B Y TTRNG I HC DC H NI NGUYN TH THU H NH GI TNH HNH S DNG COLISTIN TI KHOA HI SC TCH CCBNH VIN BCH MAI KHA LUN TT NGHIP DC S H NI - 2013 B Y T TRNG I HC DC H NI NGUYN TH THU H NH GI TNH HNH S DNG COLISTIN TI KHOA HI SC TCH CCBNH VIN BCH MAI KHA LUN TT NGHIP DC S Ngi hng dn: 1. TS. L Th Dim Tuyt 2. ThS. Nguyn T Sn Ni thc hin: 1.BmnDclmsngihc Dc H Ni 2. Khoa Hi sc tch cc BV Bch Mai H NI 2013 LI CM N Trc tin, ti xin gi li cm n chn thnh v su sc ti: -TS. L Th Dim Tuyt Khoa Hi sc tch cc, Bnh vin Bch Mai. -Ths. Nguyn T Sn B mn Dc lm sng, Trng i hc Dc H Ni. L nhng thy c tn tnh hng dn v gip ti trong sut qu trnh thc hin kha lun ny. Ti xin cm n Bnh vin Bch Mai, c th l Phng K hoch Tng hp, khoa Hi sc tch cc,khoa Dc v Phng Lu tr bnh n Bnh vin Bch Mai to iu kin ti c th thc hin kha lun ny. Ti cng xin gi li cm n ti Ban gim hiu, cc Phng ban Trng i hc Dc H Ni cng ton th cc thy c gio trong trng cho ti nhng kin thc qu bu trong qu trnh hc tp ti trng. Cui cng, ti xin gi li cm n su sc ti gia nh v bn b lun bn cnh, ng vin ti trong lc kh khn cng nh trong qu trnh thc hin kha lun ny. H Ni, ngy 22 thng 5 nm 2013 Sinh vin Nguyn Th Thu H MC LC T VN ....................................................................................................1 Chng 1. TNG QUAN..................................................................................3 1.1. Tng quan khng sinh colistin ........................................................................3 1.1.1. Lch s ra i v s dng ...........................................................................3 1.1.2. Cu trc ha hc v dng bo ch............................................................... 4 1.1.3. c im dc ng hc ............................................................................5 1.1.4. c im dc lc hc............................................................................... 6 1.1.5. Phn ng bt li ca colistin.......................................................................8 1.1.6. Ch nh v chng ch nh.........................................................................9 1.1.7. Liu dng v ch liu........................................................................... 10 1.1.8. Phi hp thuc trong iu tr .................................................................... 12 1.1.10. Tng tc thuc...................................................................................... 17 1.2. Tng quan v nh gi s dng thuc.......................................................... 18 1.2.1. Khi nim, mc tiu, ngha.................................................................... 18 1.2.2. Phm vi p dng ca DUE/MUE.............................................................. 19 1.2.3. Cc bc thc hin quy trnh DUE/MUE................................................. 19 Chng 2. I TNG V PHNG PHP NGHIN CU.................. 21 2.1. i tng nghin cu .................................................................................... 21 2.1.1. Tiu chun la chn ................................................................................. 21 2.1.2. Tiu chun loi tr ................................................................................... 21 2.2. Phng php nghin cu .............................................................................. 21 2.2.1. Thit k nghin cu.................................................................................. 21 2.2.2. Phng php thu thp s liu.................................................................... 21 2.2.3. Ni dung nghin cu ................................................................................ 22 2.3. Phng php x l s liu............................................................................. 27 Chng 3. KT QU NGHIN CU........................................................... 28 A. KT QU KHO ST.............................................................................. 28 3.1.c im c bn ca nhm BN nghin cu................................................. 28 3.1.1.Phn b tui v gii tnh ca nhm BN .............................................. 28 3.1.2.Bnh mc km trn nhm BN.................................................................. 29 3.1.3.Can thip trn nhm BN.......................................................................... 31 3.1.4.Chc nng thn ca nhm BN................................................................. 33 3.1.5.Thi gian iu tr ti khoa ca nhm BN................................................. 34 3.2.c im bnh l NKBV v VK hc (trc khi dng colistin) lin quan n NKBV ca nhm BN nghin cu.................................................................. 34 3.2.1.Bnh l NKBV........................................................................................ 34 3.2.2.Vi khun hc (trc khi dng colistin) lin quan n NKBV................... 37 3.3.c im s dng khng sinh ca nhm BN nghin cu ........................... 40 3.3.1.Cc khng sinh c ch nh trc colistin ............................................ 40 3.3.2.Cc khng sinh phi hp cng colistin trong phc iu tr .................. 43 3.3.3.Mi tng quan gia ch nh ca colistin vi bnh l NKBV v VK hc........................................................................................................................... 45 3.3.4.Thi gian s dng colistin ....................................................................... 49 3.3.6.Pha ch thuc, ng dng, thi gian truyn tng liu/ngy ca colistin . 52 3.4.Mt s gim st trong qu trnh s dng colistin........................................ 55 3.4.1.Gim st vi sinh....................................................................................... 55 3.4.2.Gim st chc nng thn.......................................................................... 58 3.4.3.Gim st ADE ......................................................................................... 60 B. KT QU NHGI.............................................................................. 60 3.5. nh gi ch nh colistin.............................................................................. 60 3.6.nh gi s phi hp thuc ......................................................................... 61 3.7.nh gi liu dng, ch liu .................................................................... 61 3.8.nh gi pha ch thuc, ng dng, thi gian truyn tng liu/ngy ..... 63 3.9.nh gi vic gim st vi sinh trong qu trnh dng thuc........................ 64 Chng 4. BN LUN................................................................................... 65 4.1. Ch nh iu tr ca colistin......................................................................... 65 4.2. S phi hp thuc vi colistin....................................................................... 68 4.3. Liu dng ....................................................................................................... 70 4.4. Gim st trong qu trnh iu tr ................................................................. 71 KT LUN V XUT............................................................................. 72 TI LIU THAM KHO PH LC Ph lc 1: PHIU THU THP THNG TIN BNH NHN BNH VINBCH MAI Ph lc 2: HNG DN S DNG COLYMYCINE 1.000.000 UI Ph lc 3: TIU CHUN CHN ON NHIM KHUN BNH VIN Ph lc 4: DANH SCH BNH NHN TRONG NGHIN CU DANH MC BNG Bng 1. 1: Hiu qu hip ng ca vic phi hp polymycin vi cc khng sinh khc15 Bng 2. 1: Phn loi chc nng thn theo Clcr............................................................ 23 Bng 3. 1: T l phn b theo tui v gii tnh ca nhm BN (n = s BN) ................. 28 Bng 3. 2: T l phn b s loi bnh mc km trn mi BN...................................... 29 Bng 3. 3: T l phn b cc loi bnh mc km trn nhm BN................................. 30 Bng 3. 4: T l phn b s lng can thip trn mi BN........................................... 31 Bng 3. 5: T l cc loi can thip trn nhm BN....................................................... 32 Bng 3. 6: T l phn b loi chc nng thn ca nhm BN....................................... 33 Bng 3. 