• Nghien ciru - Ky thuit
Khao sat phan vng co hai (ADR) lien quan
r r
den thuoc can quang chu-a iod ghi nhan trong CO" sfr dir lieu bao cao ty nguyen tu-
can bo y ti giai doan 2006 - 2012
Nguyin Phuvng ThiiyS IVan Thj Thu Hang', Nguyin Hoang Anh'*
Nguyen Quoc BinhS Nguyin Van Doan^
' Trung tam Quoc gia ve Thong tin thuoc vd Theo doi phdn irng co hai cua thuoc ' Trung tdm Ichu vvc TP. Ho Chi Minh ve Thong tin thuoc vd
Theo doi phdn ung co hai cua thuoc, Benh vien Cha Ray 'Trung tdm Di Ong Mien dich idm sdng, Benh vi^n Bach Mai
* E-mail- [email protected] S u m m a r y
The fact that in the last three years, the National Center of Drug Information and Adverse Drug Reactions Monitoring (DI&ADR) received a number of ADR reports related to iodine-containing contrast media including anaphylactic shocks, led to this study aiming at reviewing the characteristics ofADRs and detecting signal of anaphylatic shocl< related to iodine-containing contrast media in the national spontaneous ADR reporting database from 2006 to 2012. The total number of ADR reports received was 190. The incidence of ADR reports related to contrast media in the national database accounted for 1.4%, in which ioxitalamic acid was the most frequently reported (49.5 %). The most frequently experienced ADRs were the general disorders (78.4%), followed by skin and appendages disorders (42.1%) and gastrointestinal disorders (22.1%). The most popular ADRs were rigors (20%), pruritus (20%), vomitting and nausea (17.9%). The incidence of anaphylatic reactions and anaphylatic shocks accounted for 30.5%. The percentage of fatal cases related to iodine-containing contrast media was 3.7%. As the proportional ratio of reporting was 2.74 and iC^^^ > 0, the signal of the relationship between anaphylatic reactions and anaphylatic shocks was identified.
Keywords: Contrast media, anaphylatic shock, adverse drug reactions, spontaneous reporting.
D|it v a n d e n g h i e m trpng n h u s o c p h a n v p , n g u n g h 6 h i p , - . . . ..^,..x -. ,..,,. .^ ,.1 , . ngung t u i n hoan, CO giat ...Nhung phan dng nay Cung vdi SM" phat tnen cua ky thuat chan doan , . ,,_. .., , ^ , , , . . I . . , . , t „ / , , , - . t h u c n g khong ti&n ugng dup'c truce, ed the xay hinh Snh, thuoc can quang ngay cang d u g e s u , „;f ^ .^ ^ . , . , . / ^ . \ . , ^ , . ,< _a -• . J..1 u i u-i u^* L- *u i r a c jeu thuong dung vol triSu ehung ram rp k h d dyng npng rai, trong d d p h i bien nhat la thuoc . . . . . . . . ^ *
„ » , . . - . • • > . , u - u u - phat trong vong 1 gio sau khi tiem thuoc, gay kho can quang ed chua lod v m so lug'ng bgnh nhan *^ ^ ^ .. , , . .1 , .
„ . . , . . , . . . . . . . . a. - T - khan cho can bd y te trong viec phat hien, x u tn su dgng l§n tdi hang tripu nguai moi nam. Tuy CO M i a n o n u ^ ^ . , a <? K V . lilu tiSm qua dudng tTnh maeh Idn hon n h i l u so ^^ ^ ^ pndt\g.
vdi e i c t h u l c khac nhung dp an toan eua t h u l e Trong ba nam g i n d a y Tnjng tam Dl & ADR c i n quang (t dug'c chCi y v i day Id loai thuoc nay Q u i c gia da nhan d u g c n h i l u bao cao v l t h u l e chf {Ju(?e s d dgng vdi mgc dieh chan do§n. Trong can quang ehua iod, bao g i m ea eae trudng hgp nhdng nam g i n day, n h i l u nghiSn edu djch te t u vong do s l e p h i n ve nghi n g d cd lien quan cdng bd m i i lo ng$i v l vigc s u dgng t h u l e can d i n t h u l c can quang. Nghidn edu nay d u g c thyc quang vd nguy ay xiy ra c^c phan u n g t u o n g hipn n h l m mo ta d$c d i l m phcin dng c6 hgi cOa ty dj dng t h u l c vdi t? I§ u d c tinh t d 3,8% d i n t h u l c c i n quang, p h i t hi^n sg' hinh thSnh tin 12.7% i'l. trong dd bao g i m cde p h i n dng eo hgi hi$u v l phan dng phan v? vii s l e p h i n v§ lign T4iP CHi DUQC HOC - 2/2014 (S6 454 N A M 54)
• Nghien CIJPU - Ky thuat
quan d i n t h u l e can quang trong c c s d d u lieu bao eao ADR giai doan 2006 - 2012.
