Tap ciu THONG TIN YDL OC Sd 7 nam 2010
CONG TRINH NGHIEN CUU
NGHIEN CUU DAC DIEM LAM SANG, CAN LAM SANG VA DIEU TR| NGO DOC ZOLPIDEM
Pham Due * TOM TAT
Muc tieu: danh gia dac diem lam sang, can lam sang va dieu tri ngd ddc Zolpidem. Ddi tdOng va phUdng phap: tien cdu, quan sat md ta 30 benh nhan (BN) ngd ddc Zolpidem dieu tri tai Trung tam Chdng ddc (TTCD), Benh vien Bach Mai td 01/2003 den 06/2005. Kit qua:
24/30 BN (80%) BN udng lieu gay me > Img/kg can nang, trong dd 66,7% BN d mdc do nhe, 20% mdc do trung binh, 13,3% mdc khdng trieu chdng (theo phan do PSS), khdng cd mdc do nang va td vong. Trieu chdng lam sang: dc che than kinh, giam phan xa gan xUdng va giam trUdng luC cd. Khdng cd rdi loan can lam sang nao dang ke. Dieu tri chinh la rda da day, udng than hoat va truyen dich giai ddc. Hau hit BN deu nhanh chdng phuc hdi sau 6 gid dieu tri vdi diim Glasgow la 14-15 (trung binh 14,9); khdng cd biin chdng hay td vong, thdi gian dieu tri trung binh 1,2 ngay. Kit luan: Zolpidem la thudc ngii an toan, trieu chdng ngd dgc nhe, it biin chdng, phuc hdi nhanh vdi dieu tri han chi hap thu va truyen dich giai dgc.
SUMMARY
Clinical and laboratory features and treatment of Zolpidem poisoning
Objectives: to evaluate clinical and laboratory features and treatment of Zolpidem poisoning patients. Methods: a prospective and descriptive study was performed on 30 patients who ingested overdoses of Zolpidem and treated at the Poison Control Center, Bach Mai hospital from 01/2003 to 06/2005. Results: 24/30 patients (80%) ingested doses above lmg/kg, In which: 66.7% mild poisoning, 20%> moderate and 13.3%> asymptomatic, no patient had severe poisoning or died. Clinical features were altered mental status: decreased tendon reflexes and decreased muscular tone. No remarkable changes in laboratory and imaging parameters were observed. Main treatment were gastric lavage, administration of active charcoal and intravenous fluid infusion. Most of the patients improved after 6th hour of treatment with Glasgow coma score at 14-15 (mean 14.9). No patients had complications or died. The mean bedtime was 1.2 days. Conclusions: Zolpidem is a safe sedative. Its poisoning is mild, with few complications. The condition improves quickly with gastroic lavage and intravenous fluid infusion.
I. DAT VAN OE
Zolpidem (Stilnox) la loai thuoc ngu cho la cd dpc tinh thap. Tuy nhien, thudc cd the gay hdn me neu dung qua lieu 1 mg/kg can nang [4] va thdc te van cd nhu'ng BN ngd ddc Stilnox vao cap cud tai cac benh vien. O Viet Nam, chUa cd nghien cu'u nao ve ngp dpc Zolpidem. Cac bao cao lam sang chi dUa ra cac thong ke chung la ngp dpc thudc ngu va thuoc an than [1,2,3,5,6].
Nghien cull nay la mpt phan cua de tai NCKH cap bp ddpc thdc hien td 2003-2007 tai TTCD nham muc tieu: danh gia dac diem lam sang, can lam sang va dieu tri cua ngp dpc Zolpidem.
II. OOI Tl/ONG VA PHl/ONG PHAP 1. Ddi tUOng
Cac BN ngd dpc Zolpidem vao dieu tri tai TTCD Benh vien Bach Mai trong thdi gian 2 nam td 01/2003 den 01/2005 dap dng cac tieu chuan sau:
- Cd udng thudc ngu Zolpidem.
- Xet nghiem ddc chat trong dich da day, mau, nddc tieu dUdng tinh .
- Loai khdi nghien cdu cac BN: uong phoi hpp nhieu loai thudc khac nhau.
2. Phddng phap nghiin cdu
* Thiet ki nghien cdu. tien cdu, md ta.
' TS., Benh vien Bach Mai
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Tap chi THONG TIN YDlfOC S3 7 ndm 2010
* Cac chi tieu nghien cu'u:
- Cac trieu chdng lam sang, bien chdng:
tan suat gap cua moi loai.
- Ty le va gia tri cac thay ddi bat thu'dng cua cac thdng so can lam sang danh gia chdc nang gan than: AST va ALT, bilirubin, ure, creatinin, natri, Kali mau.
