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ThesisUniversity of Iceland>Heilbrigðisvísindasvið>Meistaraprófsritgerðir>

Please use this identifier to cite or link to this item: http://hdl.handle.net/1946/10435

Titles
  • Paracetamol intoxications: A population-based study in Iceland

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    Parasetamóleitranir og lifrarskaði: Lýðgrunduð rannsókn á Íslandi

Published
February 2012
Abstracts
  • Background: Paracetamol is the most common cause of acute liver failure (ALF) in the US and many countries in Europe. Most data on paracetamol toxicity originate from liver transplant centres and tertiary referral institutions. The proportion of patients with paracetamol overdose who develop liver injury in a population-based sample is largely unexplored. The aim of this MPH thesis was to analyze the population-based annual incidence of paracetamol overdoses, prevalence of liver injury and the risk factors for hepatotoxicity and outcome in unselected patients presenting to hospital with paracetamol toxicity and/or overdose
    Methods: This was a retrospective and descriptive cohort study. Search for the diagnosis of paracetamol toxicity and liver failure was undertaken in a teaching hospital serving a population of approximately 220,000 inhabitants in Iceland over a six-year period, from 2004 to 2009. Medical charts were reviewed for relevant characteristics, the proportion of intentional vs. unintentional toxicity, liver tests and outcome.
    Results: In this population-based study 1913 visits were reviewed, and 346 (18%) involved paracetamol overdoses. The annual population incidence for all drug-related overdoses over the six years declined from 200.5 to 117.3 per 100,000 inhabitants (p<0.001). Likewise, the annual incidence of paracetamol overdoses declined from 32.8 to 17.3 per 100,000 inhabitants (p<0.05). The female/male ratio in the paracetamol cases was 2.8. The largest age-group by far was 16-25 years with 40% of the total cases. There were 290 index visits by patients over the age of ten. The female to male ratio was 2.7. Of the total cohort 22% were admitted to the acute medical ward, and 11% needed intensive care. N-acetylcysteine was administrated in 59% of the cases. Twenty-five percent were discharged directly home after presentation to the emergency room. There was acute ethanol consumption in 41% of the cases. Visits caused by accidental overdoses constituted 7% (20/285) of the total cohort. Males were more likely to overdose due to therapeutic misadventures for medical effects (p<0.05). The accidental group had higher peak aminotransferase levels (p<0.005) in spite of lower serum paracetamol P<0.05). There was acute liver failure (ALF) in 3.1% (9/290) of the index visits. The proportion of males was higher although not significantly so (p=0.07). The median age for males was also higher (p<0.05). In the intentional group 1.5% developed ALF, compared to 15% of the accidental group (p<0.05). Only one patient died from ALF.
    Conclusions: The annual incidence of paracetamol toxicity was high in this population-based study but declined over the period. Young females with intentional toxicity accounted for most of the cases, whereas accidental toxicity was more common in older males. The occurrence of ALF was low and associated with accidental overdose. The use of NAC was very frequent, and serious outcomes were very rare. Most patients had favourable outcomes.

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    Inngangur: Parasetamól er algengasta orsök bráðrar lifrarbilunar í Bandaríkjunum og mörgum löndum Evrópu en þetta hefur ekki verið rannsakað á Íslandi. Flestar eitranir af völdum parasetamóls tengjast of háum skömmtum af lyfinu. Það er óljóst hversu stór hluti sjúklinga með lyfjaeitrun af völdum parasetamóls hlýtur lifrarskaða og hverjar horfur sjúklinganna eru. Það er ennfremur óljóst hve stór hluti sjúklinga hefur fengið eitrun af völdum sjálfskaða eða óhapps. Markmið rannsóknarinnar var að kanna lýðgrundað nýgengi eitrana af völdum parasetamóls. Einnig að rannsaka afleiðingar parasetamóleitrunar svo sem áhættuþætti lifrarskaða, algengi bráðrar lifrarbilunar og afdrif sjúklinga.
    Efniviður og aðferðir: Rannsóknin var lýðgrunduð afturskyggn og lýsandi cohort rannsókn sem náði yfir upptökusvæði Landspítala háskólasjúkrahúss (LSH) sem taldi u.þ.b. 220.000 manns. Gagna var aflað úr tölvukerfum LSH um alla þá sem leitað höfðu til spítalans vegna eitrana af völdum lyfja eða voru greindir með lifrarbilun á árunum 2004 til 2009. Upplýsingar um inntekin lyf, einkenni og blóðgildi sjúklinga voru unnar úr sjúkraskrám.
    Niðurstöður: Í fyrri hluta rannsóknarinnar voru 1913 tilfelli vegna lyfjaeitrana frá 2004 – 2009 og þar af 346 (18%) af völdum parasetamóls. Nýgengi lyfjaeitrana fækkaði úr 200,5 í 117,3 fyrir 100.000 íbúa (p<0.001) á 6 árum. Einnig fækkaði nýgengi eitrana af völdum parasetamóls úr 32,8 í 17,3 fyrir hverja 100.000 íbúa, (p<0,05). Hlutfall kvenna á móti körlum var 2,8:1 og hlutfallslega flestar eitranir voru í aldurshópnum 16-25 ára.
    Annar hluti rannsóknarinnar tók aðeins til fyrstu komu vegna parasetamól-eitrunar á LSH á árunum 2004 – 2009. Af 290 komum var hlutfall kvenna á móti körlum 2,7:1. Hlutfall sjúklinga sem lagðir voru inn á lyfjadeildir í kjölfar skoðunar var 22% og 11% þurftu að leggjast inn á gjörgæslu. Alls fengu 58% meðferð með N-acetylcysteine (NAC). Sjúklingar útskrifaðir beint heim eftir komu á bráðamótttöku voru 25%. Í sjö prósentum tilfella (20/285) var um óhappaeitrun að ræða og i þeim hópi var hlutfall karla hærra (p<0,05). Í óhappatilvikunum voru lifrarensím hærri (p<0,005) þrátt fyrir að blóðgildi parasetamóls hafi verið lægra. Bráð lifrarbilun var í 3,1% tilfella (9/290). Karlar voru marktækt eldri og hlutfall þeirra hærra en kvenna, en ekki var marktækur munur þar á, (p=0,07). Í vísvitandi tilfellum fengu 1,5% bráða lifrarbilun en í 15% óhappatilfella. Einn sjúklingur lést vegna bráðrar lifrabilunar af völdum parasetamóls.
    Ályktanir: Nýgengi eitrunar af völdum parasetamóls var nokkuð hátt en tilfellum fækkaði á rannsóknartímabilinu. Konur í aldurshópnum 16-25 ára voru hlutfallslega flestar af þeim sem vísvitandi tóku inn ofskammt parasetamóls en í óhappatilvikunum var hlutfall eldri karla hærra. Tilfelli bráðrar lifrarbilunar voru fá og frekar tengd óhappaeitrunum. Notkun NAC var algeng og alvarleg tilfelli fá. Afdrif flestra sjúklinga voru góð.

Issued Date
03/01/2012


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