D d i l u ' O ' n g v a P h u ' O ' n g p h a p n g h i e n
D o i l u p ' n g n g h i e n c u u
T i t ca cac bao eao t y nguyen eua can bS y t l v l phan dng c6 hai eua thuoc (bao eao ADR) nghi ngd lien quan tdi t h u l e can quang ehua iod, d u g e gui d i n ; d u g e to chdc tham djnh va luu t r u tai Trung tam Dl & ADR Q u i e gia t d thang 1/2006 d i n thang 12/2012.
Phu'O'ng phap n g h i e n c u u Thiet ke nghien cOu
Mo ta e l t ngang thong qua h l i euu d i j lieu t u eae bao cao ADR.
Danh gia biin co bit lai
B i l n CO b i t lei d u g c ma hoa va d u g e phan loai he c c quan (Sytem Organs Classification) theo T u ( J i n thuSt n g i i ADR cua To ehue Y t l t h i gidl (WHO -Adverse Reaction Terminology)'^. M i l lien quan giua t h u l c va ADR d u g c danh gia d y a tren thang quy k i t m i l quan he nhan qua cua To chdc y t l t h i gidi P'. Muc dp nghiem trgng cua ADR d u g c phan loai theo H u d n g d i n cua Hgi nghj q u i c t l dong thuan (ICH-E2D){3|, bao g i m hai mue "nghiem trpng" va "khong nghiem trpng" trong do cac trudng hp'p d u c c danh gia la nghiem trpng bao gom t u vong, de dpa tinh mang, de lai di chdng nang ne hoac vTnh vien, e i n nhap vien d l dieu tri hay keo dai thdi gian n i m vien, gay dj tat bam sinh c thai nhi va cac ADR gay hgu qua t u c n g tg'.
Ngi dung nghien cu'u
- Thong tin ve bao cao lien quan tdi t h u l c can quang: so lugng bao eao, ty le s l bao eao t h u l e can quang tren tong s l bao eao.
Thong tin v l t h u l c can quang: S l lugng ADR ghi nhan, ty le gap ADR vdi cac biet dug'c cua t h u l e can quang.
- T h d n g t i n ve ADR:
+ M i i quan he giua t h u l c nghi ngd va ADR.
+ Cac he c c quan bj anh h u d n g . + Cac ADR nghidm trpng (phan dng phan vp va s l e phan ve dup'c xac dinh theo H u d n g dan dong thuSn eua Vipn cae benh dj dng va nhilm frung Q u i c gia Hoa Ky '*0-
+ Cac bien phap d u c e s u dgng d l x u tri phan dng phan v e / s l e phan v# lien quan d i n thuoc can quang {theo Phac do d p c d u s i c phan ve cua Bg Y t l nam 1999 va H u d n g dan x d tri cac phan u n g e l p tinh eua t h u l c can quang cua Hiep hpi chan doan hinh anh ni^u sinh dye Chau Au {ESUR)f^).
+ Y l u t l nguy c c liSn quan d i n viec xuat hien phan ung phan v e / s I c phan ve d y a tren Hudng dan Hiep hgi chan doan hinh anh nieu sinh due ChauAu(ESUR)i=i.
Danh gia hinh thanh tin higu phan ung phan v e / s l e phan ve cua t h u l e can quang t u ca sd d u lieu (CSDL) cua To c h d c Y te The gidi va cua Vi#t Nam.
X^ ly dip lieu
- Toan bg diJ/ lieu d u c e nhgp li#u va x u ly bang e h u c n g trinh Microsoft Office Excel 2007.
Cae b i l n khong lien tue d u g e t h i n g ke theo tan s u i t va ty le p h i n tram.
