B Y T TRNG I HC DC H NI NGUYN TUN SN PHN TCH CC TRNG HPPHN V GHI NHN TBO CO ADR TI VIT NAM GIAI ON 2010-2013 KHA LUN TT NGHIP DC S H NI 2015 B Y T TRNG I HC DC H NI NGUYN TUN SN PHN TCH CC TRNG HPPHN V GHI NHN TBO CO ADR TI VIT NAM GIAI ON 2010-2013

KHA LUN TT NGHIP DC S Ngi hng dn : 1. TS. Nguyn Hong Anh 2. DS. L Th Thy Linh Ni thc hin: Trung tm DI&ADR quc gia H NI 2015 LI CM N TrchttixinbytlngbitnchnthnhvsusctiTS.Nguyn HongAnhPhGimcTrungtmDI&ADRQucgia,gingvinb mn Dc l trng H Dc H Ni. i vi ti, thy lun l tm gng sng v tinh thn trch nhim cng nh s am m, nghim tc trong cng vic. Ti xin c by t lng bit n chn thnh v su sc nDS L Th Thy Linh Ging vin trng H Y Dc Hi Phng, ch l ngi tn tm du dt v hng dn ti. Ch dnh rt nhiu thi gian v tm huyt h tr v lng nghe, gip ti gii quyt t nhng vn nh nht. Ti xin gi li cm n chn thnh n Th.S Trn Thu Thy, cn b Trung tm DI & ADR Quc gia, ch l ngi nhit tnh ch bo v to iu kin thun li cho ti trong qu trnh thc hin kha lun.ng thi, ti cng xin gi li cm n ti DS. Nguyn Hong Anh -cn b Trung tm DI & ADR Quc gia. Anh l ngi lun gip v to iu kin cho ti hon thnh kha lun ny Ti xin cm n cc anh ch cn b Trung tm DI & ADR Quc gia to iu kin v gip ti. Ni y lun to cho ti cm gic gn gi, thn thin v gn b vititrongsutthigianthchinkhalun.Xincmnccthycgiob mn Dc L h tr em thc hin kha lun. Cui cng, ti xin gi li cm n ti gia nh v bn b ti, nhng ngi lun bn, ng vin v khch l gip ti vt qua nhng lc kh khn v mt mi nht trong thi gian hc tp v lm vic. H Ni, ngy 12 thng 5 nm 2015 Sinh vin Nguyn Tun Sn MC LC T VN ................................................................................................................. 1 CHNG 1. TNG QUAN ............................................................................................ 2 1.1.TNG QUAN V PHN V ............................................................................... 2 1.1.1.Khi nim phn v ...................................................................................... 2 1.1.2.Tiu chun chn on phn v .................................................................... 4 1.1.3.Tc nhn gy phn v ................................................................................. 6 1.1.4.D phng vx tr cc trng hp phn v .............................................. 8 1.1.4.1.D phng phn v ....................................................................................... 8 1.1.4.2.X tr bng adrenalin v cc bin php khc ............................................ 10 1.2.H THNG BO CO T NGUYN V PHN NG C HI CA THUC .......................................................................................................................... 11 1.2.1.H thng bo co t nguyn v phn ng c hi ca thuc ..................... 11 1.2.2.S hnh thnh tn hiu phn v t c s d liu v bo co t nguyn .... 12 1.3.MT S NGHIN CU V CC TRNG HP PHN V TRONG C S D LIU BO CO T NGUYN ............................................................................ 13 CHNG 2. I TNG V PHNG PHP NGHIN CU ............................. 15 2.1.I TNG NGHIN CU ............................................................................. 15 2.1.1.i tng nghin cu ............................................................................... 15 2.1.2.Tiu chun xc nh bo co ADR lin quan n cc trng hp phn v .. ...15 2.1.3.Quy trnh la chn bo co lin quan n cc trng hp phn v v bo co khng lin quan n cc trng hp phn v ................................................... 15 2.2.PHNG PHP NGHIN CU ....................................................................... 17 2.2.1.Kho st c im bo co ADR lin quan n cc trng hp phn v . 17 2.2.2.nh gi s hnh thnh tn hiu ca cc trng hp phn v vi mt s thuc c th da trn bo co case v non-case ...................................................... 18 2.3.PHNG PHP X L S LIU ................................................................... 19 CHNG 3. KT QU ................................................................................................ 20 3.1.C IM BO CO LIN QUAN N CC TRNG HP PHN V GHI NHN T H THNG BO CO ADR CA VIT NAM GIAI ON 2010 2013. ........................................................................................................... 20 3.1.1.S lng v t l bo co phn v ............................................................ 21 3.1.2.Thng tin v bnh nhn............................................................................. 21 3.1.2.1.Thng tin v tui, gii .............................................................................. 21 3.1.2.2.Thng tin v tin s d ng ....................................................................... 22 3.1.2.3.Thng tin v bnh mc km lin quan n tnh trng d ng ca bnh nhn .................24 3.1.3.Thng tin v thuc nghi ng ..................................................................... 24 3.1.3.1.Thng tin v ng dng ca thuc nghi ng .......................................... 24 3.1.3.2.Thng tin v nhm thuc nghi ng gy phn v ...................................... 25 3.1.3.3.10 hot cht nghi ng nhiu nht .............................................................. 28 3.1.4. Thng tin v phn v ..................................................................................... 29 3.1.4.1.Thng tin v thi gian tim tng xut hin phn v ................................. 29 3.1.4.2.Biu hin ca phn v trn cc h c quan ............................................... 29 3.1.4.3.Mc nghim trng ................................................................................ 31 3.1.4.4.nh gi mc quy kt ADR l trng hp phn v ................................. 31 3.1.5. Thng tin v x tr phn v ........................................................................... 32 3.1.5.1.Cch x tr ................................................................................................. 32 3.1.5.2.Kt qu sau x tr ...................................................................................... 33 3.2.NH GI S HNH THNH TN HIU CA CC TRNG HP PHN V VI MT S THUC C TH DA TRN C S D LIU ......................... 33 3.2.1.c im bnh nhn ca nhm case so vi nhm non-case ..................... 