7: Thi gian iu tr ti khoa ICU ca nhm BN............................................ 34 Bng 3. 8: T l phn b s NKBV trn mi BN........................................................ 35 Bng 3. 9: T l phn b cc loi NKBV trn nhm BN............................................. 35 Bng 3. 10: T l phn b ni xut pht NKBV ......................................................... 36 Bng 3. 11: T l phn b s VK phn lp c trn mi BN .................................... 38 Bng 3. 12: T l phn b cc loi VK phn lp c trn nhm BN......................... 38 Bng 3. 13: nhy cm ca VK phn lp trc khi dng colistin i vi thuc....... 40 Bng 3. 14: Cc khng sinh c ch nh trc colistin ............................................ 41 Bng 3. 15: S phi hp khng sinh vi colistin......................................................... 43 Bng 3. 16: Mi tng quan gia vic C colistin v thi im chn on NKBV.... 45 Bng 3. 17: Mi tng quan gia vic C colistin v vi sinh ..................................... 46 Bng 3. 18: Mi tng quan gia vic C colistin v kt qu nh danh VK ............. 47 Bng 3. 19: Mi tng quan gia vic C colistin v kt qu KS ca VK............... 48 Bng 3. 20: Thi gian s dng colistin ....................................................................... 49 Bng 3. 21: Kho st liu dng ban u ca colistin (n = s lt BN)......................... 51 Bng 3. 22: Kho st ch liu duy tr ban u ca colistin c phn loi Clcr .......... 52 Bng 3. 23: Kho st dung dch pha ch Colymycine ................................................. 52 Bng 3. 24: Kho st th tch pha 1 l Colimycine 1 MUI .......................................... 53 Bng 3. 25: Kho st ng dng ch liu duy tr ca colistin............................... 54 Bng 3. 26: Kho st thi gian truyn tng liu/ngy ca colistin............................... 55 Bng 3. 27: Cc loi vi khun phn lp c trong qu trnh s dng colistin ............ 56 Bng 3. 28: nhy cm ca VK phn lp trong qu trnh dng colistin i vi thuc................................................................................................................................... 58 Bng 3. 29: Kho st mc thng xuyn ca vic gim st creatinin ..................... 59 Bng 3. 30: T l phn b cc loi can thip trn thn ca nhm BN.......................... 60 Bng 3. 31: nh gi ch nh ca colistin.................................................................. 61 Bng 3. 32: nh gi liu dng ca colistin (n = s lt BN) ..................................... 61 Bng 3. 33: nh gi ch liu duy tr ca colistin (n = s lt BN)........................ 62 Bng 3. 34: nh gipha ch thuc, ng dng, thi gian truyn tng liu/ngy .... 63 Bng 4. 1: La chn iu tr phi hp hin nay cho A. baumannii a khng..67 DANH MC HNH Hnh 1. 1: Cu trc ha hc ca colistin .......................................................................4 Hnh 1. 2: Chuyn ha v thi tr colistimethate v colistin .........................................6 Hnh 1. 3: Hiu qu hip ng ca vic phi hp polymyxin vi cc thuc khc trong mt s nghin cu ........................................................Error! Bookmark not defined. DANH MC CH VIT TT ADEBin c bt li ca thuc (Adverse Drug Event) BNBnh nhn CchNng ch ti trng thi cn bng trong mu (average steady state plasma concentration) CCh nh Clcr thanh thi creatinin CMS CIIG/CIIIG Colistimethasulphonate Cephalosporin th h II/III DUE/MUEnh gi s dng thuc/nh gi s dng dc phm ICUKhoa Hi sc tch cc (Intensive Unit Care) KSKhng sinh KS Khng sinh MICNng c ch vi khun ti thiu MDRa khng thuc NK/NKBVNhim khun/Nhim khun bnh vin VKVi khun 1 T VN KtkhiAlexandreFlemingphthinraPenicilinvonm1928,viciutr nhim khun tri qua mt chng ng di.Ngy nay c tnh c tng cng hn 100 hot cht c s dng nh nhngvkh chng li VK. Tuy vy, chin thng cn bnhnhimkhunvncnliuthcskhkhn.NhiuloiKScsdng trong qu kh hin nay tr nn tht bi do nhng cch thc khng khng sinh xut hin vi khun. S xut hin ca nhng chng VK gram m a khng cng vi l vic cha cthmnhngKSmidnnsuynghcnphicnhngcchthcmichocuc chin chng limi e da ny. Mt cch thc hin iuny l nhn li nhng loi khng sinh c khng c s dng trong mt thi gian di. Colistin, c pht hin vo nm 1949 v s dng rng ri trn ton cu trong thuc nc nh tai, nh mt v thuc tim tnh mch iu tr cc bnh nhim trng gy ra bi trc khun Gram (-) trong nhiu thp k cho n thp nin 80 l mt thuc trong s ny[44]. ColistincbnhvinBchMaichnhthcavoiutrtthng 08/2011.Nm 2012, mt ti kho st thc trng s dng colistin trn ton bnh vin ctinhnh.Ktqukhostchothyskhngthngnhtvchnh,liu dngcngnhvntheodiiutr[7].Do,Hngdnsdngkhngsinh Colimycin1.000.000UIcabnhvinBchMaichnhthccbanhnhvo ngy 20/03/2012 vi mc ch a ra nhng khuyn co cn thit cho cc nhn vin y ttrongthchnhlmsng.Saumtnmtrinkhai,victhchinHngdnny nhthno,gialthuytvthctluncmtkhongcchnhtnhnhng khong cch y ang tn ti ra sao, mc no v l do dn n s tn ti ca n, c l cn thit phi c s kho st, so snh v nhng nh gi s b. 2 Xut pht t l do , chng ti tin hnh thc hin ti: nh gi tnh hnh s dng colistin ti Khoa Hi sc tch cc (ICU), Bnhvin Bch Mai. Vi cc mc tiu: 1.Kho st c im bnh nhn v bnh l nhim khun trn bnh nhnc chnh colistin ti khoa Hi sc tch cc, Bnh vin Bch Mai. 2. Kho st tnh hnh s dng colistin ti khoa. 3. nh gi vic s dng colistin theo Hng dn s dng colistin ca bnh vin. 3 Chng 1. TNG QUAN 1.1.Tng quan khng sinh colistin 1.1.1.Lch s ra i v s dng Colistin thuc nhm KS polymyxin.Nhm KS ny gm nhiu loi khc nhau, A Elnhngloictmthy.TrongsnychcpolymyxinBvpolymyxinE (colistin sulphate/colistimethate sodium) l c ngha trn lm sng. Colistin(polymyixinE)lmthnhpccchuipolypeptidecolistinAvB, cphnlplnutintiNhtBnvonm1949tslnmencaBacillus polymyxavar.colistinusccchngvikhuntmthytrongmutcatnh Fukushima[44]. Ktkhibtucavosdngtrnlmsngnm1959,colistinc dngtimbpiutrccnhimkhundoVKgrammgyranhngdndn thucbthaythbiKSaminoglycosiddonhngtcdngkhngmongmunca n bao gm c c tnh trn thn v thn kinh. Kt qu l vic s dng colistin gim t u nhng nm 1970 n u nhng nm 2000[14, 44]. Gn y c mt s gia tng ln cc bnh nhim trng do VK Gram (-) a khng thuc(multidrug-resistantMDR)gyra,cbitlPseudomonasaerugginosa, Acinetobacter baumannii v Klebsiella pneumonia. Cng vi , nhng pht hin lm sng gn y v hot ng, c tnh dc ng, s dng trn lm sng, s gia tng khng,ctnhvvicphihpthuccacolistincxemxt.Trninvitro, colistin chng minh tc dng rt tt vi nhiu loi trc khun Gram (-) bao gm c nhng VK k trn. Xu hng s dng KS ny trn lm sng ngy cng tng ln trong thp k va qua.C th rng colistin s l la chn iu tr cui cng chng li cc mi nguy him ny trong th k 21 [14, 46].4 1.1.2.Cu trc ha hc v dng bo ch 1.1.2.1. Cu trc ha hc Cu trc ha hc[22]: Hnh 1.1:Cu trc ha hc ca colistin 1.1.2.2.Dng bo ch Ccdnchtcacolistincdnglmthuctrnlmsnghinclcolistin sulfat v colistin natri methansulfonat (hay colistimethate sodium - CMS)[14]. Cc dng bo ch ca colistin sulfat gm: - Vin nn: 1.500.000 UI ( tng ng 50mg colistin base).- Siro: 250.000 UI/5ml. - Thuc dng ti ch: thuc nc nh tai, nh mt; thuc m tra mt. Dng bo ch ca CMS: thuc tim dng bt500.000 UI/l (tng ng 40mg colistinnatrimethansulfonathoc16,66mgcolistinbase);1.000.000UI/l(tng ng 80mg colistin natri methasulfonat hoc 33,33mg colistin base)[5]. C hai dng colistin sulfat v CMS u c th s dng theo ng kh dung [22]. 5 1.1.3.c im dc ng hc 1.1.3.1. Hp thu ColistinsulfatvCMShpthurtkmngtiuha(chkhong0,5%)v khng c hp thu qua da lnh. Tim bp CMS tng ng 150 mg colistint Cpeaktrung bnh 5 7,5 g/ml v nng hot tnh khng khun trong huyt thanh c th pht hin 12 gi sau khi dng. ng tnh mch: CMS tng ng 5 7 mg/kg colistin/ngy chia 3 liu (ti a 70 100 mg 8 gi 1 ln) bnh nhn x nang 14 53 tui t Cpeak trung bnh l 21,4 g/ml sau liu u v 23 g/ml trng thi cn bng. Ctrough trung bnh sau 8 gi l 2,8 g/ml sau liu u v 4,5 g/ml trng thi cn bng. Cpeak ng tnh mch cao hn nhng gim nhanh hn so vi tim bp. Kh dung ng ming: CMS tng ng 66,66 mg colistin base (2 triu IU) bnh nhn x nang 12 48 tui c Cpeak l 0,17 g/ml v duy tr trong 1,5 gi[5, 22] 1.1.3.2. Phn b Sau khi tim bp hoc tnh mch, CMS phn b rng khp cc m ca c th nh gan, thn, phi, tim v c (colistin lin kt thun nghch v tn ti ko di trong cc m nhng CMS th khng gn kt). Tuy nhin, thuc ch t c nng khng ng k trong dch khp, dch mng phi hoc dch ngoi mng tim. Tng t nh vy vi ch mt nng nh t c trong dch no ty khi tim bp hoc tnh mch CMS bnh nhn bnh thng hoc vim mng no.Thuc c th i qua nhau thai, do ch nn s dngcolistintrongthikmangthaikhimlich,timnngvttrisovinguy hicthcivithainhi.Tllinktviproteinhuyttngcacolistintrn 50% cn CMS th thp hn[5, 22, 34]. 