JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol.12 - N''7/2017
Danh gia ket qua dilu tri benh nhan lao ph6i khang da thudc b^ng phac d6 4a tai Benh vien 74 Trung uong
To assess the results of treatment multidrug resistance pulmonary tuberculosis patients with regimen 4a at 74 Central Hospital
Dang Van Khoa, Ph^m Gia Nh^t Senh vien 74 Tmng uang
Tom tat
Muc tieu: Danh g i l ket q u i dieu tri benh nhan lao phdi khIng da thudc bang phac dd 4a. Doi tugng va phuang phdp: Nghien cQu dieu tri cho 136 benh nhan lao phdi khIng da thude b i n g phle do 4a: 8(Z E Km Lfx Pt Cs)/ 12(E Z Lfx Pt Cs) tai B&nh vien 74 Trung uang tU n l m 2011 - 2015. Kitqud vd kit ludn: Qan\\
gia dupe 110 benh nhan, chuyen 26 benh nhan, thanh cdng 74,6% (khdi 65,5%, hoan t h l n h 9,1%), that bai 10,0%, bd trj 13,6%, chet 1,8%; soi trUc tiep AFB(-)/ely MTB(-) sau 8 thang cua li§u trinh 4a dat 91,0%, nhijffig trUdng hop soi AFB(-H)/dy MTB(+) sau 8 t h i n g eCia lieu trinh 4a deu that bai dieu tn; tac dung khdng mong muon cQa thudc (ADR): Sd ea ed d l y bung - chan I n chiem 40,4%, non - budn non chiem 66,9%, viem da day chiem 22,8%, chong mat - u tai chiem 34,6%, dau khcfp ehiem 37,5%.
Tdkhda: Lao phoi da khIng thudc, phac do 4a.
Summary
Objective:To assess the results of treatment multidrug resistance pulmonary tuberculosis patients with regimen 4a. Subject and method: Research treatment regimen 4a: 8(Z E Km Lfx Pt Cs)/ 12(E Z Lfx Pt Cs) for 136 patients with multidrug resistance (MDR) pulmonary tuberculosis (TB) at 74 Central Hospital from 2011 to 2015. Result and conclusion: Assessed 110 patients, transferred 26 patients, successful rate was 74.6%
(cured 65.5%; completed 9.1%), failure rate was 10.0%, give up treatment rate was 13.6%, death rate was 1.8%). After 8 months of treatment, 91% of cases had AFB-smear negative (-) and MTB<ulture negative (-).
The ease had AFB-smear positive (-1-)/ MTB-eulture positive (+) after 8 months of regimen 4a were failure;
the adverse drug reaction (ADR) of treatment regimen 4a: Dyspepsia rate was 40.4%; vomiting- nausea rate was 66.9%, gastritis rate was 22.8%, dizziness-tinnitus rate was 34.6%, aching joint rate was 37.5%.
Keywords: Multidrug resistance pulmonary tuberculosis, regimen 4a.
