Y HQC VigT NAM T H A N G 9 - S6' 1/2012
DANH GIA HIEU QUA AN T H A N , G I A M D A U VA TAG DUNG KHONG MONG M U O N CUA DEXMEDETMIDIN AT BENH NHAN SAU MO TIM MOT
T 6 M TAT
De danh gia hieu qua an thBn, giam dau va t^c dung khong mong muon cija dexmedetomidin 6 b|nh nhan (BN) sau nro bm m6, mot nghien ciiu l§m sang mu ddn, ngau nhien, o6 doi chiihg dirt?c tieh hanh 6 60 BN an than sau mo bSng dexmedetomidin tTo§c midazolam. C^c dii so v@ an ttian, giam dau vS cac t^c dgng l<hdng mong muoh duijc danh gia. K^ qua khSng dinh dexmedetomidin 00 hieu qua an tian vd gi^m dau sau mo tc% hcAi hSn (p <
0,05) ntiutig <ic tac dgng khong mong muon tuttng t i / midazolam (p>0,05).
Tiekhosr. dexmedetomidin, midazolam, an thSn, giam dau, motim md.
ABSTRACT:
SEDATIVE, ANALGESIC AND INDESIRABLE EFFECTS OF DEXMEDETOMIDIN I N POST-SURGICAL CARDIAC PATIENTS
To evaluate the sedative, analgesic and indeslrable effects of dexmedetomidin in post-surgical cardiac patients, a RCT was conducted In 60 pts under either dexmedetomidin or midazolam-based sedation.
The variables of sedation, analgesia and adverse effects wered analysed around extubation and 24 houre afterwards. The results conclude demedetomidin gives more sedative and analgesic effect with the same incidence of indesirable actions.
Key words: Dexmedetomidin, midazolam, sedation, analgesia, c^wn heart surgery
I. OiihT V A N o i
Midazolam thifdng duWc dung an than tai phong Hoi sii'c nhutig c6 nguy cd keo dai thcfi gian t h d may va suy t h d sau rut noi khi quan (NKQ) [ 4 ] . Ngutfc lai, dexmedetomidin cho an dian kem giam dau ma khong \Sz che thd [ 2 ] , [3]. Nghien di\x nay c6 3 muc tieu:
1) Danh gia hieu qua an ti\an cua dexmedetomidin db$nh nhan sau motim md.
2} Oanh gia hi$u qua giam^ dau cua dexmedetomidin db$nh nhan sau motim md.
3) Danh gia cac tac dung khong mong muon aJa dexmedetomA^in d cac benh nhan nay.
II. 0 6 l TUpNG VA PHUONG P H A P NGHIEN COU 1 . S o i t i r i n g : T i ^ u chuan chon gom BN
* Benlivi4nVietDii!c
Phan bl^n khoa hpc: PGS.TS. Nguyen HOu U&c
Nguyen Quoc K i n h * , Quach Minh Chinh*
>18 tuoi dude mo tim md, phan suat tong mau EF > 5 0 % va EuroScore ^ 6 diem. Tieu chuan loai trUr gom khong dong y tham gia nghien cii^i;
benh tam than kinh; benh man tinh ve phdi, than, gan; nghien thuoc phien, tai bien gay me hoi su'c ho3c phau thuat, t h d may > 24 gid, suy than cap, bloc nhT that dp 2-3.
2. Phu'dng phap:
2.1. Thiet ke nghien c&u: Can thiep lam sang, mu ddn, ngau nhien, c6 doi chifng du'dc thu'c hien tai phong Hoi su'c Tim benh vien Viet BLTC tu*' 6/2010 den 2/2011. Nhom 1 (30 m) diing dexmedetomin va nhom 2 (30 BN) dung midazolam de an than sau mo.
2.2. Cac tieu chidanh gia:
' Hieu qua an than: Diem an than Ramsay tai cac thdi diem ngay tru'dc, trong va ngay sau rut NKQ roi cu" 4 gid/ian trong 24 gid dau sau do.
Mu'c do dung nap NKQ khi tap thd vdi m i i t tot (thoai mai), trung binh (kho chju) va kem (khong chju diTdc NKQ). So Ian tang giam lieu thuoc an than. Thdi glan IUXJ ong NKQ sau mo.