33 3.2.2.Tn hiu ca cc trng hp phn v ca mt s hot cht trn c s d liu .................................................................................................................. .34 CHNG 4. BN LUN ............................................................................................. 38 KT LUN V XUT........................................................................................... 46 KT LUN .................................................................................................................... 46 XUT ...................................................................................................................... 47 DANH MC K HIU V CC CH VIT TT ADRAdverse drug reactions Phn ng c hi ca thuc ATCAnatomical Therapeutic Chemical H thng phn loi thuc da trn c quan gii phu, tc dng iu tr, tnh cht ha hc PEFPeak expiratory flow Lu lng nh th ra WAOWorld Allergy Organization - T chc d ng th gii UMCUppsala Monitoring Centre - Trung tm theo di Uppsala NSAIDsNon-steroidal anti-inflammatory drugs - Thuc chng vim khng steroid NIAID/FAANVin Quc Gia v D ng v Bnh truyn nhim Hoa K v H thng gim st Phn v v D ng thc n RORReporting odds ratio - T sut chnh bo co CI95% Khong tin cy 95% SpO2 bo ha oxi trong mu WHOWorld Health Organization-T chc Y t Th Gii DANH MC BNG Bng 1.1: Mt s nh ngha lin quan n phn vTrang 3 Bng 1.2: Tiu chun chn on cc trng hp phn vTrang 5 Bng 3.1: Thng tin v tin s d ng ca bnh nhn Trang 22 Bng 3.2: Thng tin v thuc tng gy d ng v thuc nghi ng cng nhm trong bo co phn v Trang 23 Bng 3.3: Thng tin v bnh mc km lin quan n tnh trng d ngTrang 24 Bng 3.4: ng dng ca thuc nghi ngTrang 25 Bng 3.5: Thng tin v nhm thuc nghi ng gy phn v Trang 26 Bng 3.6: 10 hot cht nghi ng nhiu nhtTrang 28 Bng 3.7 :Thi gian tim tng xut hin phn vTrang 29 Bng 3.8: Biu hin phn v trn bnh nhnTrang 30 Bng 3.9: Biu hin nghim trng ghi nhn t bo co phn vTrang 31 Bng 3.10: Cch x tr ghi nhn t bo co phn vTrang 32 Bng 3.11: c im bnh nhn gia nhm case v non-caseTrang 34 Bng 3.12: ROR hiu chnh ca nhng thuc hnh thnh tn hiu phn v Trang 35 DANH MC HNH V, TH Hnh 2.1: Quy trnh la chn bo co ADR lin quan n cc trng hp phn v Trang 16 Hnh 3.1: Kt qu quy trnh la chn bo co case v non-caseTrang 20 Hnh 3.2: S lng v t l bo co phn v theo tng nmTrang 21 1 T VN Phnvlmtlphnngdngnghimtrng,khiphtnhanhvcth gy t vong [52]. y c coi l mt trong nhng trng hp nguy him nht trn lm sng do din bin nhanh, c th gy t vong v khng th d on c. Trn thgii,tlcctrnghpphnvcbocohngnmvokhong3,2-49,8/100.000dn.Hinnay,vicsdngrngriccthuctrongiutr,s trng hp phn v do thuc ngy cng tng v gy ra nhiu hu qu ng tic [48]. Ti nhiu quc gia, cc nghin cu v cc trng hp phn v da trn d liu bocoADRtnguyncthchin.ylngundliuquantrng nh gi vic hnh thnh tn hiu v a ra nhng cnh bo kp thi lin quan n an ton trong s dng thuc. Ti Vit Nam, theo tng kt ca Trung tm DI & ADR Quc gia, trong nm 2012 c 374 bo co phn v c tip nhn chim 11,55% tonbbocoADR[8].ylmtconslnvngquantmvtnhhnh phn v Vit Nam. Tuy nhin, cho n nay cha c nghin cu no nh gi chi tit v bo co ADR lin quan n cc trng hp phn v ghi nhn t h thng bo co t nguyn ca Vit Nam. Xut pht t thc t trn, vi mc ch cung cp thng tin gip thc hnh d phng, pht hin v x tr phn v hp l, chng ti thc hin ti Phn tch cc trng hp phn v ghi nhn t bo co ADR ti Vit Nam giai on 2010-2013 vi hai mc tiu sau: 1.Kho st c im cc trng hp phn v ghi nhn t h thng bo co ADR ca Vit Nam giai on 2010 - 2013. 2.nhgishnhthnhtnhiucacctrnghpphnvvimts thuc c th da trn c s d liu bo co ADR. 2 CHNG 1. TNG QUAN 1.1.Tng quan v phn v 1.1.1.Khi nim phn vVo nm 1901, thut ng phn v - anaphylaxis ln u tin c s dng biCharlesRichetvPaulmthintngquanstckhitimdungdch glycerin chit xut t si xc tu mt loi sa bin vo vt, th v sau l ch. nh ban u ca th nghim l to min dch vi c t ca loi sa bin cho cc vtnuiny.Tuynhin,khithchinhthycmthintngkhcxyra. Sau ln tim th nht nhm to min dch, nhng con ch nhy cm hn vi c t ln tim th hai, chng mt l v cht nhanh chng. Phn ng xy ra liu thp hn liu to min dch rt nhiu, hn na hnh thc t vong cng khc vi khi dng liu c. iu ny ny din ra tri ngc vi nh to min dch ban u v h gi hintngnylphnv-anaphylaxis("ana"trongtingHyLpcnghal "chng li" cn "phylaxis" ngha l "bo v"). Pht hin ny gip Charles Richet ot gii Nobel nm 1913 [34]. Khinimnynhanhchngccngnhntrnlmsng.nnm1925, Arthur Coca vit mt chng v phn v trong cun sch v min dch ca ng. Tuy nhin, vo thi im , hiu bit v hin tng ny mi ch dng li trn mt s m hnh ng vt, v cng cha ghi nhn c ca t vong no do tng nhy cm trn ngi, mc d c rt nhiu bnh nhn phi tim thuc trong khong thi gian di. V th mt cu hi c t ra l: liu con ngi c thuc nhm ng vt min nhim vi phn v? [34]. n khi thuc c s dng rng ri hn, c nhngbng chngcho thy con ngi cng c nguy c gp phn v v n nm 1945, hin tng ny cRobertCookenhnghalmttupmindchcbitcaproteincmng (hapten) nhy cm trong c th ngi hoc ng vt v c th coi phn v nh mt loi d ng [34].Cng vi s gia tng chng mt cc loi thuc mi v vic k n nhiu thuc mt lc, th s lng cc trng hp phn v cng tng ln tng ng, phn nhiu trongsxyraquatrunggianmindchIgE.Do,vonm1970,phnv (anaphylaxis) c nh ngha l "mt phn ng d ng ton thn khi pht nhanh 3 do s gii phng IgE ca cc cht trung gian t t bo mast v basophil". Tuy nhin c nhng trng hp ghi nhn c, phn ng xy ra theo mt c ch khc m khnglinquanntrunggianmindchIgE.Vvy,thutng"anaphylactoid reaction"craimtnhngbinccbiuhinlmsngtngt nhng khng qua trung gian min dch IgE [34].Ktkhixuthin,cnhiutranhlunvthutngny,nm2003,T chc D ng Th gii (WAO) ngh khng s dng thut ng "anaphylactoid" v tt c cc bin c trn, bt k thng qua c ch no cng u gi chung l phn v(anaphylaxis).Trong,phnvcphnloitheocchthngquamin dchhockhngthngquamindch.Cctrnghpphnvkhngthngqua min dch c coi l tng t thut ng "anaphylactoid", v cc trng hp thng qua min dch tip tc c phn thnh nhm qua trung gian IgE v khng qua IgE [19, 20]. Tuy nhin, cho n nay thut ng anaphylactoid vn c nhiu nghin cusdng.Skhcbitgiavicsdngccthutng"anaphylaxisv anaphylactoid"caWAOsovicchnhnghatrcyctrnhbytrong bng 1.1 Bng 1.1 Mt s nh ngha lin quan n phn v [34] nh nghanh ngha theo WAOnh ngha trc y Phn v - anaphylaxisCthchockhng thngquancchmin dch Chsdngchocc trnghpphnvthng qua trung gian IgE AnaphylactoidKhng s dngChsdngchocc trng hp phn v khng thng qua trung gian IgE V d v phn v -Phnngxyrakhi truynmulinquanti IgG hoc IgM -Phnvdochtcn quang(giiphngtrc tip histamin) -Phn v do d ng tm - Phn v thng qua min dch,khngquatrung gian IgE -Phnvkhngthng quamin dch - Phn v thng qua min dch, qua trung gian IgE - Anaphylactoid reaction - Anaphylactoid reaction - Anaphylaxis 4 Cc cuc tranh lun ny vn tip din vi n lc a ra mt nh ngha c chpnhnrngri.Thng7nm2005,VinQucgiavDngvBnhtruyn nhim Hoa K phi hp vi H thng gim st Phn v v D ng thc n triu tpcuchpthhaivphnv,viidint16tchcvcccquanchnh ph khc nhau n t Bc M, Chu u, v c. Ti y, cc chuyn gia thng nht a ra mt nh ngha rng v phn v nh sau: ''phn v l mt phn ng d ngnghimtrng,khiphtnhanhvcthgytvong''.nhnghanynhm phn nh din bin v mc nghim trng ca phn v v c th s dng cho c gii y khoa v trong cng ng [48]. 