Marmara Medical Journal Volume 12 No: 1 January 1999 C A N A L F E N T A N I L O R D I L T I A Z E M P R E V E N T M Y O C A R D I A L I S C H E M I A D U E T O T R A C H E A L I N T U B A T I O N ? (R e c e iv e d 23 S e p te m b e r, 1998) B i n n a z A y , M . D . * / Z e y n e p E t i , M . D . * / A b d u r r a h m a n Y a y c ı , M . D . * H a k a n T e z c a n , M . D . * * / N u r a l B e k i r o ğ l u , P h D . * * * / F . Y ı l m a z G ö ğ ü ş , M . D . *
* D e p a rtm e n t o f A ne sthesiolo gy and Reanim ation, S cho ol o f M edicine, M arm ara University, Istanbul, Turkey. " D e p a rtm e n t o f Cardiology, S cho ol o f M edicine, M arm ara University, Istanbul, Turkey.
" D e p a rtm e n t o f B iostatistics, S cho ol o f M edicine, M arm ara University, Ista nb ul, Turkey.
A B S T R A C T
Objective:
T h e a im o f th is s tu d y is to e v a lu a te th e e ffic a c y o f a lfe n ta n il an d d iltia z e m to a tte n u a te th e c a r d io v a s c u la r re s p o n s e s to la ry n g o s c o p y an d tra c h e a l in tu b a tio n a n d th e ir e ffe c ts on th e o c c u rra n c e o f m y o c a rd ia l is c h e m ia in p a tie n ts w ith c o ro n a ry a rte ry d is e a s e .Methods:
T w e n ty e ig h t p a tie n ts A S A ll- lll, 4 0 -8 0 y e a rs old, s c h e d u le d fo r e le c tiv e a b d o m in a l s u rg e ry w e re ra n d o m ly a s s ig n e d in to th re e g ro u p s . A n e s th e s ia w a s in d u c e d w ith 0.2 m g /k g e to m id a te an d 1.5 m g /kg s u c c in y lc h o lin e i.v. in all p a tie n ts . In g ro u p I (n = 1 0 ) 15 p g /k g a lfe n ta n il i.v. a n d in g ro u p II (n= 10) 0 .2 m g /kg d iltia z e m i.v. w e re a d m in is te re d 2 m in u te s b e fo re la ry n g o s c o p y . In g ro u p III (n = 8 ) (c o n tro l) no m e d ic a tio n w a s a d m in is te re d . S y s to lic , d ia s to lic , m ean a rte ria l p re s s u re , h e a rt rate, ra te -p re s s u re p ro d u c t and S T s e g m e n t c h a n g e s in D ll an d V 5 le a d s w e re re c o rd e d b e fo re an d a fte r in d u c tio n at 1., 3., 5. m in u te s o f in tu b a tio n .Results:
M e a n a rte ria l p re s s u re w a s s ig n ific a n tly lo w e r in th e a lfe n ta n il a n d d iltia z e m g ro u p 1 m in u te a fte r in tu b a tio n . T h e re w a s no s ig n ific a n t d iffe re n c e in h e a rt rate b e tw e e n g ro u p s . R a te -p re s s u re p ro d u c t w as g re a te r th a n 11000 in all p a tie n ts of d iltia z e m and c o n tro l g ro u p s a n d in 9 p a tie n ts o f a lfe n ta n il g ro u p .Conclusion:
A lth o u g h 0 .2 m g /kg d iltia z e m and 15 p g /k g a lfe n ta n il i.v . a tte n u a te d th e h y p e rte n s iv e re s p o n s e to tra c h e a l in tu b a tio n , th e y w e re fo u n d to be in e ffe c tiv e in d e c re a s in g th e in c id e n c e o f m yo c a rd ia l is c h e m ia in c o ro n a ry a rte ry d is e a s e . K e y W o r d s : M y o c a rd ia l is c h e m ia , a lfe n ta n il, d iltia z e m . T ra c h e a l in tu b a tio n , h e m o d y n a m ic re sp o n s e . I N T R O D U C T I O N L a ry n g o s c o p y a n d tr a c h e a l in tu b a tio n c a u s in g s ig n ific a n t in c re a s e s in a rte ria l b lo o d p re s s u re and h e a rt ra te lead to d e le te rio u s e ffe c ts on m yo c a rd iu m of p a tie n ts w ith c o ro n a ry a rte ry d is e a s e (C A D ) (1). P a tie n ts w ith C A D a re fre q u e n tly a n e s th e tiz e d for c a rd ia c s u rg e ry as w e ll as n o n -c a rd ia c o p e ra tio n s . In th e s e p a tie n ts , E C G s h o u ld be u s e d to id e n tify m y o c a rd ia l is c h e m ia a n d rh y th m d is tu rb a n c e s during th e s tre s s o f a n e s th e s ia a n d o p e ra tio n . P re vio u s s tu d ie s s h o w e d th a t, 8 9 % o f th e S T s e g m e n t in fo rm a tio n in th e c o n v e n tio n a l 12 lead E C G is found in le a d V 5 (2). O n e m m o r g re a te r h o riz o n ta l-d o w n s lo p p in g S T s e g m e n t d e p re s s io n , tw o m m or m ore ST s e g m e n t e le v a tio n fro m b a s e lin e fo r m o re th a n sixty s e c o n d s is c o n s id e re d a sign of m y o c a rd ia l isch e m ia until p ro v e n o th e rw is e (3-5).T h e aim o f th e s tu d y is to e v a lu a te th e e ffic a c y of a lfe n ta n il an d d iltia z e m to a tte n u a te th e c a rd io v a s c u la r re s p o n s e s to tra c h e a l in tu b a tio n an d th e ir e ffe cts on th e o c c u rra n c e o f m y o c a rd ia l is c h e m ia in p a tie n ts w ith C A D .
P A T I E N T S A N D M E T H O D S
A fte r o b ta in in g In s titu tio n a l E th ic s C o m m itte e a p proval and p a tie n ts ' w ritte n c o n s e n t, 28 p a tie n ts w ith CAD,
A S A ll- lll, a g e d 4 0 -8 0 y e a rs an d s c h e d u le d fo r e le ctive a b d o m in a l s u rg e ry w e re ra n d o m ly a s s ig n e d into three g ro u p s . In all p a tie n ts , a n e s th e s ia w a s in d u ced with 0 .2 m g /kg e to m id a te an d 1.5 m g /k g s u c c in y lc h o lin e i.v. In g ro u p I (n = 1 0 ) 15 p g /k g a lfe n ta n il i.v. and in g ro u p II (n = 1 0 ) 0 .2 m g /k g d iltia z e m i.v. w e re a d m in is te re d 2 m in u te s b e fo re la ry n g o s c o p y an d in tu b a tio n . In group III (n= 8) (c o n tro l) no m e d ic a tio n w a s a d m in iste re d . A n e s th e s ia w a s m a in ta in e d w ith 5 0% N 20 in oxyg e n
Marmara Medical Journal Volume 12 No: 1 January 1999
and is o flu ra n e (M A C w a s m a in ta in e d a c c o rd in g to th e h e m o d y n a m ic p a ra m e te rs d u rin g m a in te n a n c e of a n a e s th e s ia ). A fiv e lead E C G w a s a tta c h e d on a rriva l to th e o p e ra tin g ro o m and le a d II and V 5 w e re d is p la y e d c o n tin u o u s ly . A 20 G c a n n u la w a s in se rte d into th e radial a rte ry fo r b lo o d p re s s u re m o n ito riz a tio n . S ysto lic, d ia s to lic , m e a n a rte ria l p re s s u re (M A P ), h eart rate, ra te -p re s s u re p ro d u c t (R