Y Hgc TP. Ho Chi M i n h * Tap 16 * So 4 * 2012 N g h i e n cmi Y hgc
PHAN l/NG V 6 l THUOC CHONG LAO:
NGTOEN CUtr HOI CtfU TAI BENH VIEN PHAM NGOC THACH
NguySn Thi Bich Ym*, Nguyen HOu Lan*
TOMTAT
Dat van de: Phdn img vai thuoc chong lao (PlfTCL) trong qud trinh dieii. trj co the dnh Hwang deh sit tuan ihii vd ket qud dieu tii lao cho ngiem benh. O Viet Nam, solieu vePlTFCL con chua nhieu.
Muc tieu: Mo td vePLtTCL cua cdc benh nhdn (BN) dim tri noi tru tai benh vien Pham Ngoc Thach, thdnh -pho Ho Chi Minh, Viet Nam trong nam 1010.
Phuongphdp nghien cuu: Nghien dm hoi cieu hosa cua 315 BN lao bi PUTCL.
KA qud: Trong so 315 BN nhap vim vi PUTCL tai binh vien Pham Ngoc Thach trong nam 2010, cd 203 (64,4%) nam vd 112 (35,6%) nie; tuoi trung binh 46 (tie 15-91 tuoi). Thud'c nghi ngd gdy phdn img thudng Id lifampidn (88/315, 27,9%), pyrazinamide (81/315, 25,7%) vd streptomycin (78/315, 24,8%). boniazid vd eihambutol it gap han (theo thd tu Id 43/315, 13,7% vd 33/315,10,57o). Trieu chimg deBN nhap vien thieang gap nlml (149/315, 47,3%) Id ti'liu chiing veda nhie man ngiia, nhiem doc da, mdy day, phu mach, do da todn thdn, hoi chimg Stevens-Johnson; tiep iheo Id cdc trieu chimg non, buon non, dau bung (51/315,16,2%), vdng da (27/315, 8,6%). Thua: chong lao duac ngung sie dung vd khi cho 177/315 (56,2%) BN diing lai thuoc voi lieii luang khdc nhau, cd 128/177(72,3%) BN tdi xudi him trieu chung phdn img vdi thuoc, 26/177 (14,7%) BN idiong CO trim chieng phdn img vdi thuoc vd con 23/177 (13%) BN co phdn img vdi thuoc kliong rd rdng.
Kei luan: Nghien cieu ndy cho thdy quy ti-inh thu thuo'c hien nay duac sir diing rdi da dang vd Idiong dua tren bdng chimg tot. Nghien cim tie'n cim dua tren bdng chung vd quy tiinh thu thud'c cdn dieac phdt trien de hudng dan ldm sdng thuc hien thu: thuoc cho BN bi phdn img v&i ttiuoc Idti dang dieU b-i lao.
Tie khoa: Benh nlmn lao, thuoc Ididng lao, phdn img vdi thuoc ABSTRACT
ADVERSE REACTIONS OF ANTI-TUBERCULOSIS DRUGS: A RETROSPECTIVE STUDY IN PHAM NGOC THACH HOSPTTAL
Nguyen Thi Bich Yen, Nguyen Huu Lan * Y hoc TP. Ho Chi Minh * Vol. 16 - No 4 - 2012:215 - 221 Introduction: Adverse drug reactions (ADRs) due to anti-tuberculosis thei'apy can effect on adherence and outcome. In Vietnam, data of anti-TB-induced ADRs are limited.
Objectives: To describe ADRs to antituberculous agents among in-patient admissions at Pham Ngoc Thach Hospital, Ho Chi Minh City, Viet Nam in 2010.
Methods: A retrospective study reviewed 315 records of all TB patients with ADRs.