1.1.2. Tiu chun chn on phn v Biu hin lm sng ca phn v c th xuthin trn bt k h cquan no, nhng ch yu gp trn da, h h hp, h tiu ha v h tim mch. Cc du hiu v triu chng rt a dng bao gm: my ay, ph mch, kh th, th kh kh, ph n ng hhp trn, chng mt, h huyt p, bun nn, nn, auqun bng, da, nhc u v au ngc [52]. xc nh cc trng hp phn v th khng c tiu chun vng m u da vo cctriu chng trn lmsngv cnhiu b tiu ch c xut nh tiu ch ca ca Vin Quc gia v D ng v bnh truyn nhim Hoa K [48], ca Hi hi sc Anh [52] v ca Ruggeberg v cng s [45]. Trong , tiu chun xc nh ca Vin Quc gia v D ng v bnh truyn nhim Hoa K l b tiu ch c p dng trong hu ht cc nghin cu cng nh hng dn ca cc hi chuyn mn v phn v. Kt qu t mt nghin cu so snh gia b tiu ch ny vi b tiu ch ca Ruggeberg v cng s p dng trong chn on cc trng hp phn v cho kt qu tng ng [17]. Tiu chun ny c xy dng vi mc tiu gip cho vic chn on n gin, nhanh chng. B tiu ch c th ny c trnh by trong bng 1.2 di y 5 Bng 1.2: Tiu chun chn on cc trng hp phn v [48] Bnh nhn s c chn on l phn v khi tha mn mt trong ba tiu ch sau:Tiu ch 1. Khi pht cp tnh, c tn thng ca da/nim mc, hoc c hai (v d, ban my ay, nga hoc ban gin mch, sng mi-li-li g) V T NHT MT TRONG CC TRIU CHNG SAU a. Tn thng ng h hp (v d kh th, th kh kh, co tht ph qun, th rt, gim PEF, gim oxy mu) b. H huyt p, hoc c triu chng lin quan (v d ngt, tiu khng t ch) Tiuch2.Haihocnhiutriuchngsauyxyranhanhchngsaukhitip xc vi mt d nguyn c kh nng gy d ng:a. Tn thng trn da/nim mc (nh ban my ay, nga hoc ban gin mch, sng mi-li-li g)b. Tn thng ng h hp (nh kh th, th kh kh, co tht ph qun, th rt, gim PEF, gim oxy mu)c. H huyt p hoc cc triu chng lin quan (nh ngt, tiu khng t ch)d. Triu chng tiu ha dai dng (nh au qun bng, nn) Tiu ch 3. H huyt p xy ra nhanh chng sau khi tip xc vi cht gy d ng c bit n: a.Trssinhvtrem:huytptmthuthp(tytheotui)hocgimhn 30% huyt p tm thu * b.Ngiln:huytptmthu 1 ngy hoc khng c thng tin Case Bo co khng lin quan ti ADR (bo co ng c, t st, bo co cht lng thuc, bo co khng lin quan ti thuc) Loi khi nghin cu C Khng 17 Quy trnh ny gm cc bc: -Bc 1: Loi khi nghin cu nhng bo co khng lin quan n ADR (bo co cht lng, bo co ng c t st, bo co khng lin quan n thuc) v bo co thiu mt trong cc thng tin tui, gii, thuc nghi ng v m t biu hin ADR. -Bc 2: Xc nh bo co case (bo co phn v) theo cc trng hp trnh by ti mc 2.1.2. -Bc 3:LoikhinghincunhngbocoADRcbiuhinging phnvnhngcthigianxuthinADRtnhtlndngthuccui cng trn 1 ngy hoc khng c thng tin.-Cc bo co ADR cn li, c xp vo non-case. 2.2.Phng php nghin cu 2.2.1.Kho st c im bo co ADR lin quan n cc trng hp phn v Mthicudliutccbocophnvgiaion2010-2013.Ccch tiu m t bao gm: S lng v t l bo co phn v trn tng s bo co ADR Thng tin v bnh nhn -Tui, gii tnh-Tin s d ng (d ng thi tit, thuc, phn hoa, cn trng) -Thng tin v cc bnh mc km lin quan ti tnh trng d ng Thng tin v thuc nghi ng -Slngbocotheohotcht(nhmthuc,thuccth).Trong, nhm thuc c phn loi da trn c s phn loi m ATC. Trong h thng phn loi ATC cc thuc c chia thnh nhm khc nhau da vo 18 cquangiiphuhayhthngmchngtcng,ngthidavo cc c tnh ha hc, dc l v tc dng iu tr ca thuc [1], [63]. -Thng tin v ng dng ca thuc nghi ngThng tin v phn v -ThigiantimtngxuthinADRktlndngthuccuicng. Thi gian tim tng xut hin phn v l khong thi gian tnh t ln cui cng dng thuc nghi ng n khi xut hin biu hin ca phn v -Biu hin ca phn v trn cc h c quan-PhnloimcquyktADRltrnghpphnvtheoVandeKlauw [57] (xem Ph lc 1) -Mc nghim trng ca cc trng hp phn v theo Brown [13] (xem Ph lc 1) Cch x tr v kt qu sau x tr -Cchxtr:tlbocodngadrenalin/thoxyhocthngkhnhn to/b th tch tun hon/corticoid/ khng histamin H1/khng histamin H2 x tr trn tng s bo co phn v -T l t vong do trn tng s bo co phn v. 2.2.2.nh gi s hnh thnh tn hiu ca cc trng hp phn v vi mt s thuc c th da trn bo co case v non-case Thucclachnnhgishnhthnhtnhiuvicctrnghp phn v l nhng thuc c tn sut bo co phn v cao nht da trn thng tin v thuc nghi ng ghi nhn t bo co phn v. S hnh thnh tn hiu vi cc trng hp phn v thng qua t sut chnh bo co (ROR) hiu chnh theo phng php case/non-casetrncsktnidliuvbococathucclachnvi ton b d liu v bo co ADR ni chung Vit Nam [23]. Thng tin v c im tui, gii ca bnh nhn, nm gi bo co v thng tin v cc thuc c la chn 19 scthngktheo2nhmcasevnon-casequaccnm,trsRORsc hiu chnh theo cc thng s trn [28]. Trong :a l s case ca thuc c la chn b l s case ca tt c cc thuc cn li trong c s d liu c l s non-case ca thuc c la chn d l s non-case ca tt c cc thuc cn li trong c s d liu. S hnh thnh tn hiu v cc trng hp phn v i vi cc thuc trong c sdliuvtrongccnmcxcnhthngquagitrROR.Tnhiuc hnh thnh i vi mt thuc trong mt khong thi gian nht nh khi tho mn c 2 iu kin sau: -C t nht 3 bo co cc trng hp phn v lin quan ti thuc -Cn di khong tin cy 95% ca ROR ln hn 1 (CI95%>1) [23], [59]. 2.3.Phng php x l s liu Ton b d liu c nhp, x l trn phn mm Microsoft Office Excel 2010 vSPSS16.0.Ccbinkhnglintccthngktheotnsutvtlphn trm. Cc bin lin tc c c trng bi gi tr trung bnh lch chun. Kim nhMann-WhitneyUcsdngvi2binlintckhngtheophnphi chun, kim nh X2 vi c s dng so snh t l. Gi tr ROR tng ng vi tngthucvkhongtincy95%ctnhtonvhiuchnhtheotui,giiv nm bo co tnh trn nguyn tc tnh t sut chnh OR bng m hnh phn tch hi quy logistic trong SPSS 16.0. 