- Hieu qua giam dau: Thdi diem yeu dau dung morphin PCA lieu dau sau mo (ke tiT khi tap thd). Lu'dng morphin tieu thu tnang 24 gid dau sau mo. Diem dau VAS tai IH1,H2, H3 va diem VAS trung bInh H (4 - 24) t'li-c ciia H4 den H24.
- Cac tac dung khong mong muon: Tuan hoan: tan so tim, huyet ap trung binh HATB. Ho hap: tan so thd, khf mau triTdc va sau rut NKQ, Sp02 trung binh H (4 - 24). Buon non va non, ret run, nhjp tim cham, tang hoac t u t huyet ap (thay doi > 2 0 % mu'c nen).
2.3. Mot so tieu chuan: Diem an than Ramsay (RSS): 1 (kich thich, giay dua), 2 (hdp tac), 3 (nam yen nhutig theo lenh), do 4 (ngu, dap ijtig nhanh), 5 (ngu, dap l i ^ g cham), 6 (ngu s3u, khong dap utig). Diem dau VAS (visual analogue scale): 0 - 1 0 diem (0 tudng u'ng khong dau va 10 la dau khong chju dude).
2.4. Cach tieh h^nh: Gay me, phau thuat, tuan hoan ngoai cd the va hoi su'c nhu* thu'dng qui. Cac BN du'dc an than d phong Hoi su'c vdi lieu thuoc tang iiay giam de duy tri RSS 2-3 diem
Y H(?C VI6T NAM THANO 9 • S61/2012
trong thd may. Nhom 1 nh?n dexmedetomidin llSu
dau 1 ^g/kg/10 phiit roi diSu chlnh 5 phuVISn trong lihoang 0,2-0,7 Mg/l<g/gid v j tiep tyc thuSc i<hl tap cai miy thd, i<hl rut NKQ v4 24 gIS dSu sau do. Nhom 2 nh^n midazoiam iiilu dau 1
^g/i^g/phut iBI dieu chlnh oi' 5 phut/On moi iSn 0,5 (ig/l<g vJ ngiihg Ithi t$p cai mSy thd. Khi bSt dau tap thd, ci 2 nhom dung PCA morphin vdi iiSu bolus 2 mg, thdi gian i(hoi 10 phut vi i<h&ng cd III. KiT QUA
Bing 1. oac diem vji the tranq trtfdc mg, phSu thujt va q^v me
i i u duy tri. Thdi dilm nghien dsa gBm HI, H2 va H3 lu'dng ilhg vdi ngay truSc, trong vJi ngay sau khi rilt NKQ; sau dd cu' 4 gid/iSn tuBng uhg vdi H4, H8, H12, H16, H20VJH24.
2.5. Xij' ly sS ll$u: Sir dMng phan mSm SPSS 12.0. So s^nh 2 gi^ tr| djnh tinh bSng test X^ v i hai gii tri djnh lu'dng cua 2 nhdm bSng test t-Student. P < 6,05 i i cd y nghia thSng kS.
Cac d9c di£m
The tr^ng b^nh nhan
Thdi gian (Phut) Thuoc gay me Nh$i lu'dng tu*
>
•1 1
TuSi (nSm) Gldi:nam/n(i'(BN)
C8n njng (kg) EF(%) Dl^m EuroScore Thay (± SLTa) 1 van tim Thay (isCra) > 2 van tim
THNCT (phut) Gay me (phut) Mo (Dhiit) Propofoi (mg) Sevofluran (MAC) Vecuronium (mg) Sufentanil (^g) ihauc
4 -,
3 • 2 •
1
Nh6m 1 (n = 30) X ± S D h o « c B N
40,93 ± 14,31 15/15 BN 51,43 ± 6,63 60,00 ± 3,89 5,03 ± 1,47
9BN 21 BN 65,52 ± 20,95 217,00 ± 65,71 179,67 ± 59,22 341,33± 103,74 1,20 ± 0,41 9,53 ± 1,70 95,33 ± 11,81 C^c dac diem ve the trang b^nh nhan tru'dc mo ( h a i nhdm (p > 0,05).