I . D a t v a n d e MDR-TB eao; h l n g nam nUdc ta ed khoang 4500
„ . . , ,. . ^ ^ . , , .J ngudi m I c MDR-TB, nhUng p h l t hien va thu dung Benh lao Wiang da thuoc (multidrug resistance ^ j . ^ ^^j f ^ ^ p . ^ g ^ ^ ^ j , ^^holng 30%) [4]. Di^u trj ubereulos.s-MDRTB)la:Ngua, benh maetrLfckhuan ^ ^ p . ^ g ^ - ^ . ^ ^ ^ , j . ^ ,^hd khan, tdn kem lao (Myeobaaenum tubercuos^ -^MTB) eo khang ^^^i gian va tien bae la ganh nang cho edng Xk nfampicin (RIF, R) va isoniazid (INH, H) t r d len [2]. ^^ . ^ ^ ,^^ ^^.^ ^ ^ - ^ ^ . ^ ^^f
f r r n n n nnTy-rZ''^ , . ' v ° ' ' \ • ' ? . , , n " ° ' . ^ ' ' Theo \NHO (2008), dUa ra quy tae dieu trj MDR- (CTCLQG) (2015). V e t Nam dung thU 11/30 nUac co ^ ^ ^ . ^ ^ . ^ ^ ^ ^ ^ , ^ ^.^ ,.^^ ^ . ^ { ^ , g , , ,,3, .^uoc chdng lao chSc chan hoac g^n nhir chSc chSn con Ngay nhgn bai: 05/S/20I7. ngay chdp nhan ddng: 10/5/2017 nhay v6i MTB, thcll gian keo dai it nhat 18 thang; cac Nguaiphdn hai: Bang Van Khoa, nghien cOtu theo hi/6ng nay cho ket q u i thanh cong Email- [email protected] - Benh vien 74 Tnmg irong
52
t TAPCHIYDUOCLAMSANGIO; Tap 12-56 7/2017
trong k h o i n g 60 - 80% [6j. CTCLQG (2009) dUa ra phle dd ehuan 4a: 8(Km, Z, E, Lfx, Pto, Cs) (PAS)/ 12(Z,
\\ E, Lfx, Pto, Cs (PAS)) de I p dung dieu tri chung cho d c trudng hop MDR-TB phat hidn dUpc [2].
The benh lao phdi k h I n g da thudc (LPKDT) A F B / ( + ) la ngudn lay chinh nguy hiem va t h u d n g M gap hon d so vdi d c the MDR-TB khac nen d n
dupc giam sat quan ly dieu tri tang cUdng hPn.
Hien p h l e do 4a cdn chUa dupc ap dung trong toan qude, c l n dugc khao sat danh gia day du ban ., trong thuc tien. Vi v l y ehung tdi tien hanh nghidn
cUu nay vdi mue tieu:
Nhdn xit kit qud dieu trj loo phoi khdng da thuoc bang phdc do 8(Km, Z, E, Lfx, Pto, Cs)/ U(Z, E, Lfx, Pto, s Cs) tgi Binh vien 74 Trung dong.
^ Ddnh gid tdc dung khdng mong muon cua cdc
•^ thudc sd dung trong phdc do 8(Km, Z, E, Lfx, Pto, Cs)/
1 12(Z,E,Lfx,Pto,Cs).
n 2. Odi tuong va phUcmg phap
2.7.0ditd^g
Tiiu chudn Ida chgn
136 benh nhan LPKBT > 16 tuoi, ed ehi dmh dieu tri (DT) phac do 4a tai Benh vien 74 Trung Uong nam2011-2015.
Chan d o l n xae dinh LPKOT: Khi cd lao phdi do _'. MTB khang rifampicin (RIF, R) vd isoniazid (INH, H)
". (xae dmh bang Haintest hoac cay khang sinh do MTB
^ tren mdi trUdng Lowenstein Jensen) [2], I Phac dd 4a [2]: 8(Km Z E Lfx Pt Cs)/12(E Z Lfx Pt Cs).
,5 Giai doan 1 (tan edng) la 8 t h i n g ddng g Kanamycin (Km), Pyrazinamid (Z), Ethambutol (E), Levofloxacin (Li^), Prothionamid (Pto), Cyeloserin (Cs); giai doan 2 (duy tri) la 12 t h i n g van dung d c
• thudc tren nhung khdng cd Kanamycin (Km).
j.r Chi djnh dieu trj phae do 4a [2]: Cle benh n h i n ,3 MDR-TB mdi (chUa dieu trj lao l l n nao), benh nhan f- MDR-TB cd tien sii dieu trj thudc ehdng lao hang 1 fj (first line drug - FLD) nhung: Bd trj, tai phat h o l e that j( bai phac do 1, 2 ( p h l n loai theo quy dinh cCia
CTCLQG - 2009).
