Morfin n Ketamin 1996

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212

C om par ison o f mor

ph ine and m orphine

w ith ketam ine for

postoperat ive analgesia

Kei t h B . J a ve r y DO, T od d W . U sse r y M D,

H e r b e r t G . S t e g e r ph D , G e o r g e W . C o l c l o u g h M D

Pu r p o s e :

The purpose o f th i s s tudy was to compa re morph ine

wi th ke tamine to morph ine a lone in a doub le -b l ind inves t iga-

t ion o f pos t surg ica l pa in con tro l.

Metho ds: For ty - two ASA 1 and 2 pa t ien t s undergo ing e lec t i ve

microd iscec tom y we re admin is tered e i ther I rag . m1-1 o f mor-

p h i n e

n =

20) or I mg . m1-1 o f bo th morph ine and ke tamine

(n = 22) v ia i v pa t ien t con tro l led ana lges ia (1VPCA). Pa in

re l i e f and s ide e f f ec t s were assessed a t 24 h r a f t e r surgery .

Resu l t s :

The mean (SD) v i sua l ana logue sca le (VAS) pa in ra t -

ing o f 2 .3 ( l .67 ) for pa t ien t s rece iv ing mo rph ine w i th ke tamine

was low er (P < 0 .001) than the VAS scores o f pa t ien t s rece iv -

ing on ly morph ine 4 .5 (1 .54) . P a t ien t s rece iv ing morph ine a nd

ke tamine a l so had le ss d i f f i cu l t y w i th s ide e f f ec t s , repor t ing

less nausea (P < 0 .05) , prur i tus (P < 0 .001) , and ur inary

re ten t ion (P < 0 .05) . A l though dysphor ia i s repor ted to be a

comm on s ide e f f ec t o f ke tamine , compla in t s o f dysphor ia we re

rare in bo th groups , w i th on ly one sub jec t (5%) in the mor-

ph ine wi th ke tamine group and three (15%) sub jec t s rece iv ing

morph ine a lone repor t ing th i s s ide e f f ec t .

C o n c l u s i o n :

IVPCA ke tamine in combina t ion wi th morph ine

prov ides su per ior pos t surg ica l pa in re l i e f a t lower dosage a nd

wi th f ew er s ide e f f ec t s than morp h ine a lone .

Objec t i f Cette ~tude en doub le aveug le visai t ?~ com par er la

kd tamine assoc i~e ~ la morph ine avec la morph ine seu le u t i -

l isde dans l e bu t de t ra i t e r la dou leur pos topdra to i re .

M # t h o d e : Q u a r a n t e -d e u x p a t ie n t s A S A 1 e t 2 pr o g r a m m d s

pou r un e microdisco~'dectomie ont ref u 1 rag. m1-1 de m or-

ph ine (n = 10) ou 1 m g .ml - j ?~ la fo i s de morph ine e t de kd ta -

K e y w o r d s

ANALGESIA: po stop era t ive ;

ANALGESICS: ke tam ine , m orp hin e;

SURGERY orthopaedic

From the Department o f Anesthesiology, U niversity o f

Kentucky C ollege of Medicine.

Address correspondence to :

Dr. Keith B. Javery,

Department o f Anesthesiology, Universi ty of Kentucky

Medical Center, 800 Rose Street, N-202, Lexington, KY

40536-0084 U.S.A.

Accep ted fo r pub l ica t ion 8 th Sep tember , 1995.

mine i v (n = 22) par un d i spos i t i f d 'ana lgds ie au tocon tr~ l~e

(PCAIV) . L e sou lagem ent e t l e s e f f e t s seconda ires on t ~ t~ ~va-

luds 24 h apr~s la chirurgie.

Rdsu l ta t s : La moyenne (ET) de la va leur dd termin~e sur une

dche l le v i sue l le ana log ique (EVA) de 2 ,3 (1 ,67) pour l e s

pa t ien t s qu i ava ien t re fu m orph ine-k~tamine d ta i t p lus basse

(P < 0 ,001) que ce l l e des pa t ien t s sous m orph ine 4 ,5 (1 ,54).

Les pa t ien t s sous morph ine-kd tamine on t eu auss i moins d ' e f -

f e t s seconda ires don t moins de nausde (P < 0 ,05) , de prur i t (P

< 0,001), e t de r~tention urinaire (P < 0,05). B ien que la dys-

phor ie su i t un e f f e t seconda ire f rdquen t de la k~ tamine , e l l e a

~t~ rarement rappor t~e dans l e s deux groupes , a vec un seu l

su je t (5%) du groupe morph ine-k~tamine e t t ro i s du groupe

morph ine seu le (15%) .