Results: Of the 315 patients admitted with suspected antituberculous iherapy-assodated ADRs, there were 203 (64.4%) males and 112 (35.6%) females; mean age was 46 (range: 15 to 91) years old. "The majority of ddected ADRs were attributed to lifampidn (88/315, 27.9%), pyrazinamide (81/315, 25.7%) or streptomycin (78/315, 24.8%). Isoniazid and ethambutol were suspected as the causative agent less frequently (43/315, 13,7%
and 33/315, 10,5%, respectively). The highest percentage of ADRs (149/315, 47.3%) causing hospital admission
*BeDh vien Pham Ngpc Thach, Tp. Ho Chi Minh.
Tdc gid lien lac. BS. Nguyen Hiiu Lan DT: 09131858^ Emad: nguyenhuulanl965@gmaiLcom
N g h i e n ciiu Y hoc Y Hpc TF. H o C h i M i n h * Tap 16 * So 4 * 2012 was skin rash, toxidennia, urticaria, angioedmia, erythroderma, Stevens-Johnson s)fndrome; nausea, vomiting, abdominal pain (51/315, 16.2%), icterus (27/315, 8.6%). Anti-tuberculosis drugs weie stopped and tlien rechallenged in 177/315 (56.2%) patients with different doses, of whom 128/177 (72.3%) developed re- inb-oduction reactions, 26/177 (14.7%) had no recurrence of ADR symptoms and tlie remaining (23 patients, 13%) had unclear reactions.
Conclusion: This study demonstrates that method of antituberculosis drugs rechallenging is highly variable and not based on good evidence. It is necessary to deoelop a prospective evidence base and a clinical aligorithm to guide clinicians in the reintroduction ofanti-TB drugs after the development of ADR in patients with TB.
Key words: TB patient, antitubermhus agent, adveise drug reactions.
DATVANDE
Phan ling voi thuo'c thuong gap trong thuc hanh y khoa. Ta't ca cac thu6'c dieu tri b?nh deu CO the gay phan iing ba't Ipi cho benh nhan. Viec dieu trj benh lau dai voi nhieu locii thuo'c lam tang kha nang bi phan iing vcH thuo'c. Theo To chiic y te the giai (WHO), phan iing voi thuoc
"La nhiing phan ung dpc hay co hai khong dupe mong dpi doi voi thu6'c, xay ra 6 lieu th6ng thirong khi dupe sir dung tren nguoi de du phong, chan doan hoac dieu tri benh hay de thay doi chiic nang sinh ly"«. Cac phan ung nay dan toi vipc ngimg dieu tri thuo'c do, hoac la nguyen nhan de benh nhan nhap vien"^'.
Lao la mpt b|nh nhiem khuai pho bieh d Viet Nam. Theo WHO, nam 2010, tan sua't lao tai Vi?t Nam la 290 ca benh/100.000 dan (ke ca nguoi nhiem HIV), ti sua't lao moi hang nam la 180/100.000 dan("). Dya vao chien lupc DOTS th6ng qua mang luoi cho'ng lao tuye'n co so, deh nam 2007, chuang trinh cho'ng lao qu6'c gia (CTCL(3G) nuoc ta da dat dupe muc tieu ciia WHO dgt ra la phat hien tren 70% cac ca lao phoi moi AFB (+) va dieu tri lanh b?nh tren 85%
nhung ca nayf"». Tuy nhien nhiing thach thiic ciing dang gia tang, do la tinh hinh lao/HIV, lao da khang thuoc, sieu khang thuoc xua't hien. Vi v^y, mac dil dupe dieu tri va quan ly, lao van la mpt van de siic khoe dang lo ngai ciia Viet Nam.
Phan ling voi thuoc chong lao lam phuc tap them vi?c dieu tri lao, lam tiiay doi hay gian do?n dieu tri, va cung la ly do quan trpng lam BN kem tuan thii dieu tn lao. Trong mot nghien cuu ve ke't qua dieu hi lao 6 597 BN lao phoi
moi tai 16 benh vi|n quo'c gia 6 Nhat nam 1996 bj ngimg hay gian doan isoniazid va rifampicin trong thoi gian dieu tri laoP', cac tac gia thay ty 1? khoi benh (ca'y am hoa sau tho"! gian dieu trj) 6 nhom BN bi gian doan isoniazid va rifampicin (88,9%) thap hon so vcii nhom kh6ng bi gian doan (98,9%).
