Tài liệu ôn tập cho kỳ thi tuyển viên chức ngành y tế năm 2017 bai giang gay me hoi suc i file 3

i.-

METHOHEXITAL
(Brictal)

I:'
Methohexita1 1a mot oxybarbituric tac dung nhanh va manh, thoi gian
;; hoat dQng ngan. Tren lam sang Sl:r dung duoi ten Brietal. Lan d§.u tien sir
k' dung narn 1957. Day la loai thuoc khong duoc ua chucng va co nhieu bat lei:
~: dau nci tiern, van dong bat thudng, nac, heat hoa 6 dong kinh thai duong,
~~
~.

t:
l,- I. TfNH CHAT L Y HoA
t'.
~.
Methohexital khac chu yeu voi thiopental la kh6ng c6 nguyen tv luu
e-.
;. huynh trong c6ng thuc cau tao hoa h9C. Thudc tan trong rna kern hen so vdi
; thiopental (ty len dan/nude la 65; nguoc lai thiopental la 89). pKa 7,9. Ty l~
~ kh6ng ion hoa la 76% d pH 7,4.
~,

Thuoo duoc trinh bay duoi dang bot dB diroc pha va dung ngay. Trong 19 50
ml chua 500mg Brietal sodium dung dich pha 1% c6 pH = 11. Dung dich pha
c·
r6i kh6ng duoc dB qua 24 gid vi thuoc kh6ng vilng ben trong dung dich nuoc.
L
[Co
Methohexital kh6ng tUdng hQp voi Ringer lactate va silicon. Kh6ng GUQc

~. tl'l;)ll laIl vui cac dung dich 'acid (sulfate d' Atropine). Kh6ng uu<,Jc uvng trong
dic dt,mg C\lb&ng nhlja.
C6ng thuc h6a h9c.

r

o=C
~H-C==C

I

CH3

n.

DLfQC DONG HQC

Methohexital g~n voi protein huyet t11dng 18. 75% chuyBn hoa qua gan do
Qonooxygenase, phV thu9C VaGcytochrom P450. Day cling la lo?i thuoc gay
~ Ird cam ling men gan.
Thuoc thch tru qua th?n d d,;ll1gchuy6n h6a. Bien d6i sinh h9C va chuydn
. boa kh6ng r6 nct. Thdi gian ban huy 2 don 4 gid. Hai den 4 l§.n ng&n hem

481


.~

:~

;;ll

t

thiopental. Th& tich phan ph6i 1,5 Mn 2 l/kg iJ nguoi IOn va Ire em I. ?,;,
l/kg. Thoi gian ban huy rat ng~n duoc giai thich bAng dQ thanh thai tro~:~
huyet tuong cao, llml/phut/kg voi nguoi 16n. Tre em la 18ml/phut/kg. H¢ ::~'~
bai suat d gan ucc tinh 0,5 (trong khi do thioperital la 0,15 den 0,20).
;~
.J.~
•

Thuoc qua rau thai.

.~
'1

."~

;\

~~

III. DVQC Ll)'C HQC

.;~

($
.:]~

1. Tac dunq tren than kinh trung lfdng

':~

Tac dQng tren than kinh trung uong g~n giong voi thiopental, mac •.::.;~
thuoc heat dong rigan va thai tru nhanh so vdi thiopental nhung tac d1.p' :·r
keo dai. Theo doi chuc nang nao va dien nao nguoi ta thay v§.n con c6 :~'~
thay etch tu 8 den 12 gid sau khi dung methohexital. Nhieu tac gia da g~ r.!j
nhirng con dong kinh trong hie slt dung methohexital voi cac b~nh nha11 .,'~
tien slt dQng kinh. Methohexital c6 kha nang lam hO<:J.t
hoa, gay co gi~t
slt dVng voi lieu lUQng cao va cung c6 th~ gay hO<:J.t
hoa 6 dQng kinh vi .
kich thich dQt ngQt, bat chQt luc khdi me.
Thuoc c6 tac dVng gay ngu, hoan toan voi lieu cao. C6 th~ g~p hi~n tll.
kich thich, hung phan. uc ch§' trung tam h6 hap, trung tam v~n m0ch, tr
tam dicu nhi~t khi slt dvng lieu cao. Trung tam non khong bi llC che. GiZ~/
ap h,tc nQi SQ, luu lUQng mau nao va tieu thv oxy cua nao.
'
:::(of
2. Tac
. dyng tren tim m~ch

,

'

~

Tac dVng tron tim m<:J.chc6 th~ so sanh voi thiopental ca (j tren n~

kh08 m<:J.nhcling nl11.td ngudi m~c b~nh tim. Lieu 2 mg/kg cua methohexi
tudng dUdng lieu thiopental 4 mg/kg.
.
'
Slt dvng lieu 1,5 mg/kg kh~i me ~ nguC!i kh08 m0nh: ap h;tc dQng m':
giam (·15%) luu htQng tim giam (·11%), suc can ngo<;tivi giam (·4%), ,
tim tang vua (+7%). 'rac dVng tren huyet dQng hQc rat 1'6 khi slt dVng
cao. Tron b~nh nhan co cao huyet ap, methohexitallam
giam huyct ap it
thiopental. Khi duy tri methohexital
bAng truyen et~ gay me, hiu lUQng
, ...
"
thay doi tu 60-120.mcg/kg/phut v:6i nhung b~nh nhan c6 gay me ph6i
oxy va prooxyde d'azote, ap h;tc dQng m<;tchgiam (-13% den -33%), hiu 111
tim giarn (·26% den - 38%).
"
Luu lUQng tim giam dUQc giai thich bAng tac dVng.,t1ccheco b6pCd~
, (inotrope nagative) va do giam mau t'inh m<;tchtr~ ve. C6 thl-~6i, anh hll:'
tron SllC chua cua tlnh m<:J.chva co sQi Cd la h~u qua rat xau,
methohexital voi b~nh nh8.n tliieu khoi luc;ingtu~n ho~m hoiftcsuy tim.
Tieu thl,l oxy Cd tim tang khoang 35% cung nhli tang hiu lUQng
m0ch vanh. Tang hiu lUQng mall m~lch vanh thll phat d§.n den giam suc
m<;tchvanh, ap h,lc tV6i it thay d6i.
')~'

482

"

ca

cac 100.i thuoc lam tang tieu thu oxy co tim, ,~
methohexital c6 th6 lam suy mach vanh vci nguy co thieu mau. Heat dOng
than kinh phe' vi giarn. C6 th6 n6i methohexital khorig phai la thuoc sir dung
tot cho benh nhan truy tim mach va suy tim.
Giong

nhu

tat

3. Tac dunq tren he hap

La thuoc co tac dung uc che h6 hap va su uc che nay co th6 so sanh vci
thiopental, ire che' trung tam ho hap gay ngung tho phu thuoc lieu Sli dung
va toc dC)tiern. Ngung tha thuorig g~p vao phut dEiu tien. Thuoc lam giarn
tan so va th6 tich tha.
Khi truyen methohexital voi luu lucng 60mcg/kg/phut tren benh nhan
gay me phoi hop oxy va N20, PaC02 cao len khoang 50mmHg va truyen voi
luu luong 120 mcg/kg/phut thi PaC02 la 52 mmHg. Su uc che' nay khorig
thay d6i voi kich thich ph~u thu?t.

,
".,
~

Tinh tr0.ng ho, nac, co th£t thanh quan, khi phe quan g~p nhieu hdn
thiopental, d~c biQt a tre em nh6 duoi 1 tu6i.

4. M9t

so tac

dyng khac

Khong gay dd tli cung. Thu{)r. lam giam [lp h;rc nh5.n cciu, methohexital
giai ph6ng histamin. Tac dVng khong dang b~ tren
ehuy6n hoa. it lam thay d6i chlic nang gan. Khong lam ?mh huang den chuc
, nang th?n, Day cung la mOL Lhuoc gay h00.t hoa men CP450 cua gan khi
cung keo dai.
it. gay bien chung

!

