Outcomes of Patients With Premature Discontinuation of the 21-h Intravenous N-Acetylcysteine Protocol After Acute Acetaminophen Overdose

Lucyk, Scott; Yarema, Mark; Sivilotti, Marco L.A.; Johnson, David W.; Nettel-Aguirre, Alberto; Victorino, Charlemaigne; Bailey, Benoît; Dart, Richard C.; Heard, Kennon; Spyker, Daniel A.; Rumack, Barry H.

doi:10.1016/j.jemermed.2015.12.004

Cited by 9 publications

(15 citation statements)

References 26 publications

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“…Currently, definitions for acute liver injury from acetaminophen vary among different research groups and there is still no international consensus. A study performed in North America uses aminotransferase cutoff level of 100 U/L, while studies from the UK uses 150 U/L and Australia‐New Zealand guideline uses 50 U/L . Such differing criteria being used in the UK and Australia‐New Zealand impact treatment since ALI indicates continuation of NAC therapy after the standard regimen …”

Section: Discussionmentioning

confidence: 99%

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

Chomchai

2017

Pharmacoepidemiology and Drug

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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 log 10 (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 log 10 (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.

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Section: Discussionmentioning

confidence: 99%

“…Psi parameter, a composite mathematic parameter of timed acetaminophen concentration and onset of NAC therapy, was calculated for each patient. High‐ and low‐psi groups were defined as psi parameters of more than or equal to 5 mM‐hour and less than 5 mM‐hour, respectively …”

Section: Methodsmentioning

confidence: 99%

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

Chomchai

2017

Pharmacoepidemiology and Drug

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“…The effect NAC in both normalizing glutamate levels and reducing drug relapse (Reissner et al, 2015) likely results from its high antioxidant activity. N-acetylcysteine is also used to treat an acetaminophen overdose due to its high antioxidant activity, being a precursor of cysteine and glutathione (Lucyk et al, 2016). …”

Section: Maintenance Of Chronic Ethanol Intakementioning

confidence: 99%

Acquisition, Maintenance and Relapse-Like Alcohol Drinking: Lessons from the UChB Rat Line

Israel

Karahanian

Ezquer

et al. 2017

Front. Behav. Neurosci.

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This review article addresses the biological factors that influence: (i) the acquisition of alcohol intake; (ii) the maintenance of chronic alcohol intake; and (iii) alcohol relapse-like drinking behavior in animals bred for their high-ethanol intake. Data from several rat strains/lines strongly suggest that catalase-mediated brain oxidation of ethanol into acetaldehyde is an absolute requirement (up 80%–95%) for rats to display ethanol’s reinforcing effects and to initiate chronic ethanol intake. Acetaldehyde binds non-enzymatically to dopamine forming salsolinol, a compound that is self-administered. In UChB rats, salsolinol: (a) generates marked sensitization to the motivational effects of ethanol; and (b) strongly promotes binge-like drinking. The specificity of salsolinol actions is shown by the finding that only the R-salsolinol enantiomer but not S-salsolinol accounted for the latter effects. Inhibition of brain acetaldehyde synthesis does not influence the maintenance of chronic ethanol intake. However, a prolonged ethanol withdrawal partly returns the requirement for acetaldehyde synthesis/levels both on chronic ethanol intake and on alcohol relapse-like drinking. Chronic ethanol intake, involving the action of lipopolysaccharide diffusing from the gut, and likely oxygen radical generated upon catechol/salsolinol oxidation, leads to oxidative stress and neuro-inflammation, known to potentiate each other. Data show that the administration of N-acetyl cysteine (NAC) a strong antioxidant inhibits chronic ethanol maintenance by 60%–70%, without inhibiting its initial intake. Intra-cerebroventricular administration of mesenchymal stem cells (MSCs), known to release anti-inflammatory cytokines, to elevate superoxide dismutase levels and to reverse ethanol-induced hippocampal injury and cognitive deficits, also inhibited chronic ethanol maintenance; further, relapse-like ethanol drinking was inhibited up to 85% for 40 days following intracerebral stem cell administration. Thus: (i) ethanol must be metabolized intracerebrally into acetaldehyde, and further into salsolinol, which appear responsible for promoting the acquisition of the early reinforcing effects of ethanol; (ii) acetaldehyde is not responsible for the maintenance of chronic ethanol intake, while other mechanisms are indicated; (iii) the systemic administration of NAC, a strong antioxidant markedly inhibits the maintenance of chronic ethanol intake; and (iv) the intra-cerebroventricular administration of anti-inflammatory and antioxidant MSCs inhibit both the maintenance of chronic ethanol intake and relapse-like drinking.

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“…Finally, there is a cohort of patients with paracetamol poisoning who can be defined as having a low risk for developing hepatotoxicity with acetylcysteine treatment . This group may respond favourably to an abbreviated course of acetylcysteine.…”

Section: Future Directions and Trialsmentioning

confidence: 99%

“…Finally, there is a cohort of patients with paracetamol poisoning who can be defined as having a low risk for developing hepatotoxicity with acetylcysteine treatment. 10,11 This group may respond favourably to an abbreviated course of acetylcysteine. Benefits of this approach may include reduced hospital treatment times and earlier referral for mental health assessment and admission.…”

Section: Future Directions and Trialsmentioning

confidence: 99%

N‐acetylcysteine regimens for paracetamol overdose: Time for a change?

Wong

Graudins

2016

Emerg Medicine Australasia

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Paracetamol overdose is one of the commonest pharmaceutical poisonings in the world. For nearly four decades, intravenous acetylcysteine regimens have been used to treat most patients successfully and prevent or mitigate hepatotoxicity. However, the rate of occurrence of adverse reactions to acetylcysteine is quite high, and there is a potential for these to be reduced. Recent studies show that distributing the loading-dose of acetylcysteine over the first few hours of treatment may decrease the incidence of adverse reactions. In addition, varying the duration of acetylcysteine administration may potentially benefit certain cohorts of poisoned patients, depending on their risk of developing hepatotoxicity.

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Outcomes of Patients With Premature Discontinuation of the 21-h Intravenous N-Acetylcysteine Protocol After Acute Acetaminophen Overdose

Cited by 9 publications

References 26 publications

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

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

Acquisition, Maintenance and Relapse-Like Alcohol Drinking: Lessons from the UChB Rat Line

N‐acetylcysteine regimens for paracetamol overdose: Time for a change?

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