1.1.3.3. Chuyn ha v thi tr CMS l mt tin cht khng hot ng ca colistin, N b thy phn sau khi tim 6 tnh mch gii phng dng colistin hot ng[14]. Khi dng ng ung, thuc o thi qua phn di dng khng i. Thi gian bn thi trong huyt tng sau khi dng CMS tim bp hoc tnh mch ngitrngthnhchcnngthnbnhthngl1,58givnhanhhntrem. Trongvng24gi,trungbnhcthti80%liuthuctimxut hintrongnc tiu.i viBN suy thn, nng thuc trong huyt thanh cao hn v thi gian bn thi kodihn.BnhnhncClcrdi20ml/pht,thigianbnthicolistinl1020 gi.Mt s bnh nhn v niu, thi gian bn thi l 2 3 ngy. DngCMSothichyunhqutrnhlccuthndidngkhngi hoc dng chuyn ha.Colistin to thnh hu nh khng thi tr qua thn ( 10 ml/pht: chia 2 3 ln/ngy Pha ch thuc Dung dch pha ch: NaCl 0,9% Thtchphach:50ml/1lColymycine1 MUI ng dngTruyn tnh mch ngt qung Thigiantruyn tng liu/ngy Tng thi gian: 30 pht 2 gi 27 Gim st vi sinh BNclymubnhphmnuicynh danh VK. Nu bnh phm dng tnh cn xc nh li nhy cm ca KS da theo kt qu KS Ch thch: (*)=NKBVcaBNccncvochnoncabcsghitrongbnhn. Ngoi ra chng ti cng ghi nhn li cc du hiu trn thc t lm sng ca BN v so snh vi tiu chun chn on NKBV (Ph lc 3) [3].(**) = Khng trn lm sng c ngha l trc ch nh colistin, trong cc phc trc BN c dng 3 loi KS (-lactam, aminosid, quinolon) nhng trn thc t lmsngccduhiunhimtrngcaBNvnkhngccithinsauqutrnh dng thuc. 2.3. Phng php x l s liu S dng phn mm SPSS 16.0 thng k v phn tch s liu. 28 Chng 3.KT QU NGHIN CU Nghin cu tin hnh kho st, nh gi 137 bnh n ca nhng BN iu tr ti khoaICUtrongkhongthigiant20/03/2012n20/03/2013thuctiuchunla chn v thu c nhng kt qu nh sau: A. KT QU KHO ST 3.1. c im c bn ca nhm BN nghin cu 3.1.1.Phn b tui v gii tnh ca nhm BN Tui vgii tnh lmt trong nhngc im c bnkhi nghin cu trnmt nhm i tng. Tui cng l cn c tnh Clcr v liu dng khuyn co trn BN ca nhng ch tiu v sau. Nghin cu tin hnh kho stmt s c imv tui vgii tnh ca nhm BN vi t l phn b c th hin qua qua bng 3.1. Bng 3.1:T l phn b theo tui v gii tnh ca nhm BN (n = s BN) NamNTng (trung bnh) Ch tiu n%n%n% 10 - 2021,432,253,6 21 40128,7139,52518,2 41 603324,11611,74935,8 61 - 803525,61712,45238,0 Tui > 8021,542,964,4 tui trung bnh58,2 16,953,7 20,556,4 18,5 Gii tnh8461,35338,7137100,0 Nhn xt:29 TngsBNnghincul137ngigm84nam(61,3%)v53n(38,7%). Khong phn b tui tng i rng vi BN nh tui nht l 18 tui v BN ln tui nht l 90 tui.Nhm BN c khong tui t 41 60 chim t l gn tng ng nhm BNckhongtuit6180vlhainhmtuichimphnlntrongnghincu (ln lt l 35,8% v 38%). tui trung bnh ca nhm BN l 56,4 18,5. Tui gi l mttrongnhngyutnguyclinquantinhiuloiNKBVthnggptikhoa ICU,nhtltui>60[28].NhmBNnychimtlkhcaotrongnghincu (42,4%). Nghin cu cng ghi nhn c mt trng hp BN mang thai ti khoa. Tuy nhin, trong qu trnh iu tr BN b sy thai v tnh trng bnh l qu nng. 3.1.2.Bnh mc km trn nhm BN Bnhmckm ca BN c xc nh l nhng bnh l cghi trong bnh n khng thuc bnh l NKBV. Bnh mc km c th l mt trong nhng yu t lm tng nguy c NKBV BN do thng quavickho st bnhmckm c thgip nhn nh loi NKBV tt hn. 3.1.2.1.S loi bnh mc km trn mi BN Nhngbnhmckmtrncngmtcquancxpvocngmtloibnh mc km.T l phn b s loi bnh mc km trn mi BN c th hin qua bng 3.2. Bng 3.2:T l phn b s loi bnh mc km trn mi BN S loi bnh mc kmS bnh nhnT l (%) 16144,6 25540,1 31712,4 442,9 Tng137100,0 S bnh mc km trung bnh1,7 0,8 30 Nhn xt:Khoa ICU l mt khoa rt c th v BN iu tr khi phn ln BN vo khoa u tri qua qu trnh iu tr bnh nhng khoa khc hoc t nhng ni khc n vi dinbinnhngbnhttrcnngln.CcBNcngthngmcmtlcnhiu bnhtrnnhiucquankhcnhau.Nghincughinhnc100%sBNc khostucbnhmckm,trongchimtllnnhtlmc1loibnh (44,6%) v mc 2 loi bnh (40,1%) v c 2,9% s BN mc ti 4 loi bnh mc km. 3.1.2.2.Cc loi bnh mc km trn nhm BN Cc loi bnhmckm c phn loi theo nhm c quan.Bnh l nhim trng c xp ring mt loi, tch ring vi NKBV. Cc loi bnh mc km khc c xc nh gm bng xng, Guillain Barr, hi chng Raynaud, a chn thng, hn m sau ngng tun hon, cc bin chng nng trong qu trnh iu tr gm sc nhim khun v suyatng.TlphnbccloibnhmckmtrnnhmBNcthhinqua bng 3.3. Bng 3.3:T l phn b cc loi bnh mc km trn nhm BN Loi bnh mc kmS lt bnh nhnT l (%) Bnh l chuyn ha145,9 Bnh l c xng khp41,7 Bnh l h hp2811,8 Bnh l huyt hc62,5 Bnh l no208,4 Bnh l thn tit niu187,6 Bnh l thn kinh20,8 Bnh l tiu ha3012,6 Bnh l tim mch3715,5 31 Bnh l ung bu t min104,2 Bnh l nhim trng239,7 Khc4619,3 Tng238100,0 Nhn xt: Chimtlcaonhttrongccloibnhmckmlnhmbnhltimmch (15,5%). iu ny ph hp vi nhm BN > 60 tui trong nghin cu chim n 42,4%. Tip n l nhm bnhv tiuha (12,6%),h hp (11,8%). Cc loi bnhmckm cng chim 1 t l ln trong kho st (19,3%) v cc bin chng nh sc nhim khun v suy a tng gp kh thng xuyn trn nhm BN. 3.1.3.Can thip trn nhm BN Bn cnh bnh l mc km, cc can thip cng l mt trong nhng yu t nguy c gy NKBV trn BN. Can thip nhiu loi cng nh can thip nhiu ln c th lm tng nguy c mc NKBV.Cc loi can thip c tin hnh kho st l nhng yu t nguy c lin quan ch yu ti mt s NKBV thng gp ti khoa ICU: NK phi, NK huyt, NK tit niu sinh dc, NK lin quan n ng thng, NK bng, vim mng no.3.1.3.1.S lng can thip trn mi BN S lng can thip trn mi BN c th hin qua bng 3.4. Bng 3.4:T l phn b s lng can thip trn mi BN S lng can thipS bnh nhnT l (%) 042,9 1128,8 22316,8 33626,3 43122,6 32 51813,1 675,1 764,4 Tng137100,0 S can thip trung bnh3,4 1,6 Nhn xt: Hu ht cc BN nm khoa u c can thip (97,1%). Mt BN c th tip xc vi nhiuyutgynguycnhimkhun.SBNc3v4loicanthipchimnhiu nht(26,3%v22,6%).Nghincucngghinhnc6BN(4,4%)ccanthip cng lc 7 loi. 3.1.3.2. Cc loi can thip trn nhm BN T l cc loi can thip ghi nhn trn nhm BN c th hin qua bng 3.5. Bng 3.5:T l cc loi can thip trn nhm BN Loi can thipSBNT l (%) t ni kh qun m kh qun9468,6 Th my11382,5 Catheter tnh mch i5943,1 Catheter tnh mch trung tm6748,9 Catheter ng mch quay2216,1 Chc dn lu dch/ Chc d dch/Chc ht kh7151,8 Sonde tiu75,1 Khc3122,6 Nhn xt: 33 Loi can thip c s dng nhiu nht trn nhm BN l th my. C ti 113/137 BN thc hin chc nng h hp theo hnh thc ny. Can thip t nikh qunm khquncngcthchintrnphnlnBN(94/137).Chcdnlu/chcdcc dch(dchmngphi,dchmngno,dchbng)cnglmttrongnhngcan thip c tin hnh thng xuyn ti khoa vi mc ch thm d c im dch cng nh lymu bnh phm nh danh VK.Mt s can thipkhcghi nhn c nhm mng phi, soi ph qun cng c tin hnh trn 22,6% BN. 3.1.4.Chc nng thn ca nhm BN Kho st chc nng thn ca BN ngay trc khi dng colistin da vo gi tr Clcr caBN.GitrnycxcnhbngcngthcCockroftGault(mc2.2.3.1) thng qua cn tui, gii, cn nng v nng creatinin huyt thanh ca BN (gn nht ngay trc dng thuc). Trong 137 BN nghin cu c 64 BN (46,7%) khng ghi nhn ccnnngdokhngnhgicchcnngthn.Tlphnbloichc nng thn ca 73 BN xc nh c cn nng c th hin qua bng 3.6. Bng 3.6:T l phn b loi chc nng thn ca nhm BN Loi chc nng thn Clcr tng ng (ml/pht) S bnh nhnT l (%) Bnh thng 801723,3 Suy thn nh50 - 24 gi l 76 BN (66,1%). Trong s126 BN c sdng liu duy tr, sBN c s hiu chnh liu l 36 BN (28,6%). LiudngkhuyncoctnhtontheoHngdniutr,phthuccc thnh phn: tui, gii, cn nng, Clcr v Cch. (quy c theo gi tr MIC). Nghin cu ch tin hnh kho st v so snh liu dng ban u ca bnh nhn m khng kho st liu hiu chnh trong qu trnh iu tr v l do liu tnh ton ph thuc cn nng. c th BNkhoaICUl nhng BN nng, thigian nmkhoako dikhin th trng BN c th thay i theo 2 xu hng: th trng suy kit nhanh hoc vi mt khi lng dch truynlnthngxuyncavocthdnncnnngBNcththayi ngk.Chnhvvytnhtonliuskhngchnhxcnukhngccncvo cn nng thc t ngay ti thi im dng. Trong khi vic ghi nhn cn nng khng th tin hnh y v nhng l do khch quan. Do , vi vic ghi nhn c cn nng ngay trc dng thuc tng i chnh xc ca hn na s BN, chng ti ch tin hnh kho st liu dng ban u. SBNghinhnccnnnggnnhtvithiimdngthuctrong nghin cu l 73/137 BN.Tuy nhin, trong s 73 BN ny ch c 67 BN dng liu np v 67 BN dng liu duy tr. Do , nghin cu tin hnh kho st v so snh liu dng thctsoviliukhuyncoca67BNdngliunpv67BNdngliuduytr. Kt qu kho st liu dng ban u ca colistin c th hin qua bng 3.21. 