N.

sO'

Dl)NG TREN LAM SANG

1. S& dyng de; khdi me
Methohexital m0.nh hdn thiopental 2,5 den 4 lc1ntheo nhieu tac gia. Lieu
[rung binh 1,5 mg/kg dUdng tinh m<;lchd6 khai me. NgUdi ta dung dung dich
'1'% (500 mg trong 50ml dung dich pha,_ glucose 5% ho~c NaCl 9%0). Tr.uyen
fJC dC)20 .Mn 30 -m-g/phut d6 giam bot phien n0.n co Cd, th?m chi
c~c cli
'':~il1g co gi?t. Mat tri giac thu dlic;JCkhoang 30 giay. Khai me b&ng
methohexital doi khi co mQt so tac dVng khong thu?n lc;Jinhu co Cd, cli dOng
~,it thudng trong 40% so bQnh nhan khong chic;Jctien me. Cac Cli dC)ngbat

tihVdng nay co th6 giam bot khi duc;JCtien me bAng pethidin. Ho va nac g~p
.C!'Dng20 den 30% trudng hQp va se giam bot trong nhung bQnh nhan duc;Jc
tt]en me.

ca

Tiem lieu duy nhat sau 1den 5 phut b~nh nhan c6 th§ ma m£t quan sat,
r.:a Idi dung ngay sinh thang de sa u 6 den 7 ph t1t va ng6i khong r&n S\1trc;J
:;pup sau 9 den 10 phUt.
Methohexital c6 th{hap thu dli9C qua dU'(ing bem bttp va dUdng h?u
r.ro.,Dn,
du m0.nh d§ dam bao gay me. Dlidng h~lu man trvc trang sli dVng cho
483

ii

"'1

Ii
II
11

III'

II
Ii
I'
II
I

1
I

!


tre em. C6 th~ dung 25 mg/kg dung dich 10%. Ket qua tot trong 85truorig hop va trong khoang 15 phut. D~ gay ngu, nong dQ cgtn thiet
duoc ij trong m au 2mcg/ml. Duong bern bap it dU<;JC
sli dung (6mg/kg

dich 2%).
2. S& dunq d~ duy tri

me

C6 th6 truyen methohexital 0,1% lien tuc d6 duy tri me, trung binh . '
den 150 mcg/kg/phut. C6 th~ phoi hop voi tat en cac thuoc gay me
thuong. Thoi han tinh keo dai ra thco thoi gian duy tri thuoc. Voi cU9C
me trong 12 phut,
m~t thu duoc thucng xuyen sau 3 phut, Khi dung' "
tri me, doi khi g~p bucn non, non sau me va cac bien loan ve dien nao
dai dang' sau khi da mat cac trieu chung tren lam sang.

rna

3. S& dunq d~ an than (Sedation)

. C6 th6 dung methohexital d6 gay ngu nhe phoi hop voi gay te vung,
d~c tinh duoc dong hoc cua thuoc, c6 th6 sli dung nhu thiopental d~
nao. Nhung do tinh chat gay dQng kinh, cli dQng bat thudng nen

khong dUQcdung trong chi dtnh nay.
4. Chi dlnh

-

Tien me cho tre em.
Gay me cho b¢nh nhan ngo(;litrli va thdi gian ngiin
Duy tri me
C6 th~ gay me trong ph§.u thu~t th~n kinh (c6 tang ap IlfC nQi
trong ph§.u thu~t miit, san khoa (m6 de), gay me cho b¢nh nhan
day d~y.

5. Chong

chi djnh
Brit bUQC:
- Thieu phudng ti¢n hoi suc.
- Porphyrin
- Nh0y d m vfii h,uhiturir.
Tuong dOL:
Di~}ngklnh

-

Soc giam khoi lU<;Jngtu~n h03.n
Suy tim, suy v3.nh n~ng
Phv nil c6 thai (3 thang d~u)
Tre em nh6 (vi ty l~ bien chung cao)

6. Lieu IVc;:1ng

Thdi gian chd tac dVng: 0,5 . 1 phlit (tInh m0ch)
3 - 4 phlit (bdm tiem di~n)
484


Thci gian hoat dong:

3 - 6 phut

,',

N'guiti lon:

"

Dung dich 1% (500mg/50ml) duong tinh mach khdi me 1,5 - 2 mg/kg;
tinh mach cham.
,.

,,'

~.

t~·

~~

Duy tri: 113lieu khci me, cu 5 - 10 phut lai tiern nhac lai.
Truyen lien tuc: Dung dich 0,1% (50 mg/500ml); 1 mg/ml

3 - 6 mg/phut (hoac 60 - 120 giot/phut
Dung born tiern dien (SE)
Dung dich 1% (500mg/50ml); 10mg/ml.
180 - 360 mg/gid (hoac 18 - 36 ml/gio)
Tre em
Duong hau man. DD 10% (500mg/5ml); 100mg/ml; 25mg/kg.
Duong tiern bap (rat dau)
Dung dich 2% (500mg/25ml); 20mg/ml stt dung 6mg/kg.

~" Chu y giarn lieu d benh nhan co benh mach vanh, suytim, thieu khci
f~(,1ng twin hoan va nguci cao tu6i.
a:
v:

,,",

A

tv.
TAl BIEN VA PHIEN NAN
~
.
r

~,
c-

Tai bien di lIng hiern g?P, ty l~ 1/30000 cas bieu hien truy. tim mach.
Suy thd, ngung thd co th~ g?P, phu thuoc lieu luong, tee dQ tiem. Doi khi
~5Jr.@iPco that thanh khi phe quan,

l( .

i: Cling nhu cac thuoc nh6m barbituric thuoc gay heat hoa men gan, lam
~;ting ho:;tt dQng clla acid delta amino - levulinic va gay ra can porphyrin cap
~111.,1i..; d'
~iUli
ung l'~eo d"al.
~:

t,

Bien c~ung,:>t:;t~ch~~tie~: dau don noi t~~m: dau .truac canh t~~ ho:;ic l~ng
f'ililn tay. Co the g<.tPVlem tmh mslch 3% VOldung dlCh 1%, 6% Val dung dlCh
~':~:!.'4.Khi tiem duai da, b~p thit co th6 bt phu ne.
.
~

Tiem nh§.m dQng m?ch, day la bien chung rat n?ng d§.n den thieu mau
t·~.ichAo13iE{n ch{tng nay n;;U1g h0n d thiopentaL

~:- Sli

uu0ng h~u man vai tre em, co th6 gay 1'a kfch thich t?i ch6 vai
t~~u chung 106t mang nhay h~u mon.
" :-Jgoai ra c6 th6 g?P nac, tang tiet nllac bQt.

,.
~:
r.

Ul;lIlg

,.

AT

;,:Wt TLfdNG TAC THUOC
~

r

Tang tlem h;iC tac dv.r-{gngll do thuoc clla morphin, neuroleptic,
~"'duxen, hypnovel.

cac thuoc

~

,
fi'

485

.


Tang tiern luc tac dung uc che:

I

'>

rim machxiac
thucc'D'Lubocurarin, gay liet hach (ganglioplegiques), chen ( ii
.
~
H6 hap; cac .thuoc Imiprarnin
'.;!
Kh6ng tuong hop 1y hoa vci chat kim vi khuan (Bacteriostatiqu-:.f~
Ringer-lactate, silicon, atropin, succinylcholin, gian co khorig khu cue,
.

'~!

VII. DUNG QUA LIEU
Suy h6 hap: ho tro ho hap
Suy tim mach: dieu tri h9i chung

486


GAMMA-OH
(Gamma-hydrroxybutyrate

-

G H B)

'c

[,

;

Day la thuoc me tinh mach kh6ng phai barbituric (N6 chinh la 4 hydroxybutyrate
hoac goi la Gamma-OH). Day la mot thufic aa duoc
~. nghien cuu, it a9c va c6 tac dung gay ngu. ThuQC c6 cau tao rat gan vdi acid
~, amino butyric (GABA), Thuoc duoc nghie n cuu tu 1960 va duoc slt. dung
~
nhieu tu 1963.
f

f

~,-'

".~:.:.

1 I. TfNH CHAT L Y

HoA

Cau true cua Gamma-OH glin gui voi acid gamma - aminobutyric
!2 (GABA) rna nhorn amin QUQcthay the bang nh6m hydroxyd (OH). Day la
&.' dang muon natri cua acid gamma hydrobutyric.
~.
Cong thirc:
I

r~

I
f'

~;~

f

---

CH2

_. --

CH2

---

COONa

t

~
.'

<-

~:'
t.

~.

Khi sir dung tiern tinh mach, ngay ca khi tiem lieu rnanh (1-2 g/kg) nguo:
~. ta ,cung khorig' quoan sat othay th§ ceton trong nude tibl,;..GHB dang bot, mau
fi: trang, vi tinh the, hut am manh, vi man va tan trong nuoc. Dung dich 6n
~~,dinh, n6 cho phep tr,inh bay duoi d?ng ong tiem. pH thuQC l.-';t kiem (9,50),
~, tT9ng luQng phan tlt. 13. 126.
~.
GHB aa· aUQc t6ng hQp tu cau true vang, butyrolacton.
Va r6i
r butyrolacton aUQcQua VaGtulin hoan bien a6i thanh GHB nhc; m9t lactonase
duy nhit co m~t trong mau (HOTH va GIARlVIAN 1966 - 1968).
.
Thuoc trinh bay duoi hai d?ng.
D?ng tiem: ong 10ml c6 chua 2g (200mg/ml)
acid gamma
hydroxybutyric.
D?ng uong: Lo?i xir6, bao g6m phlin acid gamma - hydroxybutyric
vang va phlin Gamma - hydroxybutyrate.