- Tin hieu t u CSDL eua To chdc Y t l TTil gidi: D u g e truy s u i t b i n g cong cu Vigisearch cua Trung tam giam sat thuoc quoc t l (Uppsala Monitoring Center) va dug'c bleu thj qua chi s l IC (Information Component) va ICg^g '^.
Tin hieu t u CSDL cua Vigt Nam: S d dung p h u c n g phap PRR (Proportional reporting ratio) tren e c s d k i t n l i d d li#u v l bao eao thuoc can quang vdi toan bp d u ligu v l bao eao ADR noi Chung c Viet Nam. Day eung la ehi s l dugc s u dgng trong CSDL bao cao ADR ChSu Au (Eudravigilanee). PRR d u g e tinh theo edng thdc:
PRR= (a/a+b): (c/c+d)
V d i a, b, c, d dug'c dmh nghTa n h u trong bang sau:
Thuoc nghiin cdv Tit ci c^c thuic con I9I (Thuic can quang) trong ca s& dii' lifu ADR 1^ soc phan \
Tat ca cSc ADR con Igi khfing phai la soc phan v#
T . ^ CHi DirpC HQC - 2/2014 {S6 454 N A M S^^
• Nghien cipu - Ky thuat
I d b i n g tren eung tfnh dup'c x^ theo edng t h d c :
•^ = [(ad-be)^ x (a+b+c+d)]: [{a+b)(a+e)(b+d) (c+d)]
Tfn hi$u se dug'c hinh thanh d y a tren 3 tieu c h i ' n P R R £ 2 , % 2 > 4 , a > 3 .
K4t qua
Thdng t i n v l bcio cao lien q u a n t d i t h u l c can quang
So luvng bao cao lien quan tai thuoc can quang
Trong 7 nam (2006 - 2012), da co 190 bao e^o ADR li§n quan d i n t h u l c can quang trong t i n g s l 13801 bao eao ADR d u c c ghi nhan t d he t h i n g bao cao t y nguyen cfla Viet Nam (1,4%). K i t qua chi t i l t d u g c trinh bay trong bang 1.
Bang 1 : So luang ve bao cao ADR lien quan din TCQ giai doan 2006-2012 Nam
2006 2007 2008 2009 2010 2011 2012 Tong
S6 lirc'ng bio cio ADR lien quan t&i TCQ cd chira iod
18 29 26 16 11 35 55 1S0
Tong s6 bio cao ADR
704 1328 2032 2499 1807 2407 3024 13801
Tyle so bao cao TCQ chira iod/ tong so bao cao (%)
2.56 2,18 1,28 0,64 0,61 1,45 1,82 1,4
S6 luvng ADR lien quan tai TCQ chira iod
44 82 52 35 21 48 76 357 S l lugng bao cao ADR v l t h u l e can quang
cd xu hudng giam d i n trong giai doan t u nSm 2007 - 2010. Tuy nhien, trong 3 nam t r d Igi day cCing vdi s y gia tang cOa tong so b^o cao ADR, so lugng b^o eao ADR tien quan d i n TCQ eung c6 xu hudng tang vdi ty lg t u c n g ung t u 0 , 6 1 % I6n1,82%.
Thdng tin ve thuic can quang dieac bio cAo
Ca s d d u ii^u ghi nhSn b^o cdo ADR cua t i t ca cdc thuoc can quang dugc s d dgng trong d i l u trj, trong 6d s l lugng b^o e^o lien quan d i n Telebrix (acid ioxitalamic) c h i l m 49,5 %, sau dd la Xenetie (iobitridol) c h i l m 25,8% va Ultravist (iopromid) c h i l m 15,8%. C c s d d u li$u cung da ghi nhan duge bao cao vdi cae t h u l c can quang mdi d u g c s u dung nhu Pamiray (iopamidol), lopamiro (iopamidol) va Omnipaque (iohexol) (bang 2).
