{"id":1031,"date":"2020-07-29T11:41:42","date_gmt":"2020-07-29T08:41:42","guid":{"rendered":"https:\/\/tatd.org.tr\/tatdtoks\/2021\/09\/17\/asetaminofen-intoksikasyon-tedavisinde-fomepizol-bir-vaka-serisi\/"},"modified":"2022-03-23T00:38:55","modified_gmt":"2022-03-22T21:38:55","slug":"asetaminofen-intoksikasyon-tedavisinde-fomepizol-bir-vaka-serisi","status":"publish","type":"post","link":"https:\/\/tatd.org.tr\/toksikoloji\/2020\/07\/29\/asetaminofen-intoksikasyon-tedavisinde-fomepizol-bir-vaka-serisi\/","title":{"rendered":"Asetaminofen \u0130ntoksikasyon Tedavisinde Fomepizol: Bir Vaka Serisi"},"content":{"rendered":"

<\/h3>\n

Bildi\u011fimiz \u00fczere; Asetaminofen<\/strong>\u00a0\u00fclkemizde \u00e7ok s\u0131k kullan\u0131lan bir ila\u00e7t\u0131r. Asetaminofen intoksikasyon vaka y\u00f6netiminde\u00a0ise akla ilk olarak\u00a0N-asetilsistein (NAC)<\/strong> tedavisi\u00a0 gelmektedir.\u00a0 Asetaminofen intoksikasyonlar\u0131nda ba\u015fka bir tedavi modalitesi olan Fomepizol <\/strong>tedavisi ise yeterince yayg\u0131n kullan\u0131lm\u0131yor. Asetaminofen intoksikasyonlar\u0131nda fomepizol kullan\u0131m\u0131na dikkat \u00e7ekmek i\u00e7in Wartman ve ark.<\/strong><\/a> ge\u00e7en sene yay\u0131nlad\u0131klar\u0131 bir vaka serisi \u00fczerinden konuyu tart\u0131\u015fmay\u0131 hedefliyorum.<\/em><\/p>\n

D\u00fcnyada en s\u0131k re\u00e7etesiz kullan\u0131lan analjezik ve en s\u0131k rapor edilen zehirlenme etkeni olmas\u0131 a\u00e7\u0131s\u0131ndan asetaminofen, t\u00fcm ila\u00e7lar aras\u0131nda farkl\u0131 bir konumdad\u0131r. \u00c7o\u011funlukla karaci\u011ferde matabolize olan bu ilac\u0131n yakla\u015f\u0131k %5\u2019lik bir k\u0131sm\u0131 sitokrom P450 2E1(CYP2E1) enzimi ile metabolize olduktan sonra N-Acetyl-P-Benzoquinone(NAPQI) ortaya \u00e7\u0131kar ve bu madde ciddi hepatotoksisite olu\u015fturur. Y\u00fcksek doz asetaminofen al\u0131mlar\u0131nda olu\u015fan y\u00fcksek miktarda NAPQI, karaci\u011ferde ciddi hepatotoksik etki g\u00f6sterir ve bu da laboratuvar de\u011ferlerinde karaci\u011fer fonksiyon testlerinde ciddi y\u00fcksekliklerle kendini g\u00f6sterir (1-3).<\/p>\n

Genel anlamda standart IV N-asetilsistein (NAC) tedavisi asetaminofen intoksikasyonu hastas\u0131nda etkili olsa da erken IV NAC tedavisine ra\u011fmen hepatotoksisite g\u00f6r\u00fclen ve karaci\u011fer nakil ihtiyac\u0131 olan hastalar bildirilmi\u015ftir(2,3).<\/p>\n

Fomepizol CYP2E1 enziminin potent bir inhibit\u00f6r\u00fcd\u00fcr(4). Fomepizol\u00fcn ger\u00e7ekle\u015ftirdi\u011fi CYP2E1 enzim inhibisyonu ile, asetominofenin NAPQI ya d\u00f6n\u00fc\u015f\u00fcm\u00fcn\u00fc azaltt\u0131\u011f\u0131 g\u00f6sterilmi\u015ftir(5-7). Ancak bu konuda yap\u0131lan klinik \u00e7al\u0131\u015fma say\u0131s\u0131 yetersizdir(8).<\/p>\n