II. DUQC f)QNG HQC:
DUQc dQng h9C cua Gamma-OH chua dltQC hoan toan biet het. Thuoc
r ~hong he g~n voi protein mau. Thuoc qua rau thai, chuy§n hoa thuoc d gan
~::qua trinh di h6a cua Gamma-OH sat nh$.p voi vang Krebs do acid succinic.
;,:

487


HOSlt dong duoc hoc cua y OH la su gQP lai cua hai chat chuyen

hoa GABA

T(f~

butyro1acton. Nguoi ta thay la GHB kh6ng chiu 81,1' beta oxy hca, dean t,~.
duorig nhieri duoc sir dung trong vorig tricarboxylic r6i no duoc chuyen ho'
mot phan qua ph6'i (2/3 lieu trong 6 giC!)d dang CO2 va H20. M9t phan du,;
chuyen sang lacton va acid succinic, chat cuoi cung ducc thai tru d nude ti~!~..
81,ibai suat d nLIOCti6u cua GHB co th6 xac dinh duoc qua so 1VQngc ~,.~
acid succinic (theo Jouany va Coll 1960).

III. DUQC LtJC HQC
1. Tren than kinh trung

Ltdng

.:

Tac dung chu yeu tren than kinh dern, thuoclarn tang su phan cue cua ~:.
bao than kinh dern, ngar; trd trong choc lat khu.:cue than kinh va d§.n truY8J~
luorig than kinh. Tac dung ngu sau, tac dVng ngu don thu~n. Th(ji gian n:g~I~
thu dVQctren ngvC!ilOn khi su.:dvng lieu 50-60 mg/kg 1a 90 den 120 phut.
Hoan toan kh6ng c6 tac dVng giam dau, vi v~y khi gay me phai ph6i h
voi thu6c giam dau. Tinh nhanh, tlnh hOEmtoan va yen tlnh - nhung t,
gian tlnh thay d6'i theo tu6'i, tinh trSlng cua b~nh nhan. D6i khi sau khi ti'·
thuoc, c6 th~ quan sat thay hi~n tUQng rung gi~t co. Nhin chung c6 th~ t '
hi~n tUQ'ngnay b~ng tien me voi thu6c barbituric hay tiem kern theo C1'J1'(~J
voi diazepam.
:'~
Gamma-OH lam giam ngu:6ng dQng kinh. Khi dung lieu n10nh, c6
gay co gi?t. Gamma-OH c6 tac dVng tren phan XSlmonosynaptic; Khi [ie.~,:

\ tInh mSlch GHB, lam giam bien dQ dap ling cua phan XSlco tren dQng v$.t ~j
bi c£t bo nao, va g£n voi vllng tuy <) dta phuong, d5.n den lic ch§' phan J:' ~
monosynaptic. Tac dVng cuoi cung nay duoc so sanh nhu GABA. Dac tirit~
nay duQ'cgiai thich la do tac dVng giam tn10ng Ive (hypotonisant) cu~ G~~
va ket qua tang tiem lvc cua thu6c gian co.
'
GHB lam tang t6'ng hQ'p acety1cholin cua nao. Lam tang so'
dopamin cua nao (GE8SA va COLL 1968). Tac dVng lam mem co cua no" ,:A
Lh~ Ly l~ vO.i ~I,i I.~l.r~t', Il(~nt',
~lupCl.~nirl ~18Y LI'()rl~, h~ thon~ n~o<;tith~~~
(extrapyramIdal),
gWI thlCh lQ'l Ich cua no trong su' d\mg VOl b~nh nh 'l'~
Parkinson (theo GRECIA va COLL 1971).
,!,i
Uc che trung tam dieu nhi¢t va trung tam v~n ffiSlCh. Phan X0
thanh quan giam, phan XSlmi m£t mat nhung ph an X0 giac mSlc con. ap l~~,,~
nOi t:l~, hiu lUljIlg'IWiu ll~tO va Lieu thy. oxy nao giam.
'
·'z

~i

tii

htq:~:l

(t?

2. Tae dyng

tren tim m<:teh

"J

~~

.

Thuoc it anh hUdng den ap l\IC dQng m0ch, khi khdi me, huyet ap gi~J
nhE;)sau d6 trd ve binh thu'C!ng.
:';$
Dap ling voi kich thich dau th6 hi~n b~ng tang huyet ap, tang hu)~ . "
ap 1a do thieu UtC dVng giam dau, trimh hi~n tUQ'ng nay b~ng cho th
giam dau.

488


Gamma-OH lam cham nhip tim. Cham rihip tim c6 thg ty l~ voi tac dung
itc che cua GHB (j " 6 nhan cam keo ding" dac biet la S1,1ire che (j dau mut
nhay cam cua rihi va cac tirih mach Ion, noi chiu trach nhiern ve phan X<:J.
Bainbridge. Uc che' co tim it, lam giarn hru luong tim, voi ly le la rihip tim
'. cham va gia m thg tich phut tam thu. Lam tang tinh hung phan cua co tim.
Nguoi ta th ay kali mau giarn, rna kali nieu khorig tang khi sv dung y OH voi
r nhfrng dieu tr i khac "s1,1phari eve la i-Repolar isant" glucose uu trueing +
~.insulin, cac thuoc liet than kinh. Theo doi ECG s6ng T det c6 thg de phorig
••b~ng cho KCl.

fi. 3. Tac dunq tren h6 hap .

t.

GHB kh6ng gay suy h6 hap va bao t6n s1,1nhay cam cua trung tam h6
~.Mlp ..voi CO2, N gu2Ji ta thay tang bien dQ va giam tiln so th(j, tang th6 tich
~ ~hi luu thong. Ho hap/phut va tieu thv oxy khong thay d6i. Thuoc lam giam
tiet phe quan, lam tang suc cang ng1,1cph6i (compliance). GHB uc chEf phan
; 1:? h~u thanh quan cho phep d?t nQi khi qUEm khong cfrn gian co, d?c bi~t (j
r tre em ho?c c6 thg tranh gay te t<:J.ich6 (j thanh quan.

l

r4. Tac dyng
i"

tren gan th~n

1:
Trong th1,1c nghi~m
f'lb~n m:;mh me.

tren dQng v~t, thlr dUQc hO<:J.tdQng gian m<:J.chgan-

;.

Ngoai ra, thuoc lam giam th2Ji h?n bai tie't ure trong nltoc ti6u, kh6ng
~,~B.mtang ure· mau .. N6 etoi l~p voi sv di hoa nitei va cho phep tiet ki~m
~p'rotein trong h6i suc.
~5.M9t so tac dyng khac

k

Tren tv cung, GHB lam tang truong l1,1c,bien dQ va t&n so co b6p; tang
~~cJng l1,1cco khi phoi hQ'p vai thuoc trQ' de (oxytocine). Vi v~y, nguCJi ta
~lhuyen phai th~n tr<;mg trong khi sv dVng Gamma-OH
vai nhung b~nh
~&han dang dltQ'Ctruyen oxytocin. Cling thCJi gian lam tang bien dQ co b6p tv
t~'lUng,GHB lam gian tli cung de dang, n6 cung rat thu vi khi sv d\lng trong
~~iM
kh6 (BARRIER va COLL 1963). NguCJi ta cung thay khong co lir. .r.he h6
;.~p va tu~n hoan
thai nhi, dieu nay eta chung minh b~ng test Apga'r binh
:;~u2Jng trong 88% so trudng hQ'p gay me m6 ete. (LAJf,'I" - C;ORSTN va COIl
;'1972), khi tiem t<:J.ich6 kh6ng c6 s1,1kich thich cho tinh m<:J.ch.Day la t~c
tdiung cua muoi acid beD va di.c lipid kh6ng gay ra phan ling m0-ch to-i cho.
t])k~mgiam nhan ap, gian d6ng tv. Giam truong Ivc co (do tac dVng uc chEf
r~J'Y)nhuQc co c~n. Lam tvt nh~ nhi~t dQ.

a

;WW. TAl BIEN, PHIEN N~N
Rung gi~t co thudng g?P khi kh(ji me (j nhung b~nh nhan khong dUQc
rl~n me va', c6 th6 de phong, sva chua dUQc b~ng barbituric
ho?c
lenzodiazepi~
tiem truoc. N gUdi ta cung c6 th6 tranh etuQ'c hi~n tUQ'ng nay
~"

L
~.