Ciing nhu cac khang sinh khac, tac dung phy do thuoc lao ra't da d ^ g tren lam sang. Mpt s6'nghien ciiu da nhan thay yeu to'co dia, chiing tpc chau A cnia b#nh nhan dong vai tro quan trpng trong sir xua't hien phan iing voi thuo'c chong laoi^-i^J. Phan ung voi thuoc chong lao lam cho viec dieu tri lao bi gian doan, co the phai thay doi cong tiiirc thuoc, va anh hirong toi ke\
qua dieu tri lao.
B|nh vien Pham Ngpc Thgch la benh vi|n chuyen khoa lao va benh phoi tuye'n cuo'i tai khu vuc phia Nam Viet Nam, thuong tiep nhan dieu tri cac truong hpp phan iing voi thuoc chong lao. Hang nam, so benh nhan nhap vien vi phan ung vcH thuoc khoang 300 nguoi. Cho deh nay, van chua co nhieu thong tin ve tinh hinh phan iing vcii thuo'c chong lao tai benh vien Pham Ngpc Thgch, va anh huong a i a no tcH viec dieu hi lao. Chiing t6i tieh hanh mot nghien ciiu hoi ciiu tren benh nhan phan img voi thu6'c chohg lao nhap benh vi?n Pham Ngpc Thgch trong 2010, nham mo ta mpt so dac diem lam sang va xet nghiem a i a nhiing benh nhan nay. Chiing toi hy vpng nhiing s6'li?u buoc dau CO the lam co so cho nhiing nghien cihi sau hon ve loai benh nay trong tuong lai.
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Y Hgc TP. H o Chi M i n h * Tap 16 * So 4 * 2012 N g h i e n ciiu Y hpc
D O m r O N G - F H U O N G PHAP NGHIEN CLfU Hoi ciru ho so toan bp cac benh nhan lao nhap benh vi|n Pham Ngpc Thach vi phan iing voi thuo'c chohg lao trong nam 2010. Thu thap cac thong tin tir ho so benh an ve tuoi, gidi, tien sir di ling va benh tat khac; thoi gian phan iing vol tiiuo'c; t n | u chiing phan iing voi thuo'c; kha nang cac thuo'c nghi gay ra phan img cho BN va phan dp nang ciia phan iing voi thu6'c cung nhu cac chi so'xet nghifm.
Mpt thu6'c dupe cho la co kha nang gay ra phan ling cho benh nhan khi cac trieu chiing hogc daii hieu phan iing khong con niia sau khi BN ngimg tiiuoc va tai xua't hien khi thii dieu tri lai vol thu6'c do^^'.
Phan dp nang ciia phan iing voi thu6'c (PUT): Theo Hartwigi^)
Dp 1: Co 1 PUT xay ra nhung khong thay doi dieu tri voi thuo'c nghi ngo.
Dp 2; PLTT xay ra co the doi hoi n g u n g dieu tri voi thuo'c nghi ngo hoac doi thuo'c, nhung khong can thuo'c giai dpc hay cac dieu tri dac hieu khac. Khong keo dai thoi gian nam vien ciia BN.
Dp 3: PUT xay ra co the doi hoi ngimg dieu tri vcSi thuo'c nghi ngo hoac doi thuo'c, va/hoac can thu6'c giai dpc hay cac dieu tri dac hieu khac. Khong keo dai tiioi gian nam vien cua BN.
Dp 4: Muc 3 va tang thoi gian nam vien a i a BN it nhat 1 ngay, h o | c PUT la ly do BN nhap vien.
Dp 5: Miic 4 va can dieu tri tich cue.
Dp 6: PUT gay ton hai viiih vien cho BN.
Dp 7: PUT true tie'p hay gian tiep gay hi vong cho BN.
Dp nang ciia nhiem dpc gan 6 benh nhan diing thu6'c lao dupe chia lam 4 miic, dua vao chi so transaminase (AST, ALT) va bilirubin toan phanfi^J.