20 CHNG 3. KT QU Sau khi p dng quy trnh la chn bo co case v non-case trnh by trn hnh 2.1, kt qu thu c nh sau: Hnh 3.1: Kt qu quy trnh la chn bo co case v non-case trong c s d liu bo co ADR T12701bocotnguynlutrtitrungtmDI&ADRQucgiagiai on 2010-2013, sau khi loi 609 bo co, c 1302 bo co case (bo co phn v) v 10790 bo co non-case c a vo nghin cu. 3.1.c im bo co lin quan n cc trng hp phn v ghi nhn t h thng bo co ADR ca Vit Nam giai on 2010 - 2013 12701 bo co t nguyn 609 bo co loi khi nghin cu 68 bo co cht lng thuc, 8 bo co ng c, 3 bo co khng lin quan n thuc 489bocothiumttrongccthngtin tui/gii/thuc nghi ng/m t ADR 41 bo co c biu hin ADR ging phn v nhngthigiantimtngktlndng thuccuicngtrn1ngyhockhngc thng tin 1302 bo co case 205bococcnbytmtlsc phn v hoc phn ng phn v 1097bocokhngcmtlphnv nhngthamntiuchunchnoncc trng hp phn v 10790 bo co non-case 21 3.1.1.S lng v t l bo co phn vS thay i v s lng v t l bo co phn v qua cc nm trong giai on nghin cu c th hin trong hnh sau: Hnh 3.2: S lng v t l bo co phn v theo tng nm Nhn xt: Slngbocophnvtngdnquaccnmt161boco(nm2010) ln213boco(nm2011)v330boco(nm2012),nnm2013slng bo co phn v tng gn gp i (330 ln 580 bo co). Tuy s lng tng nhng tlbocophnvtrntngsbocoADRcatngnmvngimcn nh v dao ng trong khong 8,9 - 10,9% quanh gi tr trung bnh l 10,3%. 3.1.2.Thng tin v bnh nhn 3.1.2.1. Thng tin v tui, gii 161 231 330 580 8,9 9,6 10,9 10,6 024681012141601002003004005006007002010 2011 2012 2013S BC caseT l vi tng s bo co nghin cu (%) 22 Tuicabnhnhntrongccbocophnvtrittrmisinh(di1 thng), n tr s sinh (1 thng n 1 tui), tr nh (2-6 tui), tr ln (6-12 tui), tr v thnh nin (12-18 tui), ngi trng thnh (18-60 tui) v ngi cao tui (trn 60 tui). V gii, t l phn v n chim 54,5% v cao hn nam. Thng tin c th v tui v gii ca bnh nhn ghi nhn t bo co phn v s c trnh by chi tit ti bng 3.11 mc 3.2. 3.1.2.2. Thng tin v tin s d ng Trong 1302 bo co phn v c 749 bo co c khai thc tin s d ng ca bnh nhn, 10 trng hp khng khai thc v 543 bo co (chim 41,7%) khng c thng tin v vic khai thc tin s d ng. Thng tin v tin s d ng ca bnh nhn trong 749 bo co trn c m t trong bng 3.1 Bng 3.1: Thng tin v tin s d ngTin s d ng S lng bo co (n=1302) C tin s d ng thuc gy phn v18 (1,4%) C tin s d ng thuc cng nhm vi thuc gy phn v17 (1,3%) D ng thuc khc hoc thuc khng r loi79 (6,1%) D ng khc (phn hoa, cn trng, thi tit..).17 (1,3%) D ng khng r loi21 (1,6 %) Khng c tin s d ng579 (44,5%) Khng thu c thng tin18 (1,4%) Nhn xt: ng ch l c 18 bnh nhn (chim 1,4%) c tin s d ng vi chnh thuc nghinggyphnvv17bnhnhn(1,3%)ctinsdngvithuccng nhm vi thuc nghi ng gy phn v. 18bocophnvmbnhnhnctinsdngvichnhthucnghi nggyphnvlinquannnhngthucsau:amoxicillin(3trnghp), 23 penicillin (2 trng hp), cotrimoxazol (2 trng hp), huyt thanh khng c un vn SAT (2 trng hp), paracetamol (2 trng hp), ampicillin (1 trng hp), ceftriaxon(1trnghp),cefadroxyl(1trnghp),cefalexin(1trnghp), cefuroxim(1trnghp),vancomycin(1trnghp),tramadol(1trnghp). Trongc2bocotngngviceftriaxonvSAT,bnhnhntnggp phn v vi nhng thuc ny trc . Vi 17 bo co phn v m thuc nghi ng gy phn v cng nhm vi thuc tng gy d ng cho bnh nhn, thng tin v thuc nghi ng v thuc c tin s d ng s c trnh by c th trong bng di y Bng 3.2: Thng tin v thuc tng gy d ng v thuc nghi ng cng nhm trong bo co phn v Thuc c tin s d ngThuc nghi ng gy phn v S lng bo co cefotaxim ceftriaxon3 ceftazidim1 cefuroximcefotaxim1 ampicillin amoxicillin/acid clavulanic1 amoxicillin1 Khng sinh penicillin* ampicillin/sulbactam1 amoxicillin1 cefotaxim1 Khng sinh cephalosporin*Cefalexin 1 Khng sinh beta-lactam* amoxicillin 1 cefadroxil1 ibuprofendiclofenac1 NSAIDs* diclofenac1 floctafenin1 meloxicamcelecoxib1 *: Khng r thuc c th 24 3.1.2.3. Thng tin v bnh mc km lin quan n tnh trng d ng ca bnh nhn Thngtinvbnhmckmlinquanntnhtrngdng(henphqun, vim mi d ng, vim da d ng, eczema) ghi nhn c t bo co phn v c trnh by trong bng sau: Bng 3.3: Thng tin v bnh mc km lin quan n tnh trng d ngBnh mc km S lng bo co (n=1302) C bnh mc km lin quan n tnh trng d ng30 (2,3%) Khng c bnh mc km lin quan n tnh trng d ng273 (21,0%) Khng c thng tin999 (76,7%) Nhn xt: Slngbocokhngcthngtinvbnhmckmchimtlln (76,7%).Trongsbococthngtincnlic21%bnhnhnkhngcbnh mc km lin quan n tnh trng d ng v 30 bo co (chim 2,3%) bnh nhn c bnh mc km lin quan n tnh trng d ng, trong bao gm: 28 bnh nhn hen ph qun, 1 bnh nhn vim mi d ng v 1 bnhnhn vim da d ng. 3.1.3.Thng tin v thuc nghi ng 3.1.3.1. Thng tin v ng dng ca thuc nghi ng 1302 bo co phn v ghi nhn c tng ng vi 1559 lt thuc nghi ng csdng.Thngtinvngdngcanhngthucnycthngkti bng 3.4 di y 25 Bng 3.4: ng dng ca thuc nghi ng ng dngTn sut T l (%) (n=1559) Tnh mch932 59,8 Ung295 18,9 Tim bp137 8,8 Test da29 1,9 Tim di da15 1 Gy t14 0,9 t hu mn7 0,4 Kh dung2 0,1 Ngm di li1 0,1 ng mch1 0,1 Bm vo t cung1 0,1 Thy chm 1 0,1 Khng c thng tin124 8 Nhn xt: ngdngphbinnhtcathucnghingtrongccbocophnvl ng tnh mch vi 932 lt dng (chim 59,8%), ng ung vi 295 lt dng (18,9%) v ng tim bp vi 137 lt dng (8,8%). ng ch c 29 trng hp phn v xut hin ngay khi thc hin test th phn ng. Ngoi ra, phn v cng c th xyra khi s dng thuc vi bt kng dng no nh gyt, tim di da, t hu mn, kh dung, ngm di li, ng ng mch, bm vo t cung v thy chm. 3.1.3.2. Thng tin v nhm thuc nghi ng gy phn v Thuc nghi ng trong cc bo co phn v c phn loi theo c quan gii phu m thuc tc ng v cc h dc l trn c s m ATC. Thng tin thu c c trnh by trong bng 3.5 di y: 26 Bng 3.5: Thng tin v nhm thuc nghi ng gy phn v Nhm thuc - m ATC S lng bo co T l %(n=1302) H c quan H dc l Khng khun tc dng ton thn J J01C khng khun nhm beta-lactam, cc penicillin 1209,22 J01D - khng khun beta-lactam khc * 68552,61 J01G - khng khun nhm aminoglycosid443,38 J01M - khng khun nhm quinolon 423,23 J01X - cc thuc khng khun khc282,15 J06 - huyt thanh min dch v cc immunoglobulin 211,61 J01E - sulfonamid v trimethoprim 141,08 J07 - cc vaccin141,08 J04A - cc thuc iu tr lao 120,92 J01B - cc amphenicol100,77 J01F - macrolid v lincosamid60,46 J05 - thuc chng virut ton thn 10,08 H thn kinh (N) N02 - thuc gim au 685,22 N01 - thuc gy m v gy t382,92 N05 - thuc an thn100,77 N06 - thuc hng thn30,23 N03 - thuc chng ng kinh 20,15 N07 - thuc khc v h thn kinh50,38 Mu v c quan to mu (B) B05 - cc cht thay th mu v dch truyn614,69 B02 - thuc cm mu60,46 B01 - thuc chng huyt khi 40,31 27 H c quan H dc l S lng bo co T l %(n=1302) H c xng (M) M01A -NSAIDs 554,22 M03 - thuc gin c 191,46 ng tiu ha v chuyn ha (A) A07 - thuc iu tr tiu chy, vim rut/chng nhim khun 221,69 A02 cc khng acid, thuc iu tr lot d dy t trng v y hi 201,54 A03 - thuc chng co tht, khng cholinergic v iu ha nhu ng rut 131 A11 - vitamin 110,84 A16 - cc thuc khc60,46 Htimmch (C) C01 - thuc iu tr tim443,38 C03, C08, C09 - Cc thuc khc (li tiu, gin mch, chn knh calci, tc dng trn