,
i

489


khi co su ton trorig pha thiu thiu ngu cua nguoi benh. Nhip cham

AVG'.J.~"'""I!'I".

th~ gap, de phorig bang khi tien me cho sV dung atropin. Tren tre em
biet hay g~p ki6u th(j Cheyne - Stokes luc h6i tinh, khong d6 lai hau
tren h6 hap. Trang thai ngu ga kco dai sau h6i tinh, tang tiet nude bot
g$.p 6 giai dean khci me.
Giarn kali mau (lam r6i loan tinh hung phan co tim, kha nang chiu
thich cua co tim). Van ch uyen kali (potassium) ngay trong te bao co th.~
den giarn kali rnau tram trcng tren benh nhan da co thieu hut kali mall,
rihu ngiroi ta da kh6ng bu cho benh nhan kali du truoc m6.
Khi dung thuoc qua lieu: bi~u hien ngu ga keo dai,

V. SLJDl)NG TREN LAM SANG
1. Chi dinh
1.1. Trong gay

me

•

GHB gay me phan li.
Day la thuoc gay ngu, it d9C, rihung kh6ng co tac dung giarn dau.

dl,lng co th§ phoi hc;Jpthuoc giam dau rieng bi~t ,dextromorarnid, p
ho~c la phoi hc;Jpbao g6m neuroplegic va thuoc giam dau (cholprov~·1"dextromoramid, droperidol va phenoperindin).
La thuoc ngu be) sung duc;JcIva chQn cung neuroleptanalgesie,
vi
lam tl,lt huyet ap va lICche ho hap.
•
GHB tiem tren ngudi 16n lieu 50rng/kg: (noi chung co th§ tiem
d~u 4 gram), (j tre em lieu cao han (80 den 100 rng/k g). D§ de
chung run gi?t d~u rnut (chan tay), ngudi ta tiem cung rn9t hie
diazepam va kh6ng kich thich bQnh nhan, giac ngu xua't hiQn
phlit luc wiy c6 lh~ ct~t canul vi, b~nh nhan co nhuc;Jc co c~n, tl,lt
Giai do~n nay cling d§ dang thvc hi~n gay te t?i ch6 vung luBi va.
m6n. C6 th§ c1~t n9i khi quan rna kh6ng kh6 khan. Sau d6 p
neuroleptanlgesie.
Nhu V?y bQnh nhan v§.n ngu d~y du rna s1't·
cung neuroleptanalgesie:
kh6ng lam tl,lt huyet ap, kh6ng ch?rn
va kh6ng lICche h6 hap.
Khi sv dl,lng GHB c6 th§ cho b~nh nhan th(j may rna kh6ng c~n
phai dung thuoc gian co. Trong m9t so ph~u thu$.t bl,lng, ngvc, tiet ._
d.n phoi hc;Jpgian co.
Tiern nh&c l?i GBB tli'phlit 90 b~ng nva lieu ban d~u.
•

V6i ky thu?t SV dl,lng d§ duy tri ~e, no lam tl,lt nh!? nhi~t d9 co
th§ g$.p trong m9t so chi dinh, ngudi ti da ket hc;Jplam l?nh sinh ly,
tl,lt nhiQt dQ rat sau rna kh6ng gay ruh. Phuong phap nay ra't d~c bi
490

- - -------------~------_rr:
l;:
~'

r.~"

rr

t

hop voi phau thuat mach nao, c6 tac dung bao v~ te bao nao tranh thieu oxy
t 6 nhung truong hop nhu vay c6 th~ sir dung thuoc manh nhu la
~. chlopromazin (chang h,;1.11
la dung dich dong mien: "Cocktaillytique").
~'
Trong tinh trang giarn kali mau, c6 th6 truyen glucose voi kali.
8v dung don thuan GHB

f,:.

t~.~ Gamma-OH c6 th§ S11 dung don thuan trong tat ca cac truong hop (X quang

n~ so nao,

tim mach) rna trong cac gay me X quang ay, ng.roi ta quan sat dVQCsu

t, yen tinh can thiet rna v§,n darn bao tv thd va dieu kien huyet dong' 6n dinh.
~.

Tren tre em, hau het cluing d§ khiep so va kho bao trong cac truong hop
F gay me chup dong mach, chup nao, ho~c thong tim, ngvdi ta sv dVng
[! Gamma-OH rat tot voi tre em d nhung trvdng hc;!pd6 ngvdi ta sv dVng d§
nQi soi va d~c bi~t trong soi phe quan d tre em (VIALARD 1965)

t
~"

.

r

'NgVdi ta sV d\mg trong thay bang bong ho~c nhung thay bang gay dau
d6~. Vi do ynh khong dQc cua GHB v6i gan th~n ngu'di ta c6 th§ sV dVng
nhac di nhac lai.

r~

f{

f{..

fi·

•

?

•

?

?')

8v dVng trong san khoa va mo de

~

Trong giai dO:;lngian, GHB dVQcchi dinh d~c bi9t trong de kh6 vi thuoc
~:'co tac dVng ngu va tac dVng cua oxytocin, y OB lam tang bien dQ hO:;ltdQng
~;'cua co b6p tv cung de dang lam gian nd (BARRIER va COLL 1963). Tren
~,thai nhi khong c6 sv thay d6i ve tim thai. C6 th§ b~t d~u gay me khi c6 tv
~'i:ling md 3cm d ngvdi de con d0. va 5Cl11d ngvdi de con so. 86 rau thtldng la tlj
~'nhien tren san phv de con d0 va chi 80 Apgar thi thon man. Chong chi dinh
~ sU: dVng voi san phv c6 huyet ap cao.

r~

Gay me trong m6 de: GBB 50mg/kg kh6ng dQc voi thai nhi; Theo
~\\iJROT (1964), gay me b~ng thiopental chi so Apgar tren 6 d 4,6% trvdng
~)lQP, tren 8 trong 4%. Con voi GBB chi' so Apgar tren 6 trong 92% tntdng
bl)v va tl'ell 0 (J 77%.
t:, 1.2. SUdl.,mg hOI sue

r

[ft 1.2.1. Trong t h?'
cJ may
f
L

Sv dVng voi nhung trVcJng hQp chan thvClng 89 nao n~ng, ho~,~ ti~h dVQctrong khoang 2 gid theo may va b¢nh nhan c6 th~ tv thd ngay sau
~'_!tllidung may. C~n thiet dung nh~c 10.i,cu hai gid!l~n. Tac dVng nhvc;!c co
[:;~:~amtrvong Ivc co) cua GHB cho phep suc cang gian ngvc ph6i tot han. Doi
r, tthi ngvdi ta quan sat dVQcngu ga d b~nh nhan.
.
F
f :'2.2. GiClyen tTnhb$nh nhan trang v?n chuyen
l Do tinh 6n dinh ve tim mach va h6 h£tp cua GHB cho phep sV dVng lam
l, ~ventinh benh nhan da chan thvong trong khi v~n chuy§n. Thuoc kh6ng lam
~'tr,1thuyet ~p va khong gay uc chc nguy hi6m cho ho hap.
k
?

I'

~.
~;1

t
fi'

491


1.2.3. Hoi chung than kinh tuy song va uon van (Neurologiques
tetanos)

medulla;

V6i Ul..C dung lam suy giarn phan X9-mono synaptic, nguo: ta s11 d~
eEB d~ dieu tri ucn vim la hct sue logic. Phoi hop GHB vci diazepam d
phcp kiern scat duoc can co giat.
1.2.4.

Sa df.jng voi berth

nhen

co kali meu

cao ve suy then cap

D~ van chuycn kali tu ngoai te bao vao trong te bao, GHB duoc dung Pl!
hop truyen huyet thanh ngot uu trucng voi insulin, d6i khi giup cho vuot 'I;j[
su nguy hi~m cua kali mau cao voi co tim va giai dean doi cho 19C mau.
2. Chong

chi dinh

Thieu phuong tien h5i sue
- Nhip cham tim do roi loan d§.n truyen nang.
2..2. Tuoriq dOI- NgQ dQcruou cap tinh.
- Gay me toan than ng~n
- Cao huyet ap n~ng kh6ng dieu trio
- Chung d¢ng kinh (Epilepsie)
- Chung kinh giat (eclampsie)
- Ciarn kali mau,
2.1. Bat bU9C -

3. Lieu Ilf<;1ng

Slr

dyn9

ThCiigian chd tac d\lng 4 - 10 phut
Tac Ul;lIlg kGu uNguCiiIOn.
Khdi me: 50 - 70 mg/kg tiem tInh nwch
Duy tri 25 - 35 mg/kg tiem tinh m9-ch
811d\lng t1'uyen lien t\lc:
Lieu khdi me: 40mg/kg (tInh m9-ch)
Duy tri 15-30mg/kg/gid (8E)
.j
.".
1'1'8em: khdi me 60 mg/kg + 2 mglkg thiopental trong cung m¢t born ti~,-'-:::~

VI. TLfdNG TAe THUOe
Tang tiem h;tc tac d\lng Gamma - OH do barbituric, neuroleptia
thuoc halogen (lam ch$-m nhip tim)
Tang tiem h;iC tac d\lng thuoc gian co.
Kh6ng tuong hQp ly hoa voi: dext1'omoramid, promethagine

492


KETAMIN

(ketalar)

u

r

r
i:i

t
i:

La th uoc me tinh mach khorig phai barbituric c6 tac dung ngan. Thudc
me tinh mach duy nhat c6 tinh chat giarn dau, ail ducc sU: dung rQng rai
trong rihieu narn nay, d$c bict d cac nude dang ph at tri~n.
Thuoc duoc t6ng hop narn 1962. CORENN sV dung lfin dfiu tien narn
1966, dua VaGthi truong tir narn 1970.