- Cac bien phap dieu tri dang dUdc ap dung: ty le ap dung.
- Hieu qua dieu tri: ty le td vong va ty le cac bien chdng thudng gap.
* Phan tich so lieu, phan mem SPSS 16.0.
III. KET QUA 1. Dac diem chung
Tdng sd: 30 BN, Nam: 8, chiem 26,7%, Nd: 22 (73,3%).
2. Dac diem lam sang ngd ddc Zolpidem
Bang 2: Cac trieu chdng lam sang ngo dgc Zolpidem fn=30J
Trieu chdng SdBN TL %
Hdn me 2 6,7
Ly do vao vien (trieu Ld md, cham chap 10 33,4 56,7
chdng ban dau) Met mdi, buon ngu 2 6,7 56,7
Ngu sau 3 9,9
Dau dau, chdng mat, ndn 5 16,7
Khac 8 26,7
Glasgow 15 9 30,0
Glasgow 10-14 14 46,7
Glasgow 7-9 6 20
Cac trieu chdng thudng Glasqow < 6 1 3,3
Cac trieu chdng thudng Donq td co (1mm) 1 3,3
gap (khi den vien) Donq td gian (5mm) 1 3,3
Phan xa gan xUdnq (PXGX) giam 19 63,0
TrUdnq lUc cd qiam 18 62,1
Suy hd hap 0 0
Ndn 18 62,1
Tut huyet ap 1 3,3
Tanq huyet ap 1 3,3
Trong so cac ly do vao vien cd 56,7% la roi loan y thdc. Khi den vien, 70% BN cd Glasgow dUdi 15 diem, nhUng thap nhat chi 6 diem. Kem theo cd PXGX giam, trUdng ldc cd giam va ndn. Diem Glasgow trung binh la 12,5.
Bang 3: Mot so thdng so lam sang khac thddng gap
n Nho nhat Ldn nhat Trung binh SD P
Glasqow luc vao 30 6 15 12,5 2,75 <0,05
Glasqow sau 6 qid 30 14 15 14,9 0,25 <0,05
Ddnq tu liic vao (mm) 30 1,5 5,0 2,9 0,86 <0,05
Donq tU luc ra (mm) 30 2 4 3,1 0,82 <0,05
Nhip thd (Ian/phut) 30 14 20 17,2 1,7
Sp07 (%) 30 80,0 100,0 96,9 3,7
Huyet ap toi da luc vao
vien (mmHq) 30 60 150 110,7 15,74
Tudi trung binh: 25,5±8,5 (tre nhat: 18, gia nhat: 50 tud'i).
Bang 1: Lieu Zolpidem thdc te cac BN da udng (mg)
Lieu Zolpidem
BN da udng SdBN TL %
< 50 5 20
60-100 10 40
> 100 10 40
Tonq 25 100
Trunq binh 138 ± 8,9 Hau het 24/30 (80%) BN udng lieu ddc (>lmg/kg can nang). Lieu trung binh 137,6±89,83 (mg) nhd nhat 40mg, Idn nhat 400mg. Mdc do ngd dpc: theo PSS nhdm nhe 20 BN (66,7%)^ nhdm trung binh 6 BN (20%), nhdm khdng trieu chdng 4 BN (13,3%).
Tap chi THONG TIN YDlfQC S3 7 ndm 2010
Sau 6h dieu tri, diem Glasgow trung binh tang td 12,5 len 14,9, hau het cac BN da tinh tao nhd binh thudng.
3. Dac diem can lam sang cua ngp dpc Zolpidem Bang 4: Cac xet nghiem sinh hda va huyet hgc
Loai xet nghiem n Nho nhat Ldn nhat Trung binh Do lech chuan
Ure (mmol/l) 27 2,5 7,5 5,2 1,2
DUdng (mmol/l) 25 3,0 8,0 4,8 1,2
Natri (mmol/l) 30 130,0 147,0 139,4 3,7
Kali (mmol/l) 30 2,90 4,70 3,7 0,4
Clo (mmol/l) 26 96,0 111,0 104,4 3,9
Creatinin (umol/l) 16 54,0 118,0 85,1 19,8
Honq cau (tetra/l) 27 3,2 5,2 4,3 0,4
Bach cau (qiqa/l) 27 4.T 15 8,1 2,3
BC trunq tinh (qiqa/l) 27 42 81 65,6 11,9
BC lympho (giga/l) 27 12 49 27,0 10,2
Tied cau (qiqa/l) 27 158 324 214,0 39,3
Hematocrit (lit/lit) 27 26 47 38,2 5,1
Hemoglobin (qam/lit) 27 84 148 128,3 14,0
AST (U/L) 25 8 60 23,0 10,2
ALT (U/L) 25 7 65 24,9 12,3
Cd 13,3% BN giam kali mau (<3,5mmol/l), 2 BN (6,5%) ha Natri mau <135mmol/l. Chi cd 1 BN tang AST va 1 BN tang ALT, tuy nhien gia tri tang khdng cao (60 va 65U/L) chUa du de
4. Dac diem dieu trj ngp dpc Zolpidem Bang 5: Cac bien phap dieu tri
nghi tdi ton thUOng gan. Dien tim trong 30 trUdng hdp nghien cdu deu cho ket qua binh thudng, khdng gap mpt trUdng hpp nao cd roi loan ve dien tim.