Miic 0: AST / ALT / bilirubin < 3 lan gicji han tren cua tri so binh tiiuong.
Miic 1: AST / ALT / bilirubin tii > 3-5 lan gioi
han tren aia tri so binh thuang.
Miic 2: AST / ALT / bUirubin tii > 5-10 lan gidi han tren cnia tri so'binh thuong.
Miic 3: AST / ALT / biUrubin tir > 10 lan gicH han tren cnia tri so binh thuong.
Cac so' lieu sau khi thu t h | p se dupe ma hoa va nhap vao may vi tinh, sii dung phan mem th6hg ke SPSS 16.0 de xii ly. Chung toi sii dung phep Idem Mann-Whitney de so sanh su khac biet giiia hai nhom benh nhan cho cac bieh dinh lupng va phep kiein x^ de so sanh su khac biet ve ty Ie giira hai nhom benh nhan cho cac bieh dinh tinh. Thp'c hien phep kiein chinh xac ciia Fisher (Fisher's Exact Test) neu co tren 20% so' 6 trong bang cheo co tan so' mong dpi nho hem 5.
Ta't ca cac phirong phap Idem dinh gia thuye't dupe thuc hien bSng each sir dung kiem dinh 2 ben (two-sided alternatives). Nguong y nghia la 0,05 (p < 0,05) de chap nhan hay bac bo gia thuye't tho'ng ke.
KETQUA Tuoi, gioi va the lao
Trong nam 2010, benh vien Pham Ngpc Thach thu nhan dieu tri npi tni 315 benh nhan CO phan iing voi thuo'c cho'ng lao, trong do co 203 BN nam (64,4%) va 112 BN nu (35,6%). Ty le nam/nir la 1,8/1. Tuoi trung binh ciia BN la 46 + 17,5 tuoi (hi 15-91 tuoi). Tuoi trung binh benh nhan nam la 48 + 17 tu6i, nir la 44 ± 19 tuoi (p <
0,05). Co 71/315 (22,5%) BN > 60 tuoi. Khong c6 khac biet co y nghTa th6'ng ke ve ty le benh nhan theo Ilia tuoi va gioi tinh (p > 0,2).
Trong so' BN bi phan iing voi thu6'c ch6'ng lao nhap vien nam 2010, lao phoi AFB (+) va AFB (-) chie'm 48,6% (153/315 BN), lao ngoai phoi chiem 25,1% (79/315 BN), 13,7% BN la lao phoi da khang thuo'c (MDR).
Da so' benh an khong co thong tin ve tien sii hiit thuo'c la, uo'ng nrpu hay ma tiiy ciia BN do nhan vien y te kh6ng hoi, voi ty le hfong ung la 69,5%, 75,9% va 74%. 80/315 (25,4%) BN CO tien sii dieu tri lao truac tu 1 deh 4 lan. So BN co tien sir di iing thu6'c lao la
N g h i e n cmi Y hpc Y Hgc TP. H o C h i M i n h * T a p 16 * So 4 * 2012 23/315 nguoi (7,3%) va 3 truong hpp co tien
sir dj ung vcii cac thu6'c khac (1%).
Benh kem theo
Ngoai m^c lao, 129/315 (41%) benh nhan trong nghien cniu nay co kem them cac benh khac. Nhieu nha't la nhiem HIV (46 BN - 14,6%), sau do la tieu duong (20 BN = 15,5%).
Con Igi la cac benh khac nhu hen phe' quan, b^nh phoi tac nghen man h'nh, vay ne'n, xo gan, gout, suy than man...
Trong thoi gian nam vien, da so' BN khong dupe chah doan nhiem HBV, HCV va HIV, voi ty 1? tuong ling la 70,2%, 69,8% va 56,8%. Trong so' BN dupe lam xet nghiem, ty le BN co HBsAg (+) la 8/94 BN (8,5%), anti-HCV (+) la 15/95 BN (15,8%) va HIV(+) la 46/136 BN (33,8%).