Bing 2: S6 luvmg bio cao ADR lien TT Ten biet dirac
1 Telebrix (acid ioxitalamic) 2 Xenetie (Iobitridol) 3 Ultravist (iopromid) 4 Pamiray (iopamidol) 5 lopamiro (iopamidol) 6 Omnipaque (ioiiexo!) T6ng
quan dSn cac 2006 2007
15 18 3 10
1
IB 29
toai thuoc cin quang khic nhau 2006
18 5 3
26 200S
12 1 3
(6 2010
3 4 4
11 2011
8 14 12 1 35
20f2 20 16 7 7 5 55
T6ng 94 49 30 4 8 5 190
Tili%
49,5 25,8 15,8 2,1 4,2 2,6 100
Th6ng tin ve phin img co h?i cua thuic cin quang
Cdc p h i n dng cd hgi cOa t h u l c cdn quang
(TCQ) d u y e phan logi theo he e c quan cua c c t h i , trong dd cac phdn dng phdn vg vi s l e p h i n vg d u g c coi Id r l i logn toan thSn.
TJPCHi DirqC HQC - 2/2014 (S6 454 NAM 54)
• Nghien CLPU - Ky thuat
Bang 3: Phin loai biSu hien ADR cua TCQ theo he STT
1 2 3 4 5 6 7 8 9 10 11 12 13
ADR R6| loan toan than R6I loan da va mo difoi da R6| loan tieu hoa Roi logn tim mach
R6I loan than kinh trung irong va ngoai Roi loan ho hSp
Roi loan nhjp tim
ROi loan chuyen hoa va dinh du'ong Roi loan mach ngoai vi R6| loan thj giac Roi loan thinh giac va ti§n dinh ROI loan gan mat Thieu thong tin v§ ADR
Tong
bien
ca quan bi anh huang Tan so
149 80 42 25 21 20 8 3 3 1 1 1 3 357
Tyle%(n=190) 78,4 42,1 22,1 13,2 11,1 10,5 4,2 t 1,6 1,6 0,5 0,5 0,5 1,6 100%
Cae phan ung cd hai cua thuoc can quang anh hudng tren n h i l u he c c quan, trong do n h i l u n h i t la r l i loan toan than (78,4%), r l i loan da va mo d u d i da (42,1 % ) v a r l i loan tieu hda (22,1%).
Cac phan ung co hai t h u d n g gap bao gdm ret run (20%), ngda (20%), budn non, non (17,9%).
Thdng tin ve benh nhan trong bao cao lien quan tai thuoc can quang
T u a n g ung vdi tong so 190 bao cao ADR lien quan d i n thuoc can quang, 190 benh nhan da gap phai bien c l b i t Igi khi s d dung loai t h u l c nay. Thdng tin phan b l tuoi va gidi tinh eua benh nhan d u a e trinh bay trong bang 4.
Bang 4: Dac didm vi tudi va giai tinh cua benh nhan
So benh nhan (n=190) Tyle(%)
<18 18-60
>60 Khong co thong tin
7 131
36
n u gidi (64,0%) chiem ty le Idn han nam gidi (35,4%).
Thong tin ve phan u n g phan v § / s l c phan ve lien quan den thuoc can quang
Phin img phan ve/s6c phin ve lien quan den thuoc can quang
Cac phan dng lien quan den t h u l c can quang (TCQ) trong e c s c d u li§u d u c c xep vao mdc dfl nghiem trpng chu y l u la cac phan dng phan vS, s i c phan ve va t d vong.
Bang 5: So truang hop ghi nhan duac ADR nghiem trong cua TCQ
^. 2006 2007 2008 2009 2010 2011 2012 Tong Tyll%
^"^ n=l8 n=29 n=26 n=16 n=11 n=35 n=55 n=m « = f » Soc
phanve/ ^ Plian ling piian ve
14 31 58 30,5
68,9 19,0 8,4
Tiivong 0 3,7
Giol tinh Nam NO'
Khong co thong tin 67 121 2
35,4 64,0 1,05 Da so benh nhdn nam trong do tuoi t r u d n g thanh (18-60 tuoi), c h i l m 68,9%. Benh nhan
So ADR nghiem trgng (phan ung phan ve/s6c phan ve) lien quan d i n t h u l e can quang ghi nh|n d u g e la 58 bdo cao, chiem 30,5% t i n g so bdo cao nhdn dug'c eua t h u l c edn quang, Ddng luu J la so lugng bao eao phan d n g phan v g / s l c ph3n v§ ed xu h u d n g tang len va tap trung ehCi y l u trong 2 nam 2011, 2012. D d ghi nhdn d u g c Id 7 t r u d n g hep t u vong (3,7%) trong do, 5 tordng h e p t u vong dug'c ghi nhan tnang nam 2012.