51 Bng 3.21:Kho st liu dng ban u ca colistin (n = s lt BN) Liu npLiu duy trSo snh vi liu khuyn con%n% Thp hn1014,92334,3 Bng2943,31217,9 Cao hn2841,83247,8 Tng67100,067100,0 Nhn xt: Ktqukhostchothy,vichliunp,sBNcdngliutngt liukhuyncochimtllnnht(43,3%).Gitrliunptrungbnhl3,40,8 (l)vikhongdaongl16(l).Trongkhi,vichliuduytr,sBN dngliucaohnliukhuyncolichimtlcaonht(47,8%),chimtlthp nht(17,9%)lsBNdngliutngt.Gitrliuduytrtrungbnhl3,51,4 (l) vi khong dao ng cng tng t liu np (1 6 l). 3.3.5.2.Ch liu duy tr theo phn loi Clcr NghincutinhnhkhostchliuduytrcphnloiClcrtheonh Hng dn iu tr.Ch liu duy tr theo phn loi Clcr c kho st 73 BN c tnh ton c Clcr (tc c ghi nhn c cn nng) vi 2 BN c Clcr < 10 ml/pht v 71 BN c Clcr >10ml/pht.Trong71BNcClcr>10ml/pht,chghinhnc65BNcdng liu duy tr. Kt qu kho st c th hin qua bng 3.22. 52 Bng 3.22:Kho st ch liu duy tr ban u ca colistin c phn loi Clcr Clcr < 10 ml/phtClcr > 10 ml/pht T l (%)S bnh nhn Ch liu S bnh nhnT l (%) 1 ln/ngy46,2 100,022 ln/ngy2132,3 3 ln/ngy3553,8 4 ln/ngy34,6 5 ln/ngy23,1 100,02Tng65100,0 Nhn xt: C 2 BN ca nhm c Clcr < 10 ml/pht u dng ch 2 ln/ngy. Nhm BN c Clcr > 10 ml/pht c ch dng chim phn lnl chia tng liu thnh 3 ln/ngy (53,8%). Ch dng 2 ln/ngy cng cp dng ph bin trn nhm BN nyvi tl32,3%.Ccchliukhcchchim1tlnh(13,9%).Theo1skhuyn co, colistin nn dng vi ch 2 4 ln/ngy [22, 34]. 3.3.6.Pha ch thuc, ng dng, thi gian truyn tng liu/ngy ca colistin 3.3.6.1.Pha ch thuc Kt qu kho st cc loi dung dch pha ch thuc c th hin qua bng 3.23. Bng 3.23:Kho st dung dch pha ch Colymycine Loi dung dchS lt bnh nhnT l (%) NaCl 0,9%13593,7 Glucose 5 %96,3 Tng144100,0 53 Nhn xt: DungdchphachColymycineghinhnctrnnhmBNgm2loi,trong dungdchNaCl0,9%csdngchyu(93,7%),mtphnnh(3,6%)l dung dch Glucose 5%. Xttrntngs137BNnghincuthsBNdngthuccphachbng dungdchNaCl0,9%l135BN(98,5%),s cnlil2BNchdngthucphach bng Glucose 5% (1,5%). Nghincutinhnhkhostthtchphach1lColymycine1MUIvikt qu thu c th hin qua bng 3.24. Bng 3.24:Kho st th tch pha 1 l Colimycine 1 MUI Loi th tch (ml)S lt bnh nhnT l (%) 15010,4 1008535,0 7531,2 6020,8 506426,4 4031,2 25208,3 2020,8 Khc6325,9 Tng243100,0 Nhn xt: Bng3.24.chothy,huhtcclthuccsdngtrnnhmBNtrong nghin cu c phavi cc loi th tch chn l 50mlv 100ml (61,4%), trong chim t l nhiu nht l loi th tch 100 ml. Nhng loi th tch khc y bao gm: 500/4,5(1ltBN);200/4,5(1ltBN);250/4(2ltBN);200/3,5(1ltBN); 250/3 (1 lt BN); 200/3 (14 lt BN); 100/3 (40 lt BN); 50/3 (3 lt BN). 54 Xt trn tng s 137 BN nghin cu th s BN c Colymyxin pha 1 l trong th tch 50 ml dung dch l 64 BN (46,7%), s cn li khng pha theo th tch ny chim s lng nhiu hn l 73 BN (53,3%) 3.3.6.2.ng dng Chliunp:nghincughinhnc126BNdngngtruyntnh mch/126 BN c s dng liu np. Ch liu duy tr: kho st ng dng ca 126 BN c s dng liu duy tr. Kt qu ca kho st c th hin qua bng 3.25. Bng 3.25:Kho st ng dng ch liu duy tr ca colistin ng dngS lt bnh nhnT l (%) Truyn tnh mch ngt qung12293,1 Truyn tnh mch mt ln53,8 Bm tim in duy tr32,3 Kh dung10,8 Tng131100,0 Nhn xt: ngtruyn tnhmch ngt qung l con ng a thuc ch yuvi 93,1% lt BN c s dng. Bn cnh l 3 ng truyn khc cng c ghi nhn trong nghin cu: truyn tnh mch tng liu 1 ln/ngy, bm tim in lin tc 6,5 ml/h v kh dung qua camun kh qun. Bng kt qu cng cho thy, trong s 126 BN c s dng liu duy tr, s BN dng ng truyn tnh mch ngt qung l 122 BN (96,8%), s BN khng dng thuc theo con ng ny l 4 BN (3,2%). Khostngdngtrntngs137BNnghincu,vitiuchcsdng ng truyn tnh mch ngt qung (vi liu np: truyn tnh mch 1 ln) cho kt qu 55 s BN tha mn tiu ch l 131 BN (95,6%). S cn li khng c a thuc theo con ngnyl6BN(4,4%).ylnhngBNsdngngthi2loiliu,viliu np l ng truyn tnh mch nhng vi liu duy tr l con ng khc. 3.3.6.3.Thi gian truyn tng liu/ngy Ktqukhostthigiantruyntngliu/ngycacolistincthhinqua bng 3.26. Bng 3.26:Kho st thi gian truyn tng liu/ngy ca colistin Tng thi gian truynS lt bnh nhnT l (%) 30 pht 2 gi11455,6 > 2 gi9144,4 Tng205100,0 Nhn xt: Phn nhiu BN c truyn tng liu/ngy trong khong thi gian t 30 pht 2 gi (55,6%). Bn cnh , cc thi gian truyn tng liu khc cng chim 1 t l khng nh (44,4%) vkh a dng: 2,5 gi; 3 gi; 5 githm ch c nhng trng hp BN c truyn tng liu trong vng 10 gi. Bngktqucngchothy,trongtngs137BNnghincuth114BN (83,2%)c tng thi gian truyn trong vng 30 pht 2 gi, s cn li 23 BN (16,8%) khng truyn thuc trong khong thi gian ny. 3.4.Mt s gim st trong qu trnh s dng colistin 3.4.1.Gim st vi sinh Vic gim stvi sinh trong qu trnh iu tr c ngha l BN c ly mu bnh phm nui cy nh danhvikhun, xc nh li nhy cm ca VK i vi KS da 56 trn kt qu KS. Nh vy, trng hp BN c bnh phm cy dng tnh th VK phi c lm KS mi xt l c gim st vi sinh. SBNclymubnhphmtrongqutrnhdngthucl71/137BN (51,8%) bao gm 34 BN ch c bnh phm cy ra m tnh, 37 BN c bnh phm cy ra dngtnh(cthkm/khngkmbnhphmmtnh).TrongsBNcbnhphm cy ra dng tnh, c 4 bnh nhn c VK cy ra khng c lm KS. Nhvy, s BN cghi nhn cgim stvi sinh trong qutrnh iu tr l 67 BN (48,9%). 3.4.1.1.Cc loi vi khun phn lp c Kho st 71 BN c lymu bnh phm trong qu trnh iu tr thu c tng s 83 mu bnh phm, em nui cy phn lp li VK cho kt qu l 49 mu dng tnh (59,0%)v34mumtnh(41,0%).TngsVKcnhdanht49mubnh phmdngtnhl78VK.CcloiVKphnlpctrongqutrnhBNsdng thuc c th hin qua bng 3.27. Bng 3.27:Cc loi vi khun phn lp c trong qu trnh s dng colistin Loi VKS lt BNT l (%) Acinetobacter baumannii4151,9 Pseudomonas aeruginosa1215,6 Stenotrophomonas maltophilla67,8 Burkholderia cepacia45,2 Klebsiella pneumoniae45,2 Escherichia coli33,9 Chryseobacterium indologenes11,3 Chryseobacterium meningosepticum11,3 Empedobacter brevis11,3 Gram m Klebsiella oxytoca11,3 57 Pseudomonas putida11,3 Tng7596,1 Enterococcus faecalis22,6 Staphyllococcus aureus11,3Gram dng Tng33,9 Tng78100,0 Nhn xt: Trong tng s 78 VK c phn lp, VK Gram (-)vn chimi a s (96,1%) v xu hng VK so vi trc khi BN dng thuc vn khng c s thay i khi hu ht VKcyravnlnhngtrckhunGram(-)akhngthucmngulA. baumannii (51,9%), tip nlP. aeruginosa (15,6%).S a dngv chng VKvn duytrvi13loiVKnhtrckhichnhthuctuynhincmtschngthay i. 3.4.1.2.Kt qu khng sinh ca VK vi khng sinh colistin Tngs78VKphnlpcc74VKclmKSbaogm72KSca Gram (-) v 2 KS ca Gram (+).Trong s ny, s KS c lm vi colistin l 40/74 v 100% KS ca ca VK Gram (-). Ttc40VKclmKSvicolistinuchoktqunhycmvithuc, khngcVKnonhycmtrunggianhaykhng.Trongsnychc37VK (92,5%) c tr kt qu KS km theo gi tr MIC. nhy cm ca cc VK phn lp trong qu trnh dng colistin i vi thuc c th hin qua bng 3.28. 58 Bng 3.28: nhy cm ca VK phn lp trong qu trnh dng colistin i vi thuc Loi VK S VK nhy colistin S VK c xc nh MIC T l (%) Khong dao ng (g/ml) A. baumannii353497,10,125 1,000 P. aeruginosa3133,30,500 S. maltophilla11100,00,500 K. pneumonia11100,03,000 Nhn xt: SloiVKclmKSvicolistinvnduytr4/13tngtnhtrckhi dngthuc.TuynhinlnnyS.maltophialthchchoP.putida.ChngA. baumannii vn l VK c phn lp ra nhiu nht v c t l KS ln nht. T l tr ktquKSkmtheoMICl97,1%,gitrcntrnMICcakhongdaongc tng ln so vi trc khi dng thuc.3.4.2.Gim st chc nng thn Hu ht cc c tnh nghim trng nht ca colistin l c tnh trn thn v thn kinhulinquannvicdngliucaohnliukhuyncovdngtrnBNsuy gim chc nng thn [34], do vic gim st chc nng thn c s hiu chnh liu ph hp cho BN l vic ht sc cn thit. 3.4.2.1.Gim st nng creatinin huyt thanh Nghin cu kho st mc thng xuyn ca vic gim st nng creatinin huyt thanh trn nhm BN thng qua vic thng k rng gia cc ngy c gim st. SBNcgimstnngcreatininhuytthanhtrongqutrnhdngthucl 120/137BN(87,6%).SBNkhngcgimstl17BN.Trongsnyc10BN khng ghi nhn gim st do BN ch dng thuc 1 ngy, s cn li l 5 BN dng thuc 2 59 ngy v 2 BN dng thuc 4 ngy nhng khng ghi nhn cgim st. Kt qu kho st trn nhm 120 BN c gim st nng creatinin huyt thanh v mc thng xuyn ca vic gim st c th hin qua bng 3.29. Bng 3.29:Kho st mc thng xuyn ca vic gim st creatinin rng gia cc ngy gim st (*)S lt bnh nhnT l (%) 1 ngy37363,3 2 ngy12020,4 3 -5 ngy9115,4 > 5 ngy50,9 Tng589100,0 (*) = Ly mc ban u l thi im ch nh colistin. Nhn xt: Kt qu kho st cho thy, khong cch gia cc ngy nh lng creatinin huyt thanhchimphnlnl1ngy,iuchothyhuhtccBNcgimst creatininhngngy.Bncnh,khongcch2ngycngchimmtphnkhng nh.Nhvy c ththy rng,vic xt nghim creatininkh l thng quy trong qu trnh BN dng thuc.Theo ti liu khuyn co, nn theo di chc nng thn thng qua nh lng nng creatinin trong mu 2 ngy/ln [16]. 