C o n c l u s i o n :

En PCAIV, la k~ tamine assoc ide ~ la morph ine

procure une sou lagement pos topdra to i re de la dou leur f i des

doses p lus fa ib les e t avec moins d 'e f f e t s seco nda ires que la

morph ine seu le .

I n t r a v e n o u s m o r p h i n e i s c o m m o n l y u s e d a s a n a n a l -

g e s i c i n t h e p o s t o p e r a t i v e p e r i o d f o r m a j o r s u r g e r y a n d

i s th e s t a n d a r d b y w h i c h a l l o t h e r a n a l g e s i c s a r e g a u g e d .

K e t a m i n e h a s b e e n u s e d a s a n i n t r a v e n o u s a n a e s t h e t i c .

T h e r e p o r t e d E D s 0 f o r t h e a b o l i t i o n o f r e s p o n s e t o

p a i n f u l s t i m u l a t i o n i s 1 .3 r a g . k g - l . I K e t a m i n e h a s a l s o

b e e n u s e d i n s u b - a n a e s t h e t i c d o s e s a s a n a n a l g e s i c f o r

b o t h a c u t e a n d c h r o n i c p a i n r e l ie f . 2 -s T h e a n a l g e s i c

e f f e c t s o f k e t a m i n e o c c u r a t p l a s m a c o n c e n t r a t i o n s

b e t w e e n 1 0 0 a n d 1 5 0 n g . m 1 - 1 . T h e s e c o n c e n t r a t i o n s

h a v e b e e n a c h i e v e d b y i n f u s i o n s a s l o w a s 3 t o 4

l ag- kg - I . r a i n - I a f t e r an i n i t ia l l oad i n g dose . 6 S ucces s f u l

a n a l g e s i a w i t h o u t a n i n i t i a l l o a d i n g b o l u s h a s b e e n

r e p o r t e d w i t h i n f u s i o n s o f 1 4 b t g. k g - l . m i n 1 .

K e t a m i n e h a s m a n y d e s i r a b l e q u a l i t i e s a s a n a n a l -

g e s i c. I t d o e s n o t s u p p r e s s c a r d i o v a s c u l a r f u n c t i o n i n t h e

p r e s e n c e o f a n i n t a c t n e r v o u s s y s t e m ; 7 i t does no t

d e p r e s s t h e l a r y n g e a l p r o t e c t i v e r e f l e x e s ; 8 it d e p r e s s e s

v e n t i l a t i o n l e s s t h a n o p i o i d o r n o n o p i o i d a n a e s t h e t i c

a g e n t s ; 9 a n d i t m a y s t i m u l a t e r e s p i r a t i o n ~ D e c r e a s e d

a i r w a y r e s i s t a n c e h a s b e e n r e p o r t e d i n p a t i e n t s w i t h

r eac t i ve a i r way d i sease a f t e r ke t ami ne admi n i s t r a t i on . l ~

CAN J ANAESTH 1996 I 43: 3 / pp212-5



Javery

e t a l :

MORPHINE AND KETAMINE 213

Adverse s ide e f fec t s a s soc ia ted wi th sub-anaes the t i c

doses o f k e tam ine inc lude to le rance , ~2 accum ula t ion o f

m e tabo l i t e s , 13 pos tope ra t ive m a la i s e , 14 and ca rd iov ascu-

la r exc i ta t ion . One o f the m os t d i s conce r t ing s ide e f fec t s

o f k e t a m i n e i s i t s a d v e r s e p s y c h o m i m e t i c e f f e c t s ,

inc lud ing d izz ines s , f r igh ten ing dream s , depe rsona l i za -

t ion , and ha l luc ina t ions . These reac t ions appea r to be

m o re com m o n in adu l t s than in ch i ld ren 15 and in w om en

than in men . 16

T h e c o m b i n a t i o n o f m o r p h i n e a n d k e t a m i n e

i v

has

been s tud ied w i th va r ied re su l t s. S om e au thors have rec -

o m m e n d e d t h is c o m b i n a t i o n b e c a u s e o f i m p r o v e d r e s p i -

ra to ry ra te s and l e s s s l eep ines s fo r the s am e degree o f

ana lges ia , j4 Othe rs have repor ted inc reased ana lges ia

whe n ke tam ine i s added to m eper id ine , ~7 bu t h ave no ted

a n i n c r e a s e i n t h e p s y c h o m i m e t i c e f f e c t s w i t h k e t a m i n e