If Thude ehdng lao dung 6 n g l y / 1 tuan (nghi ehu IK nhat), cleh dCjng va lieu lupng moi thude theo quy ,(« dmh cCia CTCLQG 2009 [2].
H Tiiu chudn logi trd
^ Benh nhan khdng thudc ddi tupng lua chon.
Benh n h i n LPK£)T ed kem: CIc bdnh I n h hUdng nhieu ddn ket qua dieu trj lao: H1V(+), dai t h I o dudng, suy tim giai doan 3 t r d len, benh ung thU; cac tinh trang benh cd ehdng chi djnh hole khdng cd k h i n l n g dung thudc trong phac do (PE)) 4a: Suy gan/suy than nang t r d len, dj Ung vdi thude, rdi loan tam than, m i t trf nhd, hdn me, benh phai m d thdng da day...
2.2. Phdong phap: Hdi eUu, md ta, cat ngang loat bdnh.
2.3. Ky thuat chpn miu: Chon mau thuan tien, khdng xae suit.
2.4. Thdi gian, dia diem: TU thang 01 den t h i n g 12 nam 2015, tai Benh vien 74 Trung UPng.
2.5. Cach tien hanh
Lua ehpn benh I n Xii danh sach dieu tri benh nhan LPKDT tai Benh vien 74 Trung UPng du tieu ehuan lUa ehpn nghien cdu (NC). Thu thap thdng tin vao mau benh an nghien cdu.
Ndi dung nghiin cdu
Ghi nhan thay ddi trieu chdng l l m sang: Toan than, CO nang, thuc the; d n lam sang: X-quang phdi, ket qua soi true tiep (TT) AFB va d y MTB bdnh pham d d m trong q u i trinh didu trj; danh gia ket qua khi ngUdi benh ket thue dieu tri.
Ghi nhan d c trieu chUng benh do ADR (Adverse Drug Reaction - t i e dung khdng mong mudn cua cac thudc) va cac chi sd sinh hda mau (SHM) bat t h u d n g do ADR eua ngUdi benh trong q u i trinh dieu trj p h l e do 4a.
Cdc chi tieu nghiin cdu
Ho sa benh an benh n h i n nghien eUu do d c bac sy chuydn khoa hd hap tai B a n nguyen dieu tri MDR - TB Benh vien 74 Trung UPng tham kham theo ddi dieu trj, q u I n ly ADR dung hudng dan eua CTCLQG 2009 [2].
Soi ddm TT tim AFB (nhudm Zielh neelsen), d y d d m khang sinh d d MTB (mdi trudng Lowenstein Jensen), d y ddm MTB theo ddi dieu trj (mdi trUdng MGIT) tai Benh vien 74 Trung uang deu theo quy djnh cua CTCLQG [1].
MUc dp tdn thuang X-quang phoi theo ATS 2000.
Danh g i l ket q u i dieu trj theo quy djnh cua CTCLQG 2015 [1].
2.6. Xdlysdlieu:Qang p h l n mem SPSS 16.0.
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JOURNAL OF 108 - CLINICAL MEDICINE A N D PHARMACY V o L 1 2 - N " 7 / 2 0 n
3. Ket q u i
3.1. Oac diem chung
Tuoi trung blnh cua benh nhan la: 41,43 ± 12,67 tuoi; nam 106/136 (77,9%), nO 30/136 (22,1%), t} le nam/nO la 3,5/1. Ket qua nghien cdu cOa chiing toi tuong doi phu help so vdi: Phan Thuang Bat (2008) [6), Nguyen Huy Dung (2014) [5]; nam gicii mac benh LPKBT da thUc sir cao hon nff gidi.