Thuoc nghi gay phan iing cho BN BN dieu tri thu6'c cho'ng lao co the bi phan ling voi 1 hay nhieu loai thuoc. Trong so' BN ma chiing toi khao sat o nghien ciiu nay, co 131 (41,6%) BN nghi bi phan img voi 1 loai thuo'c lao, 29,8% BN nghi co phan iing cimg Iiic voi 2 de'n 6 loai thuo'c chong lao. Thuo'c nghi ngo gay phan ung cho BN thuong gap nha't la rifampicin (88/315 27,9%), pyrazinamide (81/315, 25,7%) va streptomycin (78/315, 24,8%) sau do la isoniazid (43/315, 13,7%), va etiiambutol (33/315, 10,5%). Co 37 truong hop phan iing voi thuo'c ch6'ng lao hang hai (11,8%). 90 BN (28,6%) khong ro thuo'c gay phan iing. S6' lupng thuo'c lao bi phan ung (phan ung voi 1 loai thuo'c lao, 2 loai thuoc lao, tren 3 loai thuoc lao) kh6ng khac biet co y nghia thong ke giiia benh nhan chua dieu tri lao hay da dieu tri lao trong tien sir (p > 0,2), benh nhan dang dieu tri cac cong thuc khac nhau (SHRZ, EHRZ, SHREZ, cong thiic dieu tri lao da khang) (p > 0,7).
Trieu chiing phan ung voi thuoc chong lao khien BN nhap vien
149 (47,3%) BN nhap vien co trieu chiing ve da (man ngiia, do da toan than, may day, nhilm dpc da, hpi chiing Stevens-Johnson, phu
mach...). Sau do la trieu chiing ve tieu hoa (non, buon non, dau bung) (51 BN, 16,2%), vang da (27 BN, 8,6%), chong mat, ii tai (20 BN, 6,3%), ngat xiu, soc, met ngay cang tang (20 BN, 6,3%), sot (10 BN, 3,2%), dau khop (9 BN, 2,9%), te da, te moi (5 BN, 1,6%), va cac trieu chirng khac.
Chi CO 296 BN co ghi nhan thoi gian tir khi dieu til lao deh khi co trieu chiing phan iing voi thuo'c trong benh an. Thai gian trung vj tir khi dieu tri lao deh khi BN co trieu chiing phan ung voi thu6'c la 27 ngay (tir 1-350 ngay). Trong do, 16,2 % (48 BN) CO phan iing trong tuan dau tien sau khi dimg thuo'c, 66,2% (196 BN) co phan iing tix)ng tiiang dau tien, 86,8% (257 BN) co phan ling trong vong 2 thang dau tien sau dieu tri lao.
Thai gian trung vi tir khi BN co trieu chihig phan ling voi thuoc deh khi vao vien la 7 ngay (tir 1-300 ngay).
Trong 293 BN (93%) dupe thii men gan va bilirubin, co 210 BN (71,7%) co chi so men gan binh thuang; 25 BN (8,5%) co viem gan miic dp 1 (men gan, bilirubin toan phan > 3-5 lan gioi han tren ctia tn so'binh tiiuong); 23 BN (7,9%) co viem gan miic dp 2 (men gan, bilirubin toan phan tir 5-10 lan gioi ban tren cua tri so' binh tinrong); 35 BN (11,9%) co viem gan miic dp 3 (men gan, biUrubin toan phan > 10 Ian gioi han tren ciia tri s6'binh thuong).
Ket qua thu thuoc bang dtrong uong Trong thoi gian nam vien, chi 177 BN dupe tiiir tiiuoc (56,2%). Trong so do, 128 BN (72,3%) xua't hien lai trieu chiing phan iing voi thuo'c, 26 BN (14,7%) kh6ng co trieu chiing phan iing voi thuoc va 23 BN (13%) co phan iing khong ro rang. So' ngay tnmg binh BN ngimg dieu tri lao deh khi lam sang on dinh de thu thuo'c la 8,3 + 9,5 ngay (trung vi 6 ngay, tir 0-90 ngay).
