D I E N O A N Y HOC Nghien ciru khoa hpc
DAC DIEM LAM SANG VA DIEU TRI NGO DOC PARACETAMOL TAI TRUNG TAM CHONG DOC - BENH VIEN BACH MAI
Pham Due*
TOM TAT
Muc tieu.' ddnh gid dgc diim ldm sdng, can ldm sdng vd nhdn xit dieu tri ngp dpc paracetamol tgi Trung tdm Chdng dpc Binh viin Bgch Mai (TTCD). Phuong phap nghien ciru.- tiin cieu, quan sdt md td.
Ddi tuong nghien ciru.- gdm 49 BN udng ngp ddc paracetamol dieu d-i tgi TTCD tir 09/2003 din 09/2005.
Ket qua.- 98% BN udng liiu paracetamol > I50mg/kg cdn ndng nhimg chi cd 22,2%) cd ndng dp a mirc dp ngd dpc vd 7 BN (14,3%) cd viim gan nhiim ddc. Ndn xudt Men trong vdng 1-3 gia sau udng a 40 (81,6%) BN. Hpi chimg ldm sdng ciia viem gan nhiim dpc (gan to dau, vdng da) gap a 8,2%, sau 3 - 4 ngdy vdo viin; hpi chung can ldm sdng bao gdm tdng AST (34,7%), ALT (24%) GGT (18,4%,) vd tdng bilirubin true dip (26,5%), gidm ti li prothrombin (20,4%,); hg kali mdu cung thuang gap vdi ti li 63,3%. Tdng AST vd ALT la 2 ddu hieu din sdm nhdt (sau 10-96 gid). Dieu tri chinh gdm rua dg ddy: 33 BN (67,3%): udng than hogt: 34 BN (69,4%,) vd udng N-acetylcystein: 48 BN (98%), truyen dich. Kit qud dieu tri tot vai thdi gian ndm viin ngdn (3,47 ngdy), tie vong 1 do hdn mi gan din mupn. Ket luan.- trieu chung ngp dpc paracetamol sdm la ndn, cdc thay ddi can ldm sdng thuang gap nhdt la tdng AST, ALT, GGT, BLRB, gidm prothrombin vd hg Kali Ndn sdm vd cdc biin phdp riea dg ddy, udng than hogt gop phdn ldm gidm hdp thu paracetamol.
N-acetylcysstein duang udng cd hiiu qud diiu tri ngp dpc paracetamol.
I. DAT VAN DE
Paracetamol la thudc ha sdt giam dau dugc xep vao loai thudc khdng can don. Thudc nay cd hang tram biet dugc khac nhau [2] va dugc sir dung nhieu nhat vi vay cung trd thanh nguyen nhan gay ngd ddc nhieu nhit tai cac nude phat trien [5], [6].
0 nudc ta, paracetamol cung dugc su dung rdng rai va dugc mua ban tu do tren thj trudng va gay ra nhieu vu ngd ddc. Bai bao nay la ket qua cua dd tai cip Bd ve "Ngd ddc thudc thudng gap..." vdi muc tieu:
Ddnh gid dgc diim ldm sdng (LS), can ldm sdng (CLS) vd kit qud diiu tri cita ngp dpc parac- etamol cd trong thudc chiea cdm cum tgi Trung tdm Chdng dpc, Benh viin Bgch Mai
Trung tdm Chong dpc, Binh viin Bgch Mai
II. DOI TU'ONG VA PHU'ONG PHAP NGHIEN c u t !
1. Doi tuong
- Gdm 49 benh nhan (BN) ngd ddc paracetamol dieu trj tai Trung tam Chdng ddc, Benh vien Bach Mai trong thdi gian tir 09/2003 din 09/2005 va dat cac tieu chuan sau:
+ Vao vien sau khi udng, tiem paracetamol.
+ Xet nghiem djnh tinh paracetamol (+) trong djch da day hoac trong nudc tieu.
2. PhuoTig phap
- Nghien ciru quan sat md ta tien ciiru.
- Cac thdng sd nghien cii'u:
+ Theo ddi cac dau hieu lam sang, dac biet phat
44 I Y HOC LAM SANG So 53 (Thang 06 / 2010)
D I E N D A N YHOC
Nghien ciru khoa hpc
hien cac dau hieu viem gan, suy than.
+ Cac dau hieu can lam sang ciia viem gan, suy than nhiem ddc: AST, ALT, Bilirubin, GGT; Ure, dudng.
+ Theo ddi viec dieu trj riia da day, udng than hoat, diing N - acety ley stein: lieu, thdi gian, bien chirng va cac dieu trj khac.