P P ) w h ic h is th e p ro d u c t o f h e a rt rate m u ltip lie d by s y s to lic a rte ria l p re s s u re and S T s e g m e n t c h a n g e s in lead II an d V 5 w e re re c o rd e d b e fo re in d u c tio n (T 1), a fte r in d u c tio n (T 2), a t 1. (T 3), 3. (T 4 ), 5. (T 5 ) m in u te s o f in tu b a tio n . S T s e g m e n t d is p la c e m e n t w a s m e a s u re d at a p o in t 0 .0 8 s e c o n d a fte r th e J p oint. >1 m m h o riz o n ta l o r d o w n -s lo p p in g S T s e g m e n t d e p re s s io n o r > 2 m m S T s e g m e n t e le v a tio n fro m b a s e lin e fo r m o re th a n 6 0 s e c o n d s w a s c o n s id e re d a s ig n ific a n t sign o f m y o c a rd ia l isc h e m ia . A lso E C G fin d in g s an d C P K -M B le v e ls w e re e v a lu a te d at 6., 12., 24. h o u rs p o s to p e ra tiv e ly . R e s u lts w e re a n a ly s e d s ta tis tic a lly w ith A N O V A , F rie d m a n , T u k e y K ra m e r a n d D u n n 's M u ltip le C o m p a ris o n te s ts (p < 0 .0 5 ). R E S U L T S T h e th re e g ro u p s w e re c o m p a ra b le in re s p e c t to age, w e ig h t a nd se x (p > 0 .0 5 ) (T a b le I) T h e re w a s no s ig n ific a n t d iffe re n c e in M A P b e tw e e n th e g ro u p s b e fo re in d u c tio n . T h e d e c re a s e in M A P a fte r in d u c tio n in a lfe n ta n il a n d d iltia z e m g ro u p s c o m p a re d w ith th e c o n tro l g ro u p w a s s ig n ific a n t (p < 0 .0 5 ). T h e in c re a s e in M A P in re s p o n s e to la ry n g o s c o p y a n d in tu b a tio n in th e c o n tro l g ro u p c o m p a re d to a lfe n ta n il a n d d iltia z e m g ro u p s w a s s ig n ific a n t (p < 0 .0 5 ) (T a b le II). T h e re w a s no d iffe re n c e in h e a rt ra te b e fo re in d u c tio n o r im m e d ia te ly a fte r la ry n g o s c o p y a n d in tu b a tio n b e tw e e n th e th re e g ro u p s (p > 0 .0 5 ). In d iltia z e m and c o n tro l g ro u p s th e in c re a s e in h e a rt ra te im m e d ia te ly a fte r la ry n g o s c o p y a n d in tu b a tio n w a s s ig n ific a n t (p < 0 .0 1 ) (T a b le III).
R P P w a s s ig n ific a n tly lo w e r in th e a lfe n ta n il g ro u p c o m p a re d w ith th e c o n tro l a fte r in d u c tio n an d th re e m in u te s a fte r la ry n g o s c o p y (p < 0 .0 1 ). It w a s a lso s ig n ific a n tly lo w e r in th e a lfe n ta n il a n d th e d iltia z e m g ro u p s c o m p a re d w ith th e c o n tro l a fte r la ry n g o s c o p y a n d in tu b a tio n (p < 0 .0 0 1 , p < 0 .0 5 ) (T a b le IV).
In e a c h g ro u p , 2 o f 10 p a tie n ts (2 0 % ) had S T s e g m e n t d e p re s s io n d u rin g in tu b a tio n . C P K -M B le v e ls in c re a s e d a b o v e 2 4 lU /m l in 5 p a tie n ts of a lfe n ta n il and c o n tro l g ro u p a n d 4 p a tie n ts of d iltia z e m g ro u p (p > 0 .0 5 ). O n e p a tie n t in th e c o n tr o l g ro u p h a d d o c u m e n te d m y o c a rd ia l in fa rc tio n 6 h o u rs a fte r th e o p e ra tio n .