Co 111 BN thii streptomycin voi lieu dau tien trung binh la 634 + 222 mg (tif 25- lOOOmg); 150 BN dupe thii rifampicin voi lieu
Y Hoc T P . H o C h i M i n h * Tap 16 * So 4 * 2012 N g h i e n cmi Y hgc
dau tien la 259 ± 151 mg (tir 37-600mg); 175 BN dupe thir isoniazid voi lieu dau tien la 217
± 87 mg (rii 50-400 mg); 179 BN duoc tiiii ethambutol voi lieu 703 ± 288 mg (tir 100- 1200mg); 150 BN duoc thii pyrazinamide vch lieu 794 ± 420 mg (tir 60-1600 mg).
Khi thir thuoc, 23 BN (13%) co thoi gian tie khi diing thuoc deh khi xua't hien lai tiieu chiing phan iing duoi 6 gio, 69 BN (39%) co thai gian xua't hien phan iing tir 6-48 gio sau dimg thuoc, 53 BN (30%) co thoi gian xua't hien phan iing tren 48 gio va 32 BN (18%) kh6ng dupe ghi nhan thoi gian co phan ung.
Trong phac do tai dieu tri duoc chi dinh cho BN, thu6'c nghi phan iing bi loai bo trong 88,5% cac truang h o p . Co 107 BN (34%) kh6ng nhan dupe chi dinh dieu tri sau khi ra vien.
BANLUAN
Phan ling voi thu6'c trong dieu tri lao la mpt yeii to' quan trpng anh huong de'n ke't qua dieu tri cho benh nhan. Nhiing nghien ciiu khac nhau dua ra nhirng so lieu khac nhau ve tinh hinh phan iing voi thuo'c ch6'ng lao 6 timg khu v\rc. Trong nghien ciiu nay, chiing toi thay BN phan iing voi thuoc chong lao thuong 6 Ilia tuoi trung nien tro len, trung binh la 46 tuoi; co 32,7% BN la nguoi tren 55 tuoi. Co 25,4% BN co tien sir dieu tri lao truoc, va 4 1 % BN co mac them nhirng benh man tinh khac, dac biet la tinh trang nhilm HIV (35,7%). 7,3% BN co tien sii phan iing voi thuoc cho'ng lao nhung vh\ duoc dieu tri lao vol phac do co thuoc nghi phan iing, co tiie do bac SI tuyen co so chua chii y den viec khai tiiac tien sir phan img voi thuoc cua nguai benh h ^ o c khi dua ra chi dinh dieu tri. Nhieu tac gia nhan tha'y phan iing voi tiiuoc chong lao thuong gap 6 nguoi co tien sii dieu ti-j lao.
CO tien su di ling thuo'c, hut thuo'c la, hoac BN Ion tuoi'^'^^'. Mpt nghien o i u ciing cho tha'y BN lao CO miic IgE toan phan va IgE dgc hieu, interleukin (IL)-6 va interferon (IFN) gamma cao hon nguoi khoe manh, chiing to BN lao CO tang miic man cam hon nguoi binh thuong. Sau khi dieu tri lao khoi, miic IgE va mpt so' cytokin (IL-6, IFN gamma) trong huye't thanh cnia BN giam xuo'ngf. Vi vay, viec khai tiiac ky tien sir phan iing vch thuoc truoc dieu tri lao la ra't quan trong, co the gop phan han che' tinh trang phan iing vai thuo'c xay ra sau nay.
Ve lam sang, chiing toi tha'y 47,3% BN nhap vien vi trieu chiing phan iing da 6 cac miic dp khac nhau nhu man ngiia, do da toan than, may day, nhiem dpc da, hpi chiing Stevens-Johnson, phii mach.... Trieu chiing ve tieu hoa (non, buon non, dau bung...) xual hien 6 16,2% BN; cac trieu chiing khac co ty le it hon. Viem gan gap trong 28,3% cac BN co phan iing vdi thu6'c cho'ng lao nhgp vien. Trong so' hp, 70% BN cd miic dp viem gan tnmg binh va nang, vdi cac chi s6'transaminase va bilirubin toan phan trong mau tang hon 5 lan gidi han tren cua chi so'binh thuong. Theo Richard Zaleskis, ne'u viem gan miic dp nhe (mtic 1), BN khong can thay doi dieu tri, nhung c&i dupe theo doi chgt che, thudng xuyen hem ve Iam sang va xet nghiem.