3.4.2.2.Can thip trn thnS BN c can thip lcmu trong qutrnh dng thuc l 48BN (35,0%).T l phn b cc loi can thip trn thn ca nhm BN c th hin qua bng 3.30. 60 Bng 3.30:T l phn b cc loi can thip trn thn ca nhm BN Loi can thipS lt bnh nhnT l (%) Lc mu ngt qung2850,0 Lc mu lin tc2850,0 Tng56100,0 Nhn xt: T l BN can thip lc mu ngt qung v lc mu lin tc l tng ng nhau. Trong s 28 BN c can thip lc mu ngt qung, c 13 BN (46,4%) c s hiu chnh liu khong thi gian can thip lc mu, s cn li vn duy tr liu nh c. 3.4.3.Gim st ADE Nghin cu khng ghi nhn c ADE no (khng xt n ADE trn thn) trong sut qu trnh dng thuc ca nhm BN. B. KT QU NHGI 3.5. nh gi ch nh colistin Ktqunhgichnhcolistincncvoccktqukhostphntng quan gia vic C colistin vi chn on NKBV v vi sinh SBNcbnhphmtrckhidngthucphnlpcVKGram(-)vcho ktquKSnhycolistin,akhngvicckhngsnhkhcl:24BN.ycng chnh l nhng BN c chn on NKBV trc khi dng thuc. Kt qu nh gi ch nh c th hin qua bng 3.31. 61 Bng 3.31:nh gi ch nh ca colistin Ch nhS bnh nhnT l (%) Ph hp2417,5 Khng ph hp11382,5 Tng137100,0 Nhn xt: Kt qu nh gi cho thy, t l BN c ch nh ph hp Hng dn kh khim tn (17,5%), s cn li l 82,5% c ch nh khng ph hp. 3.6.nh gi s phi hp thuc S BN c s phi hp colistin vi cc KS khc trong phc iu tr l 137/137 BN.HuhtKSuccngphtcdngvicolistin/hipngtcdngcng colistintrntcnhngybnh.KtqunhgitlBNcsphihpthucph hpHngdnl99,4%,scnli0,6%khngphhpthucvcpphihp colistin v vancomycin. 3.7.nh gi liu dng, ch liu Kt qu nh gi liu dng ca colistin trn nhm BN nghin cu c th hin qua bng 3.32. Bng 3.32:nh gi liu dng ca colistin (n = s lt BN) So snh vi liu khuyn co Ph hpKhng ph hp Liu dng S BN n%n% Liu np672943,33856,7 62 Liu duy tr671217,95582,1 Nhn xt: S BN s dng liu np l 126 BN (92%) v tng t vi liu duy tr cng l 126 BN (92%). Tuy nhin chng ti ch ghi nhn c cn nng thc t ca 73 BN, trong s ny c 67 BN s dng liu np v 67 BN s dng liu duy tr. Do , chng ti ch tin hnh kho st cng nh nh gi trn nhng i tng BN ny. nhgiliudngcanhm73BNghinhnccnnngtheoHngdn iu tr, c 43,3% BN dng liu np ph hp vikhuyn cov 17,9% BN dng liu duy tr ph hp vi khuyn co, phn ln s BN khng dng liu ph hp khuyn co. nh gi liu ni chungtheo cc tiu ch ca Hng dn, chng ti xt trn 73 BN ghi nhn c cn nng. Tuy nhin vi tiu ch 1 l BN phi c dng ng thi liu npvliu duy tr, chng ti loi tr 6BN c thigian dng thuc < 24gi (c ngharngBNmichcsdngliunp).Do,nhgiliudngtheo Hng dn, chng ti s nhgi trn nhm67 BN. Kt qu kho st cho thy c 61 BN c dng c 2 loi liu, 44 BN trong s ny c khong cch 2 liu 24 gi v ch c 5/44 BN c liu dng bngvi liukhuyn co. Nhvy, t l BN c nhgi liu dng ph hp Hng dn l 7,5%, s cn li khng ph hp l 92,5%. Tng t nh vy, vic nh gi ch liu duy tr cng ch thc hin c trn 67 BN c s dng liu duy tr v ghi nhn c cn nng. Kt qu nh gi ch liu duy tr ca colistin trn nhm BN nghin cu c th hin qua bng 3.33. Bng 3.33:nh gi ch liu duy tr ca colistin (n = s lt BN) So snh ch liu vi khuyn co Ph hpKhng ph hp Phn loi Clcr S BN n%n% Clcr < 10 ml/pht22100,000,0 63 Clcr > 10 ml/pht655686,1913,9 Tng675886,6913,4 Nhn xt: Tng s BN tnh ton c Clcr nh c ch s cn nng c l 67 BN bao gm 2 BN c Clcr < 10 ml/pht v 65 BN c Clcr > 10 ml/pht. C 2 BN c Clcr < 10ml/pht uc dng ch liu l 2 ln/ngytng t khuyn co. Trong tng s 65 BN c Clcr > 10 ml/pht, c 56 BN c dng thuc vi ch liu l 2 3 ln/ngy tng t khuyn co. Nh vy, hu ht cc BN thuc nhm ny (86,1%)cchliuphhpviHngdniutrv13,9%BNcchliu dng khng ph hp. Nh vy, nh gi trn tng s 67 BN dng liu duy tr th kt qu c 86,6% BN cchliuphhpHngdniutrv13,4%BNcchliudngkhng ph hp.3.8.nh gi pha ch thuc, ng dng, thi gian truyn tng liu/ngy Ktqunhgiphachthuc,ngdng,thigiantruyntngliu/ngy c th hin qua bng 3.34. Bng 3.34:nh gipha ch thuc, ng dng, thi gian truyn tng liu/ngy (n = slt BN) So snh vi Hng dn iu tr Ph hpKhng ph hp Ch tiu nh gi S lt BN n%n% Dung dch pha ch14413593,796,3 Th tch pha 1 l thuc2436426,417973,6 ng dng 13112293,196,9 64 Thi gian truyn tng liu/ngy20511455,69144,4 Nhn xt: S lt BN c s dng dung dch pha ch thuc NaCl 0,9 % theo nh Hng dn l 135 BN. Nh vy, s lt BN s dng thuc vi dung dch pha ch ph hp Hng dnl93,7%,mtphnnhscnlikhngphhpl6,3%.Ngcli,phnhn th tch dng pha ch 1 l Colymycine khng phi l 50 ml (73,6%). Ch c 26,4% lt BN s dng thuc pha trong th tch 50 ml/1 l l ph hp vi Hng dn. nh gi ng dng thuc: 100% BN dng ng truyn tnh mch cho ch liunplphhpviHngdn.Vichliuduytr,huhtccBN(93,1%) csdngngtruyntnhmchngtqung,scnlisdngngtruyn khng ph hp khuyn co l 6,9%. ThigiantruyntngliutheonhHngdnltrongkhongt30pht2 gi. S lt BN c thi gian truyn tng liu/ngy c nh gi ph hp khuyn co l 55,6% BN, s cn li khng ph hp l 44,4%. 3.9.nh gi vic gim st vi sinh trong qu trnh dng thuc KtqukhostchothysBNcghinhncgimstvisinhtrongqu trnh dng thuc l 67/137 BN.Nh vy, nh gi vic gim st vi sinh trong qu trnh dng thuc c 48,9% BN cthchinphhpviHngdniutr,scnlikhngphhpl51,1% BN. T l hai nhm l tng ng nhau cho thy vic gim st vi sinh vn cha c thc hin thng quy. 65 Chng 4. BN LUN 4.1. Ch nh iu tr ca colistin Kt qu nghin cu cho thy, trong tng s 137 BN nghin cu, s BN t c c 3 tiu ch caC l24 BN, chimmt tlkh thp (17,5%)BN c ch nh ph hp Hng dn, s BN c ch nhkhng ph hp l 82,5%. iu ng nghavi vic, nu xt v mt tun th Hng dn ca cc bc s trn lm sng th t l tun th l 17,5% v phn ln l khng c s tun th vi t l 82,5%. Vy l do ti sao c mt t l khng tun th hng dn ln nh vy? Liu rng nguyn nhn xut pht t bn thn Hng dn hay t pha nhng ngi thc hin n? Mt trong nhng nguyn nhn dn n mt t l thp nh th ny c l xut pht tnhngiukinkhchtchcaHngdn.phnphngphpnghincu chngticpn3tiuchnyvBNmuncchnhphhpthphit ng thi c 3 tiu ch ca Hng dn, c ngha l phi m bo tiu ch v bnh cng nh tiu ch vmt vi sinh. Chng ti s bn lun s bt cp trong vic tun th tng tiuchthngquavicbnlunthiimCthuc,haynicchkhclphntch mi tng quan gia vic C colistin vi chn on NKBV v vi sinh l gii cho t l thp ni trn. T l BN t c qua tng tiu ch s c s thu hp dn. Ni dung 3 tiu ch xin c nhc li nh sau:BN c chn on NKBV trc khi dng colistin. BN c bnh phm phn lp ra VK Gram (-) trc khi dng colistin. KScaVKGram(-)trnnhycolistinvkhngngthi3loiKS(-lactam,aminosid,quinolon)trnKSv/hockhngtrnlmsng.66 4.1.1. Mi tng quan gia vic C colistin v bnh l NKBV Ktqukhostchothyrng100%BNtrongnghincucchnonNKBV, tuy nhin trong s ny c 1 BN chn on sau khi dng thuc v trc dng do nghi ng, s BN c chn on NKBV trc khi dng thuc l 136 BN (99,3%). Nh vy c th thy rng vi tiu ch u tin th hu ht s BN u t c. Tuy vy, cng cn phi ni rng vic t c 1 s lng ln BN nh th ny l do khi t ra tiu ch ca Hng dn chng ti b qua mt iu kin. iu kin y trong Hng dn iu tr l NKBV c chn on phi km theo mc nng. y cng chnh l mt mt hn ch ca ti v vi c th chuyn mn, chng ti kh c th nh gi mc nng ca nhim khun. Qu trnh thu thp thng tin, chng ti cng ghi nhn c mc nng vn c ghi nhn trong bnh n, bin bn hi chn hoc trong phiu ch nh colistin. Tuy nhin s lng nhng BN c y cc c s ny l khng nhiu. Chnh vvy chng ti quyt nh thu hp iu kinkho st, c ngha l BN ch cn c chn on NKBV trc khi dng colistin l t c tiu ch 1. 