I —.—Nh6ml —— Nli4m2 |
,', \ " _ f-8 f ' ?:«.
f i - - l ~\—-I " • • • • 1 - " i
Nhdm 2 (n = 30]
A* ± SD hole BN 40,50 ± 13,98
14/16 BN 51,37 ± 6,34 61,86 ± 4,76 5,06 ± 1,41 8 BN 22 BN 61,90 ± 23,74 210,00 ± 60,00 180,40 ± 55,74 364,00 ± 119,10 1,24 ± 0,43 10,13 ± 2,15 100,00 ± 16,81 d3c diem phau thuat
1 1 1
P
>0,05
>0,05
>0,0S
va gay me
Thfti diJm ngay tnrdc,trong, ngay sau v i 24 gib sau rilt NKQ
* p <0,05 gilta g i i Irj hai nhdm A timgth6i diJm Hlnh 1. Oi€m an t h i n Ram say ngay truiAc, trong vd sau Kit NKQ
Nh$n xit: Ngay tru'dc, trong, ngay sau va 24 gid sau rijt NKQ, miit an thSn luon dat RSS 2 - 3 diem d nhom 1, cao hdn (p < 0,05) so vdi RSS Iu6n 1 diem d nhom 2.
fia/i9 2 S o i a n d 'eu chlnh lieu an than, mu'c do dunq nap va thdi qian liAi onq NKO;
f)ieu chlnh lieu thuoc, m 6 t tf$
dung n^p v i thdi glan luti NKQ Dieu chlnh lieu an
than de RSS 2-3 diem Mu'c do dunq nap onq
l^ntSng Ian giam Tot
Nhdm 1 (n = 30)
^ ± 5 D h o $ c B N 0 1,5 ± 0,51 24 BN (80%)
Nhdm 2 (n = 3 0 ) X ± S D h o i i c B N
1,7 ± 0,47 0,3 ± 0,54 7 BN (23%)
P
<0,05
Y HQC VIET NAM THANB 9 • s6 1/2012 NKO khi t i n thd 1 Trung binh
LUu 8ng NKO sau mS (qid)
6 BN (20%) 4,27 ± 1,50
23 BN (77%) 5,56 ± 1,20
<0,05
<0,05
Nhan x^t; Oe dat RSS 2 -3 diem khi thd may, can giam lieu d nhdm 1 va tang lieu d nhdm 2.
Nhdm 1 dung nap NKQ tot hdn va thdi gian iuU NKQ it hdn (p< 0,05) nhdm 2.
Bang 3. Tinh tranq qiam dau sau md d hai nhdm
Hieu quk giam dau sau mo Nhdm 1 ( n = 3 0 ) Nlidm 2 ( n = 3 a )
^ ± S D Thdi diem can PCA morphin lieu (^u (qid)
Tong so Ian ygu cSu PCA morphin 13,77 ± 4,19 18,10 ± 4,49 Tonq lieu morphin bpriq 24 qid (mq)
Olem dau VAS:
H3 H (4 - 24):
H I 2,0 ± 0
2,17 ± 0,38 3,20 ± 0,65
3,13 ± 0,51 3,40 ± 0,62 3,95 ± 0,73
<0,05 Nhan x^t; BN nhdm 1 can morphin lieu dau cham hdn, so IBn ySu cBu PCA morphin it hdn, tdng lieu morphin 24 gid dau it hdn nhulig dl^m VAS thap hdn nhdm 2 (p < 0,05).