use 18

T h e c o m b i n a t i o n o f lo w d o s e k e t a m i n e a n d m o r p h i n e

has been used a t our ins t i tu tion to p rov id e be t t e r ana lge -

s i a w h e n m o r p h i n e ( I V P C A ) h a s p r o v e d t o b e i n a d e -

qua te . The com bina t ion s eem s to be a s a fe and re l i ab le

m e t h o d o f p r o v i d i n g p o s t o p e r a t i v e a n a l g e s i a t h a t i s

s u p e r i o r t o m o r p h i n e a l o n e . T h e p r e s e n t s t u d y w a s

under tak en to de te rm ine i f the add i t ion o f sub-anaes the t -

i c d o s e s o f k e t a m i n e t o m o r p h i n e d e l i v e r e d b y I V P C A

w o u l d p r o v i d e b e t t e r a n a l g e s i a t h a n m o r p h i n e a l o n e ,

a n d m i n i m i z e u n t o w a r d s i d e e f f ec t s . A P C A a p p r o a c h t o

drug adm in i s t ra t ion was used to obv ia te the a rb i t ra ry

d o s i n g g u i d e l i n es n e c e s s a r y w i t h i n f u s io n s . U s e o f P C A

avoids under - o r ove rdos ing ana lges ic , a l lowing the

pa t i en t to t i t ra te the dose o f op io id to ach ieve e f fec t ive

ana lges ia. 19

e t h o d s

B a s e d o n p i l o t s tu d y e x p e r i e n c e w i t h t h e s t u d y ' s d e p e n -

den t m easures , a to ta l s am ple s i ze o f 40 was ca lcu la ted

a s n e c e s s a r y t o d e m o n s t r a t e e x p e r i m e n t a l e f f e c t s a t a n

a c c e p t a b l e c o n f i d e n c e l e v e l. F o l l o w i n g a p p r o v a l o f t h e

U n i v e r s i t y o f K e n t u c k y M e d i c a l I n s t i t u t i o n a l R e v i e w

B o a r d , 4 2 A S A 1 a n d 2 p a t i e n ts b e t w e e n t h e a g e s o f 2 1

a n d 5 5 y r w h o w e r e t o u n d e r g o e l e c t i v e l u m b a r

m i c r o d i s c e c t o m y g a v e i n f o r m e d c o n s e n t b e f o r e e le c t i n g

to pa r t i c ipa te in the s tudy . P a t i en t s were random ized in

a d o u b l e - b l i n d f a s h i o n t o r e c e i v e I V P C A c o n s i s t i n g

e i t h e r o f m o r p h i n e 1 m g . m1 -1 o r m o r p h i n e w i t h k e t a -

m i n e 1 m g . m 1 -1 o f e a c h . B A R D a m b u l a t o r y I V P C A

p u m p s w e r e p r o g r a m m e d t o d e l i v e r 1 m l o f s o l u t i o n

wi th a lock out o f s ix m inu tes . No basa l in fus ion was

used .

P a t ie n t s w e r e p r e - m e d i c a t e d i n t h e h o l d i n g a r e a w i t h

m i d a z o l a m , u p t o 0 .0 5 m g - k g-1

i v

N o p r e o p e r a t i v e o p i -

o i d s o r n o n s t e r o i d a l m e d i c a t i o n s w e r e u s e d . G e n e r a l

a n a e s t h e si a w a s i n d u c e d w i t h t h i o p e n t o n e 5 m g . k g -1

and t rachea l in tuba t ion was fac i l i t a t ed wi th succ iny l -

cho l ine 1 .5 m g. kg 1 . P a t i en t s were a l lowe d to rece ive

fen tan y l up to 2 k tg . kg 1 wi th in 2 0 m in a f t e r in tuba t ion .

A n a e s t h e s i a w a s m a i n t a i n e d w i t h i s o f l u r a n e a n d 1 0 0 %

o x y g e n w i t h v e c u r o n i u m b r o m i d e f o r m u s c l e r e l a x a ti o n

d u r i n g t h e r e m a i n d e r o f t h e c a s e . P a t i e n t s w e r e t h e n

t a k e n t o t h e p o s t o p e r a ti v e r e c o v e r y r o o m w h e r e , u p o n

o b t a i n i n g a d e q u a t e c o g n i t i v e f u n c t i o n , t h e y w e r e

i n s t ru c t e d o n t h e u s e o f th e I V P C A u n i t a n d c o n n e c t e d

t o t h e I V P C A p u m p . P a t i e n t s w e r e r e t u r n e d t o t h e i r

w a r d s w i t h t h e p u m p s f u l l y o p e r at i o n a l. N o s u p p l e m e n -

ta l ana lges ia o r s eda t ion was adm in i s te red to the

pa t i en t s dur ing the i r pos t surg ica l hosp i t a l s t ay .