4.1.2. Mi tng quan gia vic C colistin v vi sinh Trong s 137 BN nghin cu, c 88 BN (64,2%) c ch nh colistinkhi cha bit kt qu VK. V nu xt trong 136 BN t tiu ch 1 trn th s c 87 BN (1 BN chn on NKBV sau khi dng thuc)(64%) c ch nh khi cha bit kt qu VK, s BN bitktquVKchchim36%(49BN).iuchothyrngphnlnBNvn c dngkhng sinh theokinh nghim lm sng. Theomt nghin cu ti BV Bch Maivo nm 2012 cng cho thy rng, c 41,8% BN c ch nh colistinkhi cha bit VK[7].Nh vy, s BN t c 2 ch tiu u tin ch cn l mt con s kh khim tn so vi ban u (49 BN). Tuy nhin, khi cng ngh khng cho php v cc ngun lc hn ch thvic dng KS theokinh nghimvn l tr ct iu tr nhimkhun[17].Mt s 67 ti liu cho thy s cn thit ca vic s dng khng sinh theo kinh nghim cho BN vimphithmy.Tuynhincctiliucngkhuyncorngmcsdng khngsinhtheokinhnghimcnphthucvocsdcht,tnhhnhVKvtnh khng thuc ca a phng[26, 38]. Nhvy,sBNcnhgicCphhpHngdniutrchcn chim17,5%vi24BN.Tuynhin,trongqutrnhkhostngoivicghinhnli chn on NKBV ca bc s, chng ti vn thu thp cc du hiu lm sng v cn lm sng ca BN so snh vi cc tiu chun chn on NKBV. T nhng thng tin kho stcvbnhlNKBVcngnhtnhtrngcaBNngaytrcthiimdng thuc,nhngthngtinvccKSdngtrcnhngkhngpnghiuqutrn BN, chng ti nhn thy rng s chm tr trong vic ch nh thuc do phi i cc kt qu vi sinh tr v (kt qu vi khun v KS) c th e da n tnh mng BN. Mt s ti liu cng bn lun v vn ny v h nhn thy rng iu ny c bit ng cc khoa iu tr tch cc[17]. Nh vy, vic cc bc s khng tun th c nhng l do khchquanxutphttHngdn.Bnhcnh,tnhhnhkhngthucngycng giatngvvnvsinhbnhvinchacquantmy(mttrongnhng nguy c tng t l NKBVv mc nng ca bnh) cng l nhng l do dn ti tnh trng ny. Nu xt t pha nhng ngi pdng Hng dn trn lmsngvmc tun thHngdnthbncnhvicphiaranhngquytnhiutrtheokinh nghim xut pht t l do cn nhc nguy c/li ch trn BN (nguyn nhn khch quan) cngcnphininnhngnguynnhnchquanxutphttphabcs.yl mctintngvoHngdn.HngdncaBVBchMaituyrtngngn nhng khng c nhng bng chng i km theo cc khuyn co. C s ca Hng dn l mt phn rt quan trng trong vic quyt nh s tun th.Tuy nhin thc t tm hiu chng ti thy rng c nhng ti liu c s tng ng vi khuyn co v ch nh trongHngdn.CthnhcunSanford[20],mttiliukhnitingvnhng 68 khuyn co s dngkhng sinh theo bnh l nhimkhunv theo tc nhn gy bnh. Ti liu khuyn co i vi vim phi bnh vin ni chung, kt qu VK phn lp l mt s VK nh: A. baumannii, Klebsiella, Burkholderia th Imipenem l la chn ban u v colistin s l la chn thay th nu VK khngImipenem. Nhvy c th thy rng, s cht ch trong ch nh ca Hng dn l hon ton c c s. Ni tm li, vic nh gi con s 17,5% hay 82,5% khng th ch n thun nh gi vic tun th ca bc s khi ch nh colistin trn lm sng m nhng con s y cn phnnhcnhngbtcptrongvicpdngHngdndocnhngnguynnhn khch quankhc.Skhng tun th xutpht t c hai pha, dovy sliu nhgi ch mang tnh tng i v cn c nhng ci nhn khch quan khi xem xt. 4.2. S phi hp thuc vi colistin HngdnsdngKSColymyxincaBVBchMaiarakhuyncov vickhngsdngcolistinncvnnphihpviccKSkhcnh carbapenem, rifampicin, fluoroquinolon k c khi VK khng vi cc KS ny v hiu qu hip ng c chng minh. KtqukhostVKcphnlptrnmubnhphmtrckhiBNdng colistinca nghin cucho thy trc khun Gram (-) A. baumannii chim t l ln nht (70,5%).Trnthgiickhnhiunghincucthitksnglcvnh gi hiu qu phi hp ca colistin vi mt s loi KS khc trn tc nhn gy bnh ny (Hnh 1.3) . Theo bo co ca mt nghin cu, hiu qu hip ng ca colistin v carbapenem trn cc chng A. baumannii a khng/khng carbapenem c th t t 75 100%. Khi lachncarbapenemhipngcngcolistin,meropenemcvllachntthn imipenem domeropenem cphn t nh hn, nh thuc c th xm nhpvo cc c quan ch t nng cn thit, ngoi ra thuc an ton hn liu cao hn, t c trnthnkinhvmtporinkhnglvnlngykhngmeropenemnhvi 69 imipenem [12]. Mt nghin cu on h hi cu trn 258 BN ca Falagasv cng s cngchothysphihpcolistinvmeropenemchotcdnghipnglnn 83,9% v 85% i vi Acinetobacter a khng v Pseudomonas a khng[18]. iu tr kt hp rifampicin v colistin cng l mt trong nhng la chn thay th c bn lun cho vic iu tr cc nhim trng do VK Gram (-) a khng gy ra. Hu htccnghincuuchothytcdnghipngcacolistinvrifampicincth ln n 100% i vi A. baumannii a khng thuc [14]. Theo mt bo cokhoa hcgn y cho thy nhng la chn phi hp KS hin nay cho A. baumannii a khng (Bng 4.1)[2]. Bng 4.1:La chn iu tr phi hp hin nay cho A. baumannii a khng A. baumannii a khng (in vitro)A. baumannii a khng (lm sng) Polymyxin B + ImipenemColistin + Rifampicin Polymyxin B + RifampicinColistin + Sulfoperazone/sulbactam Polymyxin B + Imipenem + RifampicinColistin + KS khc (gm c Meropenem) Polymyxin B + CecropinCarbapenem + Sulbactam Polymyxin B + Rifampicin + Ampicillin/sulbactam Carbapenem + Cefoperazone/sulbactam Polymyxin B + Rifampicin + Sulfoperazone /sulbactam Colistin + Carbapenem + Sulbactam hoc Colistin + Carbapenem + Rifampicin Tygecycline Tigecycline + Carbapenem Tigecycline + Colistin Tigecycline + Colistin + Carbapenem KtqunghincuvsphihpcolistinviccKSkhctrnlmsngcho thy colistin c th phi hp vi 1 (61,6%), 2 (31,9%) hoc 3 (6,5) loi KS khc. ng ch trong s nhng phc phi hp, nhm carbapenem chim n 86%. Trong khi 70 khiphnlpvikhunthA.baumanniichimtllnnht(70,5%).Ktqut mtnghincukhctiBVBchMai(2012)[7]cngchothytrongcckhngsinh phi hp vi colistin, carbapenem chim t l ln nht trong cc phc phi hp 2, 3 v 4 khng sinh vi t l ln lt l 39,1%; 35,1%; 9,3%; tip theo l cc tetracycline (24,6%) gm minocyclin v doxycyclin. Trong cc carbapenem s dng trong phc phi hp, imipenem/meropenem c s dng nhiu nht vi tn sut 35/39. S lngA. baumannii phn lp cng chim t l cao nht vi 50,3%. Nh vy c th thy nhm KScarbapenemhinangllachnhngutrongphcphihpvicolistin iu tr NKBV. Mc ch ca vic phi hp c s tng ng vi vicA. baumannii a khng thuc ngy cng chim 1 t l cao trn lm sng v c s cho vic phi hp ny cp n trn.Trongccphcphihp2v3KS,lunctnht1KSphihpcng colistin c ph tc dng trn VK Gram (-). Ring vi phc phi hp 1 KS, nhm KS glycopeptid (vancomycin) c phi hp cng colistin 1 BN. Mt s nghin cu ch ra sc mnh tng hp ca vic phi hp colistin v vancomycin trn in vitro i vichngA.baumanniiakhng.Lmtkhngsinhvbnchtkhngctcdng trnVKGram(-)dokchthcphntlnvkncnhngkhiphihpcng colistin, colisin ny s lm thay i tnh thm ca mng t bo VK, t to iu kin cho vancomycin thm nhp vo[21, 42].Tuy nhin v nghin cu ch mi tin hnh trn in vitro nn chng ti nh gi s phi hp ny l khng ph hp. 4.3. Liu dng Kt qu nh gi v liu dng trn nhm 67 BN cho thy, s BN c dng liu ph hpvikhuyncochchim7,5%,scnlikhngphhpl92,5%.TlBN dng liu ph hp thp khng ch da vo thc t lm sng m mt ln na cng phi ni n s cht ch cckhuyn co ca Hngdn hay chnh l nhng tiu ch dng nh gi. Nhng bnh nhn dng liu ph hp i hi phi c s dng ng thi 71 liunpvduytrvikhongcchhailiul>24gibncnhvicmbomc liu dng ph hp vi khuyn co. Nghin cu cng nhn thy cmt skhkhn trongvickho stv nhgi liu dng trn BN. y chnh l vic liu tnh ton theo Hng dn ph thuc Clcr v gi tr MIC. Gi tr Clcr ph thuccn nng,tuy nhin ghinhn cn nng ca BN ti thi im dng thuc thng xuyn gp phi tr ngi trong mt nghin cu hi cu. y l mt ch s lm thu hp c mu BN kho st liu dng. Gi tr MIC ph thuc voktquvisinh,tuynhinquakhostvictrktquKSchacthng xuyn, do vy vic tnh ton liu so snh phn ln phi da vo gi tr quy c MIC =1(trongkhiktqukhostkhongdaongMICcaVKcyratrckhidng thuc l 0,125 0,380). Do , khi so snh liu dng thc t ca BN (c th c tnh theo mt cn c no khc) c th lm sai lch kt qu thc s. 4.4. Gim st trong qu trnh iu tr c tnh trn thn l mt tc dng ph quan trng ca colistin.Vic gim st cht ch chc nng thn, c bit l trong 5 ngy iu tr u tin l mt vic lm cn thit [14]. Hng dn cng khuyn co BN cn c theo di thng xuyn trong qu trnh iu tr tuy nhin mc thng xuyn l bao nhiu ngy/ln hoc bao nhiu ln/ngy vn cha c ni r. Chnh v vy chng ti ch tin hnh kho st tn sut gim st m khng nh gi vic gim st chc nng thn trn BN. 72 KT LUN V XUT A. Kt lun Quanghincu137bnhncaBNiutrtikhoaICU,BVBchMaitrong thi gian t 20/03/2012 n 20/03/2013 thuc tiu chun la chn, chng ti rt ra mt s kt lun sau: 1. c im BN nghin cu. Tng s BN trong nghin cu l 137 BN bao gm 61,3% nam v 38,7% n. Khongphn b tui rng (18 90 tui), phn ln BN > 60 tui (42,4%). 100%BNcbnhmckm.Sbnhmckmdaongt14bnh, trong chim t l cao nht l BN c 1 bnh mc km (44,6%) v bnh l mc km chim t l cao nht l nhm bnh tim mch (15,5%). Hu ht cc BN u can thip (79,1%). S can thip trn mi BN kh nhiu,daongt17canthip,thngthngl3canthip/1BN. Nhng can thip haygp nht trn nhm BNl th my (82,5%)v t ni kh qun m kh qun (68,6%). PhnlnBNtrongnghincucchcnngthnsuygim(76,7%), chim t l cao nht l suy thn mc nh (38,4%). ThigianiutrtikhoacaBNkhdi,daongt160ngy, trung bnh l 18,2 12,1 ng. 2.c im bnh l NKBV, VK hc v s dng thuc trn BN nghin cu 100% BN trong nghin cu c chn onNKBVvi hu ht lvim phi bnh vin (90,4%). Cc NKBV trn bnh nhn phn ln xut pht t khoa ICU (63,3%). SBNcmubnhphmdngtnhtrckhidngthucl(49,6%). BN ch yu mc 1 VK (80,9%). Hu ht VK c phn lp l VK Gram (-),chim95,5%.LoiVKcphnlpchimtlcaonhtlA. 73 baumannii (70,5%) vi gi tr MIC dao ng t 0,125 0,380. Carbapenem l nhmkhng sinh c ch nh nhiu nht trc colistin (34,6%). 