Table I. D e m o g r a p h i c d a t a of p a t i e n t s ( M e a n i S D )
ALFENTANIL DILTIAZEM CONTROL
P a t i e n t s (n) 10 10 8
S e x (M/F) 6/4 6 / 4 5/3
Age (year) 6 6 . 5 ± 5.5 6 4 . 2 ± 3 . 5 6 6.1 ± 3.2
W e i g h t (kg) 7 0 . 2 ± 2.5 7 4 . 6 ± 5.2 7 0 . 3 ± 3 . 8
Table II. M e a n a rte rial p r e s s u r e of p a t i e n t s ( m m H g ) ( M e a n ± S D )
ALFENTANIL DILTIAZEM CONTROL
T1 1 0 0 . 0 ± 1 2 . 4 0 1 0 5 . 5 ± 6 . 4 3 1 1 1 . 6 2 ± 1 2 .9 5 T2 9 8 . 4 ± 1 5 . 8 5 * 9 6 . 1 0 ± 1 1.6 1 * 1 1 4 . 8 7 ± 1 1 . 7 6 T3 119.1 ± 3 2 . 3 9 * 1 2 5 . 3 ± 1 9 . 0 7 * 1 5 4 . 5 0 ± 1 8 . 1 5 T4 1 1 3 . 0 ± 1 7 . 2 8 1 1 6 . 0 ± 2 1 . 6 1 3 0 . 7 5 ± 14.61 T5 1 0 5 . 5 ± 2 9 . 7 9 1 1 1 . 0 ± 2 6 . 2 4 1 0 8 . 3 7 ± 1 6 . 6 3 * p<0.05 compared to control 8
Marmara Medical Journal Volume 12 No: 1 January 1999
T a b l e III. Heart rate of patients (Beat/min) (Mean+SD)
ALFENTANIL DILTIAZEM CONTROL
T1 8 1 . 7 + 1 3 .3 3 8 7 . 6 0 + 1 8 .6 7 9 2 . 6 3 + 2 8 52 T2 7 7 . 5 ± 12.31 * 9 4 . 1 0 + 1 7 .4 4 1 0 1 . 2 5 + 2 4 . 7 0 T3 9 4 .8 ± 1 9 .6 0 1 0 9 . 6 + 2 0 . 0 2 *** 1 1 3 . 6 3 + 2 4 . 3 0 * * T4 8 7 . 7 ± 18.11 9 9 . 6 0 ± 1 9 .6 8 1 0 2 . 3 0 ± 21 46 T5 7 5 . 0 + 1 3 .9 2 8 2 . 1 0 + 1 2 .7 8 8 2 . 7 5 + 2 0 13 * p < 0 .0 5 c o m p a r e d with control * * p < 0 01 wi th in t h e g r o u p * * * p < 0 . 0 0 1 w it h in t h e g r o u p
T a b l e IV. Rate-pressure product of patients (Mean+SD)
ALFENTANIL DILTIAZEM CONTROL
T1 1 1 8 2 1 . 7 + 2 5 5 3 . 7 1 4 1 3 4 . 4 + 3 7 0 7 . 9 1 7 9 4 6 . 0 ± 4 9 6 6 . 2
T2 1 0 7 4 0 . 0 + 2 7 0 9 . 9 * * 1 3 5 2 4 9 ± 3 3 3 3 . 6 1 7 1 3 8 . 2 ± 4 9 7 4 . 6
T3 1 5 8 6 4 . 5 + 4 8 0 0 . 4 * * * 1 9 9 6 7 . 0 + 4 0 6 8 . 7 * 2 5 8 9 5 . 3 ± 6 0 5 3 . 9
T4 1 3 0 8 5 . 6 ± 5 6 6 2 . 7 * * 1 6 7 5 3 . 4 + 4 7 8 5 3 2 1 3 4 0 0 ± 3 9 5 0 . 9
T5 1 1 4 4 2 . 5 ± 3 6 2 5 . 7 1 2 7 3 6 + 3 3 4 4 . 7 1 3 2 7 0 3 ± 3 2 0 0 0
* p<0.05, **p < 0 .0 1 , ***p < 0 .0 0 1 compared with control
D I S C U S S I O N
P a tie n ts s u ffe rin g fro m a n g in a p e c to ris a re p a rtic u la rly p ro n e to d e v e lo p in g in tra o p e ra tiv e m y o c a rd ia l is c h e m ia . T h e n a rc o tic a n e s th e tic te c h n iq u e s havin g th e a d v a n ta g e o f m in im a l m y o c a rd ia l d e p re s s io n are o fte n u sed in p a tie n ts w ith c o ro n a ry a rte ry d is e a s e (6). T o a tte n u a te th e c a te c h o la m in e an d c a rd io v a s c u la r re s p o n s e s to b rie f b u t in te n s e n o x io u s stim u li such as tr a c h e a l in tu b a tio n , a lfe n ta n il m a y be th e m o s t a p p ro p ria te n a rc o tic a g e n t (7). D iltia z e m ; a ca lc iu m c h a n n e l b lo c k e r w ith p o te n t v a s o d ila to r y a n d h y p o te n s iv e p ro p e rtie s ha s b e e n u sed fo r tre a tm e n t of h y p e rte n s io n a n d a n g in a p e c to ris (8).