3.2. Banh gia ket qu^ dieutri lao phoi khang &a thuoc bang phac 06 4a 3.2. l.Jhay doi trieu chiing iam sang
Bdng 1 . Thay d o i t r i e u chufng lam sang t r o n g d i e u t r i
^•^—^--..^.^^^ Thdi gian Trieu chijmg "^ .__
S6t Ho, khac ddm Ho ra mau Dau nguc Khdthd Ran am, no Ran rit, ngay
n(%) n(%) n(%) n(%) n(%) n(%) n(%) PfO-f;
TrUdc dieu trj (0) (n = 136) 42 (30,9) 136(100) 42 (30,9) 75(55,1) 37 (27,2) 134(98,5) 49 (36,0)
4 t h a n g (n = 132) 23 (17,5) 130(98,5) 39 (29,5) 51 (38,6) 32 (24,2) 111 (84,1) 43 (32,6)
8 thang (n = 122)
0 86 (70,5)
22(18) 22(18) 19(15,6) 60 (49,2) 25 (20,5)
14thang (n = 101)
0 64 (63,4)
9 (8,9) 11 (10,9) 10(9,9) 19(18,8) 13(12,9)
OiiPD(EI (n = 91) 5 (3,7) 27 (29,7)
4 (4,4) 9 (9,9) 5(5,5) 14(15,4]
5(S,5)
<0,05
Benh nhan nghien cUu g i l m dan do: Chuyen don vj dieu trj khac 26 ca, chuyen phae dd khIe 2 ca, bo trj 15 ca va t d vong 2 ea.
Trieu chUng l l m sang g i l m rd theo thdi gian dieu t n (DT). Sd it ca van cdn ho khac ddm, khd thd, tiic ngue va ho ra mau, ran am ran nd du da dUpe dieu trj khdi ve vl sinh lao; nguyen nhan do d c di chdng hang (eu), xo, vdi, xep phdi... g l y nen. Ket qua nghien eUu nay k h i phu hpp vdi nghien cUu cOa Nguyen Anh Quan (2012) [4].
Thay ddi d n n l n g trung blnh eua ngudi benh: Tang td47,96 ± 7,87kg (trUdc ST) len 50,15 ± 7,83kg (sau
€)T), ed khae biet vdi p<0,05; phu hpp vdi Phan ThUpng Dat (2008) [6]. Ngudi benh tang d n da g i l n tiep noi len phac do 4a la cd hieu q u i .
3.2.2. Thay ddi triiu chdng can Idm sdng
Bdng 2 . K^t quA x e t n g h i e m v i IchuSn lao km t i n h t r o n g d i e u trj - J ^ ^ * *•"** ^^^ nghiem
Thcri gian Trudc dieu tri (n = 136) Thang 2 (n = 135) Thang 4 (n = 132) Thang 6 (n = 125) Thang 8 (n = 122) T h a n g l l (n = 112) Thang 14 (n = 101) Thang 17 (n = 94) Ket thuc phac do (n = 91)
Soi AFB(-) n{%) 5 (3,7) 29(21,5) 93 (70,5) 106(848) 111(91) 102(91,1)
91 (90,1) 85 (90,4) 82(90,1)
CayMTB(-) n(%)
0 9(6,7) 90 (68,2) 106(848) 111(91) 102(91,1)
91 (90,1) 85 (90,4) 82(90,1)
TAP CHl Y DUOC LAM SANG 108 Tap 12-56 7/2017
Ty le soi TT AFB(-)/ d y MTB(-) hau nhU khdng thay ddi t d t h i n g thU 8 eua phae do. Theo Nguyen Anh Quan [2012), tJ' le am hda vi sinh lao trong ddm tang manh trong 3 t h i n g d i u nhung sau do hau nhU khdng thay doi [4].