100%BNcphcdngcolistinphihpvitnht1khngsinh khc v phn ln l phc phi hp 1 KS (61,6%). Carbapenem cng l nhm khng sinh c phi hp trong hu ht cc phc (86%). ThiimchnhcolistinchyulkhichabitVK(64,2%).Tip n l ch nh khi bit kt qu KS (25,6%) v ch nh khi ch bit kt qu VK chim 10,2%. SBNcdngliunpbngliukhuyncochimtllnnht (43,3%), trong khi vi liu duy tr li chim t l thp nht (17,9%). DungdchphachthuccsdngchyulNaCl0,9%(93,7%), th tch pha 1 l Colymycin l 50 ml chim t l ln nht (26,4%). 100% BN dng ng truyn tnh mch cho liu np v 93,1% BN dng liuduytrtheongtruyntnhmchngtqung.Thigiantruyn tng liu phn ln l 30 pht 2 gi (55,6%). SBNcgimstvisinhtrongqutrnhiutrl48,9%.A. baumanniivnlVKphnlpcnhiunhttrongccmubnh phmccytrongqutrnhgimst(51,9%)vigitrMICdao ng t 0,125 1,000. SBNcgimstchcnngthnthngquanhlngnng creatinin huyt tng l 87,6%. Khong cch gia cc ngy gim st ch phn ln l 1 ngy (63,3%). T l BN c can thip lcmu trn thn l 35,0%. 3.nh gi s dng thuc trn BN nghin cu T l BN c ch nh ph hp Hng dn l 17,5%. 99.4% BN c s phi hp thuc ph hp Hng dn. 74 T l BN dng liu tng t Hng dn l 7,5%. Phn ln BN c ch liu ph hp Hng dn (86,6%). T l BN ph hp Hng dn v dung dch pha ch, th tch pha ch/1 l thuc,ngdng,thigiantruyntngliulnlttngngl 93,7%; 26,4%; 93,1%; 55,6%. 48,9% BN c thc hin gim st vi sinh ph hp Hng dn. B. xut 1. Khoa ICU cn thit nn c s ghi chp cn nng y trc v trong qu trnh BN dng thuc trong bnh n tin cho nhng nghin cu hi cu nhng thng tin lin quan n liu. Vic hiu chnh liu ph hp trong qu trnh dng thuc nhm tng hiu qu iu tr v gim tnh khng thuc. 2. Cn c thm nhng nghin cu tm hiu k hn cc l do khng tun th Hng dn trong vic la chn colistin. ng thi c th xem xt li tnh kh thi ca Hng dn trn thc t lm sng. 3. Hng dn cn chi tit hn trong vic gim st vi sinh v cc ADR lin quan n thuc c bit l trn thn. Ngoi ra, hng dn cng nn cp n liu hiu chnh cho BN c can thip lc mu trong qu trnh dng thuc. 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(2012),"AnalysisofcolistinAandBinsheryproductsbyultraperformance liquidchromatographywithpositiveelectrosprayionizationtandemmass spectrometry", Journal ofChromatography B, 889, pp. 14-20. 47.Yahav D., Farbman L., Leibovici L., Paul M. (2012), "Colistin: new lessons on an old antibiotic", Clin Microbiol Infect, 18(1), pp. 18-29. Ph lc 1:PHIU THU THP THNG TIN BNH NHN BNH VIN BCH MAI ( ti: nh gi tnh hnh s dng Colistin ti khoa ICU, BV BM) Khoa: ..M bnh n:M lu tr: I.THNG TIN BNH NHN 1.H v tn:... 2. Gii tnh: Nam 1N 2 Mang thai3. Tui:.....................Cn nng:................. Chiu cao: 4. Ngy vo vin: ....../....../.......Ngy xut vin: ....../....../....... Ngy vo khoa: ../../..Ngy ri khoa: /../.. Thi gian nm vin:.................ngy Thi gian nm khoa:ngy 5.Chn on vo vin (bnh chnh, bnh mc km). -Chn on phng khm / cp cu: ............................................................................................................................................... ... -Chn on ti khoa ICU: ............................................................................................................................................... ... 6.Chn on ra vin. Bnh chnh:.................................................................................................................. Bnh mc km:............................................................................................................ Bin chng:.. II.THNG TIN BNH L NHIM KHUN 1. c im bnh l NK 1.1. Chn on NK chung: ................................................................................. 1.2. Chn on NKBV C quan NKMc Ni xut pht 1.3. Cc du hiu ca bnhNKBV:....................... 2. Cc can thip trn bnh nhn M kh qunt ni kh qunTh mySonde tiu Chc d:Sonde dn lu:.. Catheter tnh mch i Catheter tnh mch trung tm (TM cnh, di n)Catheter ng mch phi (Swan-Ganz) t ng truyn ngoi vi Can thip khc: 3. Xt nghim vi sinh. nh danh vi khunKhng sinh STTBnh phmNgy ly Ngy (gi) trKt quNgy (gi) trKt qu ../../.././. ../../.././. ../../.././. ../../.././. ../../.././. ../../.././. ../../.././. ../../.././. ../../.././. ../../.././. 4. Tm tt tnh trng nhim khun Mch = PaO2/FiO2 =/f th =HA = BC/NEUT% =/CRP = Cc Markernhim trng Nhit = Procalcitonin =Triu chng nhim trng Din bin bnh Cc yu t nguy c Bnh chnh:.. Can thip:. Ni xut pht:.. Thi gian iu tr: Cc KS dng trc Colistin Vi khun KS (MIC) III. THNG TINS DNG THUC 1. Ch phm: Colimycin 1MUI 2. Cc KS phi hp Tn nng /hm lngLiu dngSTT Bit dcHot chtLiu/1 lnS ln/24hTng liu/24h Ngy bt u Cch dng 1...././ 2...././ 3...././ 4...././ 5...././ 3. Thi gian dng Colistin S ngy dng Lin tcNgt qung Ngy (gi) bt u: ../......../ Ngy kt thc:/........./ .. L do ngt qung:........................................................................................................ 4. Pha ch thuc, ng dng, tng thi gian truyn. Ni dungCh NpCh Duy tr Pha chDung dch phaNaCl 0,9% :NaCl 0,9% : Tng th tch Th tch (1 l)50ml :50ml : ng dngMTD :MTDNQ : Tc truyn Tng thi gian truyn 5.Liu dng Dng LN trong 24h u Thi im bt uLiu dngLiu np (LN) .././. Liu ban uKhong tg (LDT-LN) > 24h Thi im bt u Liu/1 lnS ln/24hTng liu/24h Liu duy tr (LDT) .././. Liu hiu chnhKhong thi gian hiu chnh Liu/1 lnS ln/24hTng liu/24h ...../../.. - ../../.. ...../../.. - ../../.. Hiu chnh LDT ...../../.. - ../../.. L do hiu chnh liu:Do chc nng thnKhc: 6. Gim st chc nng thn trong qu trnh s dng thuc. 6.1. Gim st Creatinin huyt thanh Nng Creatinin huyt thanh (mol/l), thanh thi Clcr (ml/pht) Ln 1Ln 2Ln 3Ln 1Ln 2Ln 3Ngy(gi)Cre.ClcrCre.ClcrCre.Clcr Ngy (gi)Cre.ClcrCre.ClcrCre.Clcr 6.2. Can thip trn bnh nhn Thi im can thipNgy (gi) Lc mu ngt qungNgy (gi) Lc mu lin tc .././. - .././..././. - .././. .././. - .././..././. - .././. .././. - .././..././. - .././. .././. - .././..././. - .././. .././. - .././..././. - .././. .././. - .././..././. - .././. .././. - .././..././. - .././. .././. - .././..././. - .././. .././. - .././..././. - .././. Can thip t khi bt u dng thuc .././. - .././..././. - .././. 7. Ghi nhn ADE trong qu trnh s dng thuc Nhc c RLCH Porphyrin c tnh trn thn kinhKhc:.. .........../..../..//... .........../..../..//... .........../..../..//... .........../..../..//... .........../..../..//... Ph lc 2: BNH VIN BCH MAI HI NG THUC & IU TR Hng dn s dng khng sinh Colimycine 1.000.000 UI Dng bo ch: L bt pha tim Thnh phn:Colistine methane sulfonate natri: 1.000.000 UI tng ng:o80mg Colistin methane sulfonat natri o33.3 mg dng Colistin base Ph tc dng: Colistin l khng sinh dit khun c tc dng trn cc chng vi khun Gram m: Pseudomonas aeruginosa, Enterobacteriacea, Klebsiella spp, Acinetobacterspp, Citrobacter spp, Escherichia coli, Haemophilus influenzae.Tt c cc chng vi khun Gram dng, mt s chng vi khun Gram m nh Burkholdreria cepacia, Neisseria, Serratia, Proteus, Bacteroides fragilis v hu ht cc cu khun Gram m u khng t nhin vi thuc. Ch nh: Colistin ch c ch nh trong cc trng hp nhim khun bnh vin nng do vi khun Gram m nhy cm vi thuc v khng li cc khng sinh khc. Nhng quy nh khi s dng thuc: - Ch nn s dng colistin sau khi c kt qu khng sinh cho thy vi khun nhy cm vi thuc v khng nhy cm vi cc khng sinh nhm beta lactam, aminoside hoc quinolon. - Tham kho kin khoa Vi sinh v tnh hnh nhy khng, MIC ca vi khun i vi colistin trong bnh vin.- Tham kho kin khoa Dc v liu dng, cch dng ca thuc (nu cn cha r thng tin) - Khng c s dng colistin n c, nn phi hp vi cc khng sinh khc nh carbapenem, rifampicin, fluoroquinolon k c khi vi khun khng vi cc khng sinh ny bi v tc dng hip ng c chng minh. - Theo di nhy cm ca colistin trong qu trnh iu tr: ly mu bnh phm, tin hnh nui cy nh danh vi khun v xc nh li nhy cm ca khng sinh da theo kt qu khng sinh . - Gim st thng xuyn chc nng thn ca bnh nhn trong qu trnh iu tr thng qua theo di thanh thi creatinin huyt tng. Cch dng v liu dng: - Liu dng c xc nh cn c theo mc nhim khun, v tr nhim khun, nng c ch ti thiu ca khng sinh i vi vi khun (MIC), tui, cn nng v chc nng thn ca bnh nhn.