Cac bien phap TrUdc vao vien Tai benh vien Cac bien phap
SdSN TL % SoBN TL %
Gay non 0 0 0
RUa da day 0 0 22 73,3
Than hoat - sorbitol 0 0 17 56,7
Dich truyen 0 0 24 80,0
Thd oxy 0 0 0
Dat noi khi quan - thonq khi nhan tao 0 0 0 Cac BN chUa dupe xd ly gi trUdc vao vien vi
den thang TTCD. LUpng djch rda da day trung binh la (lit): 2,86±0,36. Khdng cd BN nao bj tai bien rda da day nhu sac phd'i, rdi loan dien giai,... LUpng dich truyen trung binh mpt ngay (lit) la: 1,47±0,72.
Bang 6: Ngay dieu tri BN ngo dgc Zolpidem Sd ngay dieu tri SdBN TL %
1 25 83,3
2 4 13,3
3 1 3,4
Tonq 30 100
Ty le BN dieu tri 1 ngay 83,3%; trung binh 1,2 ngay; ngay dieu tp trung binh: 1,2±0,48 ngay.
IV. BAN LUAN
1. Dac diem lam sang
Vdi 30 BN udng thuoc Zolpidem lieu trung binh la 137,6±89,83 (mg), phan loai PSS cho thay da so BN thupc nhdm nhe (dp 2) (chiem 66,7%), nhdm trung binh chiem 20%, nhdm khdng trieu chdng chiem 13,3%, cd the ndi ngd ddc Zolpidem la nhe nhat trong cac ngp ddc thuoc ngu va thudc an than thudng gap.
Dieu nay cang rd neu chu y rang lieu trung binh cac BN da udng la 138mg. BN uong It nhat cung 40mg, tddng dUdng vdi lieu dpc (lmg/kg can nang).
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Tap ciu THONG TIN YDlfOC S3 7 nam 2010
Trieu chung lam sang ciia ngo doc Zolpidem dUpc trinh bay 6 bang 2. Trieu chd'ng than kinh xuat hien dau tien, nhieu nhat la Id mO buon ngii (chiem 40,1%). Roi loan y thdc d mdc dp rat nhe vdi diem Glasgow trung binh 12,5. BN tinh sau 6 tieng vdi diem glasgow 14,9. Dieu nay phu hdp vdi thdi gian ban huy ciia Zolpidem rat ngan, la 2 ngay (124,5±37,9 phut) [7]. Nhd hdi tinh nhanh ma BN ngp dpc Zolpidem trong nghien cdu khdng gap nhu'ng bien chdng khac nhu viem phd'i, nhiem trung tiet nieu,... la cac bien chdng thUdng gap d cac thuoc ngii manh gay hdn me sau va keo dai nhU trong ngd dpc Gardenal.
Giam hdac mat phan xa gan xUdng va giam trUdng lut cd cung gap kha nhieu (lan lu'dt la 63% va 62,1% va triing vdi ket qua nghien cdu ciia cac tac gia Wyss P.A., Radanovic D., Meier-Abt P.J. la 51,7% [10].
Trieu chdng buon ndn, ndn chiem tdi 62,1%, trong cac tac dung phu ciia Zdlpldem khdng thay ndi den tac dung gay ndn va buon ndn. Tuy nhien, theo chung tdi cd the nhu'ng BN udng qua lieu nen gay kich dng da day rudt, dan den buon ndn va ndn.
Trieu chdng ddng td thay ddi khdng dang ke phu hpp vdi tinh trang rdi loan y thdc nhe va cung cd the ndi dd Zolpidem it anh hudng tdi than kinh thut vat va dau hieu ve ddng td la it y nghTa trong chan doan ngp dpc cap Zolpidem.