Bang 4. Anh hu'dnq ISn tu3n hoan, ho hap va cac tac dung khdnq monq muon khac TSc dsing
khong mong muffn sau mS Ian so tim (nhip/phut): H I
H3 HATB (mmHg): H I
H3 H (4-24) Tan so thd (Ian/phut): H I
H3 H (4-24) Khi mau: pH: H1/H3
PaCOi (mmHg): H1/H3 PaO; (mmHg): H1/H3 Pa02/l=i02:Hl/H3 SpO, (%): H(4 - 24) Khac: Tut huyS ap
l ^ n g huy€t ap Buon non va non Retmn
Nhdm 1 (n = 30) A* ± SD hole BN ( % )
89,20 ± 12,60 87,83 ± 11,46 82,37 ± 8,24 83,63 ± 8,07 85,35 ± 7,95 17,73 ± 2,08 16,90 ± 2,37 18, 35 ± 2,65 7,40 ± 0,04/7,41 ± 0,04 40,8 ± 3,40/ 41,0 ± 3,6 193 ± 71/202 ± 85 523 ± 202/552 ± 182
99,25 ± 0,60 5 (16,7%)
1 (3,3%) 8 (26,7%) 1 (3,3%)
Nhdm 2 (n = 30) X ± S D h o | c B N ( % )
91,03 ± 9,78 86,70 ± 13,41
95,50 ± 6,42 92,83 ± 7,08 86,12 ± 8,15 21,77 ± 1,22 19,53 ± 2,06 19,36 ± 2,55 7,42 ± 0,04/7,40 ± 0,04
40,7 ± 3,3/41,0 ± 3,6 187 ± 69/198 ± 83 520 ± 201/552 ± 188
98,65 ± 1,25 4 (13,3%)
2 (6,7%) 6 (20%) 1 (3,3%)
P
>0,05
<0,05
<0,05
>0,05
>0,05
> 0,05*
> 0,05*
> 0,05*
> 0,05»
>0,05
>0,05
C/y th/ifr. *: so sanh gia trj cua hai nhdm d cung mot thdi diem HI hoac H3.
Nh$nxeblni HATB d nhdm 1 cao hdn nhdm 2 (p < 0,05) tai HI va H3, hai nhdm khong khac nhau (p > 0,05) ve tuan hoan, ho hap va cac tac dung khong mong muon khac.
IV. BAN l U l ^
Hai nhdm nghien diu dong nhat ve the bang, loai phau thuat, cac thdi gian thao tac ( t i i n hoan ngoai cd the, gay me, phau thuat) va luBng thuoc trong gay me (bang 1).^
An tiian va giam dau lam BN de ch|u va nam yen theo may thd, tranh stress [3], [5]. Mot so phac do an than cd hoSc khong kem giam dau (midazolam ket hdp fentanyl, propofoi ket hdp sufentanil) cd the keo dai thd may va iJc che thd sau rut NKQ dii da ngCmg thuoc.
Dexmedetomidin chil van chon ioc receptor a-2A,
chu yeu tai locus coeruieus (ndi tac dong cua he a-2 adrenergic va opioidergic) nen vu^ an than vCr^ giam dau [2], [3], [7].
Ket qua nghien cdu cho thay
dexmedetomidin cho RSS 2-3 diem d giai doan
rot NKQ va 24 gid sau dd, trong khi midazolam
cho RSS 1 diem (hinh I). Be dat RSS 2-3 flilm
khi thd may, thu'dng phai giam liSu d nhdm 1 va
tang lieu d nhdm 2 (bang 2). Nhd vay, lEu
khuyen cao dexmedetomidin la cao va lieu
midazolam la chuS dii. Bang 2 cho thay nhdm 1
dung nap NKQ tot hdn va thdi gian rijt NKQ sdm
hdn so vdi nhdm 2 (thiJ tir la 80% va 4,27 ±
Y HQC VI$T NAM THANQ 9 • stf 1/2012
1,50 gid so vdi 23% v^ 5,66 ± 1,20 gid vdi p <
0,05). Riker [4] thSy dat RSS 2-3 khi thd m&y vdi liSu dexmedetomid in 0,4 ^g/ kg/g Id hoJJc midazolam 0,5-1 ng/kg/gid nhuTig rut dude NKQ sdm hdn d nhdm an thBn bSng dexmedetomidin so vdi nh6m bSng midazolam (3,7 gid so vdi 5,6 gid va p < 0,05). BAng 3 cho thSy hl§u quh glAm dau d nhdm 1 tot hdn d nhdm 2: yfiu tSu llSu morphin dau tiSn mu$n hdn (6,80 ± 1,10 g(d so vdi 5,66 ± 1,20 gid v i p < 0,05), lu^ng morphin tieu thy trong 24 gid ft hdn (7,47 ±1,04 mg so vdi 12,27 ± 1,38 mg v^ p < 0,05), mu'c d0 dau thap hdn vdi so I3n y@u c3u PCA morphin ft hdn (13,77 ± 4,19 ISn so vdi 18,10 ± 4,49 Bn v i p<0,05) va diem dau VAS thSp hdn ro r(
(p<0,05). Ludng morphin tieu thy sau mS khi an than bSng dexmedetomidin thSp hdn (p < 0,05) khi bSng propofoi [1], thllm chf gidm mpt nu^ khi ket hdp vdi dexmedetomidin so vdi dung morphin ddn thuan [7].