- Phi dng mt liu np trong vng 24 h u. Sau chuyn sang dng liu duy tr. - Liu np v liu duy tr trn tng c th bnh nhn c tnh theo cng thc: oLiu np (mg dng base) =Cch x 2 x trng lng c th (TBW/kg) oTng liu duy tr/ngy(mg dng base)= Cch x (1,5 x ClCr + 30) Bnh nhn c ClCr di 10 ml/pht: chia 2 ln/ngy Bnh nhn c ClCr > 10ml/pht: chia 2-3 ln/ngy Trong , Cch l nng ca thuc cn t c trong mu trng thi n nh. Cch c xc nh nh sau: oTrnghpcktquMIC:CchtnhtphibnggitrMICcachngvi khun phn lp c oTrng hp khng c kt qu MIC: tham kho thm khoa Vi sinh v d liu phn b MIC hin hnh ca chng vi khun gy bnh d on Cch.* Tham kho thm v liu dng bng 1 v 2. - ng dng: Truyn tnh mch ngt qung. Hng dn pha truyn thuc: - Pha 1 l thuc trong 50ml dung dch Natri clorid 0,9 %. C th truyn tng liu thuc trong thi gian t 30 pht n 2h.Phi s dng thuc ngay lp tc sau khi pha, khng bo qun li phn thuc cn tha sau khi s dng. Chng ch nh: Mn cm vi thuc. Thn trng v ch khi s dng: - Nhc c. - Ri lon chuyn ha porphyrin. - c tnh trn thn hoc c tnh trn thn kinh. Bng 1. Bng hng dn liu np MIC 1mg/ml1mg/ml < MIC2mg/ml Cn nng (Kg) Liu np (tnh theo mg base) Liu np (quy i thnh s l) Liu np (tnh theo mg base) Liu np (quy i thnh s l) 306021204 35702140 4 1/2 4080 2 1/21605 45903180 5 1/2 5010032006 55110 3 1/22207 601204240 7 1/2 6513042608 70140 4 1/2280 8 1/2 75150 4 1/23009 80160532010 85170534010 90180 5 1/236011 Bng 2. Bng hng dn tng liu duy tr hng ngy theo thanh thi creatinin (ClCr) MIC 1mg/ml1mg/ml < MIC2mg/ml ClCr (ml/pht) Liu duy tr (tnh theo mg base) Liu duy tr (quy i thnh s l) Liu duy tr (tnh theo mg base) Liu duy tr (quy i thnh s l) 10452903 206021204 307521505 409031806 5010532106 6012042407 7013542708 8015053009 90165533010 100180636011 110195639012 120210642013 130225745014 140240748015 Ghi ch: - Trng hp MIC > 2 mg/ml: nn tham kho kin dc s v liu dng - Cng thc tnh thanh thi creatinin ClCr (ml/pht): (140- Tui) xCnnng (kg) (x 0.85nu l ngii) Nng creatininehuytthanh (mol/l)x0.815 Ngybanhnh:20/03/2012 Gim c Bnh vin Ph lc 3: TIU CHUN CHN ON NHIM KHUN BNH VIN Tiu chunTriu chng Triu chng chung St > 38.3 C H thn nhit < 36 C Nhp tim > 90 ln/pht Th nhanh Thay i thc Phrhoccnbngdch dng(> 20 ml/kg/24 gi) Tng glucose mu(ngmu>140mg/dlhoc> 7,7mmol/l) Du hiu vim Tng bch cu > 12.000/l Hoc gim bch cu < 4000/l S lng bch cu bnh thng nhng t l bch cu non > 10% Protein C phn ng (CRP) > 2 ln bnh thng Procalcitonin > 2 ln bnh thng BN c t 2 tiu chun tr ln trong cc tiu chun sau Thay i huyt ng Tt huyt p (HA tm thu < 90 mmHg, HA trung bnh < 70 mmHg, hoc HA tm thu gim > 40 mmHg so vi bnh thng ca la tui Duhiurilon chc nng tng Gim oxy mu ng mch (PaO2/FiO2) < 300 Thiu niu cp(nc tiu < 0,5ml/kg/gi t nht trong 2 gi, mc d c b dch) Ph lc 4: DANH SCH BNH NHN TRONG NGHIN CU STTH v tn bnh nhnM bnh n Ngy vo khoa Ngy ri khoa 1L ng A.120216873V15/09/1208/10/12 2Nguyn Vn A. 131100043V07/02/1321/02/13 3Nguyn Th B.121100015V28/03/1223/04/12 4Nguyn Thi B.120901308V21/05/1207/06/12 5Trn Xun B.120208018V18/06/1221/06/12 6Nguyn Th B. 121100074V19/06/1212/07/12 7Nguyn Th B.120210636V07/07/1231/07/12 8Nguyn Th B.120214352V26/07/1230/07/12 9Nguyn Thanh B. 120216050V11/09/1227/09/12 10 Vn B. 120304440V12/09/1219/09/12 11Phm Vn B.121100140V09/11/1205/12/12 12L Vn B.120218479V24/12/1231/12/12 13Nguyn Th C. 120800807V19/06/1205/07/12 14Trn Xun C.130202700V17/02/1306/03/13 15Nguyn Vn Ch.120204838V22/03/1227/03/12 16Nguyn Vn D.122000239V27/03/1215/04/12 17on Vn .121100019V10/04/1224/04/12 18V Ngc .121001145V28/05/1210/06/12 19Trn Thanh D.121100307V20/07/1230/07/12 20ng Vn D.120213797V09/08/1230/08/12 21Trn Vn D.121100295V20/08/1224/09/12 22Nguyn Quang D. 120214117V21/08/1230/08/12 23Trnh Vn D.120215853V31/08/1221/09/12 24V B .120215501V31/08/1224/09/12 25Chu Th .120217717V11/11/1220/12/12 26L Vn D.120217224V21/11/1204/01/13 27Nguyn Trung D.121601002V23/11/1227/11/12 28H .120218103V28/11/1219/12/12 29Nguyn Cng D. 120037627V01/01/1323/01/13 30Nguyn Kim Gi.120216067V05/09/1228/09/12 31Nguyn Th Hng Gi. 130202465V10/02/1307/03/13 32Phm Vn H.120204669V30/03/1226/04/12 33Nguyn Ngc H. 120207927V02/04/1214/05/12 34Hong Th H.120301832V07/04/1212/04/12 35Cn Vn H.120206020V11/04/1214/05/12 36o Th H.120203305V24/04/1228/04/12 37o Huy H.121000928V30/04/1214/05/12 38Nguyn Thu H. 121100446V06/07/1223/07/12 39Nguyn Xun H.120020477V08/07/1221/08/12 40Vng nh H.120021890V16/07/1219/07/12 41L Thu H.120214207V05/08/1223/08/12 42Lm Th H.121100353V05/08/1231/08/12 43 c H.120216127V23/09/1203/10/12 44inh Vn H. 120216789V29/09/1217/10/12 45H Th H.120215285V13/10/1229/10/12 46V Th H.120216206V16/10/1224/10/12 47L Th H.120040298V06/11/1210/11/12 48Nguyn Vn H. 120218285V22/11/1230/11/12 49Phm Thanh H.120219630V04/12/1204/01/13 50 Th H.130202396V21/01/1308/02/13 51Trn Hu H.130203934V22/01/1304/02/13 52Nguyn Vn K. 120206980V06/05/1217/05/12 53Hong Hu Kh.120207496V03/05/1231/05/12 54Nguyn Ngc Kh.120014472V03/06/1228/06/12 55V Th L.120204602V06/04/1223/04/12 56L Nh L.121100111V28/04/1212/06/12 57 Th Thi L. 120025939V23/07/1207/09/12 58L Seo L.121100424V29/07/1204/09/12 59Trnh Th L.120214654V01/10/1203/10/12 60on Tin L.120217397V25/10/1209/11/12 61on Tin L.120219593V05/12/1217/12/12 62Trn Th L.120217988V06/12/1218/12/12 63Nguyn Th Tuyt L. 120210740V26/12/1208/01/13 64Nguyn Th L.130201927V30/01/1308/02/13 65Dng Th M.120200422V24/05/1203/06/12 66Nguyn Th M.120210627V13/06/1222/06/12 67Nguyn Hu M.120215454V24/09/1209/10/12 68Nguyn Nh N.120023924V15/08/1226/08/12 69Trn Th N.120026611V06/09/1225/09/12 70Phm Th N.130203726V04/01/1312/01/13 71Hong Ng.120008350V18/05/1224/05/12 72V Th Ng.120211902V15/07/1206/09/12 73L Quang Ng.121100321V23/11/1224/12/12 74Nguyn Th Ng.121100507V16/12/1226/12/12 75Phm Huy Ng.130200171V07/02/1315/03/13 76Ng Th Ng.130200094V11/02/1321/02/13 77Bi Hng Ngh.120017342V30/05/1202/06/12 78Nguyn Th Nh.120011436V27/03/1209/04/12 79Lc Vn Nh.121100209V22/06/1229/06/12 80L Thy Nh.120215483V21/09/1212/10/12 81Nguyn Th Nh.120217926V03/12/1205/01/13 82Nguyn Vn Nh.120305320V14/12/1206/01/13 83Nguyn Vn Nh.120200611V14/06/1224/06/12 84Nguyn Th Ph.121100310V30/07/1216/08/12 85Nng Vn Ph.120214923V24/08/1210/09/12 86Nguyn Vn Ph.120041557V22/11/1228/11/12 87V Th Hi Ph.120218927V04/12/1207/12/12 88Trnh Hng Ph.130200633V06/01/1321/01/13 89Nguyn Vn Ph.131400021V28/02/1312/03/13 90Nguyn Th Q.120208343V08/06/1206/07/12 91Trn Xun Q.120215846V31/08/1218/09/12 92Hong Vn Q.120216023V13/09/1224/09/12 93Tn Th Q.120031249V19/09/1231/10/12 94L Th S.120200636V18/05/1230/05/12 95 ng S. 131100047V02/02/1306/02/13 96H Quc T.120207470V01/04/1202/05/12 97 Vn T.121100449V08/07/1216/07/12 98Trn nh T.120211380V15/08/1226/08/12 99Lm Quang T.120801257V25/09/1213/11/12 100Nguyn c T.121600663V08/11/1212/11/12 101Nguyn Th T.120220285V12/11/1229/11/12 102 Th T.121100320V24/11/1213/12/12 103T Vn T.121100502V22/12/1223/01/13 104Nguyn Anh T. 121600989V29/12/1204/01/13 105Nguyn Th T.130203685V12/01/1304/03/13 106Nguyn Th Th.120204340V22/03/1211/04/12 107Ng Ngc Th.121100190V05/04/1208/05/12 108Bch Ng Th.120206651V12/05/1210/07/12 109Hong Trng Th.121100265V24/05/1228/06/12 110inh Th Th.120205284V29/05/1202/06/12 111Trn Th Kim Th. 120210905V13/06/1202/07/12 112Trn Vn Th.120211276V17/07/1226/07/12 113L Th Th.120018673V25/07/1205/08/12 114Nguyn Th Th. 120214275V25/07/1203/08/12 115Nguyn Th Th.121600741V29/08/1230/08/12 116Hong Th Th.120215093V06/09/1228/09/12 117Trn Th Th.120212385V12/09/1204/10/12 118V Hng Th.121100252V08/10/1206/11/12 119u Th Th.120040195V17/10/1227/11/12 120Lng Duy Th. 121100113V25/10/1217/11/12 121Trnh Th Th.120305106V07/11/1214/12/12 122Dip Th Th.120904477V12/12/1209/01/13 123Nguyn Th Th.130201727V31/01/1307/02/13 124Trn Khc Th.130200482V14/02/1314/03/13 125L Vn Tr.120205394V22/03/1230/03/12 126Phm Quang Tr. 120904171V30/10/1219/11/12 127Nguyn Vit Tr.130201055V21/02/1313/03/13 128Trn Th V.120206062V10/04/1220/04/12 129V Tr V.120206610V22/04/1230/04/12 130T Ngc V.120210145V08/06/1217/06/12 131Vng Vn V. 120214867V17/08/1229/08/12 132Tng Vn V.121100286V17/08/1205/09/12 133Lng Nht V.121100236V25/10/1211/11/12 134 Hu V.121100135V21/11/1219/12/12 135Trn Quc V. 120220054V23/12/1209/01/13 136ng c V.131100006V03/02/1320/02/13 137Phm Cao V.120205132V28/04/1211/05/12