment for Acetaminophen Overdose Using a Systems Model of Drug-Induced Liver Injury

An Analysis of N-Acetylcysteine Treatment for Acetaminophen Overdose Using a Systems Model of Drug-Induced Liver Injury

The In Vitro Effect of N-Acetylcysteine on Prothrombin Time in Plasma Samples From Healthy Subjects

Voluntary Ingestion of Dextropropoxyphene-Paracetamol: A Severe Two-Step Intoxication Not to Be Underestimated

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