3. Tien hanh nghien ciru
3.1. Khdm vdphan loai benh nhdn
- Kham lam sang va phan loai benh nhan theo PSS (Poisoning Severity Score - phan loai ngd ddc theo WHO).
- Djnh tinh bang sac ky ldp mdng mau xet nghiem la djch da day hoac nudc tieu BN.
- Dinh lugng paracetamol mau: lay mau d thdi diem it nhat 4 gid sau khi BN udng; djnh lugng paraceta- mol bang sac ky Idng tai Vien Kiem nghiem, Bd Y te. Ket qua dugc ddi chieu tren dd thj Rumack - Matthew de xem cd xuat hien nguy ca ngd ddc khdng [1].
Cac xet nghiem AST, ALT, GGT, Bilirubin (BLRB), prothrombim dugc thuc hien thudng qui tai Benh vien Bach Mai.
3.2. Dieu tri
- Thudc giai ddc: N-acetylcystein (NAG) vdi cac biet dugc Mucomyst, Acemuc dugc chi djnh cho tat ca eac BN dugc chan doan ngd ddc paraceta- mol.
- Lieu dimg:
+ Lieu ban dau: 140 mg/kg, lieu duy tri 70mg/kg/
lieu mdi 4 gid cho den khi XN ddc chat cho thay dudi ndng do ddc va AST, ALT ve binh thudng.
+ Cac bien phap dieu trj khac: dieu trj theo nguyen tac chung va theo thudng qui.
IH. KET QUA NGHIEN CUtJ 1. Dac diem chung
- Sd BN vao nghien ciiu: 49.
- Tuoi trung binh: 23,94 ± 9,24 (14 - 61) tudi.
- Gidi: nam 12 BN (24,5%), nir 37 BN (75,5%).
- Ly do ngd ddc: tu tir 46 (93,9%), chira cam cum 3(6,1%).
- Mirc do ngd ddc: khdng ngd ddc: 4 (8,2%)), nhe:
35 (71,4%), trung binh: 4 (8,2%), nang: 5 (10,2%), tir vong: 1 (2%).
- Viem gan nhiem ddc: 7 (14,3%).
- Lieu paracetamol da udng trung binh: 334,65 ± 211,11 (49,25 - 1136,36) mg/kg can nang. 48/49 BN (98%)) udng paracetamol vdi lieu tren 150mg/
kg hoac gap 2 - 3 (300-420mg/kg) lan ngudng gay ngd ddc. Chi cd 1 BN udng paracetamol vdi lieu <
150mg/kg can nang (49,25mg/kg).
- Ket qua djnh lugng paracetamol mau: 45/49 BN dugc djnh lugng paracetamol mau; 6/45 (13,3%)) BN cd ndng do nam d viing khuyen cao dieu trj va 4 BN (8,9%) cd ndng do nam trong viing nguy ca viem gan, nhu vay la cd 10 BN (22,2%)) cd ndng do mau d muc do ngd ddc.
- Sd biet dugc cd paracetamol da diing cho 1 BN:
1 biet dugc: 42 (85,7%), 2 biet dugc: 6 (12,2%), 3 biet dugc (2,0%).
2. Dac diem Iam sang
Bdng 1. Cdc trieu chiing ldm sdng ciia ngd ddc paracetamol Trieu chung
Kich thich Lan ldn Budn ngu Glasgow < 14 Hdn me gan
n 7 5 9 19
1
% 14,3 10,2 8,9 38,8
2
Gia trj thay doi
D I E N D A N Y HOC Nghien ciru khoa hpc
Nhin md Ndn
Dau thugng vj
Phan xa gan xuong tang Phan xa gan xuang giam Gan
mat
Gan to Vang da
Gan to +vang da Xuat huyet
Nhjp tim nhanh Cham xoang
3 40
10 8 7 1 2
1 1 20 1
6,1 81,6 20,4 16,3 14,3 2,05 4,1 2,05
2 40,8
2
110 (93-150) lan/phiit 54 (45-59) lan/phiit Nhdn xet:
- Trieu chirng sdm thudng gap nhat ciia ngd ddc paracetamol la ndn gap d 40 (81,6%)) BN; 26/40 (65%)) BN ndn trong vdng 3 gid dau; ndn keo dai den ngay thir sau.
- Hdi chirng lam sang cua viem gan nhiem ddc (gan to dau, vang da) den sau 3 - 4 ngay.
- Rdi loan ve tri giac cd the do diing biet dugc dang ket hgp vdi cafein va gardenal: kich thich budn ngii; la ma, lan. Chi cd 1 BN la hdn me gan.