TAP CHi DlTQC HQC - 2/2014 (S6 454 NAM 54)
• Nghien ci>u - Ky thuat
Yeu t o n g u y c v x u l t hien ADR Cae y l u t l nguy c c anh hudng tdi s y xuat hien ADR eua t h u l e can quang bao gom tuoi.
Bang 6: Yiu ti nguy ca lien quan din phan ung phin v^/sdc phan v0 duac ghi nhan trong c^c bao cio ADR cOa TCQ
b^nh mac kem va t i l n s u dj ung, t i l n s u di dng vdi t h u l c cdn quang ghi nhgn trong bdo cao ADR d u g e tong k i t trong bang 6.
Veil to nguy ccr Tuli cao (& 60)
B|nh tim mgch (b§nh mgch vanh, tang huyet ap ...) Tiln su dj dng (hen phe quan)
Tien sd phan dng vdi thuoc can quang
So b^nh nhan (n=190) 36 (18,9%)
13(6,8%) 3(1,6%) 2(1,1%) Tuoi cao Id y l u to nguy ca t h u d n g gap n h i t
trong nhdm benh nhan da d u c c bao eao (18,9%), sau do la nguy c c bgnh tim maeh (6,8%) va t i l n sddj dng (1,6%).
Xu tri ADR phin irng phan vi/s6c phan ve Trong ndm 2010-2012, cd t i n g s l 51 trudng hgp da dugc ap dgng ode bien phdp x u tri phan ling phdn vg/soc phan ve d u c c t i n g k i t trong bdng 7.
Bang 7: C^c bi0n phap xu tn phan Cmg phan v$/s6cphin v0 cOa TCQ
STT 1 2 3 4
Cdc bi$n phap Adrenalin Khdng histamin HI
Corticosteroid H6i sCrc CO bdn
n (%) 16(31,4) 13(25,5) 23 (45,1) 19 (34,5)
D l x u trf phan dng 23 trong tong s l 51 trudng hgp da dug'c s u dung cortieostenDid (45,1%) va 19 trong tong s l 51 trudng hgp da duge s u dung phuang phdp hoi sdc ea ban (34,5%). Ty ig s u dung adrenalin va t h u l e khdng histamine H I ehl c h i l m 31,4% vd 25,5%.
Danh gia s y hinh thanh tin hieu v l s i c phan ve doi v d i thuoc can quang
Tin hieu tip CSDL cua To chuv Yti The gidn Ca s d di> lieu ADR cua To chdc y t l t h i gidi (Vigibase) thu nhgn bao eao t d hen 80 nude thanh vien cua mang ludi gidm sat thuoc q u i e t l vdi tong so lugng bao cdo tgi thdi d i l m tmy x u l t d u ligu (01/2013) la han 7 tri$u bdo cao. K i t qua d u lieu v l ADR ciJa thuoc cdn quang t u c c s d d u ligu nay d u g c trinh bdy trong bang 8.
Bdng 8: Du li$u ve thudc cin quang tir ca sd du lidu WHO-UMC Thu6c cin
quang
lopnimide Iopamidol iobitridol loxitalamat meglumin/
loxitalamat sodium Ioxitalamic acid
ADR
S6c phan ve Soc phan v#
S6c phdn ve
S6c phan ve
S6c phdn v$
So lu-^g s6c phin v^ do
TCQ 367 300 75
56
23 IC
1,91 2,48 2,8 3,2
3,5
;c,„
1,76 2,31 2,45 2.8
2.86 Tong so tat ca ADR cua TCQ 21 763 11 968 2 325 1 266
352
Tong so tat ca cac thuoc gay ra soc phan ve
36 533 36 533 36 533 36 533
36 533
. . . . S o tniimg Quoc gia . ..^ . . ~ hapta
bao cao vong
35 37 24 38 14 10 12 4
5 1 (DQ-ll^u duqrc truy xuit tn/c tiip tie cdng C{J Vigisearch ngay 07/01/2013)
Nhtl «|y, t?i th&i aikm thSng 01/2013, Si, khac 9 ° Tu-^ng hop t i vong da ghi nhan du.p.c trong biSI vk kha nang gSy ra s6c p h i n v# cua thuoc " ^ 1 * ''^.!!^''- . _,. , . , . ,
Tin hl^u tw c c so* di^ li^u cua Vi^t Nam cin quang so vfti dc thu6c khSc trong ca sa da K^J q u j ^^1 so PRR luy tien qua c i c nSm liju cua WHO Id cb > nghTa th6ng kS ( I C ^ j > 0), d u v c trinh bay trong b i n g 9.