Bdng 3. Thay tfoi mi^c do t o n tht/img X-quang trong dieu trj
TTXQ D p i Doll Dp III
Thcri gian
n(%) n(%) n(%)
TrUdc dieu trj (n = 136)[01 25(18,4) 63 (46,3) 48 (35,3)
Thang 8 (n = 122) 62 (50,8) 30 (24,6) 30 (24,6)
Ket thuc PD (n = 91)[El
55 (60,4) 7 (7,7) 29(31,9)
P(O-E)
<0,05
>0,05 Sau dieu trj mijfc d6 ton thuong X-quang (TTXQ) phoi giam rd ret; tuong doi phu hop vdi Nguyen Anh Quan (2012) [41.
Thu gon ton t h u o n g X-quang phdi sau dieu trj (n = 91): Cd thu gpn 82 ca (90,1%), Ichdng thu gon 6 ca (6,6%): tdn t h u o n g rdng hon 3 ca (3,3%); theo Phan Thuong Oat (2008), sd ca cd thu gon ton thuong X-quang la 84,0% [6].
3.2.3. Ket qua dieu tri
Ket qua dieu t n ciia tat c^ benh nhan nghien cUu (n = 136): Thanh cdng 60,3% (l<hdi 52,9%, hoan thanh dieu trj 7,4%); that bai 8,1 %, bd tri 11 %, chet la 1,5%; chuyen la 19,1 %.
Bdng 4. Ket qui dieu trj cOa cac ca ddnh gia ducrc, bd so ca ciiuyln (n = 110)
^ ^ ^ K Q BN ^ ^ - - ^
n T y l e %
Khdi 72 65,5
Hointhanh diSu tri
10 9,1
Th^t bai 11 10,0
B6 15 13,6
Chet 2 1,8
Tong 110 100 Nghidn cUu thay bdnh nhan bd trj khi dang dieu tri ngoai tru la chfnh, cd the do ngudi benh chO quan vd benh va sU ho trp cda can bd y te co sd edn han ehe.
Theo nghien cdu dieu tri MDR-TB: Ahuja SD (2012), thanh cdng la 54,0%, that bai hole t l i p h l t la 8,0%, chdt la 15,0%, bd tri H 23,0% [7]; Nguyen Huy Dung (2013), khdi 78,5%, h o l n t h l n h 6,3%, bd tri 3,8%, t h i t bai 6,3%, chet 3,8% [5]. NhOng nghien cdu nay deu khdng ed bdnh n h i n chuyen don vj khac trong qua trinh ^ e u trj.
3.2.4. Tdc dung khdng mong mudn cua thuoc (ADR) trong qud trinh diiu tri
70
% /
60 50 40 30 20 10
r/ n Dau bung, chdn in
2 2 j
1^1
Budn riAn, Viem dg nbn ddy
34,6
Cti6ng mgt, Cita!
' [
Dau khdp
Khftng c6 ADR
ADR
Bieu d 6 1 . Sd ea ed tri&u chUng ADR trong qua trinh dieu tri (n = 136) Trieu chUng ADR cd xuat hien trong dieu tri nhung nhe, ed the kiem soat dupe.
JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY VolU-nVnQM
BIng 5. So ca co chi sd sinh hoa mau bat thUdng trong qua trinh dieu tri (n = 136)
^-—-..^^^ Benh nhan SHM bat thudng ~ ~ - — . ^ ^ AST > 1,25N (Normal - mdc blnh thudng)
ALT>1,25N BillrubinTP>lN BilirubinTT>1N Creatinin > 1N K*< 3,4mmol/l A.uric>l,25N(500Mmol/l) SHM blnh thudng
n
39 20 21 34 15 42 124
4 TJIe%
28,7 14,7 15,7 25,0 11,0 30,9 91,2 2,9 Sd ea cd thay ddi b i t thUdng ehi sd sinh hda ve chUc nang gan than la it va chu yeu d mUe nhe va vUa; khdng cd sinh hda m l u b i t thudng mUc dp nang hoae rat n l n g .