P re v io u s s tu d ie s c o n firm e d th a t la ry n g o s c o p y and in tu b a tio n a fte r th io p e n to n e an d e to m id a te a lo n e w as a c c o m p a in e d by s ig n ific a n t in c re a s e s in h e a rt ra te and a rte ria l p re s s u re a b o v e c o n tro l le ve ls (9). M ik a w a et al. (10) fo u n d th a t d iltia z e m in a d o s e o f 0 .2 m g /k g
a tte n u a te d th e in c re a s e s in b lo o d p re s s u re , h eart rate and R P P a fte r tra c h e a l in tu b a tio n c o m p a re d w ith the co n tro l g ro u p . T h e s a m e re s u lts w e re o b ta in e d in M iller e t a l's (11) s tu d y w ith a lfe n ta n il 15pg/kg. W e also o b s e rv e d th a t 1 5 p g /k g a lfe n ta n il a n d 0 .2 m g /k g d iltia z e m w e re b o th e ffe c tiv e in o b tu n d in g th a t h e m o d y n a m ic re s p o n s e s to la ry n g o s c o p y and in tu b a tio n c o m p a re d w ith th e c o n tro l g ro u p . M ik a w a et al (10) o b s e rv e d th a t th e re w a s an in c re a s e in h eart ra te a fte r in d u c tio n in p a tie n ts tre a te d w ith diltia ze m 0 .2 m g /k g and 0 .3 m g /k g . H o w e v e r in o u r study, there w a s no s ig n ific a n t d iffe re n c e in h e a rt rate b e tw e e n the d iltia z e m a n d c o n tro l g ro u p a fte r in d u c tio n w h ile s ig n ific a n t d e c re a s e w a s o b s e rv e d at th is tim e in the a lfe n ta n il g ro u p . A ls o a fte r la ry n g o s c o p y o n ly in a lfe n ta n il g ro u p , th e in c re a s e in h e a rt rate w a s not s ig n ific a n t s u g g e s tin g th a t a lfe n ta n il w a s m o re e ffe c tiv e in c o n tr o llin g h e a rt ra te c o m p a re d to d iltia z e m .
Marmara Medical Journal Volume 12 No: 1 January 1999
R ay et al (12) sta te d th a t th e p a tie n ts w ith C A D ha vin g R P P > 1 1000 ha d S T s e g m e n t d e p re s s io n an d th e in c re a s e d R P P o c c u rre d m o s t o fte n d u rin g in tu b a tio n . R ifkin et al (13) s h o w e d th a t in p a tie n ts w ith kn o w n is c h e m ic c a rd ia c d is e a s e , th e S T s e g m e n t d is p la c e m e n t c o rr e la te s w e ll w ith is c h e m ia . In M ika w a 's (10) s tu d y, In p a tie n ts tre a te d w ith 0 .2 m g /k g and 0 .3 m g /k g d iltia z e m , R P P w a s 1 4 0 0 0 an d 11914 re s p e c tiv e ly w h e re a s in o u r s tu d y R P P a fte r in tu b a tio n w a s 19967 an d 15864 in d iltia z e m an d a lfe n ta n il g ro u p re sp e c tiv e ly . A lth o u g h th e R P P s h o w e d an a tte n u a te d re s p o n s e w ith a lfe n ta n il a n d d iltia z e m a fte r la ry n g o s c o p y , in e a c h g ro u p 2 o f 10 p a tie n ts h ad S T s e g m e n t d e p re s s io n .