T * P C H f DirglC HOC - 2/2014 (S6 454 N A M 54)
• Nghien CIFU - Ky thuat
Bang 9: Danh gia hinh thanh tin hieu phan img phan ve/soc phan v$ vai thuoc can quang Nam
PRR 2006 0.82
2006-2007 2.22
2006-2000 0.91
2006-2009 1.33
2006-2010 2,02
2005-20tf 2.74 Trong giai doan 2006-2010 va 2006-2011,
k i t qua da thoa man du cde tieu chf cua p h u c n g phap PRR (bao g i m PRR > 2, x^ > 4 va s l lug'ng bao eao ddnh gia Idn han 3). N h u vay, trong CSDL bdo cao ADR cua Viet Nam, tfn hieu ve s l e phan ve trong giai doan 2006-2010 va 2006- 2011 da d u g e hinh thanh.
Ban luan
Trong giai dogn 2006 - 2012, he t h i n g bao cdo ADR t y nguyen tai Viet Nam da ghi nhan 190 bdo cdo v l eae phan ung cd hai lien quan den thuoc can quang (chiem 1,4%) trong do Telebrix (acid ioxitalamic) Id t h u l c dug'c bdo cdo n h i l u nhat (49,5 %). Cdc ADR t h u d n g gap n h i t bao gom r l i loan toan than (78,4%), r l i logn da vd mo d u d i da (42,1%), r l i loan tieu hoa (22,1%) va tim mach (13,2%). Dang chu y co 30,5% bdo cao Ijgn quan d i n phan dng phan ve va soc phan ve, s6 bao cao t d vong c h i l m 3,7%. Nhieu y l u to dnh hudng d i n s y xuat hien ADR cua t h u l c can quang, trong do tuoi eao, tien s u benh tim mach va tien s u dj dng da d u g c ghi nhan trong ede bao eao.
K i t qua cho thay ADR lien quan d i n thuoc can quang co the xay ra d l i vdi b i t ky Ida tuoi ndo va a b i t ky d l i t u c n g ndo. Tuy nhien, ty le ADR xay ra d benh nhan n u cao han han so vdi bgnh nhan nam (64,0% so vdi 35,4%). K i t qua nay phii hep vdi nghien c d u eua Bartolueei vd eong s y (2000) cho thdy phy n d cd nguy c c gap eae phdn dng muon vdi TCQ cao han nam gidi ^.
Trong eae thuoc can quang ghi nhdn dug'c trong ec s c d u lieu, chi cd acid ioxitalamic (Telebrix) la t h u l e can quang ion hoa duy n h i t va ed dp s u i t tham thdu tinh theo osmol cao trong khi cde t h u l c con lai deu thugc nhdm t h u l e can quang khong ion hoa va co dp lye tham t h I u thdp. Trong khdo sat ndy, acid ioxitalamic cd ty lg bao cao ADR cao n h i t (49,5%) t u a n g t y k i t qud trude day so sanh thuoc can quang ion hda, dp lye t h i m t h I u eao vdi t h u l c can quang khdng ion hda, dp lye t h i m thdu t h i p da d u g e eong b l . Nghien c u u t u d u lieu trong he t h i n g bdo eao t y nguyen vd bao cdo t u cong ty d u c c pham eOa C a Quan Qudn ly t h y c p h i m va D u c c pham My
(FDA) t d nam 1978 den 19941^ eho t h i y thulc can quang vdi dp s u i t tham thau tinh theo osmol cao ed ty 1^ bdo cdo A D R Idn hen cdc TCQ cd ap s u i t tham t h I u tfnh theo osmol thap tinh theo s6 t r u d n g hg'p ADR trSn 1 trigu l u c t dung (193,8 so vdi 44,4); trong do ty le phan dng nghidm trgng cua nhdm t h u l c nay cung cao hen (37,4 so vdi 10,5) va ty le t u vong la 3,9 so vdi 2,1.