I. rfNH CHAT LY HoA

i
c

r

Day la mdt phan tv c6 diu t<;1.0
vong. N6 c6 mot carbon khong doi xung v~
trinh bay dudi dang hai d6ng phan quang hoc,
N6 tan trong nude, pKa la 7,5. D9 tan trong rna rat cao, dung dich sv
dung tren lam sang d dang clorua pH rat acid, thay d6i tu 5,5 den 3,5 tuy

thea n6ng dQcua thuoc (1%, 5% hoac 10%).
'I'huoc trinh bay d dang dung dich 1%, 5%, 10%. ong fiml lieu 50mg (dung
dich 1%; 10 mg/ml), ong 5mllieu 250 mg (dung dich 5%, 50mg/ml).
Cong thuc h6a hoc

.
J1
f

.!

I

:I~

Cl

=0

II. DLfQC DQNG HQC
Do d$c tinh tan rnanh trong rna, thuoc phan phoi nhanh. Thuoc phan
phoi nhanh VaG nao (m$c dli khong b&ng thiopental). Th21i h<;1.ntac dQng
ng~n va giong nhu thiopental cling bi tac dQng bCiiSv phan phoi b;ti clla t6
chuc. Thuoc hap thu nhanh qua du21ng b~p thit, n6ng dQ thuoc cao nhat
trong mau qua hem b~p quan sat duc;JCsau 5 phlit.
Sv phan phoi clla ketamin tudng tv nhu clla thiopental.
Toc dQbien d6i sinh hQc qua gan khong anh hUdng len th21ih<;1.n
tac dVng
reuathuoc me, nhung n6 l<;lianh hl-iCinglen th21igian tac dVng sau gay me.

493

.. 1


Thuoo g~n voi protein

mau

12%. Thoi gian 1/2 doi thai tru d ngu'oi !

125· 160 phut, d tre em 80 . 120 phut. Thoi gian nay keo dai khi ket hop d!~
thoi voi thuoc halogen va diazepam.
V6i lieu tiern nhac lai, ketamin lam hoat hoa men: Lam tang kha 11.1
chuyeri hoa cua cytocrom P450 so vci nen cua n6, ban than n6 la char.
khdi dong.
'
Th~ tich phan phoi: (j ngiroi 16n la 1,9·2,7 l/kg, tre em 1,3 . 2,5 l/kg..
thanh thai (j nguoi 16n la 10· 14,5 rnl/kg/phut, tre em la 13,5·22ml/kg/phliL
Thuoc qua rau thai nhanh do n6 la chat tan trong md, Nong' dQ d thai 0:
nhat vao thci di6m 1,5 don 2 phut va thuong vuot ncng dQcua me.
Chuyen hoa: d gan 95% bdi monooxygenase cua cytocrom P450, qUlJ
phan ling: mat methyl, hydroxye hoa, va glucoro ket hop.
'. Thai tru qua nuoc ti6u (90% d dang chuyen h6a va diroi 4% d dang khfl
d6'i). Thai tru qua phan 3%. Chat chuy~n hoa chinh norketamin c6 tac &fa
yeu han ketamin 5 l~n. Con hOe;tL uOng t:ua cac chat chuy~n hoa khac enl
duc;Jcbiet.

III. OLfqc Ll/C HQC
1. Tae d9n9 len than kinh trung Ltdng

Tuy thuQc vao lieu lUc;Jng,ketamin gay ra mQt tlnh trC;lng"me phan.lj"'·j
mQt mi;it thuoc lic che hOC;ltdQng cua vo nao va du6i dBi, trong khi lC;libi
thich h~ vien va h$ ·Ivai. Tren lam sang b~nh nhan roi VaG mQt tr?ng .dJ
tang truong h,tc, giam dau, nhvng ngu nong: hai m~t mo, dang til gian, '[jil
gi$.t nhan du: phan XC;lgiac ffi?C, phan XC;lh~u, thanh quan, phan XC;l.~
vein con. B$nh nhan c6 th~ ho, tang het nu6c b9t, chay nu6c m~t, -8
truong l\ic co, c9 qu$.y ma ch~ng lien quan gi den cac kich thich m6 xe. SJ
me b$nh nhan quen cac s\i vi$c xay ra trong m6' nhvng kh6 ch~u nhalt.
thudng c6 mo mQng, ao giac. '
Cam giac nay thudng xfry ra khi dung lieu cao, khi tiem nha.nh, Cl~
nhieu l~n, hay g~p 0 ph\l nil nhieu han 0 ngudi c6 tu6'i. C6 th~ tranh ~
tUc;Jngnay b<1.ngcho benzodiazepin trong tien me.
Thuoc c6 tac d\lng giam dau be m~t han nQi tC;lng.Co che tac' d\lngd
ketamin c6 nhieu: Thuoc uc che s1,tdein truyen thea tr\lc th~n kinh V8'~
kich thich te bao, thuoc gay ngu do lam giam tac d\lng kich thich cua 6' d
cam N·methyldiaspartate,
thuoc lam giam dau do tac dQng len 6' thlf cllJ
morfinic sigma (D. Ngoai ra n6 cling tac dQng len cac 6' cam th\l serotfooo
cholin cua h$ th§.n kinh trung tWng. Cuoi cung thuoc lic che 8\i hap m
noradrenalin (5 cynap ma gay nen tang co b6p co tim.
_
Tr0nngv(Ji, kelamin lam tang ap 11,tcnQi 89, va luu IVc;Jngmau naD.. 6 ~
nhan co ap 11,tcCO2 mau binh thudng: dieu nay khorig thay ro tren sue l~
494


binh thuorig va lieu nho ketamin. Trong thuc te' co
th§ dung lieu nho gay giarn dau d benh nhan m6 S9 nao voi dieu kien PaC02
binh thucng. Nguoc 10-ikh6ng nen dung ketamin d benh nhan co benh ly n9i
so. Ne'u cho barbituric hay benzodiazepin truce S8 tranh duoc hien tuong

tang luu hrorig mau nao. Ketamin kh6ng lam thay d6i dap ling van mach
nao doi vdi CO2, PaC02 giarn se lam giarn nhe S1.;(tang ap luc nci S9 do
ketarriin, ngiroc lai PaC02 tang S8 gay con tang apluc nQi SQ.
thuc nghiem

c6 PaC02

2. Tac dunq tren tirn mach
Tren tim mach, ketamin co tac dung tuong tv nhu sv kich thich giao
cam. Ketamin lam tang ap luc dQng mach tam thu va tam truong, tang tam
thu nhieu hen tam truong, tang ap luc dong mach ph6i. Khi tiern tinh mach
huyet ap dQng mach tang cao han tiern bap; ap hjc dQng m0-ch co th§ tang
den 15% va ph1.,lthuQc VaGtoc dQ tiem, ap Ivc dQng m0-ch trd ve gia tri ban
d~u sau tiem lieu m0-nh khoang 10-12 phUt. Lieu tiem nh~c l0-i, huye't ap
oQng m0-ch khong tang nhieu b~ng luc khdi me.
I
Ketamin lam tang nhip tim va lULllUQng tim, tang suc can ngo?-i bien
: cung nhu tieu th1.,loxy co tim thu tv 30-40%.
nhung ngudi co trai tim kh08 m?-nh, tang nhu c:iu oxy cua co tim d§
dang dUQcbao dam bdi giam suc can m0ch vanh, nhung nguy co thie'u mau co
t.im se khong dUQc100-itru d b0nh nhan co bQnh m0ch vanh. Huye't dQng hQc
. thay d6i khong ty 10 voi lieu Sl1d1.,lng(0,5 de'n 1,5 mg/kg tiem tInh ll0-ch). Va
i n6 giam bot voilieu nh~c l0-i. Thay d6i huyet dQng khong co gi d~c bi~t tren
b~nh nhan c6 b~nh tim v~, tren tr~ em, Nhvngb~nh tim b~m sinh, tim co th§
: chap nh?n dUQCketamin (Fallot),'{t c6 sv thay d6i ve'slilint. C'ac't~c d1.,lngtren
" .ap Ivc dQng m?-ch tam thu va dQng m?-ch ph6i co th§ giam bot khi sl1 d1.,lng
~truoc benzodiazepin ho$.c thuoc me boc hoi ho~c Protoxyde d'azote (N02).
Co ch§' tac d1.,lngtren h~ tim m?-ch cua ketamin da dUQc bie't d~y duo
: Chung dVa chu yeu vaG sv giai phong noadrenalin va sv uc che' chie'm d00-t
rna thuoc d6i voi h~ th~n kinh tv dQng.

Trong thi nghiQm tim cho bi co l?p, ketamin c6 tac dQng tren ho?-t dQng
~uc che' cobop'cO' tim /sau phong hP,'h0 thrin kinh b.t oQng (Syst,em ,nerveux
·autonome).