h renin-angiotensin)100,77 Ccchphmhormondngngtonthn,trhormon sinh dc v insulin (H) 231,77 Thuc tc dng trn cc gic quan (S)211,61 Thuc chng ung th v tc nhn iu ho min dch (L)141,08 Thuc tc dng trn h h hp (R)120,92 Thuc tc dng trn h sinh dc tit niu v cc hormon sinh dc (G) 70,54 Thuc chng k sinh trng v cn trng (P)30,23 Cc nhm khc V08 cht cn quang513,92 Thuc ng dc60,46 Cc thuc khc151,15 Khng r131 *: Bao gm nhm khng sinh cephalosporin v nhm carbapenem Nhn xt: 28 PhnvcghinhnvihuhtccnhmthuctheophnloimATC da trn h c quan m thuc tc dng vo nh: nhm thuc khng khun tc dng ton thn, nhm thuc tc dng trn h thn kinh, mu v c quan to mu, h c-xng-khp, h tiu ha v chuyn ha, h tim mch. Nhng h dc l hay gp trong cc bo co phn v bao gm: khngkhun nhmcephalosporinvcarbapenem(685boco,chim52,61%tngsboco phnv),khngkhunnhmpenicillin(120boco,9,22%),thucgimautc dng trn thn kinh trung ng (68 bo co, 5,22%), cc cht thay th mu v dch truyn(61boco,4,69%),ccNSAIDs(55boco,4,22%)vchtcnquang (51boco,3,92%).Mtsthuckhngcbnchtdnguynvthngc cho l an ton cng c ghi nhn trong cc bo co phn v nh cc dung dch b nc, in gii (thuc nhm cc cht thay th mu v dch truyn B05) vi 36 bo co chim 3,00%, cc vitamin (11 bo co, 0,84%). 3.1.3.3. 10 hot cht nghi ng gy phn v nhiu nht C 231 hot cht khc nhau c ghi nhn trong cc bo co phn v. Bng 3.5 di y l danh sch 10 hot cht b nghi ng nhiu nht: Bng 3.6: 10 hot cht nghi ng nhiu nht STTTn thucTn sut T l (%) (n=1302) 1Cefotaxim25219,4 2Ceftriaxon1299,9 3Ceftazidim1168,9 4Cefoperazon503,8 5Amoxicillin463,5 6Ampicillin393,0 7Cefalexin322,5 8Diclofenac312,4 9Lidocain261,8 10Cefuroxim261,8 29 Nhn xt: Trong 10 thuc nghi ng c tn sut gy phn v cao nht c 8 thuc thuc khngsinhbeta-lactam(trong6thuclkhngsinhnhmcephalosporin),2 thuccnlildiclofenacvlidocain.Bathucctnsutbococaonhtl cefotaximvi252bocochim19,4%tngsbocophnv,ceftriaxon(129 bo co chim 9,9%) v ceftazidim (116 bo co chim8,9%). 3.1.4. Thng tin v phn v 3.1.4.1. Thng tin v thi gian tim tng xut hin phn v Bng 3.7: Thi gian tim tng xut hin phn v Thi gian tim tng xut hin phn v S lng bo co (n= 1302) 10 pht726 (55,8%) 1060 pht78 (6%) Xyratrongngy(khngkhaithccthigian chnh xc) 134 (10,3%) Nhn xt: Kt qu cho thy phn ng phn v xy ra nhanh sau khi s dng thuc.Hn mt na bo co phn v (55,8%) c thi gian tim tngdi 10 pht, 28% xy ra trong vng 1 gi, v ch c 6% cc trng hp xy ra sau 1 gi. C 10,3% bo co khng ghi r thi gian tim tng xut hin phn v. 3.1.4.2. Biu hin ca phn v trn cc h c quan 30 Theo quy trnh m t trn, vic la chn bo co phn v s da trn biu hin ADR trn 4 h c quan (h tun hon, h h hp, h tiu ha, cc biu hin trn da/nim mc) v tnh trng h huyt p nghim trng (nu c) ca bnh nhn.Bng 3.8: Biu hin phn v trn bnh nhn Biu hin ADR S lng bo co T l (%) (n=1302) Htunhon:hhuytp,mchnhanh,nhptim nhanh, lon nhp, mch chm khng bt c, i tiu tin khng t ch, ngt 109884,3 Hh hp: suy h hp, h th, co tht ph qun, thkh,thrt,thanhqunsng,phnghhp,ho khan ko di, khn ging 92971,4 Da/nim mc: ban , m ay, ph mch, nga da, v nga mt 71254,7 H tiu ha: authngv,tiuchy,nnlintc, au bng d di 22617,4 H huyt p nghim trng67551,8 Biu hin khc: vt v, v m hi, suy a tng, rt run, st cao, hoa mt, chng mt Nhn xt: Trongascctrnghpphnv,bnhnhncbiuhintrnhtun honvi1098bocochim84,3%vbiuhintrnhhhp(929boco, 31 71,7%). Triu chng trn da hoc nim mc c ghi nhn trn 712 bo co chim 54,7%. Biu hin trn h tiu ha xut hin vi t l thp nht (17,4% bo co).3.1.4.3. Mc nghim trng Kt qu nh gi mc nghim trng ca phn v xy ra trn bo co c phn loi theo 2 mc theo Thang nh gi mc nghim trng ca cc trng hp phn v trnh by ti ph lc 1. Ktquthucchothyc916boco(chim70,35%)nghimtrng mc 1; 380 bo co (chim 29,19%) nghim trng mc 2 v c 6 bo co (0,46%)khng xc nh c mc nghim trng do khng m t c th biu hin. Thng tinvccbiuhinnghimtrngtrong916bococphnloimc1c trnh by trong bng sau: Bng 3.9: Biu hin nghim trng mc 1 ghi nhn t bo co phn v Biu hin nghim trng mc 1S lng bo co T l (%) (n=1302) H huyt p nghim trng67551,8 Biu hin thiu oxy mu34926,8 Biu hin trn h thn kinh trung ng17713,6 3.1.4.4.nh gi mc quy kt ADR l trng hp phn v Mc quy kt ADR l mt trng hp phn v c nh gi da theo Phn loi mc quy kt ADR l trng hp phn v trnh by ti ph lc 1. Trong 1302 bo co phn v c 964 bo co mc chc chn (chim 74%) v 338 bo co mc c th (26%). 338 bo co c phn loi mc c th do 120bocotuycthigiantimtngxuthinphnvtrongvng1ginhng 32 khngcbiuhintrnda/nimmcvhhpv218bococthigiantim tng khng r hoc trn 1 gi. 3.1.5. Thng tin v x tr phn v 3.1.5.1. Cch x trTrong cc bo co phn v, c 14 bo co khng c thng tin v x tr phn v v 5 bo co ghi x tr theo phc xtr sc phn v ca B Y t nhng khng mtcth.Ngoira,thngtinvcchxtrtrongnhngbococnlic thng k trong bng di y: Bng 3.10: Cch x tr ghi nhn t bo co phn v Bin php S lng bo co T l % (n = 1302) Adrenalin75457,9 Th oxy55742,8 Truyn dch b tun hon22417,2 Corticoid80061,4 Khng histamin H135026,9 Khng histamin H2191,5 Nhn xt: S dng adrenalin: Adrenalin c s dng trn 57,9 % cc trng hp phn v. T l ny tng t 39,8% (nm 2010) ln 66,8% (nm 2013). Trong : 33 -C 594 trn 964 bo co c quy kt chc chn l phn v (62%) c dng adrenalin v 160 trn 338 bo co c quy kt c th l phn v (47%)dng adrenalin. -C 607 trn 916 bo co nghim trng mc 1 (66%) c s dng adrenalin v 145 trn 380 bo co nghim trng mc 2 (38%) s dng adrenalin. Ngoiadrenalin,bnhnhncngcxtrvinhngbinphpkhc,bao gm: -Th oxy hoc thng kh nhn to trn 42,8 % bnh nhn, t l ny cng tng t 13,0% (nm 2010) ln 54,0% (nm 2013) -Bdchtunhonvi17,2%bnhnhnvtngt18,0%(nm2010)ln 38,3% (nm 2013) -Sdngcorticoidtrn61,4%bnhnhn,tlnytngt46,0%(nm 2010) ln 69,3% (nm 2013).- Ngoi ra, c26,9% bnh nhnc x tr vi khng histamin H1v 1,5% bnh nhn c dng khng histamin H2. 3.1.5.2. Kt qu sau x tr Sau khi x tr c 25 trng hp t vong (chim 2%) v 1056 trng hp hi phc khng c di chng (81%). 