Ngoai trir HATB d nhom 2 tSng hdn nhom 1 (p < 0,05) tai HI va H3, con dc tac dung khong mong muon khac (tuan hoan, ho hap, buon non va non, ret mn) tUdng t\X nhau d hai nhom (bang 4). Chung toi khong gSp cham nhjp tim nhuYig Riker g3p 40% [4] vdi lieu cao dexmedetomidin 1,4 ng/kg/gid va Martin g3p 9% [2], deu 3ap LTng tot vdi atropin. So sanli ngay tru'dc va ngay sau rut NKQ, Surgenor thay cung lu'dng tim, su'c can mach mau he thong, sure can mach mau phoi, cac ap li/c lam day tim khong doi d nhom dexmedetomin va tSng d nhom midazolam [6].
Venn Uiay Ian so thd, SpOa, khi mau (pH, PaOi,
PaC02) tUdng t i / vdi morphin ddn thuan hoSc kfem dexmedetomin sau mo [7].
V. K^T LUAN
So vdi midazolam, dexmedetomidin eo hi^u quS an thBn tdt hdn, c6 th3m t^e dgng giam dau sau m6 nhutig t i c dyng khong mong muon lu'dng t i / nhau.
TAI L I | U T H A M KHAO
1. Herr D ( 2 0 0 0 ) , "ICU sedation after coronary bypass graft surgery: dexmedetomklin-based versus propofbl-based sedative regimens*, CardlotiiorBcIc vase anestfr, 17:576-584.
-$t 2. Martin E ( 2 0 0 3 ) , T h e role of the alpha 2- adrenoceptor agonist dexmedetomUIn In postsurgical sedation in the Intensive care unlf, Intensive Care Medicine; 18; 29-41.
Maze M, Scatflnl C ( 2 0 0 1 ) , "New agents fat sedation in Intensive care unit", Oitksi Care Medicine; 11: 881-897.
Riker R.R, Shehabi Y (2009),
"Dexmedetomidin vs midazolam for sedation of critically ill patients: a randomized trial', JAMA, 301:489-499.
Shafer A ( 1 9 9 8 ) , "Complications of sedabon with midazolam in the Intensive care unif, Cmcai C are Medicine, 26: 947-956.
Surgenor S, Rllinger M, Dodds T et al ( 1 9 9 9 ) , "Patient characteristics and treatment interventions associated with extubation time after roronary artery bypass surgery", Anesthesiology; B5.
Venn R.M, Nevirman J ( 2 0 0 3 ) , ' Effiect of dexmedetomidin for sedatton in Intensive care unit", Intenmve Care Medkine; 29: 201-207.
NGHIEN COU DIEN BIEN DIEU TRj CUNG Cfl BENH NHAN LO X £ Ml CAP DONG TUY
B&NG P H A C DO C Y T A B A B I N LIEU THUNG BJNH
T 6 M TAT
Ci^u bi cung cd bSng ph^c do cytarabin lieu trung binh c6 the keo ddi thdi gian song va thdi gian t^i p h ^ d benh nhan Id x€ mi cap dong bjy. Myc tHu: (1) Nghien cuU dien bien lam s^ng va huyS: hpc cua b|nh nhan Id xe mi d i p dong tiiy b3ng cytarabln lieu trung binh. D&ttf^ng vA phuVng phap nghien
* Dai hqcY Hanoi
Phin bl$n khoa ftpc; PGS.TS. Nguyin H i Tiianh
VQ M i n h PhiTtfng*, NguySn V a n Anh*
aht: 26 b^nh nhan Id x€ ml cap d6ng b ^ lul b^^
ho^n tocin sau dHu trj tan cong v^ tai tan cong, d u ^ dieu b1 cung cd bSng phdc ^ cytarabin lieu tmng binh, du'dc theo doi lam s^ng vh x4t nghiem huyS hoc sau dieu trj. Ketqua:!^ 1^ b^nh nhan c6 thieu mSu, xual huyet, nhiem triing, s6t tSng cao sau 7-14 ngJy dieu trj va giam thap sau 21 ngdy dieu tri. L i D ^ huy€t sSc to giam thap nhat: 98,08 ± 14,97g/l sau 18