3. Dac diem can lam sang cua ngo doc paracetamol
- Ngoai cac thay ddi ve GOT, GPT, GGT va bilirubin, ha kali mau la thudng gap hon ca.
- Cd 7 BN tang men gan gap 3 lan, dii tieu chuan chan doan viem gan nhiem ddc.
Bdng 2. Cdc trieu chung can ldm sdng
t
Sinh hoa mau
Ddng mau
Xet nghiem Ha Ure
Ha dudng mau Ha Na mau Ha K mau Tang dudng mau Tang K
Tang BLRB TP Tang BLRB TT
TangAST(>40UI/L-37°) Tang ALT (> 37 UI/L-37°) Tang ALT (> 37 UI/L-37°) Tang AST ( > 3 lan) Tang ALT ( > 3 lan) Tang GGT
Giam ti le prothrombin
BN 14 5 5 31 25 2 7 13 17 12 12 7 7 9 10
% 28,6
10,2 10,2 63,3 51 4,1 14,3 26,5 34,7 24 24 14,3 14,3 18,4 20,4
Gia tri thap nhat-cao nhat 1,7 (0,3-2,2) mmol/L
2,4 mmol/L 124 mmol/L 2,4 mmol/L 8,5 (6,5-22) mmol/L
4,9 mmol/L 98,6 (22,3-524) nmol/L
27,1 (7,3-182) nmol/L 1092 (42-5250) UI/L-37°
1191 (38-7270) UI/L-37°
1191(38-7270) UI/L-37'' 174-5250 UL'L-37°
115-7270 UI/L-37°
369,2 (50-1535) UI/L-37°
8,9 Nhdn xit:
- GOT/GPT: thdi dilm bit diu phat hien tang: 10 - 96h, keo dai 5 - 13 ngay.
- Tang BLRB va giam prothrombin: bit diu thiy bit thudng: 2 - 4 ngay; keo dai 2 - 5 ngay.
- Tang dudng mau hay gap do cac BN dugc truyin Glucoza de tranh ha dudng mau.
46 I Y HOC LAM SANG S6 53 (Thang 06/2010)
D I £ N D A N Y HOC Nghien cuu khoa hpc
4. Dac diem dieu trj NDT paracetamol
Bdng 3. Cdc diiu tri da dp dung cho BN NDT paracetamol tai Trung tdm Chdng dpc
Bien phap dieu trj Gay ndn
Rita da day Than hoat
Mucomyst (NAG) Thudc chdng ndn Bii nudc dien giai Truyen glucose
Dieu trj trieu chiing khac
BN 1 33 34 48 31 45 22 23
% 2 67,3 69,4 98,0
63,3 93,8 47,8 47,9
Nhdn xet: 98%o BN nhdm ngd ddc paracetamol nhan dugc thudc giai ddc la NAC udng trir 1 BN den mudn sau 6 ngay va da hdn me gan.
5. Ket qua dieu trj
- Tdng sd benh nhan 49; viem gan nhiem ddc: 7; tir vong: I. Nguyen nhan tir vong: hdn me gan nang do den mudn (ngay thir 5 ciia benh).
- Khdi benh 48 BN (98%). Thdi gian nim vien:
3,47 ±2,45(1 - 13 ngay).
IV. BAN LUAN
1. Ve dac diem lam sang
Bang 1 tdng ket cac trieu chirng thudng gap cua ngd ddc paracetamol. Ndn thudng gap nhat (81,6%, 40/49 BN), xuit hien sdm (65% trong 3 gid dau) va keo dai I - 6 ngay. Cac trieu chirng lam sang khac trong bang 3 la rat khdng dac hieu, ngoai cac bieu hien ciia gan mat nhu: vang da, gan to va dau chi gap d 4 BN (8,2%)) va 1 BN hdn me gan. Cdn eac trieu chirng than kinh nhu kich thich, lan lgn, budn ngu, nhin md lai cd the la trieu chirng ciia cac thanh phan khac kem theo nhu: PPA, ca- fein (gay kich thich, nhin md), gardenal (gay lan ldn giam diem glasgow, budn ngu).
Nhu vay ta thiy trieu chiing lam sang sdm cua ngd ddc paracetamol chi la ndn trong vdng 1 - 3 gid sau uong; va sau dd trieu chiing mudn sau vai ngay la cac bilu hien ciia viem gan nhiem ddc nhu vang da, gan to dau.