W e c o n c lu d e d th a t 0 .2 m g /k g d iltia z e m and 1 5 p g /kg a lfe n ta n il i.v. a d m in is te re d d u rin g in d u c tio n a tte n u a te d th e in c re a s e in ra te p re s s u re p ro d u c t a fte r in tu b a tio n and a lfe n ta n il w a s m o re e ffe c tiv e in c o n tro llin g h e a rt rate, h o w e v e r th e y w e re fo u n d to b e u n re la te d on th e o c c u rre n c e o f m y o c a rd ia l is c h e m ia in p a tie n ts w ith C A D as 2 0 % o f p a tie n ts in all g ro u p s a nd had S T s e g m e n t d e p re s s io n .
R E F E R E N C E S
/ . H artley M, Vaughan RS. P roblem s a sso cia te d with trache al e x tu b a tio n . B r J A naesth 19 93 ; 71:561- 5 6 8
2. K ap la n JA, K in g SB. The p re c o rd ia l
e le c tro c a rd io g ra p h ic le a d (V5) in p a tie n ts w ho have coro na ry a rte ry disease. A ne sthesiolo gy 1976; 4 5 :5 7 0 -5 7 4 .
3. C a rlin e r HH, F is h e r ML. R o u tin e p re o p e ra tiv e exercise testin g in p a tie n ts unde rgoing m a jo r n o n cardiac surgery. Am J C a rdio l 1985; 5 6 :5 1 -5 7 .
4. F leishe r LA, Longstan M. P eriop erative ST seg m en t changes in m o d e ra te ris k a s y m p to m a tic in d iv id u a ls m a y n o t b e m y o c a rd ia l ischem ia. A nesth Anaig
1995; 80-.SCA9.
5. M angano DT, B ro w n e r tVS. A s s o c ia tio n o f p e rio p e ra tiv e m y o c a rd ia l is c h e m ia w ith card ia c m o rb id ity a n d m o rta lity in m an u n de rgoing n o n cardiac surgery, H Eng J M ed 19 90 ; 3 2 3 :1 7 8 1 -
1788.
6. H icks HJ, M ow bray A. C a rd io v a s c u la r e ffects o f and c a th e c o ia m in e responses to high dose fe n ta n y l-0 2 f o r in d u c tio n o f a n a e s th e s ia in p a tie n ts w ith is c h e m ic c o ro n a ry a rte ry disease. Anesth Anaig
19 8 1 ; 6 0 :5 6 3 -5 6 8 .
7. S h a fe r SL, V arve l JR. P h a rm a c o k in e tic s , p h a rm a c o d y n a m ic s a n d ra tio n a l o p io id selectio n. A ne sth e sio lo g y 19 8 1 ; 74:53-63.
8. rie e d lm a n P. Drugs used fo r th e tre a tm e n t o f angina: o rg a n ic nitra te s, c a lc iu m ch a n n e l b lo c k e rs a n d beta ad re n e rg ic an tago nists. In: AG G ilm an, LS G o o d m a n . The P h a rm a c o lo g ic a l B asis o f Therapeutics. Hew York: M cM illan, 1985: 8 0 6 -8 2 6 9. H arris CE, M urra y JM. E ffe cts o f th io p e n to n e ,
e to m id a te a n d p r o p o fo l on th e h e m o d y n a m ic response to tra c h e a l in tu b a tio n . A naesthesia 1988; 4 3 :32-3 6.
10. M ikawa K, Ik e g a k i J. The e ffe c ts o f d iltia z e m on c a rd io v a s c u la r re s p o n s e to tra c h e a l in tu b a tio n . A naesthesia 19 9 0 ; 4 5 :2 8 9 -2 9 3 .
1 I . M ille r DR, M artineau RJ. E ffects o f a lfe n ta n il on the h e m o d y n a m ic a n d c a th e c o ia m in e response to tra c h e a l in tu b a tio n . A nesth A naig 1993, 76 :104 0- 1046.
12. Ray WL, E delist G. M yoca rdia l is c h e m ia d u rin g n o n card ia c s u rg ia l p ro c e d u re s in p a tie n ts w ith coro na ry a rte ry disease. A n e s th e s io lo g y 19 79 ; 5 1 :3 9 3 -3 9 7 . 13. R ifk in DR, H o o d WB. B ayesian a n a ly s is o f
e le c tro c a rd io g ra p h ic e xe rcise s tress testing. H Eng J Med 1977, 2 9 7 :6 8 1 -6 8 6 .