Bu yaz\u0131da, asetaminofen y\u00fcksek doz al\u0131m\u0131 sonras\u0131nda hastaneye ba\u015fvuran ve fomepizol tedavisi uygulanan 6 vaka anlat\u0131lm\u0131\u015ft\u0131r:<\/strong><\/p>\n

Vaka 1:<\/strong><\/h2>\n

Depresyon tedavisi alan 49 ya\u015f\u0131nda kad\u0131n hasta acil servise, \u00f6z k\u0131y\u0131m ama\u00e7l\u0131 benzodiazepinler(temazepam velorazepam) ve i\u00e7eri\u011fi bilinmeyen baz\u0131 ila\u00e7lar\u0131 almas\u0131 sebebiyle, akut ensefalopati bulgular\u0131yla getirildi. Tahmin edilen ila\u00e7 al\u0131m\u0131n\u0131n 4.saatinde kan asetaminofen d\u00fczeyi 140.8 \u00b5g\/mL ve salisilat d\u00fczeyi 45mg\/dl olarak \u00f6l\u00e7\u00fcld\u00fc. Karaci\u011fer fonksiyon testleri (AST,ALT vb.), INR ve total bilirubin d\u00fczeyi normal seviyede de\u011ferlendirildi. Hastaya tek doz orogastrik aktif k\u00f6m\u00fcr uygulamas\u0131 ve NAC 150mg\/kg IV y\u00fckleme dozu ile NAC 12.5mg\/kg\/saat IV idame doz ba\u015fland\u0131. Tekrarlayan asetominofen serum konsantrasyon \u00f6l\u00e7\u00fcmlerinde art\u0131\u015f g\u00f6r\u00fclen hastaya, idame NAC 12.5 mg\/kg\/saat dozunun yan\u0131nda, fomepizol 15mg\/kg IV 30 dakikada y\u00fckleme ve takiben 10mg\/kg\/12sa verildi. Asetaminofen seviyesinin y\u00fcksek seyretmeye devam etti\u011fi g\u00f6r\u00fcld\u00fc\u011f\u00fcnden (bkz. \u015eekil 1) NAC 12.5mg\/kg\/sat tedavisine devam edildi. Hem devam eden asetaminofen seviyesi y\u00fcksekli\u011finden hem de bununla birlikte al\u0131nan di\u011fer maddelerin varl\u0131\u011f\u0131ndan dolay\u0131 (salisilatlar vb.)\u00a0 , ila\u00e7 al\u0131m\u0131ndan 36 saat sonra bir seans hemodiyaliz yap\u0131ld\u0131. Diyaliz sonras\u0131 hastan\u0131n serum asetaminofen seviyesi \u00f6l\u00e7\u00fclemeyecek kadar d\u00fc\u015f\u00fck seviyede g\u00f6r\u00fcld\u00fc. Hasta takibi boyunca, serum transaminazlar\u0131 \u00fcst s\u0131n\u0131r\u0131n biraz \u00fcst\u00fcnde seyretti(bkz. Tablo 1). Hastan\u0131n klini\u011finde ve laboratuvar de\u011ferlerinde karaci\u011fer yetmezli\u011fine dair bulguya rastlanmad\u0131.<\/p>\n

Vaka 2:<\/strong><\/h2>\n

14 ya\u015f\u0131nda k\u0131z acil servise, bilinmeyen miktarda asetominofen ve difenhidramin al\u0131m\u0131 sonras\u0131 ensefalopati ve letarji bulgular\u0131yla ba\u015fvurdu. Hastan\u0131n serum asetaminofen seviyesi al\u0131m sonras\u0131ndaki 4. saatte 135 \u00b5g\/mL olarak \u00f6l\u00e7\u00fcld\u00fc. Hastaya NAC 150mg\/kg bir saatte y\u00fcklemenin ard\u0131ndan, 12.5 mg\/kg\/saat idame devam edildi. \u0130la\u00e7 al\u0131m\u0131n\u0131 takip eden 6.saatte, serum asetaminofen seviyesi 251.7 \u00b5g\/mL g\u00f6r\u00fcld\u00fc. Hastaya fomepizol 15mg\/kg IV 30 dakikada y\u00fcklemenin ard\u0131ndan, 10mg\/kg\/12saat idame tedavisi hastan\u0131n serum asetaminofen seviyesi \u00f6l\u00e7\u00fclemeyecek seviyelere gelene kadar devam edildi. Hastan\u0131n klini\u011finde ve laboratuvar de\u011ferlerinde karaci\u011fer yetmezli\u011fine dair bulguya rastlanmad\u0131 (Tablo 1).<\/p>\n