2. Ve dac diem can lam sang
- Ha kali mau thudng gap nhat, gap d 31 BN (63,3%)), la hau qua cua ndn. Cae bieu hien cua tdn thuong gan nhu tang AST (34,7%); tang ALT (24%) bit dau phat hien thay sau khi qua lieu thudc la 10 - 96 gid, keo dai 5 - 13 ngay, tang GGT (18,4%)) dugc phat hien thay sau 3 - 9 ngay, tang BLRB, dac biet la BLRB true tiep 26,5%) va giam ty le PT bat dau thay sau 1 - 4 ngay, keo dai 2 - 5 ngay. Nhu vay, tang GOT va GPT xuat hien sdm nhat la 10 gid, cd the sdm tdi 8 gid [2].
- Lugng paracetamol udng va ndng do paraceta- mol mau: lieu paracetamol udng trung binh d cac BN: 334,65 ±211,11 (49,25- 1136,36) mg/kg can nang. Phan Idn cac BN udng paracetamol vdi lieu tren 150mg/kg hoac gip 2 - 3 lin (300-450mg/kg) ngudng gay ngd ddc [1] [2] [7]. Tuy vay sd BN cd ndng do paracetamol mau cd kha nang gay ngd dgc chi la 6/45 BN dugc djnh lugng (13,3%)). Ndn sdm va cae bien phap tay dgc nhu rCra da day, than hoat chac chan gdp phan lam giam lugng ddc td dugc hap thu do vay giam ndng do paracetamol mau. Va nhu vay chiing ta thay cac bien phap ban che hap thu: gay ndn, rira da day va udng than hoat la cd hieu qua va can dugc ap dung cho BN cang sdm cang tdt.
DieNDAN YHOC
Nghidn ci>u khoa hpc
- 1 BN la ngudi nghien rugu, mac dii chi udng parac- etamol vdi lilu 49,25mg/kg (4g) (1 BN duy nhit diing lilu thip hon so vdi ngudng nguy ca gay ngd ddc la 150mg/kg) nhung vin bj viem gan sau udng thudc.
Nhilu tai lieu dl cap [ 1,2,3], nguy ca viem gan nhiem ddc cang cao d nhiing ngudi nghien rugu. O cac BN nay, he enzym CYP2E1 bj ethanol gay cam irng khi nghien rugu nen chuyen hda paracetamol tang len, sinh nhilu NAPQI hon (tang them tdi 22%) [8]. Viec cung cap glutathion va kha nang tai tao gan khi bj tdn thuang ciing giam d ngudi nghien rugu [4].
3. Ve dac diem dieu trj
- Cac bien phap dieu trj thdng dung nhat la cac bien phap han che hap thu (riia da day, than hoat), truyen djch giai ddc va truyen glucoza phdng ha dudng huylt va dac biet 98% benh nhan dugc udng thudc giai ddc dac hieu la Mucomyst (N acetyl cystein dang udng).
- Vdi kit qua dilu trj khdi benh 98%, thdi gian nim vien ngan (trung binh 3,47 ngay), 1 BN tir vong do den mudn ngay thii nam (van chua dugc dieu trj NAC va da hdn me gan cho hieu qua cao ciia phac dd dieu trj ciia Trung tam Chdng ddc).
- Hien tugng 98% benh nhan udng lieu cao nhung xet nghiem djnh lugng cho thay chi cd 10 BN (22,2%)) cd ndng do paracetamol nam trong vimg nguy hai cho thay ich Igi cua cac bien phap giam hap thu nhu: ndn sdm, rira da day va udng than boat.
- Dii cd 10 BN cd ndng do paracetamol mau cao va 6 BN da trong tinh trang viem gan nhiem dgc nhung nhd dugc udng NAC sdm, du da nhanh chdng khdi benh budc dau cho thay NAC dudng udng cd kha nang bao v? gan day Iiii qua trinh viem gan nhiem ddc.
TAI LIEU THAM KHAO
V. KET LUAN
1. Dac diem lam sang ciia ngo doc paracetamol La Uieu chiing sdm ngheo nan vdi ndn la thudng gap nhit (81,6%)). Bilu hien ciia viem gan gdm vang da, gan to, dau (8,2%)) din mudn hon vao ngay thir 3 - 4 ciia benh. Viem gan da xay ra cho 1 ngudi nghien rugu ngay ca khi chi udng vdi lieu 49,25mg/kg.
2. Dac diem can lam sang
Ha kali mau xay ra vdi 63,3%o BN ngd ddc parac- etamol; tang AST (d 34,7% BN) va ALT (d 24% BN) bit dau phat hien d gid thir 10 - 96 gid sau udng parac- etamol, keo dai 5 -13 ngay. Cac thay ddi sinh hda dang chu y khac la: tang BLRB true tiep (gap d 26,5%) BN), tang GGT (18,4%), giam ti le Prothrombin (20,4%)...
gap mudn hon ngay thir 2 - 4. Ndng do paracetamol mau budc dau cho thay phan anh diing tien lugng nguy ca viem gan vdi 7 ngudi viem gan nhiem ddc thi 6 ngudi cd ndng do paracetamol mau cao.