: a

I

Tren lam sang, h?u qua ~uye't dQng h9C d b911h 11ha11soc b111hthUd11g1a
tang huyet ap va luu lUQng tim, nguQc 10i d mQt so nhung b~nh nh8.n thay
. the cho cao huye't ap 1a tac d1.,lngt1.,lthuye't ap va tac d1.,lnggiam luu 1uQng
tim ty lQ voi lieu lUQng thuoc. Dieu nay phan anh tinh tr0ng thie'u h1.,ltdv
;;:rU catecholamin cua h9 th~n kinh tv dQng.
3. Tac dl;lng tren h6 hap

Ketamin trong dieu ki~n sl1 d1.,lngtren Him sang, it uc che h6 hap. Dap
rItng h0 ld{p VOl CO2 dUQCgiU: vCfng. Sau khi tieIll lieu 2 mg/kg tInh nwch,

195


thong khi phut giarn. Khi sv dung ligu cao co th6 gay ra ngung tho, hau:
tren cac benh rihan co ket hop voi cac thuoc dong ho morphin. Sv dung
mirih ketamin khong lam thay d6i khi mau dong mach.
Tiern lieu nhac Iai, tac dung tren ho hap giorig het hie kho; me,
khorig tram trorig bang; lam tang trucng Iuc co va giarn sue (complian
gian riguc ph6i.

,.
I

Ketamin khorig lam mat phan X? duong tho. Tuy nhien, tren
benh nhan co da day day, khoi me ketamin van phai de phong nguy ..
neu khong dat noi khi quan de phorig bien chirng trao nguoc, K
khorig phai la thuoc diroc Iva chen khdi me cho nguoi co da day dely.
Tren hau het voi tre em, ketamin gay tang tiet nude bot. Sv tiet
b9t nay co th6 1a nguyen nhan gay t~c nghen du'ong thd, thu'ong do co
thanh quan. Cgn phai tien me vdi cac thuoc chong cholinergic. Tren tre
(no'urisson), thay co bi6u hi¢n tim tai ~lo tang tiet d~ch duong phe
phoi hc;iPatropin (0,01 mg-O,02mg/kg) va thea d6i ho hap trong qua
dvng thuoc 1a dn thiet. Ketamin cung co tac dVng gian phe quan, chu
do d?c tinh giong theln kinh giao cam. Thuoc duc;icsv dVng cho b$nh :
hen phe quan. Tac dVng gian phe quan cua ketamin co th§ sanh
halo than va enfl uran.
4. Tae dl;lng tren m9t

so cd

quan khae

Ketamin khong lam anh h uCing den cac xet nghi$m gan, th$,n. N gUQc
GUygan th$,n it anh hUGng ueLl Tren tv cung, thuoc qua rau thai V~l kh6ng lam mat truong h,tc
cung, khong lam suy ho hap va tim mq.ch vdi thai nhi.

,.'.,

Tren m~t: thuoc lam tang ap Ivc nhan du 2-3 phut. Giam phan
m~t va dong tv. Cuoi cung, ngu'oi ta co th6 quan sat thay chung run
nhan du va chong m~t trong khi sv dVng ketamin (hay quan sat

khCiime va hoi tlnh).
5. M9t

;'l

,.
;

so tae dyng

khae

Ketamin keo dai tac dVng cua cac thuoc gian co khong khv cvc: b&ng ;
dQng van vi$c g~n voi calcium va thuoc gian co khv cvc b&ng uc che'
pheln cholinesterase huyet tu'ong. Tang tru'ong h;tc co Ian toa, chu yeu d
va ng1_ir..C6 thf~ Sli dVng cho b$nh nh6.n nhuc;ic co, sot cao ~c tinh.
kh6ng lam tv.t 1u'ai.
Lam tang ap 1vc nu'dc nao tuy nen bat lc;iikhi sV d1,ll1gtrong cae
thu$,t X quang theln kinh (Neuro-Radiologique) ketamin kh6ng gay
phong histamin. Thuoc lam tang du'ong mau do lam tang truong hjc co,
tiet ca thecolamin va cortisol.

496


-----_-~~_.

IV. LIEU LUQNG, eACH

su Dl)NG

:: 1. Chi dinh

Gay me tcan than
Cac phau thuat ngan, nho.
Bong (thay bang)
B~nh nhan cao tu6i, tre ern.icao thu thuat tharn do gay dau.
Hen phe' quan,
Thu thuat phu khoa - san khoa trong truong hop c6 giarn kho] hrcng
tuan hoan hoac co that phe quan cap.
Phoi hop gay .t e vung.
Soc nang (Temponate), van chuy§n berih nhan.
2. Chong

chi dinh

Edt buoc: Roi 10porphyri
Thieu phirong tien h6i sire
Tai bien mach mau nao, tang ap luc n9i S9.
Phinh mach nao.
Suy vanh nang, cao huyat ap, nhdi mau co tim vua rnoi qua
Tinh trang tieri san giat, san giat.
Tuong doi: Cuorig giap trang (mach nharih), nghien ruou, nghien ma tuy
D9ng kinh, tam than phan Iiet.
Ph§.u thuat mat (G1aucome).
Phau thuat tang sau.
Ph§.u thu$.t phe quan va nga ba helu thanh quan.
3. Lieu Ilf<;1ng
Thdi ginn chd bc dv.ng: 15 - GOgiay LIIlll mach

2 - 4 phut b£p thtt
'1'h0i gian tac dv.ng: 5-10 phut, tInh m3.1.

Tien me:

15 - 20 phlH, b~p Lhit.
Phoi hQp voi atropin va

thuoc

an

th§.n kinh

ho$.c

fienzodiazepin:

Ketamin: 2-3 mg/kg tiem b£p thit
,),.2.Gay me: Khdi me: 1-4 mg/kg tinh m?ch
6-13 mg/kg b£p thtt.
Duy tri me: 1/2 lieu kh0i m8 tlnh m?ch, ho$.c b:1p thtt theo bi§u hi~n tlnh
l!7.]ab$nh nhan.
497


3.3. Truyen

keo diJi:

Nguci lon: Khdi me: 2-5 mg/kg tinh mach hoac 0,12 mg/kg/phut
mach.
Duy t.ri: 0,08 mg/kg/phut.
Tre em:

Khdi me: 2 mg/kg tirih rriach.
5-8 mg/kg bap thit.
Duy tri me: 1 mg/kg tirih mach
Duong hau men: 9-10 mg/kg khdi me.
Duy tri: 1 mg/kg tirih mach neu c§.n thiet.

V. TAl BIEN, PHIEN N~N
Noli va bu6n non c6 th~ g~p nhung khong thuong xuyen. C6 khi j ,
giarn ho hap, ngung thd, ao giac, kich thich, roi loan tam than, doi khi co.''' j
con d9ng kinh. Thuoc gay tang tiet nude bot va nude mat.
N6i ban d da hiern gap, it thay dau noi tiern, ho nac, co that thanh q
hay g?P nhieu d tre em.

VI. TVdNG TAc THUOC
Thuoc chong cholinesterase: Hun mat tac dung trung uong cua keta
bsnzodiazepin: lam mat tac dung roi loan t§ m than.
Digitalic: giam Q9C thuoc.
Thuoc cudng than kinh giao cam (Sympathomimetiques):
dVng co m?ch va dieu nhip.;
Tudng ky' 15' h68 voi dextromoramid,

"

.

498

promethazin,

lam tang

barbituric .


,
"1{'
I,

f'
~.
~~;

~:

PROPOFOL

r"~;

~.
~

(diprivan)

Propofol la loai th uoc me tinh mach, che' pharn hie dE\u diroc sv dung d

~,

r'· dang khorig hoa tan trong nude (2,6 di - isopropylphcnol).

~.

Narn 1977 Kay va Rolly Lin d~u tien tiern cho nguci tinh nguyen,
l~,:rat dau
d ch6 tiern.

nhung

~
Den narn 1982, nguoi ta dua ra thuoc d dang dung dich moi, c6 ba chat
~' hoa tan, dang lipid th§ sua tren nen tang dau do tuong.
~Thudc dang sua nay duoc sv dung 1E\nd~u tier; tren nguoi VaG thang 7
[:.
nam
1983 bdi bac sl Nigel Kay d Oxford.
h'_
~,
Cac nha gay me h6i sire Phap cong bo nghien cuu VBpropofo1 tren tap chi,
~;chuyen khoa cua ho narn 1987.
~

Day cung 1a 10?i thuoc me tinh mach c6 tac dVng nhanh va tlnh cung
ea khi dung thuoc keo dai.

I~
nhanh-Ngay

r

~

I. TiNH CHAT LY HOft.
,

f:

,Propofo1 (Diprivan) 1a hQp chat fenol, diisopropyl - 2,6 - phenol. C6 cau

~~.

r Ini~:::g~hUChoah9

C:

~:
.

OH

~-

-0-

1

1,~,

_:..

~i

~: <) nhi~t

dQthong thudng. propofol1il dune- dir.h kh6ng m~u hocftcvang rom.