Khdng cd BN nao bi suy hd hap va bi bien chUng sac phdi. Nhip thd trung binh la 17 Ian/phut va dp bao hda oxy dau ngdn tay (SpO:) trung binh la 96,5%, khdng cd trUdng hpp nad nhd hdn 80%, chdng td Zdlpidem it dc che trung tam hd hap va NDC Zolpidem it cd nguy cd suy hd hap.
Trieu chdng tut huyet ap (60/30mmHg) cung nhU cao huyet ap (150/100mmHg), gap duy nhat 1 trUdng hpp. Nguyen nhan cua tut huyet ap cd the do thieu dich vi sau khi truyen du djch huyet ap BN da nhanh chdng trd ve con sd binh thddng. Ly do thieu dich d BN nay cd the do ndn nhieu ma chUa dUpc bii dich kjp thdi. TrUdng hpp tang huyet ap cd the do BN qua lo lang, sp hai khi phai vao vien hoac do sp rda da day. Theo
trieu chdng Uc che than kinh, giam phan xa gan xUdng va giam trUPng lut CP.
2. Oac diem can lam sang
Ve xet nghiem djnh tinh: ket qua tim Zolpidem trong djch da day va nUdc tied la dUdng tinh 100%, day la tieu chuan chpn BN vao nghien cdu. Neu BN den trong vdng 6 gid sau udng Zolpidem thi xet nghiem nUdc tied bang phUdng phap sac ky Idp mdng deu phat hien cd Zolpidem. Nghien cdu nay phii hdp vdi Gamier R., Guerault E., Muzard D. va cpng sU (dp nhay 100%) [8].
Ve dien bien nong dp transaminase trong huyet thanh: khao sat tren 25 BN, chiing tdi chi thay cd duy nhat 1 trUdng hpp la tang AST (3,3%) va 4 trUdng hdp tang ALT (16,4%).
NhUng cao nhat khdng vUdt qua trj so 80, chUa dii bang chdng khang djnh cd ton thUdng rd d gan. NhU vay, theo chiing tdi, Zdlpidem it anh hudng tdi gan va rat it kha nang gay tdn thUdng te bao gan, phii hpp vdi nghien cdu cua Hajak G., Bandelew B. [9] va cdng sU.
Vie cac xet nghiem sinh hda khac: ndi chung, cung khdng thay nhdng bat thUdng ve xet nghiem sinh hda mau (ure, dUdng,...).
NhUng cd tdi 31% cd ha kali mau, cd le do BN ndn nhieu. Hdn nda, djch rda da day thudng khdng cho kali, vi vay cd the la mdt yeu to gdp phan lam giam kali mau.
Tat ca BN deu cd chi so ure va creatinin mau trong gidi han binh thUdng. NhU vay, ngd ddc Zolpidem khdng tac ddng nhieu den than va khdng gay suy than.
3. Dieu tri ngp dpc Zolpidem
Hau het cac BN vao thang TTCD nen dieu tri tuyen trUdc va/hoac tren xe cap cdu la khdng dang ke. Tai TTCD BN dUdc dieu trj theo diing phac do, chu yeu la rda da day, udng than hoat va truyen djch giai dpc. Tat ca cac BN deu khdi hcan toan, ke ca 1 BN cd xuat hien tinh trang hdn me sau (Glasgows 6 diem).
Khdng cd BN nao dien bien nang, khdng cd suy gan than cap va suy da tang.
Trong nghien cdu cung khdng cd BN nao phai hoi sdc hd hap, dieu nay khac vdi nghien cdu cua Gamier va cdng sU (cd 1 BN phai hoi sdc tuan hoan, hd hap) [8], tuy nhien, nghien 20
Tup chi THONG TIN YDUOC S6 7nam 2010
benzodiazepin,... Trdng khi do, BN cua chung tdi khdng cd trUdng hdp nao udng Zolpidem ket hdp vdi cac thudc dd.
Vi vay, chung tdi cho rang viec dieu tri sdm, dung phac dc, thee ddi chat che se dat ket qua tdt, rut ngan dupe thdi gian dieu tri, tranh td vong va dien bien xau.
V. KET LUAN
* Dac diem lam sang: ngd dgc Zolpidem la ngp dgc thudc ngu tUdng ddi hiem gap, benh canh lam sang nhe, 76,7% BN d mdc dp nhe, 10% mUc dp trung binh, 13,3% mdc khcng trieu chdng, khdng cd mdc dp nang va td vong. Trieu chdng lam sang chinh la met mdi, IP mP buon ngu (76,7%) va giam diem Glasgow (trung binh 12,5).