Vaka 3:<\/strong><\/h2>\n

9 ya\u015f\u0131nda \u00e7ocuk hasta acil servise y\u00fcksek miktarda asetaminofen al\u0131m\u0131 sonras\u0131 getirildi. Serum asetaminofen seviyesi, ila\u00e7 al\u0131m\u0131n\u0131 takip eden 4.saatte 281.7 \u00b5g\/mL olarak \u00f6l\u00e7\u00fcld\u00fc ve sonras\u0131nda NAC 150mg\/kg IV 1 saatte y\u00fckleme dozunun ard\u0131ndan, 12.5mg\/kg\/saat idame dozu ba\u015fland\u0131. \u0130la\u00e7 al\u0131m\u0131n\u0131 takip eden 6.saatte, serum asetaminofen d\u00fczeri 239.7 \u00b5g\/mL g\u00f6r\u00fcld\u00fc ve hastaya fomepizol 15mg\/kg IV 30 dakikada y\u00fckleme ve takiben 10mg\/kg\/12sa idame dozu ba\u015fland\u0131. Takipte hastan\u0131n serum asetaminofen seviyesi y\u00fcksek seyretmesine ra\u011fmen(bkz. \u015eekil 1),\u00a0 ALT de\u011feri normal s\u0131n\u0131rlar i\u00e7inde kald\u0131 (bkz Tablo 1) ve hastada karaci\u011fer yetmezli\u011fi bulgular\u0131na rastlanmad\u0131.<\/p>\n

Vaka 4:<\/strong><\/h2>\n

Bilinen depresyon hikayesi olan 15 ya\u015f\u0131nda k\u0131z hasta,d\u0131\u015f merkeze \u00f6zk\u0131y\u0131m ama\u00e7l\u0131 \u00e7oklu ila\u00e7 al\u0131m\u0131 sonras\u0131 bulant\u0131 ve kusma \u015fikayeti ile ba\u015fvurmu\u015f. Ald\u0131\u011f\u0131 ila\u00e7lar aras\u0131nda yakla\u015f\u0131k 100 tablet 500mg\u2019l\u0131k asetaminofen de mevcutmu\u015f. Al\u0131mdan 2 saat sonra \u00f6l\u00e7\u00fclen serum asetaminofen seviyesi 236.1 \u00b5g\/mL olarak \u00f6l\u00e7\u00fclm\u00fc\u015f. Hastaya dozu bilinmeyen miktarda aktif k\u00f6m\u00fcr verilmi\u015f ve NAC 150mg\/kg IV 1 saatte y\u00fckleme dozunun ard\u0131ndan, 12.5mg\/kg\/saat idame dozu ba\u015flanm\u0131\u015f. Hastan\u0131n ila\u00e7 al\u0131m\u0131n\u0131 takiben 8.5 saat sonra \u00f6l\u00e7\u00fclen kan asetaminofen d\u00fczeyi 311.9 \u00b5g\/mL g\u00f6r\u00fclm\u00fc\u015f ve hasta bu nedenle hastanemize sevk edilmi\u015f. Hasta tedavisinde idame NAC dozu 18.75 mg\/kg\/saate y\u00fckseltildi ve hastaya fomepizol 15mg\/kg IV 30 dakikada y\u00fckleme ve takiben 10mg\/kg\/12sa idame ba\u015fland\u0131. Hastanemizde takip alt\u0131nda oldu\u011fu s\u00fcre boyunca hastan\u0131n serum asetaminofen d\u00fczeyi s\u00fcrekli y\u00fcksek \u00f6l\u00e7\u00fclmesine ra\u011fmen(bkz. \u015eekil 1),\u00a0 hastan\u0131n klinik ve laboratuvar de\u011ferlendirmesinde karaci\u011fer yetmezlik bulgular\u0131na rastlanmad\u0131(Bkz. Tablo 1).<\/p>\n