D a t a w e r e c o l l e c t e d 2 4 h r a f t e r s u r g e r y . T h e v o l u m e

o f d r u g w a s d o w n l o a d e d f r o m t h e 1 V P C A p u m p t o a

l a p t o p c o m p u t e r . V i s u a l a n a l o g s c o r e s w e r e c o l l e c t e d 2 4

h r a f t e r s u r g e r y f r o m p a t i e n t s u s i n g a s t a n d a r d 1 0 c m

V A S p a i n r u l e r t h a t t h e p a t i e n t c o u l d m a n i p u l a t e t o a

d e s i r e d p a in r a t in g . A V A S s c o r e o f 0 w a s d e f i n e d a s n o

pa in , whi le 10 was de f ined a s wors t pa in im aginab le .

S ide e f fec t s o f nausea , u r ina ry re ten t ion , s eda t ion , and

p r u r it u s w e r e e v a l u a t e d u s i n g a n u m e r i c a l s c a le f r o m 1

to 5 , 1 was d e f ined a s no s ide e f fec t and 5 the w ors t

s e v e r i t y o f s i d e e f f e c t i m a g i n a b le . I f t h e p a t i e n t c o u l d b e

a r o u s e d o n l y b y v i g o r o u s s t i m u l at i o n , a r a ti n g o f 5 w a s

t a b u l at e d f o r s e d a ti o n . I f t h e p a t i e n t r e q u i r e d a n y f o r m

of u r ina ry ca the te r i za t ion , th i s was recorded a s a 5 on

the 1 to 5 u r ina ry re ten t ion s ca le . In add i t ion , the in ten-

s i ty o f a n y d y s p h o r i c e x p e r i e n c e s u c h a s b a d f e e l i n g s ,

ha l luc ina t ions , n igh tm ares , o r d izz ines s , was recorded

on a 1 to 5 dysphor ia s ca le . P a t i en t s were ins t ruc ted to

s c a le t h e s e e x p e r i e n c e s o v e r t h e p r e v i o u s 2 4 h r p e r i o d .

In add i t ion , the pa t i en t ' s v i t a l s igns (b lood pres sure ,

p u l s e r a t e , a n d r e s p i r a t o r y r a t e ) w e r e r e c o r d e d e v e r y

four hours .

S ta t i s t i ca l ana lyses o f da ta were pe r form ed us ing

S P S S . 2~ D i f f e r e n c e s b e t w e e n g r o u p s w e r e a n a l y z e d w i t h

the t t e s t . Re la t ionsh ips be tween va r iab le s were inves t i -

g a t e d u s i n g P e a r s o n p r o d u c t m o m e n t c o r r e l a t i o n s . A

p r o b a b i l i t y l e v e l o f 0 . 0 5 w a s s e t f o r r e j e c t i o n o f n u l l

h y p o t h e s e s o f n o d i f f e r e n c e b e t w e e n t h e g r o u p s .

Resu l t s

Of the 42 sub jec t s enro l l ed in the s tudy , 22 were

a s s i g n e d t o t h e m o r p h i n e - p l u s - k e t a m i n e g r o u p a n d 2 0 t o

t h e m o r p h i n e o n l y g r o u p . T h e g r o u p s w e r e c o m p a r a b l e

and d id no t d i f fe r in d i s t r ibu t ion o f s ex , age , o r we igh t

(Tab le I ) .

P a t i e n t s w h o r e c e i v e d m o r p h i n e p l u s k e t a m i n e r a t e d

their p ain as l ow er (me an __+ SD; 2.3 _+ 1.67) than those

rece iv ing on ly m orp hine (4 . 5 _ 1 . 54) (P < 0 . 001) . The

m o r p h i n e g r o u p r e c e i v e d a l m o s t t w i c e a s m u c h o p i o i d

(51 . 1 _+ 20 . 8) a s the m orph ine -p lus -ke tam ine g rou p



214

(25.82 _+ 16.40) (P < 0 .001) at a grea ter hou r ly rate (2 .6

_+ 1 .1) than did those who had ketamine added (1 .2 _+

0.7) (P < 0 .001) .