221 trng hp cn li (17%) khng khai thc c thng tin v tnh trng bnh nhn sau khi x tr. 3.2.nh gi s hnh thnh tn hiu ca cc trng hp phn v vi mt s thuc c th da trn c s d liu 3.2.1.c im bnh nhn ca nhm case so vi nhm non-case cimtuivgiicabnhnhncsosnhgianhmcasevnon-case, kt qu th hin trong bng di y: 34 Bng 3.11: c im bnh nhn gia nhm case v non-case Case (n=1302) Non-case (n=10790) p Nhm tui 60 tui337(25,9%)2022(18,7%) Gii tnh N (n,%)721(55,4%)6092(56,5%)0,460 Nam (n,%)581(44,6%)4698(43,5%) Nhn xt: tuicabnhnhnnhmcasevnon-casetuykhcbitcngha thngk(p=0,000)nhngutriutrnmituikhcnhau.Vgii,tl bo co n cao hn nam c 2 nhm v kt qu cho thy khng c s khc bit c ngha thng k (p>0,05) gia nhm case v non-case. 3.2.2.Tn hiu ca cc trng hp phn v ca mt s hot cht trn c s d liu S hnh thnh tn hiu ca mt thuc c th vi cc trng hp phn v c nh gi thng qua t sut chnh bo co (ROR) hiu chnh c tch ly qua cc nm. Cc hot cht c la tnh ROR l nhng hot cht c t nht 10 bo co phn v trong 4 nm (t nm 2010 - 2013). T kt qu thng k cho thy c 30 hot cht tha mn tiu ch trn, kt qu ROR hiu chnh ca tt c cc hot cht ny s c trnh by chi tit ti bng 2 ph lc 2. Bng 3.12 di y l ROR hiu chnh canhngthucctnhtmtgitrRORchothycshnhthnhtnhiu 35 Bng 3.12: ROR hiu chnh ca cc thuc hnh thnh tn hiu phn v qua phn tch c s d liu bo co ADRgiai on 2010-2013 Hot cht20102010 - 20112010 20122010 - 2013 Khng khun cephalosporin Cefotaxim1,89 [1,19-3,02]1,89 [1,43-2,49]1,89 [1,53-2,32]2,03 [1,74-2,36] Ceftriaxon2,57 [1,61-4,08]1,45 [1,02-2,05]1,69 [1,30-2,18]1,75 [1,43-2,13] Ceftazidim2,71 [1,31-5,58]4,22 [2,93-6,09]3,16 [2,39-4,19]2,68 [2,16-3,31] Cefoperazon1,29 [0,45-3,72]1,76 [0,98-3,15]1,93 [1,23-3,04]2,19 [1,6-3,02] Cefadroxil+++*7,33 [2,22-4,22]4,99[2,08-12]3,06 [1,53-6,12] Khng khun nhm penicillin Ampicillin3,02 [1,4-6,51]1,81 [1,01-3,24]1,48 [0,95-2,33]1,61 [1,14-2,3] Benzylpenicillin+++*2,49 [0,82-7,49]2,03[0,89-4,65]2,22 [1,2-4,12] Khng khun nhm amphenicol Chloramphenicol4,45[1,52-13,03]2,06 [0,77-5,48]2,68[1,25-5,71]1,91 [0,95-3,82] 36 Hot cht20102010 - 20112010 20122010 - 2013 Cht cn quang Iobitridol0**2,76[0,74-10,3]1,24[0,43-3,59]2,2 [1,3-3,76] Iopromid+++*3,81[1,31-11,06]2,14 [0,79-5,8]3,4 [1,87-6,17] Acid ioxitalamic9,88 [1,38-70,88]12,48 [3,94-39,61]2,73[1,22-6,11]2,64 [1,43-4,99] Dch truyn tnh mch Dchtruynacid amin 4,34 [1,06-17,72]3,48 [1,44-8,42]3,02[1,4-6,52]1,86 [0,93-3,73] Thuc khc v huyt hcChymotrypsin3,66 [0,952-14,1]1,99 [0,75-5,32]2,27[1,22-4,25]1,89 [1,14-3,13] Hormon thy sau tuyn ynOxytocin0**1,8 [0,52-6,22]2,2[0,91-5,36]2,6 [1,32-5,04] Thuc gy t ti chLidocain3,38 [0,9-12,69]2,71 [1,09-6,8]4,04 [2,26-7,21]4,55 [2,99-6,92] Thuc chng tiu fibrinAcid tranexamic8,94 [0,54-14,84]8,59 [1,71-43,03] 11,48[3,63-36,58] 11,73 [4,4-31,04] *Tt c bo co lin quan ti thuc nghi ng u l bo co phn v **Khng c bo co phn v lin quan ti thuc nghi ng trong giai on tnh ROR 37 Shnhthnhtnhiuphnvbtutnm2010vi9thuc:cefotaxim, ceftazidim,ceftriaxone,cefadroxil,amoxicillin,benzylpenicillin,iopromid,acid ioxitalamic v cloramphenicol. Trong nm 2010, tt c bo co c thuc nghi ng l cefadroxil, benzylpenicillin v iopromid u l bo co phn v. Trong nhm khng khun cephalosporin, cefotaxim c gi tr ROR n nh t nm 2010 n ht nm 2011 v 2012 (1,89) v tng nh vo nm 2013 (2,03).ROR caceftriaxon,ceftazidimvcefadroxilcxuhnggimtheothigiantnm 2010n2013,tuynhinvnmchnhthnhtnhiu.Tnhiucacefadroxil mnh nht trong 3 khng sinh trn. ivi cefoperazon, ROR tng theo tng giai ontkhnghnhthnhtnhiuvo2010v2011nhnhthnhtnhiunm 2012 (ROR = 1,93[1,23-3,04]) v tn hiu tng vo nm 2013 (2,19 [1,6-3,02]). Vi nhm khng penicillin: tn hiu ca ampicillin hnh thnh t 2010 duy tr n 2011, mt tn hiu vo nm 2012 v c hnh thnh li vo 2013. Tn hiu ca benzylpenicillinhnhthnht2010,tuynhinn2011v2012mttnhiuv xut hin li vo 2013. Vinhmchtcnquang:RORcaiopromidvacidioxitalamiccxu hng gim theo thi gian, tuy nhin vn duy tr tn hiu qua cc nm (tr iopromid bmttnhiuvonm2012).Cnviiobitridol,tnhiuchxuthinvonm 2013 vi ROR = 2,2 [1,3-3,76]. Vi 3 thuc lidocain, oxytocin, v acid tranexamic, ROR tng theo thi gian t khng hnh thnh tn hiu n nm 2010 (vi acid tranexamic v lidocain), 2012 (oxytocin) cho n hnh thnh duy tr tn hiu vi ROR tng dn nhng giai on sau. Ngoi ra, tn hiu cng c hnh thnh vi cloramphenicol (giai on 2010 v n2012),dchtruynacidamintrongt2010nhtgiaion2012nhngb mt tn hiu vo nm2013 v chymotrypsinvo nm 2012 v duytr tn hiu n 2013. 38 CHNG 4. BN LUN Trong thi gian gn y,s trng hp phnv do thucxy racc c s khm cha bnh trong c nc c xu hng gia tng khin nhiu cn b y t e ngi khidngthucchobnhnhn.Bncnh,bocoADRlilnguncsd liu ch yu h tr hot ng gim st v pht hin tn hiu v cc phn ng c hi ca thuc ti Vit Nam nhm h tr cn b y t trong vic m bo an ton khi s dngthuc.Tthng01/2010,theoquynhcaBYt,TrungtmDI&ADR Quc gia l u mi thu nhn, x l, thm nh v lu trtt ccc bo co ADR t nguyn c gi v t cc c s iu tr trn phm vi ton quc. V vy, nghin cunycthchintrndliubocoADRtrong4nmlintip(2010-2013) vi mong mun cung cp mt ci nhn ton din v tt c bo co ADR lin quan n cc trng hp phn v. S lng bo co phn v tng t l thun vi tng s bo co ADR theo tng nm t 161 bo co (nm 2010) ln 231 bo co (nm 2011) v 330 bo co (nm 2012), n nm 2013 s lng tng gn gp i (580 bo co) v c xu hng tip tc tng trong nm 2014 [7]. Phn v do thuc l mt phn ng him gp tuy nhin t l cc bo co ny trong c s d liu lun cao (ch sau cc bo co v cc phn ng d ng trn da) v kh n nh dao ng t 9-11% tng s bo co nhn c. iunychothysquantmcbitcacccnbytnnhngphnng ny do mc nghim trng ca phn v trn lm sng. Phn v l mt phn ng d ng cp tnh, khi pht nhanh, hu ht cc bo co u xy ra trong vng 1 gi v c hn mt na bo co xy ra trong vng 10 pht saukhidngthuc.Do,chnonnhanhchngvchnhxccctrnghp phnvdatrnccbiuhinlmsngquytnhrtnhiuntnhtrngbnh nhn.TheotiuchunchnoncaVinQucgiavDngvBnhtruyn nhim Hoa K, phn v s c xc nh khi bnh nhn c biu hin c trng trn 2 trong 4 h c quan tun hon, tiu ho, h hp v da/nim mc. Nghin cu ca 39 chng ti cho thy, biu hin trn tun hon xy ra nhiu nht (84,3% bo co) sau n biu hin trn h hp (71,4% bo co) v trn da/nim mc (54,7% bo co), biu hin trn tiu ha t gp hn (ch chim 17,4%bo co phn v). Mt nghin cuhicuthchintincngchoktqukhtngng,mcdtl xut hin cc biu hin trn nghin cu ca chng ti thp hn mt cht v c th l giidotnhkhngythngtincabocoADR,vi98,15%trnghpc biu hin trn tun hon, 81,48% trn h hp, 72,2% trn da v 9,26% trn tiu ha [40].Ngoira,theotiuchuntrn,nubnhnhnbhhuytpnghimtrng ngaysau khi tip xc vi thuc th cng c xc nh l phn v.Trong bo co phnvchnmtnasbnhnhngpphitnhtrngny.Nhvy,theodi biu hin lm sng sau khi dng thuc l cn thit pht hin kp thi cc trng hp phn v. Phn v l mt phn ng d ng nguy him nht trn lm sng v c th gy t vong. c bit, khi bnh nhn c mt trong cc biu hin thiu oxy mu, h huyt pqumcvrilonthc(tngngviboconghimtrngmc1trong nghin cu) th tnh trng ca bnh nhn cng tr nn nguy kch. Theo kt qu ca chng ti th c ti 