4. Ket luan
TU ket qua nghien cdu tren 136 benh n h i n lao phdi khang da thude dupe dieu trj b i n g phae d d 4a ehung tdi cd ket luan:
Thay doi triiu chdng Idm sdng, can Idm sdng cda ngudl binh
Trudc v l sau dieu trj eac trieu ehUng lam s i n g deu g i l m ro ret, tan s u i t ca ed: Sdt tU 30,9% g i l m cdn 3,7%, ho ra mau tU 30,9% giam cdn 4,4%, khd t h d t u 27,2% giam cdn 5,5%, ho ddm tU 100% giam edn 29,7%, dau ngUe t d 55,1% giam cdn 9,9%, ran am no d phdi t d 98,5% g i l m edn 5,5%.
TJ' le am tinh ddm qua soi true tiep va nudi eay:
Sau 8 t h i n g sd ea soi AFB(-) /cay MTB(-) dat 91,0%, het phac dd dat 90,1%; nhQng trudng hpp soi AFB(+)/ eay MTB(-i-) sau 8 t h i n g deu t h i t bai dieu trj.
Sd ea cd thu gpn tdn thuong tren X-quang phoi trong q u i trinh didu tri ehiem tdi 90,1 %.
Kit gud diiu tri: Thanh edng 60,3% (khdi 52,9%, hoan thanh dieu trj 7,4%); t h i t bai 8,1%, bd trj 1 1 % , chet 1,5%; chuyen dja phuang 19,1%.
Tdc dung khdng mong mudn cua thuoc (ADR): Sd ca ed day bung - chan an chiem 40,4%, ndn - budn
ndn chiem 66,9%, viem da day chiem 22,8%, chong mat - u tai chiem 34,6%, dau khdp chiem 37,5%; so ea cd tang a. uric > 1,25N chlem 91,2%, tang AST>
1,25N (Normal) ehiem 28,7%, tang bilirubin TT > I N chidm 25%, Creatinin t i n g > I N chiem 30,9%, cac t i e dung phu len ehde nang gan, than d mUc do nhe v l vCra.
5. Kien nghj
Phle dd 4a nen dupc ap dung de dieu tri eho benh n h i n lao khIng da thudc rpng rai cho mpi tinh thanh,
Tai lieu tham k h i o
1. Bp Y te (2015) Hu'dng dan chdn dodn, diiu tn va du phdng binh lao. Quyet djnh so 4263/ 2015/ QD-BYT.
2 CTCLQG (2009) Hddng dan qudn ly binh lao Widng da thuoc. Ha N6i, tr. 11 -42.
3. CTCLQG (2015) Bdo cdo tdng kit hogt ddng chong lao ndm 2015 vd phuang hu'dng hogt dgng ndm 2016.
4. Nguyen Anh Quan va CS (2012) Kit qud budc 3aii diiu tri lao phoi khdng da thudc tgi Binh Dinh bdng phdc do 6km (cm) Lfx EZ Pto CS/12 Lfx EZPto.
5. Nguyen Huy Dung va CS (2014) Mdu ki dan thuoc trong CTCLQQ - ngoai CTCLQG vd kit qud dieu tri binh lao khdng da thudc tgi Binh viin Phgm Ngoc Thach. Bao cao tdng ket Du an TB care I, Ha Noi t h i n g 12 nam 2014.
6 Phan Thupng Dat (2012) Oieu tri lao phoi khar\g thudc thd phdt bdng phdc do diiu tri co cdc t/iufic khdng lao the hi hai cu vd mdi. Luan an Tien si y hpe, Oai hpc Y Thlnh phd HCM, tr. 50-54.
7 Ahuja SD,AshkinD,AvendanoM et al (2012) Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: An individual patient data meta-analysis of 9.153 pat/enfs. PLoS Med, 9:e1001300,DOIPubMed.
8. WHO (2013) Anti-tuberculosis drug resistance in the world.
9 WHO (2011) Guidelines for the programmatic management of drug-resistant tuberculosii- Update 2011.
