Does the patient history predict hepatotoxicity after acute paracetamol overdose?

Waring, W. Stephen; Robinson, O D G; Stephen, A F L; Dow, Margaret; Pettie, Janice

doi:10.1093/qjmed/hcm139

Cited by 43 publications

(32 citation statements)

References 21 publications

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“…Data were available for 858 ECG recordings that were taken from 541 patients with median (IQR) age 34 years (25-42 years), including 161 men (29.8%).The median stated dose ingested, as a multiple of the defined daily dose was similar between groups: citalopram 16 (10-30), mirtazapine 15 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27), and venlafaxine 15 (9-28). None of the patients studied developed torsade de pointes or other significant arrhythmia.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of a QT nomogram for risk assessment after antidepressant overdose

Waring

Graham

Gray

et al. 2010

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Overdose with citalopram is associated with QT prolongation and torsades de pointes, whereas this arrhythmia has not been reported after venlafaxine or mirtazapine overdose.• Uncertainty exists concerning the best means of identifying poisoned patients at greatest risk of arrhythmia, and a nomogram comparing QT and heart rate has recently been proposed based on published cases of torsades de pointes.• Few data are available concerning the performance of the nomogram in patients that present to hospital after antidepressant overdose. WHAT THIS STUDY ADDS• After antidepressant overdose patients had a broad range of heart rate and QT values, which were below the nomogram in 98% of cases (95% confidence interval 96, 99%).• Citalopram overdose was associated with a higher proportion of patients with QT values above the nomogram than venlafaxine and mirtazapine overdose, especially in those who had low heart rates.• The nomogram allowed discrimination between the different antidepressant agents and may have a role in predicting arrhythmia in clinical practice. AIMSA QT-heart rate nomogram has recently been proposed as a means of identifying patients at risk of torsades de pointes after antidepressant overdose, based on published cases of drug-induced torsades de pointes. The present study sought to examine the performance of the nomogram in patients who ingest an antidepressant overdose but do not develop arrhythmia. METHODSA retrospective case control study of patients presenting to hospital after overdose of citalopram, mirtazapine and venlafaxine was carried out. The primary outcome variable was QT higher than the nomogram, and was compared with occurrence of QTc (QT corrected by Bazett's formula) greater than Ն440 ms and QTc Ն500 ms, with comparison between drugs. Data are expressed as proportions in each group with 95% confidence intervals. RESULTSThere were 858 electrocardiograms from 541 patients. QT was higher than the nomogram in 2.4% (1.4, 4.1%), whereas QTc was Ն440 ms in 23.1% (95% CI 19.8, 26.8%), and QTc was Ն500 ms in 1.1% (0.5, 2.5%). Citalopram overdose was more likely to be associated with QT higher than the nomogram compared with the other agents (difference 7.0%, 95% CI 2.9, 11.9%, P = 0.001) and more likely to be associated with QTc Ն440 ms (difference = 11.0%, 95% CI 2.6, 19.0%, P = 0.013). CONCLUSIONSThe QT nomogram was associated with a lower false positive rate than widely accepted QTc criteria, and allowed detection of different effects of individual drugs. The nomogram offers potential advantages over QTc criteria and merits further investigation in a clinical setting.

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Section: Resultsmentioning

confidence: 99%

Evaluation of a QT nomogram for risk assessment after antidepressant overdose

Waring

Graham

Gray

et al. 2010

Brit J Clinical Pharma

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“…This retrospective analysis of prospectively collected data has several limitations. The study accuracy is dependent upon the reliability and validity of patient recall regarding the time of last ingestion, total paracetamol dose and suicidal intent, although previous studies suggest that the patient history is often accurate following paracetamol overdose [18]. The distinction between a staggered overdose and a delayed single time point overdose is occasionally a blurred one, and some overdose types may have been wrongly classified.…”