70,35% bo co phn v m c xp vo mc ny. Hn na trong nghin cu cng ghi nhn c 25 bo co t vong do phn v chim 2%, con s ny c th nh hn nhiu so vi thc t do cn b y t c xu hng ngn ngi khi bo co nhng trng hp t vong. Tuy vy, 25 bo co ny cng cho thy nhng hu qu rt ng tic ca phn v nu khng c d phng v x tr hp l. Kt qu t nghin cu cho thy phn v c th xy ra vi bt k thuc no, tuy nhincnhngnhmthucctnsutcaongch,baogm:khngkhun nhm cephalosporin v carbapenem, khng khun nhm penicillin, thuc gim au trung ng, cc NSAIDs,cht cn quang, ch phm thay th mu v m bo ti mu, thuc gy m/gy t. Kt qu ny kh tng ng vi kt qu ca mt nghin cugnythchintiBoNhatrnhthngCnhbophnvqucgia trong4nm(2007-2010).Theo4nhmthucbnghingnhiunhtl 40 NSAIDs, khng khun nhm penicillin, khng khun nhm cephalosporin v thuc gym/gyt[18].Ngoira,ccnhmctnsutgyphnvcaotrongcc nghin cu khc bao gm thuc chng ung th v tc nhn iu ho min dch, cht cnquang,ccchphmhormontcdngtonthn[44],[62].Tnsutboco mc d cung cp c mt hnh nh kh tng qut v thuc nghi ng trong cc bo cophnv,tuynhinktqunychunhhngnhiubivicsdngthuc ca bnh nhn. Do , nhm a ra mt kt qu c th gi v mi quan h nhn qu gia thuc nghi ng v phn v, chng ti tnh t sut chnh bo co (ROR) ca cc thuc c bo co vi tn sut cao. Khng sinh l nguyn nhn gy phn v nhiu nht trong cc bo co ghi nhn ti Trung tm DI & ADR Quc gia. Trong nhmcephalosporinvcarbapenem (ch yu l khng sinh cephalosporin) chim t l cao hn (52,61% bo co) so vi nhmbeta-lactamhpenicillin(9,22%boco).iunykhcbitvinhiuy vn, khi m khng khun h penicillin lun c ghi nhn l thuc c t lphn v cao nht [18, 28, 40]. C l l do chnh l do xu hng s dng khng sinh thay i, nhm cephalosporin c dng ph bin hn i vi cc bnh c triu chng nng [5] trong khi penicillin c cnh bo v phn v qu nhiu nn cn b y t cnh gic hn khi dng.Nghincucngchothy3thucctnsutgyphnvcaonhtl cefotaxim(19,4%),ceftriaxon(9,9%),ceftazidim(8,9%)uthucnhmkhng khun cephalosporin. y cng l 3 thuc hnh thnh tn hiu vi phn v ngay t nm 2010, tn hiu phn v i vi cc thuc ny tuy khng mnh nhng lun c duytrnnm2013.Cefoperazonctnsutgyphnvnhiuth4vitl 3,8%viRORtngquaccnmvcshnhthnhtnhiuvonm2012v 2013. Ampicillin v benzylpenicillin l 2 khng sinh thuc nhm khng khun beta-lactam h penicillin hnh thnh tn hiu qua cc nm tuy nhin tn hiu 2 khng sinh ny u bin mt vo nm 2012 sau xut hin li nm 2013. 41 Ti Vit Nam, sau nhm khng sinh th NSAIDs cng l nhm thuc c s dngtngiphbin.TbocoADR,chngtithuc4,22%sboco phnvcthucnghingphnvlNSAIDs.Tuynhinconsnytngi thp so vi cc nghin cu trn th gii nh nghin cu trn d liu trung tm Cnh gic Dc Italia vo nm 2003 vi 12,2% bo co phn v lin quan ti NSAIDs [28]v47,9%nghincuticcTrungtmDngBoNhanm2013 [18]. iu ny c th gii thch do thi quen s dng khng sinh ti Vit Nam dn ti t l gp v bo co phn v nhm ny cao v vt tri hn so vi cc nhm thuc khc. Kt qu nghin cu cho thy diclofenac l thuc NSAID c tn sut gy phn v cao nht trong nhm dc l ny, ging nh kt qu nghin cu thu c ca Puijenbroek nm 2002 [60],v nghin cu ca Patel ti n nm 2014 [40]. Tuy nhin khc vi cc nghin cu trn, diclofenac khng hnh thnh tn hiu phn v (ROR = 0,68 [0,49-0,94] nm 2013). Thucgyt,gymcnglnhmthuccbocovislngnhiu vi 2,38% boco phn v vc s hnh thnh tn hiu vi lidocain t nm 2011 n nm 2013. Tuy nhin, trong qu trnh gy t, gy m, thng thng phi hp nhiu thuc cngmtlc nhpropofol, fetanyl, atracurium... Do , khxc nh chnh xc nguyn nhn gyphn v, iu nyc th lm tng s bo cophn v lin quan ti cc thuc ny trong nghin cu vnh hng ti tn hiu. Thm vo ,sbocophnvcanhngthuctrongnhmnyuthn10docn mt c s d liu ln hn tip tc nh gi. Chng ti cng tham kho kt qu t ccnghincuvphnvvithucgymtrnthgii,ktquchothycha pht hin tn hiu phn v m ch thng k c nhng thuc c tn sut gy phn vcaonhttrongqutrnhgymlthuccchdntruynthnkinhcv khng sinh [29, 32, 65]. i vi nhm vaccin/huyt thanh chng ti nhn thy huyt thanh chng un vn (SAT) c tn sut gy phn v cao nht, huyt thanh khng nc rn cc loi v 42 vaccin cng c bo co phn v nhng u khng hnh thnh tn hiu. Tuy nhin, ring vi nhm vaccin, bn cnh h thng bo co t nguyn, cn c mt h thng bo co tai bin nng sau tim chng hot ng hon ton c lp. Vic khng kt nicdliugia haingunthngtinnycnggynhhngnvicnh gi ca cc thuc t d liu bo co ADR [2]. Mtktqungchlshnhthnhtnhiuvichymotrypsinvacid tranexamic t nm 2010 n 2013, trong acid tranexamic c ROR rt ln (11,83 [4,47-31,4]) mc d chng ti khng tm thy nghin cu no lin quan n phn v cahaithucny,trmtsnghincucanlhocmtvicaphnvvi chymotrypsin. Nguyn nhn c th do y l hai hot cht c s dng kh thng xuyntiVitNamnhngkhngcsdngrngritrnthgii.Theocs d liuca T chc Y tTh gii vPhn ng c hi (Vigibase)t nm 2010 ti nm 2014 c 105 bo co v chymotrypsintrong c27 bo co phn v v 795 bo co v acid tranexamic vi 17 bo co phn v [67]. Tn hiu ny cho thy c nguy c tim n vi phn v i vi 2 thuc ny, v vy cn b y t cn cn nhc vthntrngkhisdng.VicphthincnhngtnhiuvinhngADRt hoc cha c bit ti c ngha rt ln vi Cnh gic dc, tuy nhin cng phi lu rng trong giai on 2010-2013 s lng bo co case v non case lin quan ti acid tranexamic cn t (10 bo co case v 7 bo co non-case). Ngoi ra, c th do tnh cht nghim trng ca phn v trn lm sng nn cc cn b y t ch trng lm t l bo co case tng cao hn thc t. Do , vi cc tn hiu xut hin th cntiptcnhgitrongnhnggiaiontiptheo.Slngbocotngln cngngnghavivicphnnhchnhxchnthctlmsngvnkhitn hiu mnh, s l c s cho vic tin hnh nhng nghin cu dch t su hn kim chng cc tn hiu hnh thnh. Dphnglbinphpquantrngnhmgimthiucctaibin,tvongdo phn v gy ra. Vi mc ch ny, B Y t yu cu tt c cc thy thuc ti cc c s khm cha bnh trong c nc phi khai thc trit tin s d ng ca bnh 43 nhn [3]. Tuy nhin thng tin thu c t bo co phn v li cho thy ch c 749 bo co (chim73,5 %) bc s c khai thc. Khai thc tin s d ng c vai tr rt quan trong trong vic d phng d ng thuc v qua tin s d ng c th xc nh cthuchocnhmthucgydngchobnhnhn.Thngthdngthuc ln sau s nng hn ln trc nu tip xc li vi thuc gy d ng v ring vi scphnv,dngnhkhngthcgililuhn[4].Do,bYtcng arahngdnkhngcdngccthucgydngvphnvchobnh nhn.Trong hp c bit cn dng cc thuc ny th phi hi chn thng nht ch nhvcsngcangibnh,gianhngibnhbngvnbnvc binphptchccphngngaphnv[3].Nhngtheoktquchngtighi nhn c t 749 bo co trn c 18 trng hp bnh nhn b phn v khi dng li thuc tng gy d ng v 17 trng hp gp phn v khi dng li thuc cng nhm (cng nhm beta-lactam hoc NSAIDs) vi thuc gy d ng. c bit, c 2 bnhnhn bphn v khi dng ceftriaxone vSAT v litip tc b phnv khitisdng.Phnvtuylphnngdngkhdonnhngtrongnhiu