Neu viem gan miic dp trung binh (miic 2), nen ngimg dieu tri lao cang sdm cang td't, va BN can nhap vi|n de de phong suy gan ca'p. Viem gan nang (miic 3) xay ra vdi tan suat khoang 1/1000 tnrong hop dieu tri lao, cd ty Ie suy gan cap va ty le tii vong cao (2,5%)''*. Khi BN co dau hieu viem gan, ra't khd phan biet nguyen nhan do thuo'c lao hay do BN cd tinh trang viem gan hoat dpng do nhiem sieu vi, nha't la o khu vuc cd tan
N g h i e n cuu Y hgc Y Hgc T P . H o C h i M i n h "^ T a p 16 * So 4 * 2012
sua't nhiem virus viem gan cao nhu o Viet Nam.
Trong khi do, da s6' BN phan iing vdi thuo'c trong nghien ciiu nay khi vao vi?n da khong dirpc Iam xet nghiem chan doan nhiem HBV, HCV va HTV vdi ty Ie hrong img la 70,2%, 69,8%
va 56,8%. Trong so' BN dupe Iam xet nghiem HIV, chimg toi tiiay 46 BN (33,8%) cd HIV(+).
Dieu nay chiing td viec xet nghiem viem gan sieu vi va HIV cho BN lao nhap vien vi phan ling vdi thuoc chua dupe chii y diing miic.
Trong nghien ciiu nay, thuo'c nghi ngd gay phan ling cho BN thuang gap nhat la rifampicin (27,9%), pyrazinamide (25,7%) va streptomycin (24,8%); isoniazid va ethambutol it g | p hon vdi ty I? theo thii tir la 13,7% va 10,5%. Trong mot nghien ciiu hoi ciiu d Cape Town (Nam Phi) tren 65 BN bi phan iing vdi thud'c cho'ng lao cho tha'y phan ung da do tiiuo'c lao thuong gap d ngirdi nghiem HIV, chii ye'u do rifampicin (57%) va isoniazid (22%), sau dd la pyrazinamide (13%), tha'p nha't la do ethambutol, streptomycin va Ofloxacin (4%)f^. Trong mpt nghien cuu khac tai Malaysia, cac tac gia tha'y phan ting da do thuoc lao thudng gap la tit ban, hong ban da dang, may day va 97% xay ra trong 2 thang dau, nguyen nhan thudng gap nha't la do pyrazinamide*^, dac bi#t la d BN nhiem HIV.
Mpt nghien ciiu khac nhgn tha'y phan iing vdi pyrazinamide la gap nhieu nha't, sau dd de'n isoniazid va rifampicin. Etiiambutol it gap hon.
Su khac biet nay cd the phy tiiupc vao viec sir dung cac phac do dieu tri lao 6 moi nude, yeu td' di tmyen va co dia benh nhan d cac chiing tpc khac nhau»2).
Thuo'c lao hang hai cung thudng gay phan ling cho BN, nhung cho den nay, cd rat it so lieu de cgp den van de nay'^l 6 Viet Nam, so BN lao khang thuoc dupe dieu hi phac do tiiuoc lao
hang hai chua nhieu. Benh vien Pham Ngpc Thach mdi tiien khai dieu tri BN MDR tir giiia nam 2005. Deh nam 2010, tdng so BN MDR duoc dieu tri va quan ly tai benh vien la khoang 1000 ngudi. Nghien ciiu nay nghi nhan chi trong nam 2010, 11,8% BN bi phan iing do tiiuoc lao hang hai, cao dang ke' trong so' BN nhap vien vi phan ung vdi thuo'c cho'ng lao noi chung.