Section: Figurementioning

confidence: 99%

Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol‐induced hepatotoxicity

Craig¹,

Bates²,

Davidson³

et al. 2012

Brit J Clinical Pharma

142

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WHAT IS ALREADY KNOWN ON THIS SUBJECT• Paracetamol hepatotoxicity is the commonest cause of acute liver failure (ALF) in the UK.• Relatively little is known regarding the impact of staggered overdose pattern or delayed hospital presentation upon subsequent mortality or need for emergency liver transplantation.WHAT THIS STUDY ADDS• Staggered paracetamol overdoses, frequently taken to relieve pain, are strongly associated with reduced survival compared with single time point overdose.• Staggered paracetamol overdoses should be treated as high risk for the development of multiorgan failure, and should be considered for N‐acetyl cysteine treatment irrespective of admission serum paracetamol concentrations.• The King's College poor prognostic criteria may have reduced sensitivity in staggered overdose patients.AIMS Paracetamol (acetaminophen) poisoning remains the major cause of severe acute hepatotoxicity in the UK. In this large single centre cohort study we examined the clinical impact of staggered overdoses and delayed presentation following paracetamol overdose.RESULTS Between 1992 and 2008, 663 patients were admitted with paracetamol‐induced severe liver injury, of whom 161 (24.3%) had taken a staggered overdose. Staggered overdose patients were significantly older and more likely to abuse alcohol than single time point overdose patients. Relief of pain (58.2%) was the commonest rationale for repeated supratherapeutic ingestion. Despite lower total ingested paracetamol doses and lower admission serum alanine aminotransferase concentrations, staggered overdose patients were more likely to be encephalopathic on admission, require renal replacement therapy or mechanical ventilation and had higher mortality rates compared with single time point overdoses (37.3% vs. 27.8%, P= 0.025), although this overdose pattern did not independently predict death. The King's College poor prognostic criteria had reduced sensitivity (77.6, 95% CI 70.8, 81.5) for this pattern of overdose. Of the 396/450 (88.0%) single time point overdoses in whom accurate timings could be obtained, 178 (44.9%) presented to medical services >24 h following overdose. Delayed presentation beyond 24 h post overdose was independently associated with death/liver transplantation (OR 2.25, 95% CI 1.23, 4.12, P= 0.009).CONCLUSIONS Both delayed presentation and staggered overdose pattern are associated with adverse outcomes following paracetamol overdose. These patients are at increased risk of developing multi‐organ failure and should be considered for early transfer to specialist liver centres.

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“…Ideally, the patient may disclose the amount ingested and the time of ingestion; however, this information is often unreliable (13). The levels of acetaminophen in the blood combined with the Rumack-Matthew nomogram, a diagram to assess the risk of hepatotoxicity based on blood acetaminophen concentration (14), can also be used as guidance to predict tissue injury (15).…”

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confidence: 99%

Circulating microRNAs, potential biomarkers for drug-induced liver injury

Wang

Zhang²,

Marzolf³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

1,070

957

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Drug-induced liver injury is a frequent side effect of many drugs, constitutes a significant threat to patient health and has an enormous economic impact on health care expenditures. Numerous efforts have been made to identify reliable and predictive markers to detect the early signs of drug-induced injury to the liver, one of the most vulnerable organs in the body. These studies have, however, not delivered any more informative candidates than the serum aminotransferase markers that have been available for Ϸ30 years. Using acetaminophen overdose-induced liver injury in the mouse as a model system, we have observed highly significant differences in the spectrum and levels of microRNAs in both liver tissues and in plasma between control and overdosed animals. Based on our survey of microRNA expression among normal tissues, some of the microRNAs, like messenger RNAs, display restricted tissue distributions. A number of elevated circulating microRNAs in plasma collected from acetaminophen-overdosed animals are highly expressed in the liver. We have demonstrated that specific microRNA species, such as mir-122 and mir-192, both are enriched in the liver tissue and exhibit dose-and exposure duration-dependent changes in the plasma that parallel serum aminotransferase levels and the histopathology of liver degeneration, but their changes can be detected significantly earlier. These findings suggest the potential of using specific circulating microRNAs as sensitive and informative biomarkers for drug-induced liver injury.acetaminophen overdose ͉ plasma ͉ miRNA ͉ toxicity ͉ ALT

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Does the patient history predict hepatotoxicity after acute paracetamol overdose?

Abstract: Therefore, ingestion of >12 g predicted higher paracetamol exposure and increased risk of hepatotoxicity and supports the validity of patient history in this context.

Cited by 43 publications

References 21 publications

Evaluation of a QT nomogram for risk assessment after antidepressant overdose

Evaluation of a QT nomogram for risk assessment after antidepressant overdose

Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol‐induced hepatotoxicity

Circulating microRNAs, potential biomarkers for drug-induced liver injury

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