trnghpvncthphngtrnhcnutmhiuktinsdngcabnh nhn nhng trn thc t, cn b y t vn cha ch trng n iu ny. Hnna,ktqutnghincunyvnhiunghincukhcchothy phn v c th xy ra vi tt c cc thuc mi ng dng (ngay c khi th test) [28]vcthgptrncnamvnvvimilatuibaogmcmtsi tng c bit nh tr nh v ngi cao tui [34], [40]. Do , ti cc c s iu tr, lunphicsnmthpthucchngphnvtrongkhiiutrchobnhnhn. Bn cnh , cc bc s, y t (iu dng), n h sinh u cn nm vng kin thc v thc hnh cp cu phn v. D phng gip bnh nhn phng trnh phn v nhng mt khi xy ra phn v th vic x l nhanh chng hp l l vic quan trng nht gip bnh nhn thot khi tnh trng nguy him, e da tnh mng. Thng tin t bo co cho thy, vic x 44 trcctrnghpphnvlsphihpcanhiubinphpbaogm:sdng adrenalin, th oxy hoc thng kh nhn to, truyn dch, s dng corticoid v thuc khnghistamin.Trong,adrenalinccoilthuccbnvkhngcchng ch nh tuyt itrong phn v.Adrenalin c th lm thay i ngaytc khc cc du hiu nng nh co tht ph qun v tt huyt p gip bnh nhn thot khi tnh trng nguy kch. Tuy nhin theo kt qu chng ti ghi nhn c th ch c gn 60% bnh nhn c x tr bng adrenalin mc d t l ny c xu hng tng t 39,75% trong nm 2010 ln 66,84% trong nm 2013. Mt nghin cu trn c s d liu v Cnh gic dc ti Php cng cho thy ch c 57,9% trng hp phn v c s dng adrenalin [43]. Theo mt nghin cu khc ti H Lan th trn tng s 850 bo cocctrnghpphnvchc89boco(10%)csdngadrenalin[57]. Chngticngthamkhoktqutccnghincuthchinticcbnhvin, kt qu cho thy ch c 50% trng hp phn v mt bnh vin qun i ti Hoa K c dng adrenalin v ch c 20% cc bc s ti mt bnh vin New Zealand xtrngliuvngdngadrenalinkhicphnv[24],[55].iunycho thy mc d c m t y v r rng trong nhiu hng dn, nhng nhiu cn b y t vn khng x tr ng khi bnh nhn gp phn v. Nguyn nhn c th do cc cn b y t cha pht hin ra cc trng hp phn v, bn cnh l tm l e ngi cc tai bin khi s dng adrenalin. V vy gim thiu nhng hu qu ng ticlinquannphnvthvichngdnxtrngvkpthilrtquan trng. Hn ch ca nghin cu: Nghin cu thc hin hon ton trn h thng bo co ADR t nguyn nn khng th trnh khi nhng hn ch ca c s d liu ny. Hin tng bo co di mc thc t (under-reporting) khin nghin cu mi dng mc pht hin tn hiu lin quan n ADR, vic kim chng cc gi thit ny cn thc hin bng nhngnghin cu su hn. Bn cnh , cc vn lin quan n chtlngboco(bocothiuthngtin,thngtinkhngyhockhng 45 chnh xc v s thay i mu bo co qua cc nm) cng gy kh khn cho vic xc nh bo co phn v v phn tch cc c im trong bo co. V nghin cu vi phngphphicudliunnccsaisnhsaisdonhli,saisdophn loi nhm cng c th xy ra.Mc d cn tn ti nhiu hn ch nhng vi s gia tng nhanh chng v mt slng,hthngbocotnguynkhngnhcvaitrtrongthngk phn tch v nh gi hnh thnh tn hiu lin quan n ADR. Vi d liu bo co bn nm lin tip (2010-2013),nghin cu phthin c nhng kt qu ng ch vmi lin quan gia thuc v nguyc gy phn v.Bncnh , cng phnnophnnhcthctvvicphthin,dphngvxtrcctrng hpphnvticccskhmchabnh.Ktquthuccngchothyvic tng hp phn tch thng xuyn c s d liu ny l cn thit to c s cho vic xc nh nguy c v a ra nhng thay i trong qun l cng nh trong thc hnh lm sng hng n s dng thuc an ton. 46 KT LUN V XUT Kt lun Nghin cu phn tch c im v nh gi s hnh thnh tn hiu trn c sbo co phn ng c hi lin quan n cc trng hp phn v ghi nhn t h thngbocotnguyncaVitNamtronggiaiont2010n2013vghi nhn c nhng kt qu sau: V c im cc trng hp phn v ghi nhn t h thng bo co ADR ca Vit Nam giai on 2010 - 2013. -Slngbocophnvtngtheotngnm,tlbocophnvtrn tngsbocoADRcatngnmvngimcnnhvdaongtrong khong 8,9 - 10,9%. -Bnh nhn trong bo co bao gm mi la tui t tr nh di 1 thng cho nngicaotui(trn65tui).Strnghpphnvnchim55,4%v nhiu hn so vi nam. C 58,3% bnh nhn c khai thc tin s d ng, trong c 35 bnh nhn ctin s d ng vi thuc nghi ng hoc thuc cng nhm vi thuc nghi ng gy phn v. -Phn ng chyu xut hin trong vng 10 pht sau khi dng thuc (55,8% bo co). Thng gp nht l cc triu chng trn tun hon (84,3% bo co), h hp(71,4%),da/nimmc(54,7%),biuhintrntiuhatgphn(17,4%). S bo co c biu hin nghim trng mc 1 (mc cao nht) chim 70,4%. -6hdclhaygptrongccbocophnvbaogm:khngkhun cephalosporin v carbapenem (685 bo co, chim 52,61% tng s bo co phn v), khng khun penicillin (120 bo co, 9,22%), thuc gim au tc dng trn thn kinh trung ng (68 bo co, 5,22%), cc cht thay th mu v dch truyn (61boco,4,69%),NSAIDs(55boco,4,22%)vchtcnquang(51bo co, 3,92%). Cefotaxim, ceftriaxon, ceftazidim l 3 hot cht nghi ng nhiu nht vi tn sut gp trong bo co ln lt l 19,4%, 9,9% v 8,9%. 47 -Adrenalincsdngtrn57,9%trnghpphnv.Ngoiadrenalin, bnh nhn cng c x tr bng th oxy (42,8%), b dch tun hon (17,2%) s dngcorticoid(61,44%).Sauxtr,c25trnghptvong(1,92%),1056 trng hp hi phc khng li di chng (81%). V tn hiu ca cc trng hp phn v vi mt s thuc c th da trn c s d liu bo co ADR Cc thuc pht hin c tn hiu l: -Nhmkhngkhunbeta-lactamkhc:cefotaxim,ceftriaxon,ceftazidim, cefoperazon, cefalexin, cefadroxil -Nhm khng khun penicillin: ampicillin, benzylpenicillin -Nhm cht cn quang: iobitridol, iopromid, acid ioxitalamic -Cc thuc khc: khng sinh cloramphenicol, oxytocin, dch truyn acid amin Ngoi nhng thuc c ghi nhn nhiu v ADR lin quan n phn v trongccyvn,nghincucngthycshnhthnhtnhiuvi chymotrypsin v acid tranexamic. xut -nh k tng kt h thng bo co t nguyn, nh gi s hnh thnh tn hiu gia thuc v ADR. i vi cc ADR cha c ghi nhn nhiu nh phn v vi acid tranxenamic hoc chymotrypsin, cn thm d liu tip tc nh gi. Nu tn hiu mnh, cc nghin cu dch t su hn c th s cn thc hin kim nh gi thit. - Tng cng tp hun, o to cho cn b y t cc kin thc chuyn mn v pht hin x tr d phng phn v. Gio dc truyn thng v tm quan trng ca vic phthin chnh xc, d phng y , x tr ng theo hng dn ca BYttrnlmsng.Xydngmthngdnrrng,cpnht,phhp nhm gim thiu ti a tai bin do phn v ti cc c s khm cha bnh. TI LIU THAM KHO Ti liu ting Vit 1.BYt(2009),DcthQucGiaVitNam,NhxutbnYhc,pp 1198. 2.B Y t (2014), Quyt nh s 1830/Q-BYT v vic ban hnh "Hng dn gimst,iutra,phntch,nhginguynnhnphnngsautim chng". 3.B Y t (1999), Hng dn phng v cp cu sc phn v. 4.Nguyn Vn on (2011), D ng thuc, NXB Y hc, pp. 162-169. 5.NhmNghincuQucgiacaGARP-VitNam(2010),Phntchthc trng: S dng khng sinh v khng khng sinh Vit Nam, p. 26-28. 6.Trn Thu Thu (2014), Sc phn v lin quan n ceftazidim, Bn tin Cnh gic Dc. 7.Trung tm DI & ADR Quc gia (2015), Tng kt cng tc bo co phn ng c hi ca thuc (ADR) nm 2014. 8.TrungtmDI&ADRQucgia(2013),Tngktcngtcbocophn ng c hi ca thuc (ADR) nm 2012. 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