Vaka 5:<\/strong><\/h2>\n

42 ya\u015f\u0131nda kad\u0131n hasta, yakla\u015f\u0131k 200 tablet 500mg\u2019l\u0131k asetaminofen,200 tablet 200mg\u2019l\u0131k ibuprofen ve 200 tablet 2 mg\u2019l\u0131k loperamid al\u0131m\u0131 sonucu acil servise kusma, letarji ve ta\u015fikardi ile geldi. \u0130la\u00e7 al\u0131m\u0131n\u0131n 5. Saatinde \u00f6l\u00e7\u00fclen serum asetaminofen d\u00fczeyi 201.8 \u00b5g\/mL \u00f6l\u00e7\u00fcld\u00fc. NAC 150mg\/kg IV 1 saatte y\u00fckleme dozunun ard\u0131ndan, 12.5mg\/kg\/saat idame dozu ba\u015fland\u0131. Y\u00fcksek seyreden serum asetaminofen d\u00fczeyi, asetaminofen metabolizmas\u0131n\u0131 ve eliminasyonunu de\u011fi\u015ftirebilecek ek ila\u00e7lar\u0131n al\u0131m\u0131ndan dolay\u0131 hastaya, fomepizol 15mg\/kg IV 30 dakikada y\u00fckleme ve takiben 10mg\/kg\/12sa idame ba\u015fland\u0131. Y\u00fcksek seyreden serum asetaminofen konsantrasyonuna ra\u011fmen, hastan\u0131n ALT d\u00fczeyi normal s\u0131n\u0131rlarda seyretti(bkz. Tablo 1) ve hastada karaci\u011fer yetmezlik bulgular\u0131na rastlanmad\u0131.<\/p>\n

Vaka 6:<\/strong><\/h2>\n

15 ya\u015f\u0131nda k\u0131z hasta, \u00f6z k\u0131y\u0131m ama\u00e7l\u0131 100-125 tablet 500mg\u2019l\u0131k asetaminofen al\u0131m\u0131 sebebiyle d\u0131\u015f merkeze ba\u015fvurmu\u015f. Hastan\u0131n \u00f6l\u00e7\u00fclen 2.saat serum asetaminofen d\u00fczeyi 210 \u00b5g\/mL \u00a0ve 4. Saat \u00f6l\u00e7\u00fcm\u00fc 361 \u00b5g\/mL olarak g\u00f6r\u00fclm\u00fc\u015f. Hastaya d\u0131\u015f merkezde NAC 150 mg\/kg IV bir saatte y\u00fckleme dozu ard\u0131ndan 15.5mg\/kg\/saat idame dozu ba\u015flanm\u0131\u015f. Hastaya ila\u00e7 al\u0131m\u0131n\u0131 takip eden 5.5\u2019uncu saatte fomepizol 15mg\/kg 30 dk da y\u00fcklenmi\u015f ve hasta, hastanemize sevk edilmi\u015f. Hastanemize geldi\u011finde bulant\u0131 ve sa\u011f \u00fcst kadranda olmayan kar\u0131n a\u011fr\u0131s\u0131 mevcuttu. NAC IV standart inf\u00fczyon tedavisi 21 saat devam ettirildi. Hastan\u0131n hastanede yatt\u0131\u011f\u0131 s\u00fcrede, herhangi bir karaci\u011fer yetmezlik bulgusuna rastalanmad\u0131.<\/p>\n

\"\"<\/p>\n

\u015eekil 1<\/strong>. Zaman i\u00e7inde \u00e7izilen asetaminofen konsantrasyonlar\u0131 (ug \/ mL)-Klinikte ge\u00e7irilen do\u011frulanan veya tahmin edilen zaman. Konsantrasyonlar, Rumack-Matthew hatt\u0131 ve g\u00f6sterilen tedavi hatt\u0131 ile standart bir Rumack Matthew nomogram\u0131nda \u00e7izildi. T\u00fcm laboratuvar \u00e7al\u0131\u015fmalar\u0131 tek bir kurumda ger\u00e7ekle\u015ftirildi.<\/p>\n

\"\"<\/p>\n

Tablo 1<\/strong>. Asetaminofen al\u0131m\u0131ndan sonra zamana g\u00f6re AST\u00a0ve AST de\u011ferleri<\/p>\n