* Dac diem can lam sang, vdi lieu udng trung binh la 138mg (40- 400mg), hau het BN uong lieu dpc (lmg/kg can nang), tuy nhien, nghien cdu cho thay khdng cd rdi loan can lam sang nao dang ke.
* Dieu tri khong can thudc giai dgc dac hieu (Flumazenil): hau het BN deu nhanh chdng phuc hoi sau 6 gid dieu tri vdi diem Glasgow la 14-15 (14,9), khdng cd bien chdng hay td vong, thdi gian dieu tri ngan, trung binh 1,2 ngay.
* Kien nghj. cd ke hoach va bien phap de Zolpidem trd thanh thudc ngu thdng dung (cd ke ddn) dieu tri mat ngu.
TAI LIEU THAM KHAO
1. Ngo HuU Ha: Nghien cUu tinh hinh ngp doc cap cac thuoc thudng gap tai Trung tam chong dpc Bach Mai trong hai nam 2002-2003. Luan van Tot
nghiep bac si chuyen khoa cap II, Trudng Dai hoc Y Ha Npi, 2004.
2. Nguyen Dire Hy, Hoang Thanh HUdng: Tinh hinh BN ngd dpc tai khoa hdi sUc cap cUu Benh vien HUu nghi Viet Nam - Cuba, Ddng Hdi tU nam 2000 - 6/2002. Hoi nghi tap huan chdng ddc toan quoc lan thii III, thang 9/2002.
3. Lu'dng Thj San, Cao Viet Tiing: Tinh hinh ngd dpc cap tai khoa Hoi SUc Cap CUu - Vien Nhi (1997- 1998). Ky yeu cdng trinh khoa hoc cap ciru - hdi sut - chdng doc, 2000, tr. 194-198.
4. Nguyen Thj Minh Tam: Danh gia mUc dp nSng cua ngd doc cap bang bang PSS cua IPCS. Luan
van Tdt nghiep bac si chuyen khoa cap II, Tn/dng Dai hoc Y Ha Ndi, 2001.
5. Lai Phu Thudng, Nguyen Thuy Tinh: Tinh hinh ngd doc cap dieu tri tai khoa hdi sUc cap cUu Benh vien Da khoa Trung Udng Thai Nguyen trong 5 nam 1991 - 1995. Hdi thao lan thirII ve cap ciiu ngd ddc cap, thang 8/1998.
6 Pham Anh Tuan, Pham Ngoc Huy Tuan: Khao sat tinh hinh BN tu tU bang thuoc va hda chat tai khoa HSCC trung tam Cap CUu TrUng vUdng tU 6/1999 den 6/2000. Ky yeu cdng trinh khoa hoc cap cuU - hdi sdc - chdng ddc 1998 - 2001, tr.255-264.
7. Drover D., Lemmens H.: Pharmacokinetics, pharmacodynamics, and relative pharmacokinetic/pharmacodynamic profiles of zaleplon and zdlpidem. Clinical Therapeutics,
Volume 22, Issue 12 , December 2000, pp. 1443-1461.
8. Gamier R., Guerault E., Muzard D., et al.
Acute Zolpidem poisoning - analysis of 344 cases.
Clin Tox 1994; 32, pp.391-404.
9. Hajak G., Bandelow B.: Safety and tolerance of Zolpidem in the treatment of disturbed sleep: a post-marketing surveillance of 16944 cases. Int Clin Psycholpharmacol 13, pp. 157-167.
10 Wyss P.A., Radanovic D., Meier-Abt PJ.:
Acute overdose of Zolpidem (Stilnox). Schweiz Med Wochenschr, 1996, 126, pp.750-756.g PHAN TICH TIEN SU" DUNG THUOC THEO OOI TLTONG
Ddn vi tinh: ty ddng
Chi so hoat dgng 2008 2009 So sanh °7o
Chi so hoat dgng SL TL% SL TL% So sanh °7o Tien thuoc Bao hiem y te 4.572,3 57,5 6.574,0 60,9 143,8 Tien thudc tre em dudi 6 tudi cd the
KCB 612,2 7,7 747,7 6,9 122,1
Tien thudc ngudi ngheo co the 139
(khdng cd the BHYT) 96,2 1,2 117,8 1,1 122,5
Tien thudc vien phi (khong thupc cac
doi tUdng tren) 2.674,2 33,6 3.351,8 31,1 125,3
Tong sd tien thuoc da sii dung
trong BV 7.954,9 100 10.791,3 100 135,7
Ty le tien thudc trong tdng sd
tien vien phi (%) 46,1 47,9
(Nguon: Kiem tra 1.009 benh vien nam 2009 - Cue Quan ly Kham chu'a benh, Bd Y te) 21