Theo y van, cac thuo'c khang lao isoniazid, pyrazinamide and rifampicin thirdng cd kha nang gay nhiem dpc gan nhat. Phan \6n cac phan ling dpc gan lien quan de'n lieu lupng, phan khac la do man cam vdi thud'c. Cac yeu to' nguy CO chu ye'u cua nhiem dpc gan do thuo'c lao la tuoi cao, suy chnh duong, nghien rupu, nhiem HIV, va viem gan do sieu vi B va C. Suy chiic nang gan do thu6'c thudng xay ra trong vai tuan dau tien tir khi dieu tri lao. Theo doi Ig' BN ve lam sang, xet nghiem va giao due siic khde la nhirng yeu to' quan trpng giiip dir phdng va cai thien ke't qua dieu tri cho BN bi nhiem dpc gan do thuo'c lao. Quinolone la thuo'c cd the dirpc sir dung trong phac do thay the'cho BN dieu tri lao cd suy giam chiic nang gani*^). Trong nghien oiu nay, chiing tdi thay quinolone da dupe chi dinh bd sung vao phac do dieu tri cho 10,2% BN khi ra vien. Tuy nhien cd 1/3 so'BN bi phan iing vdi thuo'c khi ra vifn da khdng dupe xac dinh phac do dieu tri lao tiep tuc. Dieu nay cd the gay khd khan cho su lua chpn tiiud'c tai dieu tri cho BN tai tuye'n co sd.
Trong nghien ciiu ciia chiing tdi, sau khi nhap vien, BN cd thdi gian tnmg binh ngimg cac tiiuo'c lao la mot tuan de dieu tri trieu chiing.
Khi on dinh ve lam sang va xet nghiem, BN se dupe thii thuoc de xac dinh loai thuoc gay phan ling. Tuy vay, nghien ciiu nay chi cd 177 BN (56,2%) dupe tiiir thud'c, trong dd 72,3% co xua't
"i H g c T P . H o C h i M i n h * T a p 16 * So 4 * 2012 N g h i e n c u u Y h g c
hien lai dau hieu phan ung, 69% BN cd trieu chiing sau khi thii lieu dau tien Kr &48 gio. Mot so' hudng dSn ve tiui thuoc lao cho BN'« da khuyen cao lieu thud'c thii va quy trinh tiiir thuoc cho BN sau khi bi phan iing vdi thuoc chong lao. Trong nghien o i u nay, chiing toi tha'y cac bac si cd each tiiir tiiuoc vdi lieu lupng va quy trinh khac nhau, tiiy theo kinh nghiem ciia bac s! dieu tri, vdi lieu thud'c dau tien thudng cao hon khuye'n cao.
KETLUAN VAKHUYEN NGHI
Nghien ciiu hoi ciiu nay md ta tinh hinh phan ling do thuo'c lao d benh nhan nhap benh vien Pham Ngpc Thach nam 2010. Ke't qua nghien cniu cho thay BN thudng xua't hien phan ling vdi thud'c cho'ng lao trong vdng 2 thang dau ke tir khi dieu tri. Ngoai benh lao, mot ty le cao benh nhan bi phan iing vdi thuo'c cd mac them cac benh man tinh khac, dac biet la nhiem HIV.
Tdn thucmg dei, viem gan va cac trieu chiing d h§ tieu hda la nhiing bieu hien thudng gap nhat d BN bi phan iing vdi tiiud'c chd'ng lao. Nhiing thud'c cho'ng lao thie't yeu gay phan iing c±io BN vcii t}' le cao la rifampicin, pyrazinamide va streptomycin. Nghien ciiu nay cho thay quy trinh thii thuoc hien nay dupe sir dung ra't da dang va khong dua tren bang chihig td't. Vi vgy, nghien ciiu tieh ciiu dua tren bSng chiing va quy trinh thir thud'c can duoc phat tri&i de hucing dhx Iam sang thuc hien thii thuo'c cho BN bi phan iing vdi thuo'c khi dang dieu tri lao.
TAIUEUTHAMKHAO
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