Pa t i en t s r ece i v i ng ke t ami ne r epo r t ed f ewer s i de

ef f ec t s t han t hose r ece i v i ng morph i ne a l one (Tab l e I I ) .

They r epo r t ed l ess nausea , p ru r i t u s , and u r i nary r e t en -

t i on t han t he morph i ne g roup . The g roups d i d no t d i f f e r

i n t he amoun t o f seda t i on o r dysphor i a . No r esp i r a t o ry

depress i on was seen , and t here were no r epo r t s o f v i t a l

s i gn dev i a t i ons >30% f rom base l i ne . Th ree sub j ec t s i n

t he morph i ne g roup (15%) r epo r t ed som e d i f f i cu l t y wi t h

dysphor i a , compared wi t h on l y one i n t he morph i ne-

p l us -ke t am i ne g roup (5%) .

The on l y pos i t i ve co r r e l a t i on o f s i de e f f ec t wi t h dose

was u r i nary r e t en t i on (Tab l e 11 I) . Pa t i en t s r ece i v i ng

mo rph i ne wi t h ke t am i ne r epo r t ed a r e l a t ionsh i p be t ween

p a i n V A S s c o r e s a n d a m o u n t o f m e d i c a t i o n r e c e i v e d

( r = 0 .42 , P < 0 .05 ) and a ne ga t i ve r e l a ti onsh i p be t ween

seda t i on and dysphor i a ( r = -0 .74 , P < 0 .001).

i s cu s s i on

Our s t udy demons t r a t es t ha t t he combi na t i on o f ke t a -

mi ne i n l ow doses wi t h morph i ne , de l i vered v i a IVPCA,

prov i ded super i o r pa i n r e l i e f a t l ower dosage o f mor -

p h i n e a n d w i t h f e w e r s i d e e f f e c ts t h a n w h e n u s i n g m o r -

ph i ne a l one . Our r esu l t s suppor t t he conc l us i on t ha t

morph i ne p l us ke t ami ne i s bo t h a sa fe and an e f f ec t i ve

mi x t u re .

Pa t i en t s who r ece i ved morph i ne p l us ke t a rn i ne r a t ed

t he i r pa i n as l ower t han t hose r ece i v i ng on l y morph i ne .

Th i s d i f f e r ence was subs t an t i a l , cons i der i ng t ha t t he

m o r p h i n e g r o u p s e l f- a d m i n i st e r e d a lm o s t t w i c e a s m u c h

med i ca t i on . Thus , i t appear s t ha t t he ke t ami ne g roup

rece i ved super i o r ana l ges i a . The morph i ne-p l us -ke t a -

mi ne g roup admi n i s t e r ed l ess t han ha l f t he average

h o u r l y a m o u n t o f m e d i c a t i o n a n d h a d f e w e r p r o b l e m s

wi t h s i de e f f ec t s . These f i nd i ngs mi gh t be exp l a i ned by

t he l ower dose o f morph i ne admi n i s t e r ed , r esu l t i ng i n

fewer s i de e f f ec t s . Overa l l t he morph i ne g roup se l f -

admi n i s t e r ed l ess op i o i d , perhaps due t o u r i nary r e t en -

t i on . Th i s w as t he on l y s i de e f f ec t i n wh i ch t here was

found t o be a r e l a t i onsh i p be t ween dose and s i de e f f ec t ,

a l t hough i t was n o t observed i n t he morph i ne wi t h ke t a -

m i n e g r o u p . T h e a d d i t i o n o f k e t a m i n e h a s a m o r p h i n e

spar i ng e f f ec t , and , due t o a r e l a t i ve l y l ower dose o f

se l f - admi n i s t e r ed d rug , t h i s g roup av o i ded u r i nary r e t en -

t ion.