F:

TrQng lUQng phan tv l'/8d, r~(t it h.oa tan trong nuae, thu6c rat tan trong
~:ma vai ty 1~ dE\u/nuac la 40,4 c6 th§ so sanh vai methohexital va kern
rtthiopental. Chat hoa tan 18.lipid d?ng sua nen tang dE\u do tuong.
)

@'

,',

Diprivan dUQcbaa che dltai d?ng nhu dich.l% ;g6m ?~ll.do _~uong,10o/~Ll,2%
~tr.:,k phosphatid trung va 2,25% glycerol. H6n hQp nhu-dtch nay c6 d?ng sua.
-.
;'

~

Propofol c6 pH la 6 den 8,5 va pKa la 11. (C6 ngh1a 18.d pH sinh ly, thuoe

i'a dc;mgion hoa).
~:
f;
~.'

v

~~;':'

~.

r

499


Thuoc trinh bay duoi dang ong, 10mg/ml
Loai 20ml chua 200 mg
Loai 50 ml chua 500 mg
Loai 100mI chua 1000 mg

BilO quan

(5

rihiet d9 25°C

~C6 th~ pha pr?pofo1 tr?ng dun.g dich glucose d~ tiern tr uyen. Tuyet
khong duoc pha Val cac 10?1dung dich khac va cae thuoc khac.
.

C6 th~ pha l§.n xylocain voi propofol d~ giarn dau khi tiern thuoc.

II.

oucc
. DONG
.

I

HOC
.

Theo doi propofol c6 g&n chat ph6ng X1;l tiern cho nguo: tinh nguyen
m?nh, ...88% thuoc duoc tim thay 6 nuoc ti§u trong khoarig 5 ngay, dudi
chuyen hoa.
Propofol chuyen rat nhanh trong mau, Ty l~ propofol duoc ghi lai
qua 39% sau 10 phut - 14% sau 60 phut va 5% sau 6 gid. Gan la noi
hoa chu yeu. Qua cac nghien cuu nguoi ta khong thay su thay d6i (5 gan
thuorig so vdi nguoi binh .thuong. N gUdi ta cho rang c6 th~ con c6 ducng:
thai ngoai gan cua propofol (boi vi su dao thai trong huyet thanh la gap
hill hir;inG m.9ll r.l?Jrl grl n). Nhltng diru n8Y r.hll:l dllChat ehuy~n h6a ehu yeu la glueuronid va sulfo ket hc;iP. 90% lieu: .
d1,lngdu'<;iC
thai tru qua du'dng nu'ae ti~u, du'ai d?ng chuy~n hoa. 0,3% d
khang chuy~n hoa va a phfm la 2%. Chuy~n hoa a m~t kh6ng dang k~.
Propofol g&n voi protein la 98% - 99% (j ngu'di kh08 m?nh. Muc d<)
khang thay d6i trong tru'dng hc;ipsuy gan va suy th~n. Thuoe tham de
trong h6ng d.u va n6ng dQ propfol trong mau tOEmph§.n rat g§.n voi n6
trong huyet tu'ong (xap Xl 1).

Tren ngu'di kh08 111?nh,sau tiem thuoe du'dng tinh m?eh thuoc kh
tan nhanh len nao va die co quan khae, n8ng de)khuyeeh t{m trong ma
tien nhanh, sau rat eh~m. Du'dng bi~u dien cua n6ng dQ thuoc trong
th~ phfm tieh thanh 3 pha.
Pha 1 (T1/2a.) phan phoi tu nao den t6 chue, th,di gian ntta dCiis
,
ngan.
Pha 2 (T1I2~) tu'ong ung voi dQ thanh thai chuy~n hoa. Thdi gian nlta
thai tru 30 phut den 1 giCi.
Pha 3 (T1I2y) ntta dCiisong rat dai (thuoc tu ch6 dl,i tru a cae ma
l?i vao tu§.n hoan mau) thCii gian khoang 300 phut.
Trong th l,ie te, toc dQ thai tru th uoc nhanh han toc dQ tra l?i dong'
hoan cua thuoc. Du sao cung phai cang nh~n sl,i quay l?i hay lam
ph§.n nao toc dQthai tru cua thuoe.
.
Tinh chat ehinh du'c;iCdQng 119Cpropofol du'c;ict6ng ket theo bang 29.1500


Bang 29.1.

!

He s6

Thg tich

T1/2a

T1/20

thanh thai

phan ph6i lit

phut

phut

I

I

Our;;c o(;ng hoc propofol
T1/2y phut

llt/phut

!
: Propofol

1,97-2,19

720-1587

2,9

f
1 Propofol+fentanyl

1,29-2,10

387 - 546

1,8

34

208 222

i Propofol+halothan

1,79

460

4,1

34

184

1 Suy

1,85

2,83

39,3

404

,

thEm

5,4

45

64

284 222

;

! Suy gan

2,17

637

266

r Tu6i>65

1,45

1447

690

,
iI Wo.
01 sire

1,8

1632

1504

DQ thanh thai chuyen hoa cua propofol tang cao tren nhimg nguoi khoe
~' D19-nh.
~;.
Khi tiern truce fentanyl, thufic Hun giam glin 30% th~ tich ph an phoi cua
fi' propofol rna kh6ng lam tang dQ thanh thai, trong dieu kien do, nong dQ
~, trong mau cua propofol rit tang.
~.. 1. Anh hlfdng co dia tren chuyen h6a thuoc

f:

. .Tre em

tren.4 tu6i, d~c tinh duoc dQng h9C h5.u nhu khong c6 gi khac vdi
I" nguoi tre tu6i. Nguoi cao tu6i (65 - 85) dQ·thanh thai giam so vdi tu6i 18 - 35.
~: Trong khi do th§ tich phan phci cling giam nen thoi gian ban huy thai tru
khong khac nhau giua hai lua tu6i.
'

l

~'.•'

Trong xo gan duoc dQng h9C it c6 thay d6i so voi ngudi l?inh thuong. Kh6ng
thiy S1,1' khac nhau co y nghia giua nguoi suy th?n va ngudi kh08 m9-nh.

i:
f
.r 2. Thay

d6i

nang

de? thuoc

trong mau

~,
Nong de) thuoc trong mau ph1,lthuQc theo cach slt d1,lng. 'I'ruyen voi luu
~. hlQng kh6ng d6i, nong dQ trong mau kh6ng thay d6i. Khi thay d6i th~ tich
L uuyen nong de)trong mau thay d6i. NO.phu hQp voi yeu cliu clla gay me.
!~.

~
1"

fr,

Thi dv:

nong dQ trong mau'6,2mcg/ml;
6mg/kg/gi6' thi n6ng de) trong r?a~:
2mg/kg/gio nong dQtrong mau la 1,35 mcg/ml. Khi tiem lieu ~e)c.
r ohit, d?m dQtrong m~lUhic tlnh la 1,1 ± 0,2 mcg/ml. Truycn lien t1,lc,d?m
if di~trong mau hic md m~t'la 0,75 mcg/m1 den 2,2 mcg/ml.
k
Luc b$nh nhan nho dUQcngay sinh, th~mg
cua ban than minh thi d?m

9mg/kg/gio,
(..13 3 mcg/ml;

,.

de

r. aQ trong mau la 0,6 mcg/ml.

t~:
\.

t

;

501


Lieu can thiot d§ lam mat ph a n xa mi m at l' 2 0

6 50% so benh nhan,
.
a , 7 mcg/ml,

3,4 meg/ml

~.

gay n~.

}ro~g, m6, ~/eu ,khon~ ket hop cac thuoc dong ho morphin thi lieu c ,
thiet de lam mat cac phan xa khi dat noi khi qua?n la' 5-7 mcg I m.1 IrL'
,.;1)1,'
-ulJ ~Iln'
chinh hinh lieu su ~:~ng thap han d§ m6 bung. Khi d6ng bung can lieu d!l(;~
han khi r??ch da. LIeU nay can phu thuoc vao thuoc tien me, thuoc me " .
hop va the trang benh nhan. Thuoc qua rau thai. 'I'hudc tan trong md,
dang qua rau, thai va ty l~ nong dQ giua con va me trung binh la 0,7.
kh~c, ty l~ nang dQ mau dQng mach va tinh mach ron xap xi 1 trong
diem sinh. Tli do, eho thay su phan phoi L;J.irat' nhanh trong tuan hoan
thai nhi va chuyeri hoa 6 thai nhi cham han so voi nguoi len.
o

"

'0)

'"