Mgt nghien edu khde dug'c t i l n hdnh d 26 ec sd d i l u trj cua My (tu nam 1990 d i n 1992) cho t h i y t h u l c can quang eo ap s u i t t h i m t h I u tfnh theo osmol eao ed t j Id ADR cao hen so vdi cdc thuoc khde n l u khong s u dung thuoe d y phdng trudc khi e h i l u chup i^'.
Trong cde bdo cdo dut?c khao sdt, ty lg t u vong lidn quan d i n t h u l e can quang la 3,7%.
Ty lg nay t u c n g t y n h u mgt khao sat v l thuoc can quang d u c c t i l n hanh trong e c s d d u ligu bdo cao t y nguyen eCia My (1978-1994) eho thiy cd so l u c n g cae ea t d vong chiem 3,5% t i n g s i bao eao '^l Trong giai dogn bat d i u gidi thigu cac cdc t h u l e edn quang ap s u i t t h i m t h I u tfnh theo osmol t h i p , so lug-ng tuygt doi eae ea t d vong ghi nhgn dug'c v i n khong giam di ddng k l ^\ Tuy vay, cac nghien c u u djch te tren mgt s l lugng Idn bdnh nhan s d dgng t h u l e can quang cho t h i y ty le t u vong ghi nhan d u g e chf dao dgng td 1:100.000 d i n 1:75.000 i " « i .
Nhin chung ADR cCia TCQ rat khd d y doan trude, mac du da phdt hign dug'c ede y l u t l nguy ea lam tang ty Id xay ra ADR tren mgt s l quan the benh nhdn nhat djnh. Tuoi cao, tai s u dgng thuoc can quang tren benh nhdn dj dng vdi thulc can quang tnj'dc dd vd hen phe quan la cdc y l u to nguy c c quan trgng '^. Tnang nghidn cdu cQa Hartman vd cgng s y (1982) ''^, ea 4 b?nh nhdn ti>
vong deu tren 50 tuoi va ed t i l n s u dj dng. Theo Katayama ' " i , trong s l nhung bgnh nhan da tung s u dgng thuoe cdn quang vd ggp phdn dng, ty' lg gap ADR khi tdi s d dgng t h u l c cdn quang Id 44,0%, trong khi ty 1^ ndy d nhung bgnh nhdn dd t u n g s d dgng t h u l c can quang nhung khdng c6 phdn dng chf id 9,0%.
M6t trong nhung ADR nghi§m tn?ng dugc quan tdm n h i t cDa t h u l c edn quang Id cdc phdn
50 T^P CHI DirgfC H p c - 2/2014 (S6 454 NAM 54)
• Nghien ci>u - Ky thuat
dng nghidm trgng bao gom phdn ung phan ve va sic phan v$. Trong e c s d d u lidu cua Vigt Nam, s6 tnjdng hgp phan dng phdn vd/ s l e phdn ve chiem t j 1$ cao (30,5%). D l ddnh gia vigc hinh thdnh tfn hf^u ve dg an toan eOa t h u l c , phucng phap d u g c s u dgng pho b i l n la chf so PRR (Proportional reporting ratio). Tin hieu v l soc phdn vg/phdn dng phan ve lien quan d i n thuoc cdn quang da d u c c hinh thdnh vdi PRR la 2,74, cho t h i y thuoc can quang thue s y la nhom t h u l c c6 nguy c c cao gdy phdn dng phan v&/sle phan v$. K i t qud h l i edu e c s d d d lieu cua To chdc y t l t h i gidi cung cho t h i y s y khac biet v l kha ndng gay ra soc phdn ve cua thuoe can quang so vdi cac thule khde (IC^^g > 0).
Tuy budc dau da danh gid tin hieu lien quan d i n thule cdn quang, nghien edu nay v i n con mgt s l han c h i nhu thdng tin trong bao cao ADR khdng d l y du, kho khan trong vide xdc djnh cde y l u to nguy cc, t i l n s u bgnh nhan eung nhu chua ddnh gia d l y dO v l s y hgp ly trong x d trf cdc ADR lien quan d i n thuoc can quang. Them vdo d6, han che v l nhdn thdc cua can bg y t l vdi cdng tac bdo eao Idm eho s l lugng bao cdo ADR ghi nhdn d u g c chua phan anh d u g c tinh hinh s d dgng thulc tren t h y c t l .