W hi l e t he add i t i on o f ke t ami ne t o m orph i ne does p ro -

duce more po t en t ana l ges i a , w i t h a l ower i nc i dence o f

s i de e f f ec t s , t here m ay be a sub t l e a l t e r a ti on i n t he wa y

t he ke t ami ne o r i t s combi na t i on wi t h morph i ne a f f ec t s

t he r e l a ti onsh i p be t ween pa i n r epo r t i ng an d dos i ng . One

exp l ana t i on mi gh t be r e l a t ed t o t he e f f ec t o f ke t am i ne on

CANADIAN JOURNAL OF ANAESTHESIA

TABLE I Sample characteristics for morphine and morphine-plus-

ketamine groups

M o r p h i n e

V a r i a bl e M o r p h i n e K e t a m i n e

Sex 88 male 79 male

Age 39.5 • 7.2 37.3 • 9.9

Weight (kg) 83.9 • 10.7 78.2 • 13.1

TABLE 11 Side effects reported by patients receiving morphine or

morphine plus ketamine

M o r p h i n e

S i d e e f f e c t M o r p h i n e K e t a m i n e P

Dysphoria 1.85 • 0.366 1.95 • 0.213 NS

Nausea 2.20 • 1.196 1.39 • 0.755 <0.05

Pruritus 1.80 • 0.516 1.18 • 0. 39 5 <0 .0 01

Sedation 2.05 • 0.999 1.50 • 1.058 NS

Urinary retention 1.70 • 0.801 1.14 • 0.640 <0.05

TABLE 1II Correlations (r) between dose and side effects for mor-

phine and morphine-plus-ketamine groups

S i d e e f f e c t

M o r p h i n e M o r p h i n e K e t a m i n e

T o t a l d o s e m l . h r 1 T o t a l d o s e m l . h r I

Dysphoria 0.24 -0.4 2 0.28 0.29

Nausea -0.0 3 -0.14 0.08 0.07

Pruritus 0.01 0.25 0.06 0.06

Sedation 0.02 0.12 0.36 0.34

Urinary retention 0.5 1' 0.57t 0.21 0.17

P < 0 . 0 5 .

tP < 0.01.

t he t ha l amo-neocor t i ca l p ro j ec t i on sys t em.21 Ketamine

depresses neu rons i n t he co r t ex and t ha l amus , wh i l e

s i mu l t ane ous l y i ncreas i ng ac t i v i t y i n t he l i mb i c sys t em,

a phe nom enon t e rmed func t i ona l d i so rgan i za t ion . '22

Exci t a t i on o f l i mb i c func t i on i ng combi ned wi t h dep res -

s i on o f t ha l ami c co r t i ca l func t i on i ng cou l d a f f ec t t he

pa t i en t ' s emot i ona l r esponse o r eva l ua t i on o f pa i n sen -

sa t i on . Thus , pa t i en t s r ece i v i ng ke t ami ne m ay be expe r i -

enc i ng l ess su f f e r i ng o r emot i ona l r esponse t o a s i m i l a r

l eve l o f noc i cep t i on o r somat i c pa i n sensa t i on . Fu t u re

s t u di e s m i g h t e m p l o y m o r e s e n s it iv e m e a s u r e s o f b e h a v -

i ou r , pa i n , and su f f e r i ng t o e l uc i da t e t he r e l a t i onsh i p

be t we en pa i n r epo r t and me d i ca t i on dos i ng .

An i mal s t ud i es have demons t r a t ed po t en t i a t i on

b e t w e e n s u b - e f f e c t i v e d o s e s o f k e t a m i n e a n d m o r -

phine, 23,24 but th i s has not be en dem onst r ated in hu ma ns.

E d w a r d s

e t a l

18 com bi ned an i n fus i on o f morp h i ne a nd

ket am i ne fo r pos t opera t i ve ana l ges i a i n e l der l y pa t ien t s .

T h e a d d i ti o n o f k e t a m i n e d i d n o t i m p r o v e t h e a n a l g e s i a

o r pos t opera t i ve l ung func t i on . Increas i ng t he dose o f



Javery

et al.:

MORPHINE AND KETAM1NE 215

ketamine resulted only in an increased incidence of

postoperative dreaming. However, our findings support

prev ious studies 14,17 that the combina tion is useful, and

has an increased analgesic effect.

One of the most troubling side effects of ketamine is

the high incidence of adverse psychomimetic effects,

with a reported range from 4 to 80 . 25,26In our inves-

tigation, psychomimetic effects were clinically and sta-

tistically insignificant among our patients who received

ketamine with their morphine. Only one patient receiv-

ing the ketamine-plus-morphine mixture reported dys-

phoria compared with three in the morphine- only group.

We have found that the combination of ketamine at

low, sub-dissociative doses and morphine delivered via

IVPCA is a safe and effective means of providing post-

operative analgesia that deserves consideration as part

of the postoperative pain control armamentarium.

e f erence s

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response curves for midazolam and ketamine in premed-

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9 Bourke DL Mal i t LA Smi th TC.

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10

Reich DL S i lvay G.

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12

S l o g o f f S A l l e n G W . T h e

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Leunt LY Ba i l l i e TA .

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