Fomepizol tedavisi hastalarda, asetaminofenin toksik metaboliti NAPQI olu\u015fumunu azaltmak amac\u0131yla uyguland\u0131. 6 hastan\u0131n tamam\u0131nda NAC IV tedavisi ilk 8 saat i\u00e7inde ba\u015fland\u0131. \u0130la\u00e7 al\u0131m\u0131ndan sonra 8 saati a\u015fan s\u00fcrelerde NAC ba\u015flamas\u0131,%5-6 ihtimalle karaci\u011fer hasar\u0131 geli\u015fmesine neden olabilir(2-4). Bu hastalarda ila\u00e7 al\u0131m\u0131ndan sonraki 4.saatte, 200 \u00b5g\/mL \u00fczerindeki serum asetaminofen konsantrasyonlar\u0131 hepatik a\u00e7\u0131can y\u00fcksek risk i\u00e7erir. Bu hastalarda fomepizol kullan\u0131m karar\u0131, erken IV NAC tedavisine ra\u011fmen,en erken 4. saatte karaci\u011fere toksik olabilecek serum asetaminofen d\u00fczeyinin saptanmas\u0131 ile verildi. Fomepizol, potansiyel yarar\u0131n\u0131n yan\u0131 s\u0131ra dozlama kolayl\u0131\u011f\u0131 ve yan etki profilinin az olmas\u0131 nedeniyle kullan\u0131lm\u0131\u015ft\u0131r. Bu vaka serisindeki t\u00fcm hastalar bu t\u00fcm tedaviyi tolere etti ve ciddi bir karaci\u011fer hasar\u0131 olmadan taburcu oldular.<\/p>\n

Bu vaka serisinin retrospektif olmas\u0131 ve kontrol grubunun olmamas\u0131 en b\u00fcy\u00fck k\u0131s\u0131tl\u0131l\u0131klar\u0131ndand\u0131r. Sadece IV NAC tedavisinin hepatik hasar\u0131 \u00f6nlemede tek ba\u015f\u0131na etkili olmas\u0131 m\u00fcmk\u00fcnd\u00fcr. Bir olguda hemodiyaliz,\u00f6ncelikle salisilat toksikasyonunun tedavisi amac\u0131yla kullan\u0131ld\u0131 ve fomepizol kullan\u0131m\u0131n\u0131n olumlu etkisini, k\u0131smen g\u00f6lgede b\u0131rakm\u0131\u015f olabilir.<\/p>\n

KAYNAKLAR<\/u><\/strong><\/h2>\n
    \n
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  7. Akakpo JY, Ramachandran A, Duan L, et al. Delayed treatment with 4-methylpyrazole protects against acetaminophen hepatotoxicity in mice by inhibition of c-Jun n-Terminal Kinase. Toxicol Sci. 2019;170(1):57\u201368.<\/li>\n
  8. Yip L, Heard K. Potential adjunct treatment for high-risk acetaminophen overdose. Clin Toxicol. 2016;54(5):459\u2013459. [Epub 2016 Feb 26].<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

    Bildi\u011fimiz \u00fczere; Asetaminofen\u00a0\u00fclkemizde \u00e7ok s\u0131k kullan\u0131lan bir ila\u00e7t\u0131r. Asetaminofen intoksikasyon vaka y\u00f6netiminde\u00a0ise akla ilk olarak\u00a0N-asetilsistein (NAC) tedavisi\u00a0 gelmektedir.\u00a0 Asetaminofen intoksikasyonlar\u0131nda ba\u015fka bir…<\/p>\n","protected":false},"author":1496,"featured_media":1965,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"_lmt_disableupdate":"","_lmt_disable":"","footnotes":""},"categories":[10014,10019],"tags":[70,71,154,297,298],"class_list":["post-1031","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-akademik-blog-yazisi","category-tft","tag-asetaminofen","tag-asetaminofen-intoksikasyonu","tag-fomepizol","tag-n-asetilsistein","tag-nac"],"acf":[],"_links":{"self":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts\/1031","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/users\/1496"}],"replies":[{"embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/comments?post=1031"}],"version-history":[{"count":0,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/posts\/1031\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/media\/1965"}],"wp:attachment":[{"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/media?parent=1031"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/categories?post=1031"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/tatd.org.tr\/toksikoloji\/wp-json\/wp\/v2\/tags?post=1031"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}