3. Nhan xet dieu trj
Ndn sdm, rira da day va diing than boat da gdp phan lam giam nguy ca viem gan do paracetamol.
Viec diing NAC cd hieu qua tdt d 6/7 benh nhan bj viem gan, giup hdi phuc hoan toan.
VI. KIEN NGHI
- Khuyen cao cac nha san xuat giam lugng parace- tamol trong mdi vi, Ig thudc xudng cdn 2 - 5 gam, nham de benh nhan it cd kha nang cd du thudc de udng tdi lieu gay ngd ddc.
- Tuyen truyin, nang cao nhan thiic ciia ngudi dan ve each sir dung va mdi nguy ca cd the cd khi tu diing thudc cam ciim ndi chung va paracetamol ndi rieng.
1. Babak Mokhlesi, Jerrold B. Leikin, Patrick Murray et al (2003), Aduh toxicology in critical care, Part II: Specific poisonings. Chest, 123, 3: 897 - 900.
2. Holly Perry, Michael W. Shannon, (1998), Acetaminophen, Clinical management of poisoning and drug overdose, WB. Saunders Company, 6th ed, 664 - 674.
48 I YHOC LAM SANG S6 53(Thang06/2010)
D I E N D A N Y H O C . Nghien cii'u khoa hpc
3. Kenneth E. Bizovi, Martin J. Smilkstein, (2002), Chapter 32: Acetaminophen, Goldfrank's toxicologic emergencies, 7th ed, Mc - Grow - Hill, 480 - 497.
4. Lauterburg BH, Velez ME: Glutathione deficiency in alcoholics: Riskfactor for paracetamol hepatotox- icity. Gut 1988; 29:1153 -1157.
5. Martindale - The complete drug reference. Paracetamol, Pharmaceutical Press, 2008.
6. Melisa W. Lai et al, 2005 Annual Report of the American Association of Poison Control Centers' Na- tional Poisoning and Exposure Database, AAPCC ANNUAL DATA REPORT, Clinical Toxicology, 44:803 - 932, 2006
7. Poisindex, (2002), acetaminophen - acute, MICROMEDEX(R), Vol. Ill, Thompson Healthcare Series, USA.
8. Thummel K, Slattery J, Ro H, et al: Ethanol and production of the hepatotoxic metabolite of acetamino- phen in healthy adults. Clin Pharmacol Ther 2000; 67: 591 - 599.
SUMMARY
CLINICAL AND LABORATORY FEATURES AND TREATMENT OF PARACETAMOL OVERDOSE Objectives: to evaluate clinical and laboratory features and to assess the treatment of paracetamol poisoned patients. Method.- this is a prospective and descriptive study. 49 patients with paracetamol over-
dose admitted to the Poison control center (PCC) from 09/2003 to 09/2005 were enrolled in the study.
Results.' 49 patients were included in the study. 98% of the patients ingested paracetamol at doses higher than I50mg/kg body weight, whereas only 22.2% of them had blood paracetamol levels above the treat- ment line of the Rumack-Matthew nomogram and 14.3% of them had toxic hepatitis. Vomitting occurred within 1-3 hours after ingestion in 40 patients (81.6%). Clinical features of hepatitis (painful and enlarged liver, jaundice) were seen in 8.2% of the patients at day 3 and day 4 since admission. Laboratory features of hepatitis included increase in AST (34.7%o), ALT (24%), GGT (18.4%), direct bilirubin (26.5%), decrease in prothrombin (20.4%) and potassium (63.3%). Elevation of liver enzymes were the earliest signs that occurred at 10th - 96th hour since ingestion. Mainstays of the treatment consisted of gastric lavage in 33 patients (67.3%,), activated charcoal in 34patients (69.4%), oral administration ofN- acetylcystein in 48 patients (98%) and IVfluid infusion. The outcomes of the treatment brought about the mean hospitalization time of 3.47 days. I patient died due to hepatic failure because of late admission. Conclusion.- vomiting was the only early clinical feature of paracetamol overdose in our PCC. Laboratory features were: increase in AST, ALT,GGT, direct bilirubin, and decrease in prothrombin and potassium. Early spontaneous vomitting, early gastric lavage and oral administration of activated charcoal may contribute to reduce absorption of paracetamol. Oral administration ofN- acetylcysstein was effective in the treatment of this overdose.