III. TAe DUNG DUde LUe Hoe

•

••

I

1. Tren than kinh trung lfdng

Propofol c6 tac dVng khong d$.c hi~u len mang lipid. Trong In -'
propofol lam thay d6i chue nang cua cae kenh di~n giai va lam tang
soa t ue ehe eua die te bao. th~nkinh h~ GABA (acid gamma - aminobu
cae te bao th~n kinh h~ dopamin 6 chuQf '
'.
Propofol ehu yeu gay ngu, lam mat tri giae rat nhanh va ng~n,
song voi toe dQ tiem.
T1nh rat nhanh va chat hil)Ilg' Lclt. (4 phut 8811 khi tiem nh~e 1?,i..
phut sau khi truyen lien tve).
Tae dVng tren luu lUc;Jngmau nao, tieu thv oxy nao chua dUQc.'
nhung sau khi tiem tInh m?eh 2mg/kg va tiep theo truyen lie~
tInh m?ch 150 mcg/kg/phut, thuoc lam giam ap h,ie trong S9, giam
lUQng mau nao va ap ll,l'ctuoi mau nao. Tuy nhien v§.n duy tri dUQIC;
dieu ehlnh tt;t dQng luu 1UQngmau nao theo st;t thay d6i cua
'.
dQng m?ch va dapung v~n m?ch khi thay d6i ap 1t;tcrieng puu"....·.....
CO2 trong mau dQng m?ch (PaC02)·
Propofollam giam ap h,te dich nao tuy va ap hjc nQi nhan.
Propofol h~u nhu khong c6 tac dVng giam dau.
Trong nhung nghien cuu g~n day, ngudi ta c6 chung minh duQC,
lieu 1UQngnho propofol kh6ng du gay ngu nhung l?i lam giam
mQt ph~n 6 ngudi b§.ng cach lam giam can dau cap thu phat sau

thich b§.ng laser.
0

2. lac dl)ng tren h~ tim m~ch

Cac tac dQng ve h uyet dQng cua propofo1 da dUQcnghien cuu ~a d
v~t, ngudi kh08 m?nh va ngudi c6 b~nh 15'tim m<;tch.Vi~c gay tyt h
_
dQng m?ch n$.ng khi truyen propofollien tvc tren ch6 18.do thuoc vila co
502


s.

~~

t:

f"

t;

d~ng ire che' co b6p co tim, vira tac d
.~,
~
c~. 09ng va tinh m?ch. Ngvoc lai RI l,lng t~V: twp tren ~trvon~, IVc m?ch rnau
Val co bop co tim tren cac soi co 'tim ~N ~a ~9n~ su l~?ong t~ay tac durig doi
~t co chua darn dQ propofol kh~c nhau. cua c uot tach rei duoc u trong mQt binh

tr·

f·

Trel: ngv,CJi,khO! me b~ng propofolluon
gay ra iarn hu A',
A
!~\< trung birih vao khoang 20-30g..;: G'?
h
A',
.g
yet ap d9ng mach
ap tam tr uong (PAD).
o .. lam
uyet ap (PAS) tam thu IOn han huyet

f
t

theoSVt'u~?~Ut'
~ hOD'i
l~i. c6uOhuyet
a
ap dQng mach (PA) phu thu6c theo tung ca the:!
01 ac
Val
t A' PAt t d ,.
.
,
~.' 'A
.

UOl,
1,1
Val 20 mmHg trong 58% SOA'
trucng hop
va tren 40 mmHg trong 4g..;: '1' A 60
A?
uv
y
tIiL mmHg
c.:
o.
ren
tuot tut 20 mmHg trong 20% va 40
VOl39% cas .
~:'

•

;.;:~

~:

Do vay, sau 60 tu5i - phai giam lieu thuoc propofol.

t.',
Pro~?f~l ga,y tvt huyet
.. tvt huyet ap kern theo.

:

ap khi kh6i me nhvng

khi tiem nhi'ic l?i kh6ng co
.
I

T?~n s~ tin: COA?
X~ the giam m~c du no kh6ng lam thay d5i tinh nh?y
cam eua cac 0 cam thV vai phan X? ap h,tc, v~n gay ra mot sV oieu
chinh lc;tiphan X? ap Ivc d~n den giam ttin so tim so voi tti~ so'tvong
ung vai muc huyet ap dQng mc;tch 6 ngvCJi ti'nh.
Doi khi co nhtp ch:fl_m'xoang tren ngtiCJi IOn tu5i.
Kh6ng co roi lo?n nhtp tim, UCche' co tim vua phai.

Oi AJll s{tr. d 11t,h 8 nh n10cll ngv:;!.i vi. Th uCJng gd m tl't 6 cl en 20~/o.
Giam'vua phai luu lU(;:ingtim, giam lU:L~lltc;ing m?ch ,:,anh va tieu thv
oxy co tim giam.
Propofol it lam anh hvong tai huyet d9ng trong thu thui;tt di;tt ong n9i
khi quan cung rihv sV nhc;ty cam cua b¢nh mc;tch vanh.

:/

Tren thvc te, tae dVng gian mc;teh va h?u qua eua no se r6 r~~ 6 nguCJi
thieu khoi lV<;Jngtutin hoan, ngvCJi gia, ngvCJi suy thi;tn hoi;te suy ehue
nang that trai, eho nen phai tranh 811 dvng thuoc tren b~hh nhan
thieu khoi lu<;Jng tutin hoan.
3. Tac dl;lng tren he hap

.'
"

De ehe ho hap I giam t§.n so th6 va th6 tieh khi luu thol1g. NgUIlg Lhu
,
xay ra trung binh trong 50% so tniCJng h<;Jp(ty l~ dao d9ng 25% den
100%). Ngung th6 cang d~ dang han khi khdi me eo ket h<;Jpvoi thuoe
h9 morphin va suy th6 keo dai han.

So sanh voi thiopental
(4mg/kg), propafol (2,5 mg/kg) gay ue che h6 hap
:i keo dai han va co th~ con dai d~ng ngay ca khi co V8 da hoi tinh hoan toano
Ngung thd do propafal gi;tp nhieu han so voi mQt so thuoc
than khac (methohexital,
thiopental).
Trong m9t nghien

me toan
cuu cho
503



thay: propofol ngung thCi tren 45 .At·
0
'
1 . thi
11'
,.0
gray rong 40 Yo tntong hop. Ncrl]1Wt~i
!?-1 ioperita a 15%. Lam giarn Vt keo dai.
.

b".
;{
-

Thu.J

KhAongc? t~c dung cOA
th£tphe quankhi khci me bang propofol.
kh?ng co
dl,ln/gtre~ trvo~g luc p~e/quan va khong lam co th~tt&t~,
quan do ?lal phong histarnin. Thuoc lam giarn tinh kich thich .' - "
thanh quan, trong ~chithiopental kh6ng c6 tac dung ay. Viec dat .
thanh quan cung de dang han.
'.
.
.

t~,;,

i

Thuoc cho phep d:,!t ong noi khf quan rna khorig din thuoc gian .
KU~AR va COLL ciing chung minh c6 su lien quan giiia lieu 1 ,"
thu6c va su gian co thanh quan,
.
Pr,opofol kh6ng lam anh hudng tdi phan xa co mach mau ph6i
thieu oxy nhung lam giarn truorig lire mach mau ph6i va mach :
chung cua co thl
.
4. Cae tac dyng khac tren ngLfdj

4.1. Tae dl}ng t?i eho

Dung d~ch mdi cua propofol dvC/cpha trong lipid nhling tiem thuOc.
khi v~n gay dau ch6 tiem, d:,!cbi¢t tiem nhanh va VaGcae tinh m!?-chnh6.

a

Neu tiem
hing ban tay, 50% so b$nh nhan c6 cam giac lq_nh, 30%
cam giac dau r6 rang. Trong m9t so nghien cuu so sanh vdi thiopental
dau han 3 - 5 liin. Sv dau dan nay c6 th~ so 8anh voi tiem methohexital
eL()Illlua t.

Khi tiem fentanyl tnioc, ca~1 giac dau giam di 2 den 3 Hl.n.

Dd

tranh dau dan khi tiem, c6 th~ cho xylocain 0,1 mg/kg, lam
dang kd ty l~ dau noi tiem. Khi tang xylocain 0,4 mg/kg cung
lam cai thi$n chat IvC/nggiam dau.
Trong vang 24 gid. sau tiem tinh m!?-chpropofol, ty 1$ viem t&c
mq_chkhong cao han tiem nVdc muoi d&ng truOng.

/
I

Tiem ra ngoai b$nh nhan rat dau ddn nhvng kh6ng gay hoq_i'tli.
Tiem nh~m dQng mq_chc6 th6 gay ra dau don du dQi. Neu b~ d tay,
toa ciau cion ra kh&p canh tay va ban tay. Sau ci6 mat mau vling
phia dvoi ph~n trVoc canh taYI30 phut sau h6ng trCi lq_i,4 gid sau

ca trd lq_ibinh thVdng.
C6 th§ n6i tiem nh~m VaG dQng m!?-chc6 th§ gay can dau ni1mg,
kh6ng dd l!?-idi chung.
4.2. Giai ph6ng histamin

Trong hinh thai lipid nhu tVong, propofol kh6ng gay giai ph6ng his
tren dQng vi;tt. 6 tren ngvdi, tac dVng giai ph6ng histamin ra't yeu, ra't
504

.••••.