Ket lu|n
Ty lg bdo cdo v l t h u l c cdn quang c h i l m 1,4% t i n g so bao cdo trong ea s d d u ligu ADR tgi Vigt Nam trong dd acid ioxitalamic d u g c bdo cdo nhilu n h i t (49,5 %). Cde hd ca quan hay g§p ADR n h i t Id roi logn toan than (78,4%), da vd m6 dudi da (42,1%), tieu hda (22,1%) va tim mgch (13,2%). Cae phan dng t h u d n g ggp nhat bao gom rdt mn (20%), ngda (20%), buon non, nfln (17,9%). 30,5% bdo cdo iien quan d i n phan dng phdn v^ va s l e phan vd va 3,7% bao cdo lidn quan d i n t d vong do thuoc can quang.
Tin higu nguy c c va moi lien quan giua vi^e s d dyng thulc cdn quang va phdn dng s i c phan ve trdn bgnh nhdn, dac bi§t benh nhdn eao t u l i , t i l n sd b§nh tim mgch vd dj dng da duftyc ghi nhgn qua chi s l PRR t d c c s d d d ligu eua Vigt Nam vd ehi s l I C ^ t d ea s d d u ligu eua To chdc y t l t h i gidi.
Do v$y, vi$e xdy d y n g vd t r i l n khai quy trinh quan ly vd sd dgng thuoc cdn quang tgi ede ea s d khdm
chua benh eung nhu cap nhgt hudng ddn x u tri s l e phdn ve do thuoe ndi chung va s l e phan ve do t h u l e can quang ndi rieng ddng vai tro quan trgng giup giam thieu cdc tai b i l n lidn quan d i n t h u l c can quang trong thyc hanh.
T a i l i e u t h a m I c l i a o 1. Gueant-Rodriguez R. .VI. et al (2006),
"Hypersensitivity Reacbons to lodinated Contrast Media", Cum Phann. Des. 12, 3359-3372.
2. WHO (2012), Pharmacovigilance Toolkit, http://
www.pvtoolkit.org/index.php?option=com_content&v iew=featured<emid=435, truy cap ngay 24 thang 09 nam 2013
3. intemational Conference on Hamionization; E2D:
Post-Approval safety data management: Definitions and standards for expedited reporting. May 2004 Avai- lable from URL http://www.emea.eu.int/pdfe/human/
ich/394503en.pdf.
4. Sampson H. A. et al (2006), "Second symposium on the definition and management of anaphylaxis:
summary report-Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium", J. Allergy Clin. Immunol., 117, 391-397.
5. Thomsen H. S. (2006), Contmst media - Safety issues and ESUR guidelines. Chapter 4 Management of Acute Adverse Reactions to Contrast Media, pp. 19-25.
6 Ronald H. B M. et al (????). 'Statistical method of signal detection", Pharmacovigilance, 2nd Edition, Wiley, pp. 249-253.
7. Bartolueei F., Cecanni M., Gabnelii G. et al (2000),
"Reazioni tardive a un mezzo di contrasto radiologico (iopamidolo -Bracco)", Radiol Med., 100. 273-278.
8. David B. Spring et al (1997). Deaths related to lodinated Contrast Media Reported Spontaneously to the US Food and Drug Administration, 1978-1994:
Effect of the Availability of Low-Osmolality contrast media. Radiology, 204:333-337.
9. Bettman M.A., Heeren T, Greenfield A. et al (1997). Adverse events with radiographic contrast agents: results of the SCVIR contrast agent registry.
Rad/o/ogy 203 611-620.
10. Lasser E.C, Lyon S.G., Beny C.C (1997).
Reports on contrast media reactions, analysis of data from reports to the U.S. Food and Drug Administration.
Radiology, 203 605-610.
11. Matsuura K (1990). Adverse reactions to ionic and nonionic contrast media. Arepoh from the Japanese Committee on the safety of contrast media. Radiology:
175:621-8.
12. Hartman G.W., Mattery R.R., Witten P.M. et ai (1982). Mortality dunng excretory urography Mayo Clinic experience Am. J. Roentgenol 139 919-922.
{Ngdy nh$n bai: 09/01/2014 - Ngay thdng qua phan bi$n: 24/01/2014)
TijkPCHi Dir<?C HQC - 2/2014 ( S 6 454 NAIVI 54)